Print Friendly and PDFPrintPrint Friendly and PDFPDFETHYLENE OXIDE
CASRN: 75-21-8

See Occupational Exposure Standards

Human Health Effects:

Evidence for Carcinogenicity:

A2; Suspected human carcinogen.
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents andBiological Exposure Indices for 2002. Cincinnati, OH. 2002. 32]**QC REVIEWED**

Evaluation: There is limited evidence in humans for the carcinogenicity of ethylene oxide. There is sufficient evidence in experimental animals for the carcinogenicity of ethylene oxide. In making the overall evaluation, the Working Group took into consideration the following supporting evidence. Ethylene oxide is a directly acting alkylating agent that: (1) induces a sensitive, persistent dose-related increase in the frequency of chromosomal aberrations and sister chromatid exchange in peripheral lymphocytes and micronuclei in bone marrow cells of exposed workers; (2) has been associated with malignancies of the lymphatic and hematopoietic system in both humans and experimental animals; (3) induces a dose related increase in the frequency of hemoglobin adducts in exposed humans and dose related increases in the numbers of adducts in DNA and hemoglobin in exposed rodents; (4) induces gene mutations and heritable translocations in germ cells of exposed rodents; and (5) is a powerful mutagen and clastogen at all phylogenetic levels. Overall evaluation: Ethylene oxide is carcinogenic to humans (Group 1).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 60 139 (1994)]**PEER REVIEWED**

Human Toxicity Excerpts:

INHALATION CAUSES NAUSEA, VOMITING, NEUROLOGICAL DISORDERS, & EVEN DEATH. TRACES OF GAS IN GLOVES OR CLOTHING MAY CAUSE BURNS. ... RESIDUES IN VASCULAR CATHETERS CAN CAUSE THROMBOPHLEBITIS; IN ENDOTRACHEAL TUBES, TRACHEITIS.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 972]**PEER REVIEWED**

... A pulmonary irritant if inhaled
[American Medical Association, Department of Drugs. Drug Evaluations. 6th ed. Chicago, Ill: American Medical Association, 1986. 1524]**PEER REVIEWED**

... MAY BE DESCRIBED AS A CENTRAL DEPRESSANT, AN IRRITANT ... CONTACT WITH ... DILUTE SOLN MAY CAUSE IRRITATION & NECROSIS OF EYES ... BLISTERING ... & NECROSIS OF SKIN. EXCESSIVE EXPOSURE MAY CAUSE IRRITATION OF ... LUNGS, & CENTRAL DEPRESSION.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2167]**PEER REVIEWED**

Conjunctivitis, dyspnea, cough, vertigo, nausea and vomiting, abdominal pain, parasystole, arrhythmia, pulmonary edema, and paralysis.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

The incidence of spontaneous abortions among hospital staff who used ethylene oxide, glutaral (glutaraldehyde) and formaldehyde for the chemical sterilization of instruments was studied using data from a questionnaire and a hospital discharge register. Results showed that the frequency of spontaneous abortions was 11.3% for the sterilizing staff and 10.6% for the nursing auxiliaries (controls). When the staff were concerned in sterilizing during their pregnancy the frequency was 16.7% compared with 5.6% for the nonexposed pregnancies. The incr frequency ... correlated with exposure to ethylene oxide but not with exposure to glutaral or formaldehyde.
[Hemminki K et al; Brit Med J 285: 1461-63 (1982)]**PEER REVIEWED**

Accidental exposure of a person to an estimated concn of 500 ppm in air for 2-3 min was enough to cause temporary unconsciousness and seizures, but apparently did not produce ocular symptoms.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 419]**PEER REVIEWED**

A report of 1st to 3rd degree burns occurring postoperatively or postpartum in 19 women. The gowns and sheets used were found to contain 16-50 times the safe residual concn of ethylene oxide.
[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982. 562]**PEER REVIEWED**

Workers who had been employed for more than one year by a company producing ethylene oxide had been studied from 1960-1961. No significant differences had been found between workers permanently working in the ethylene oxide manufacturing area, those who had previously worked in this area, those working there intermittently and a further group who had never worked in ethylene oxide production. However, a subgroup of individuals with high exposure had decreased hemoglobin concn and signficant lymphocytosis. When workers were followed up from 1961-1977, those who had been exposed full-time to ethylene oxide production showed a considerably excess mortality, this being mainly due to an increased incidence of leukemia, stomach cancer and diseases of the circulatory system. Although malignancies could not be linked to any particular chemical associated with ethylene oxide production it was considered that ethylene oxide and ethylene dichloride, possibly together with ethylene chlorohydrin or ethylene, were the causative agents.
[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982. 562]**PEER REVIEWED**

The permeation of ethylene oxide through human skin was determined in vitro. Permeation studies were performed with excised skin in diffusion cells. Ethylene oxide shows that it permeated quickly. The health hazard involved in the use of ethylene oxide in sterilization of medical goods is discussed.
[Baumbach N; Dermatol Monatsschr 173 (6): 328-32 (1987)]**PEER REVIEWED**

Chronic ethylene oxide poisoning occurred collectively in four sterilizing workers of a factory manufacturing medical appliances in Izumo, Japan. All the patients presented with symptoms of multiple neuropathy, of which the chief complaints were sensory disturbance of the lower limbs and gait disturbance. One of the patients presented with delirium and visual hallucinations. ... Clinical observations of the poisoning /were analyzed/ and the causal factors from the standpoint of industrial epidemiology and safety measures for the future /were discussed/.
[Fukushima T et al; J Soc Occup Med 36 (4): 118-23 (1987)]**PEER REVIEWED**

Chromosome aberration frequencies in 61 employees potentially exposed to ethylene oxide were compared with those in unexposed control groups. Three worksites /were studied/ with differing historical ambient levels of ethylene oxide. Within worksites, groups were classified as high potential exposed, low potential exposed, or controls. Further control groups including an off-site community control group were added to give a total of 304 control individuals. Blood samples were drawn several times over a 24-month period. Aberrations were analyzed in 100 cells per sample after culture for 48-51 hours. Worksites I, II, and III respectively represented increasing levels of potential ethylene oxide exposure. At worksites I and II, no consistent differences in aberration frequencies were found among groups. At worksite III aberration frequencies in potentially exposed individuals were significantly increased compared with controls. The frequencies of cells with aberrations were 5.6% for the 2 individuals in the high potential exposure category and 2.6% for 23 persons in the low potential exposure group. The overall frequency of cells with aberrations in the matched control individuals was 1.4%. In the total control group of 304 individuals, ... significant increases in aberrations associated with smoking and increasing age /were found/.
[Galloway SM et al; Mutat Res 170 (1-2): 55-74 (1987)]**PEER REVIEWED**

A retrospective cohort study was performed on a group of 664 male workers employed for at least one month during the period 1942-1979 in a chemical factory. Both established and suspected carcinogens had been handled in the plant, primarily piperazine, but also urethane, ethylene oxide, formaldehyde, and organic solvents. A significantly increased mortality, compared with the regional death rate, was observed in the cohort. The increase was mainly due to violent deaths and cardiovascular diseases. A statistically significant increase in cancer morbidity was observed for malignant lymphoma/myelomatosis when an induction latency time /minimum/ of 10 years was used. Furthermore, an increase in bronchial cancer was noted, but it was statistically significant only when an induction-latency time /minimum of/ 15 years was used.
[Hagmer L et al; Scand J Work Environ Health 12 (6): 545-51 (1987)]**PEER REVIEWED**

Samples of blood were collected from a group of plant workers engaged in the manufacture of ethylene oxide for periods of up to 14 yr, and also from a group of control personnel matched by age and smoking habits. Peripheral blood lymphocytes were cultured for cytogenetic analysis. Selected immune and hematological parameters were also investigated. The results of these studies showed no statistically significant difference between the group of plant workers and the control group in respect to any of the biological parameters investigated in this study. Nevertheless, duration of employment in ethylene oxide manufacturing was positively correlated (p< 0.05) with the frequency of chromosome breaks and with the percentage of neutrophils in a differential white blood cell count, and negatively correlated (p< 0.05) with the percentage of lymphocytes. As the values of these parameters remained within the normal limits of control populations, the correlations were considered to have no significance for health. The amount of alkylation (2-hydroxyethyl groups) of the Nt atom of histidinyl residues in hemoglobin was also measured in an attempt to gauge recent individual exposures to ethylene oxide. Variable but, in most instances, readily measurable amounts of Nt- (2'-hydroxyethyl)-L-histidine (Nt represents the N3 atom of histidine) were found in the hemoglobin of plant workers and in the control group who had not knowingly been exposed to an exogenous source of ethylene oxide. There was no statistically significant difference between the results obtained in the control group and in the group of plant workers.
[Van Sittert et al; Br J Ind Med 42 (1): 19-26 (1985)]**PEER REVIEWED**

A study was made of the effects of ethylene oxide on the health of sterilizer workers and other personnel exposed while using ethylene oxide for sterilization of disposable medical devices. The only significant findings were obtained by chromosomal analysis of cultured lymphocytes harvested from the workers. There were significant differences in the numbers and types of chromosomal aberrations between the exposed workers and the nonexposed controls. Quadriradial and triradial chromosomal forms, which were rarely found in nonexposed populations, were increased in exposed workers. Increased numbers of sister chromatid exchanges was found in the cultured lymphocytes of some, but not all, exposed persons during the 2 yr of study. Workers (13) were removed from exposure in 1979 because of increased numbers of aberrant cells. Follow-up over 4 yr did not show a significant improvement, except for a moderate reduction in sister chromatid exchanges. Recommendations were given for a surveillance of persons working with or exposed to ethylene oxide.
[Richmond GW et al; Arch Environ Health 40 (1): 20-25 (1985)]**PEER REVIEWED**

... Dialyzer hypersensitivity syndrome presents as an acute anaphylactoid reaction, the symptoms of which may range from mild to life threatening in severity. The cause of this syndrome is unknown, but affected patients appear to have a high incidence of positive radioallergosorbent tests to a conjugate of human serum albumin and ethylene oxide, suggesting that ethylene oxide, a substance used to dry sterilize artificial kidneys, may be an offending allergen.
[Carvana RJ et al; Am J Nephrol 5 (4): 271-74 (1985)]**PEER REVIEWED**

Samples of peripheral blood were collected from 33 men who were employed in the manufacture of ethylene oxide for between 1 and 14 yr, and from 32 men from other parts of the same plant who were used as controls. Their lymphocytes were analyzed for chromosome damage. There were low frequencies of polyploidy, chromatid aberrations and chromosome breaks in the cells of the 65 men. A slightly higher frequency of chromatid aberrations was observed in the cells of the ethylene oxide workers than in those of the controls. There was a positive correlation between length of employment in the ethylene oxide group and the numbers of aberrations in the cultures of each individual. This trend was not solely attributable to the age of the men. The levels of chromatid and chromosome damage observed in this study are consistent with those in humans who were not recently exposed to known chromosome-breaking agents.
[Clare MG et al; Mutat Res 156 (1-2): 109-16 (1985)]**PEER REVIEWED**

EXPOSURE TO LOW VAPOR CONCN OFTEN RESULTS IN DELAYED NAUSEA AND VOMITING. HIGHER CONCN PRODUCE IRRITATION OF EYES, NOSE, AND THROAT; HIGH CONCN MAY CAUSE EDEMA OF LUNGS. CONTACT WITH SKIN CAUSES BLISTERING AND BURNS.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Concern about the possible adverse influence of the workplace environemnt on reproduction now extends to women health professionals. ... A postal survey of all women who graduated from US veterinary schools during the period 1970-1980 (n = 2,997; response rate = 90.2%) /was conducted/. Occupational and reproductive histories were obtained, and spontaneous abortion risks were estimated with respect to self-reported exposure to radiation, ethylene oxide, halothane and other anesthetic gases, and pesticides. Of the 2,174 pregnancies among cohort members who had one veterinary job at the time of conception, 83.3% of the conceptions occurred while the veterinarian held a job that involved exposure to pesticides, 63.2% involved exposure to radiation, 61.9% to anesthetic gases other than halothane, 50.7% to halothane, and 14.0% to ethylene oxide. Agent-specific spontaneous abortion risks were estimated for the exposed/unexposed pregnancies, and risk ratios adjusted for gravidity, history of spontaneous abortion, age and alcohol and tobacco use were derived by means of logistic regression. Estimated risk ratios were close to 1.0, and no effect was seen for hours worked per week, a measure of exposure intensity. Despite no apparent influence of the exposures on spontaneous abortion risk, caution must be exercised in interpretation of these results because of potential exposure misclassification. Importantly, the results emphasize the extent to which women veterinarians may be exposed to reproductive hazards while pregnant.
[Steele L et al; Am J Epidemol 130 (4): 834 (1989)]**PEER REVIEWED**

Eight hospital workers with chronic ethylene oxide exposure were age-sex matched with eight nonexposed controls with no significant differences in educational backgrounds and vocabulary scores. The exposed group performed more poorly on all eight measures of cognition, memory, attention, and coordination, with 71.3% less accuracy on the Hand-Eye Coordination Test. There was a dose-response relationship between exposure and the following: Continuous Performance Test and sural velocity. These findings suggest that neurologic dysfunction may result from long-term low-dose exposure to ethylene oxide, and that these effects may occur at exposure levels common in hosptial sterilizer operations.
[Estrin WJ et al; Arch Neurol 44 (12): 1283-6 (1987)]**PEER REVIEWED**

Ethylene oxide is an alkylating agent and a model direct-acting mutagen and carcinogen. This study has evaluated a panel of biologic markers including ethylene oxide-hemoglobin adducts, sister-chromatid exchanges, micronuclei, chromosomal aberrations, DNA single-strand breaks and an index of DNA repair (ratio of unscheduled DNA synthesis to NA-AF-DNA binding) in the peripheral blood cells of 34 workers at a sterilization unit of a large university hospital and 23 controls working in the univer library. Comprehensive environmental histories were obtained on each subject including detailed occupational and smoking histories. Industrial hygiene data obtained prior to the study and personal monitoring during the 8 years preceding the study showed that workers were subject to low level exposure near or below the current Occupational Safety and Health Administration (OSHA) standard of 1 ppm (TWA). Personal monitoring data obtained during 2 weeks prior to blood sampling were uniformly less than 0.3 ppm (TWA). After adjusting for smoking, ethylene oxide workplace exposure was significantly (p< 0.001) associated with ethylene oxide hemoglobin (a carcinogen protein adduct) and 2 measures of sister chromatid (the average number of sister chromatid exchanges/cell (SCE50) and the number of high frequency cells (SCEHFC). There was an apparent suppression of DNA repair capacity in ethylene oxide exposed individuals as measured by the DNA repair index; ie, the ratio of unscheduled DNA synthesis and NA-AAF-DNA binding (p< 0.01). No association of DNA repair index with smoking was found. Another important finding of this study is the highly significant correlation between ethylene oxide-hemoglobin adduct levels and SCEHFC (p< 0.01) and sister-chromatid exchanges (p< 0.02) which provides evidence of a direct link between a marker of biologically effective dose and markers of genotoxic response. In contrast, micronuclei, chromosomal aberrations and single-strand breaks were not significantly elevated in the workers. The activity of the u-isoenzyme of glutathione-S-transferase was measured as a possible genetic marker of susceptibility and a modulator of biomarker formation. However, possibly because of confounding by age, no significant relationships were found between glutathione-S-transferase and any of the exposure-related markers by ANOVA or among other independent variables by regression.
[Mayer J et al; Mutat Res 248 (1): 163-76 (1990)]**PEER REVIEWED**

A multicenter cohort study was carried out to study the possible association between exposure to ethylene oxide and cancer mortality. The cohort consisted of 2658 men from eight chemical plants of six chemical companies in the Federal Republic of Germany who had been exposed to ethylene oxide for at least one year between 1928 and 1981. The number of subjects in the separate plants varied from 98 to 604. By the closing date of the study (31 December 1982) 268 had died, 68 from malignant neoplasms. For 63 employees who had left the plant (2.4%) the vital status remained unknown. The standardized mortality ratio for all causes of death was 0.87 and for all malignancies 0.97 compared with national rates. When local state rates were used the standardized mortality ratio were slightly lower. Two deaths from leukemia were observed compared with 2.35 expected standardized = 0.85). Standardized mortality ratios for carcinoma of the esophagus (2.0) and carcinoma of the stomach (1.38) were raised but not significantly. In one plant an internal "control group" was selected matched for age, sex, and date of entry into the factory and compared with the exposed group. In both groups a "healthy worker effect" was observed. The total mortality and mortality from malignant neoplasms was higher in the exposed than in the control group; the differences were not statistically significant. There were no deaths from leukemia in the exposed group and one in the control group.
[Kiesselbach N et al; Br J Ind Med 47 (3): 182-8 (1990)]**PEER REVIEWED**

We have applied the micronucleus assay to exfoliated cells of buccal and nasal cavities to monitor the genotoxic risk in a group of workers exposed to chromic acid and in another group exposed to ethylene oxide. The first group comprised 16 subjects working in a hard type chrome plating factory showing increased chromium absorption and chromium induced rhinopathy. The second group comprised 9 subjects working in a sterilization unit, exposed to ethylene oxide concentrations lower than 0.38 ppm as timed weighted average for a working shift; 3 of them were involved in a acute exposure too. The frequency of micronucleus in buccal mucosa was within the norm for exposure both to chromium and to ethylene oxide. The micronucleus frequency in nasal mucosa was not altered in chromium platers, whereas a significant increase (p less than 0.01) in micronucleus was found in 2 out of 3 subjects involved in the accidental ethylene oxide leakage and a non-significant increase in micronucleus was found in the group chronically exposed to ethylene oxide.
[Sarto F et al; Mutat Res 244 (4): 345-51 (1990)]**PEER REVIEWED**

Work practices as well as personal and environmental exposure levels were reported among ethylene oxide sterilizer operators in health care facilities in the province of Alberta, Canada. A survey was undertaken between October of 1985 and September of 1986 concerning the use of and exposure to ethylene oxide in 174 hospitals. The first part of the survey considered all hospitals with ethylene oxide sterilizers, inquiring about their use at the facility. The second part of the survey queries workers (14 men and 151 women) concerning their work history and health status. While no detectable levels of ethylene oxide were found in environmental samples, over half of the respondents stated they could smell ethylene oxide at work. While sampling results never indicated concentrations above the provincial 15 minute time weighted average short term exposure limit of 50 ppm, personal exposure concentrations and the use of portable sterilizers were positively associated with short term symptoms such as irritations of the mucous membranes and skin. Life style behavior and exposure to other chemical irritants were not considered in the course of this study.
[Bryant HE et al; J Society of Occup Med 39 (3): 101-6 (1989)]**PEER REVIEWED**

A retrospective cohort study was conducted to examine the mortality experience of 2174 men employed between 1940 and 1978 by a large chemical company and who had been assigned to a chemical production department that used or produced ethylene oxide. Comparisons were made with the general United States population, the regional population, and with a group of 26,965 unexposed men from the same plants. Comparisons with general United States death rates showed fewer deaths than expected in the ethylene oxide group due to all causes and for total cancers. There was no statistically significant excess of deaths due to any cause. Seven deaths each due to leukemia and pancreatic cancer were observed with 3.0 and 4.1 deaths expected. Among the subcohort of men who worked where both average and peak exposure levels were probably highest, however, one death due to pancreatic cancer (0.9 expected) and no deaths due to leukemia were observed. Four of the seven who died from leukemia and six of the seven died from pancreatic cancer had been assigned to the chlorohydrin department where the potential for exposure to ethylene oxide is judged to have been low. The relative risk of death due to each disease was strongly related to duration of assignments to that department. When men who worked in the chlorohydrin department were excluded, there was no evidence for an association of exposure to ethylene oxide with pancreatic cancer or leukemia. Together with the failure to show independent ethylene oxide associations, the chlorohydrin department results suggest that leukemia and pancreatic cancer may have been associated primarily with production of ethylene chlorohydrin or propylene chlorohydrin, or both. These results emphasize the importance of examing additional concurrent asynchronous exposures among human populations exposed to ethylene oxide.
[Greenberg HL et al; Br J Ind Med 47 (4): 221-30 (1990)]**QC REVIEWED**

An epidemiological study was conducted in 55 subjects (mean age: 41) in hospitals to determine the prevalence of lens opacities and cataracts in workers exposed to ethylene oxide in six sterilization units. The relation between occupational exposure to ethylene oxide and white blood cell concentrations was also investigated. Lens opacities were observed in 19 of the 55 exposed. No link was found between the characteristics of the lens opacities and the characteristics of exposure. For cataracts, their prevalence differed significantly between the exposed (six of 21) and the non-exposed (0 of 16); there was no relation between their existence and overexposures. The risk of lens opacifications by ethylene oxide could also exist during chronic exposure to low concentrations. Linear relations were found between the logarithm of the cumulative exposure index and the logarithms of blood concentrations of polymorphoneutrophils.
[Deschamps D et al; Br J Ind Med 47 (5): 308-13 (1990)]**PEER REVIEWED**

A cohort study was carried out of mortality among 2876 men and women exposed to ethylene oxide during its manufacture and use in England and Wales. The study cohort included employees from three companies producing ethylene oxide and derivative compounds such as polyethylene glycols and ethoxylates, from one company that manufactured alkoxides from ethylene oxide and from eight hospitals with ethylene oxide sterilizing units. While industrial hygiene data were not available before 1977, since then the time weighted average exposures have been less than 5 ppm in almost all jobs and less than 1 ppm in many. Past exposures were probably somewhat higher. In contrast to other studies, no clear excess of leukemia was noted (three deaths occurred versus 2.09 expected), and no increase in the incidence of stomach cancer (five deaths occurred versus 5.95 expected) was observed. This lack of consistency with the results of earlier studies may be due to differences in exposure levels. Total cancer mortality was similar to that expected from national and local death rates from this disease. Small excesses were noted in some specific cancers, but their relevance to ethylene oxide exposure was doubtful. No excess of cardiovascular disease was found. While the results of this study did not exclude the possibility that ethylene oxide is a human carcinogen, they suggested that any risk of cancer from currently permitted occupational exposures is small.
[Gardner MJ et al; Br J Ind Med 46 (12): 860-5 (1989)]**PEER REVIEWED**

Ethylene oxide is widely used to sterilize heat-sensitive materials. Acute and chronic neurogenic effects to the central and peripheral nervous system in man and animals have been described. A cross-sectional study of 25 hospital central supply workers exposed to low levels of ethylene oxide and 24 unexposed control workers was conducted. Subjects were tested with a neuropsychological screening battery by examiners blinded to exposure status. Results were reviewed independently by 2 neuropsychologists without knowledge of exposure. Subject status was categorized as normal, impaired, or disagreement (between the two neuropsychologists). There were more subjects concordantly judged as impaired in the exposed group than in the control group. Although limited by the cross-sectional study design and the global categorization, these findings suggest that central nervous system dysfunction and cognitive impairment may result from chronic ethylene oxide exposure in hospital central supply units.
[Klees JE et al; Clin Toxicol 28 (1): 21-8 (1990)]**PEER REVIEWED**

Ethylene oxide is used to chemically sterilize heat-sensitive materials in hospitals. Neurotoxic effects of ethylene oxide have been described in animals and humans; cognitive deficits may be associated with chronic low level ethylene oxide exposure. In this study, hospital workers with chronic ethylene oxide exposure were compared with a non-exposed control group to detect neurological and neuropsychological abnormalities. Ethylene oxide breathing zone levels of up to 250 ppm in exposed subjects were reported. The exposed group had lower P300 amplitude in electroencephalographic (EEG) tests, bilaterally hypoactive distal deep tendon reflexes and poorer performance on neuropsychological tests involving psychomotor speed. Exposed subjects acknowledge more symptoms and higher levels of depression and anxiety. Nerve conduction velocities and EEG spectral analysis were simialr in both exposed and control groups as were scores on most psychological tests.
[Estrin WJ et al; Clin Toxicol 28 (1): 1-20 (1990)]**PEER REVIEWED**

A 43 yr old female licensed practical nurse, while sterilizing heat sensitive medical items, accidentally dropped and broke an ampule containing 17 gm epoxyethane. While disposing of the broken ampule, she began to experience nausea and stomach spasms. The exposure was estimated to have been of 2-3 min duration and not to have exceeded 500 ppm. Upon leaving the contaminated room, she became pale, lightheaded, and passed out for approximately 3-4 min. Convulsive movements of her arms and legs were noted during a 1-min period of apnea. She was given oxygen, began breathing, and awoke instantly without confusion or nausea. Approximately 3 min later she again felt nausea, stomach spasms, and lightheadedness and became apneic and passed out. Twitching of the extremities occurred and she was given oxygen again. Arterial blood gases, chest X rays, and routine laboratory measurements performed at that time were normal. During the 24 hr following discharge she continued to complain of random muscle twitches, nausea, and malaise.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 666]**PEER REVIEWED**

The presence of ethylene oxide in dialysis tubing has been suggested as a possible cause of allergic reactions in some patients. Ethylene oxide also is a pulmonary irritant when inhaled. It is too toxic to be applied topically as an antiseptic.
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994. 1620]**PEER REVIEWED**

Three cases of hematopoietic cancer that had occurred been 1972 and 1977 /were reported/ in workers at a Swedish factory where 50% ethylene oxide and 50% methyl formate had been used since 1968 to sterilize hospital equipment. Attention had been drawn to the case cluster by the factory safety committee. One woman with chronic myeloid leukaemia and another with acute myelogenous leukaemia had worked in a storage hall where they were exposed for 8 hr per day to an estimated 20 plus or minus 10 (SD) ppm (36 plus or minus 18 mg/cu m) ethylene oxide. The third case was that of a man with primary macroglobulinemia (morbus Waldenstrom) who had been manager of the plant since 1965 and had been exposed to ethylene oxide for an estimated 3 hr per week. (The Working Group noted that Waldenstrom's macroglobulinemia is classified in ICD /International Classification of Diseases codes/ 10 as a malignant immunoproliferative disease.)
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V60 89 (1994)]**PEER REVIEWED**

Two hundred and three workers employed for at least one year at /a Swedish factory where 50% ethylene oxide and 50% methyl formate had been used since 1968 to sterilize hospital equipment/ were subsequently followed up for mortality. During 1978-82, five deaths occurred (4.9 expected), of which four were from cancer (1.6 expected). Two of the deaths were from lymphatic and hematopoietic cancer (0.13 expected), but one of these decedents had been part of the original case cluster that had prompted the study.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V60 89 (1994)]**PEER REVIEWED**

A retrospective cohort study /was reported/ of 767 men employed at a chemical plant in eastern Texas, USA, between 1955 and 1977 where ethylene oxide was produced. All of the men had worked at the factory for at least five years and were potentially exposed to the compound. Potential exposure to ethylene oxide was determined by personnel at the company on the basis of work histories. In an industrial hygiene survey in all samples taken in the ethylene oxide production area contained less than 10 ppm (18 mg/cu m). Vital status was ascertained for more than 95% of cohort members from a combination of plant records, personal knowledge and telephone follow-up. Altogether, 46 deaths were recorded, whereas 80 were expected on the basis of US vital statistics. Death certificates were obtained for 42 of the 46 deceased subjects. Eleven deaths were from cancer (15.2 expected), and nonsignificant excesses were seen of cancers of the pancreas (3/0.8) and brain and central nervous system (2/0.7) and of Hodgkin's disease (2/0.4); no death from leukaemia was found.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V60 90-1 (1994)]**PEER REVIEWED**

18,254 employees at 14 US industrial plants where ethylene oxide had been used to sterilize medical supplies or spices or in the testing sterilizing equipment /were followed/. The plants were selected because they held adequate records on personnel and exposure and their workers had accumulated at least 400 person-years at risk before 1978. Only workers with at least three months of exposure to ethylene oxide were included in the cohort. Forty five percent of the cohort were male, 79% were white, 1,222 were sterilizer operators and 15,750 were employed before 1978. Analysis of 627 8 hr personal samples indicated that average exposure during 1976-85 was 4.3 ppm (7.7 mg/cu m) for sterilizer operators; the average level for other exposed workers, on the basis of 1,888 personal samples, was 2.0 ppm (3.6 mg/cu m). Many companies began to install engineering controls in 1978, and exposures before that year were thought to have been higher. There was no evidence of confounding exposure to other occupational carcinogens. The cohort was followed to 1987 through the national death index and records of the Social Security Administration, the Internal Revenue Service and the US Postal Service, and 95.5% were traced successfully. The expected numbers of deaths were calculated from rates in the US population, stratified according to age, race, sex and calendar year. In total, 1,177 cohort members had died (1,454.3 expected), including 40 for whom no death certificate was available. There were 343 deaths from cancer (380.3 expected). The observed and expect numbers of deaths were 36/33.8 from all lymphatic and hematopoietic cancer, including 8/5.3 from lymphosarcoma-reticulosarcoma (ICD9 200), 4/3.5 from Hodgkin's disease, 13/13.5 from leukaemia, 8/6.7 from non-Hodgkin's lymphoma (ICD9 202) and 3/5.1 from myeloma; 6/11.6 from cancer of the brain and nervous system; 11/11.6 from cancer of the stomach; 16/16-9 from cancer of the pancreas; 8/7.7 from cancer of the oesophagus; and 13/7.2 from cancer of the kidney. Mortality ratios for subjects first exposed before 1978 were virtually identical to those for the full cohort. No significant trend in mortality was observed in relation to duration of exposure, but the mortality ratios for leukaemia (1.79 based on five deaths) and non-Hodgkin's Lymphoma (1.92 based on five deaths) were higher after allowance for a latency of more than 20 years. Among the sterilizer operators, mortality ratios (and observed numbers of deaths) were 2.78 (two) for leukaemia and 6.68 (two) for lymphosarcoma/reticulosarcoma; no death from stomach cancer was seen.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V60 94-5 (1994)]**PEER REVIEWED**

Repeat plasma donors were studied to determine whether there was a relationship between allergic-type reactions during plasmapheresis and IgE-dependent sensitization to ethylene oxide gas used for sterilization of disposable fluid administration sets. Serums from 32 donors with allergic-type reactions and 84 donors who had no reactions but were exposed to the same materials and served as controls were tested for IgE antibodies to ethylene oxide. The results, expressed as an IgE ethylene oxide index, were greater than 2 in 78% of serums from donors with allergic and 12% of serums from controls. This association was significant (p< 0.0001). Reactivity of the antibodies was directed against an ethylene oxide-human serum albumin conjugate and not against human serum albumin carrier protein. IgG antibodies with ethylene oxide specificity also were present in the serums of repeat plasmapheresis donors. Each of seven rabbits immunized with an ethylene oxide-protein conjugate responded with a high serum level of antibody with ethylene oxide specificity. It was concluded that the residual ethylene oxide in fluid administration sets is immunogenic and may cause allergic reactions in plasma donors.
[Dolovich J et al; Transfusion 27 (1): 90-93 (1987)]**PEER REVIEWED**

Chromosomal aberrations and micronuclei in lymphocytes were measured in workers exposed to propylene oxide in a factory producing alkylated starch, and in workers exposed to ethylene oxide in connection with sterilization of medical equipment. Adduct levels in hemoglobin were determined as a measure of in vivo doses of the two compounds. The levels of hydroxypropylvaline in propylene oxide exposed workers were correlated in estimated exposure doses. The levels of this adduct in the unexposed group were close to the detection limit of the method. The levels of hydroxyethylvaline, recorded in the propylene oxide-exposed group were consistent with earlier data on hemoglobin alkylation in occupationally unexposed subjects. The adduct measurements revealed increased levels of hydroxyethylvaline in the two subgroups of ethylene oxide-exposed workers, ie, assemblers with a low and sterilizers with a high exposure. According to expectation the subgroups differed in adduct levels. The results of the cytogenetic study showed that the clastogenic potency of propylene oxide was lower than that of ethylene oxide, since the propylene oxide-exposed individuals had lower frequencies of micronuclei and chromosomal breaks compared to the assemblers despite a lower adduct level in the last group.
[Hogstedt B et al; Hereditas 113 (2): 133-8 (1990)]**PEER REVIEWED**

Cases of human ethylene oxide (EtO) neuropathy were reviewed and the clinical features characterized. ... The 12 patients with EtO toxicity selected for review were each engaged ln sterilizing work with EtO in the factory or hospital. Sensorimotor neuropathy developed in two patients within 3 and 5 months of exposure. They had been repeatedly exposed to EtO for up to several hundred ppm. Complaints included muscle weakness hypesthesia and a tingling sensation in distal lower limbs although distal upper limbs were also sometimes involved. Ten of the 12 demonstrated muscle weakness in neurological examinations. Needle EMG revealed neurogenic changes in eight. Histological studies of the sural nerve biopsied in three patients demonstrated mild abnormalities. Cerebrospinal fluid studies showed elevated protein in two of six patients. ...
[Ohnishi A; Murai Y; Environ Res 60 (2): 242-7 (1993)]**PEER REVIEWED**

Mortality from cancer among workers exposed to ethylene oxide (EtO) has been studied in 10 distinct cohorts that include about 29800 workers and 2540 deaths. This paper presents a review and meta-analysis of these studies, primarily for leukemia, nonHodgkin's lymphoma, stomach cancer, pancreatic cancer, and cancer of the brain and nervous system. The magnitude and consistency of the standardized mortality ratios (SMRs) were evaluated for the individual and combined studies, as well as trends by intensity or frequency of exposure, by duration of exposure, and by latency (time since first exposure). Exposures to other workplace chemicals were examined as possible confounder variables. Three small studies ... initially suggested an association between EtO and leukemia, but ln seven subsequent studies the SMRs for leukemia have been much lower. For the combined studies the SMR = 1.06 (95% confidence interval (95% CI) 0.73-1.48). There was a slight suggestion of a trend by duration of exposure (p = 0-19) and a suggested incr with longer latency (p = 0.07), but there was no overall trend in risk of leukemia by intensity or frequency of exposure; nor did a cumulative exposure analysis in the largest study indicate a quantitative association. There was also an indication that ln two studies with Increased risks the workers had been exposed to other potential carcinogens. For non-Hodgkin's lymphoma there was a suggestive risk overall (SMR = 1.35, 95% CI 0.93-1.90). Breakdowns by exposure intensity or frequency, exposure duration, or latency did not indicate an association, but a positive trend by cumulative exposure (p = 0.05) was seen In the largest study. There was a suggested incr ln the overall SMR for stomach cancer (SMR = 1.28, 95% CI 0.98-1.65 (CI 0.73-2.26 when heterogeneity among the risk estimates was taken Into account)), but analyses by intensity or duration of exposure or cumulative exposure did not support a causal association for stomach cancer. The overall SMRs and exposure-response analyses did not indicate a risk from EtO for pancreatic cancer (SMR = 0.98), brain and nervous system cancer (SMR = 0.89), or total cancer (SMR = 0.94). Although the current data do not provide consistent and convincing evidence that EtO causes leukemia or non-Hodgkin's lymphoma, the issues are not resolved and await further studies of exposed populations.
[Shore Re et al; British J Indust Med 50 (11): 971-97 (1993)]**PEER REVIEWED**

Ethylene oxide (EtO) induced mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene were characterized in 28 independently derived 6-thioguanine resistant human diploid fibroblast clones using polymerase chain reaction based techniques and Southern blot analysis. Sequence analysis revealed one single base pair deletion and 13 base substitutions nine of which were transversions: five AT-TA three GC-TA and one GC-CG. Four mutants were found to have GC-AT transitions. Seven of the point mutations caused splicing errors. Six occurred in splice site sequences and one created a new splice acceptor site 16 bp upstream of exon 9. Three splice mutations were localized at the same site in the splice donor sequence of intron 8. Fourteen mutants had large HPRT gene deletions. In seven mutants the entire HPRT gene was deleted. The remaining deletion mutants had a truncated HPRT gene where one or several exons were lost. These results show that EtO induces many different kinds of HPRT mutations, among which as many as 50% are large deletions.
[Bastlova T et al; Mutat Res; 287 (2): 283-92 (1993)]**PEER REVIEWED**

A cohort of 1971 chemical workers licensed to handle ethylene oxide was followed up retrospectively from 1940 to 1984 and the vital status of each subject was ascertained. No quantitative information on exposure was available and therefore cohort members were considered as presumably exposed to ethylene oxide. The cohort comprised 637 subjects allowed to handle only ethylene oxide and 1334 subjects who obtained a license valid for ethylene oxide as well as other toxic gases. Potential confounding arising from the exposure to these other chemical agents was taken into consideration. Causes of death were found from death certificates and comparisons of mortality were made with the general population of the region where cohort members were resident. Seventy six deaths were reported whereas 98.8 were expected; the difference was statistically significant. The number of malignancies for any site exceeded the expected number (standardized mortality ratio (SMR) = 130; 43 observed deaths; 95% confidence interval (95% CI) 94-175) and approached statistical significance. For all considered cancer sites the SMRs were higher than 100 but the excess was only significant p < 0.05, two sided test for lymphosarcoma and reticulosarcoma ICD-9 = 200; SMR = 682; four observed deaths; (95% CI 186-1745) The excess of cases for all cancers of hematopoietic tissue (ICD-9)= 200-208) also approached statistical significance (SMR = 250; six observed deaths; 95% CI 91-544).
[Bisanti L et al; Br J Ind Med; 50 (4): 317-24 (1993)]**PEER REVIEWED**

Human Toxicity Values:

No effect level: 5-10 ppm, during 10 yr; severe toxic effects: 60 min 250 ppm= 450 mg/cu m; symptoms of illness: 100 ppm= 180 mg/cu m; unsatisfactory >10 ppm= 18 mg/cu m
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983.,p. 654-655]**PEER REVIEWED**

Skin, Eye and Respiratory Irritations:

Ethylene oxide is irritating to the eyes, respiratory tract, and skin.
[Rom, W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 1992. 1034]**PEER REVIEWED**

Aqueous solutions of ethylene oxide or solutions formed when the anhydrous cmpd comes in contact with moist skin are irritating and may lead to a severe dermatitis with blisters, blebs and burns. It is also absorbed by leather and rubber and may produce burns or irritation. Allergic eczematous dermatitis has also been reported. Exposure to the vapor in high concn leads to irritation of the eyes. Severe eye damage may result if the liquid is splashed in the eyes. Large amounts of ethylene oxide evaporating from the skin may cause frostbite.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 433]**PEER REVIEWED**

Medical Surveillance:

Biological monitoring of ethylene oxide exposure by analysis of alveolar air and blood was studied in 10 workers employed in a hospital sterilizer unit. Environmemtal air, alveolar air, and venous blood were sampled during and at the end of an 8 hr workshift. The mean environmental concentration of ethylene oxide was 5.4 mg/cu m air and the mean alveolar ethylene oxide concentration was 1.2 mg/cu m alveolar air. Regression analysis showed that blood ethylene oxide concentrations were higher than environmental ethylene oxide concentrations by a mean ratio of 3 and higher than alveolar ethylene oxide concentrations by a mean ratio of 12.
[Brugnone F et al; Int Arch Occup Environ Health 58: 105-12 (1986)]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 23]**PEER REVIEWED**

The 1984 OSHA standard for ethylene oxide (EtO) mandates medical surveillance under various circumstances. When performed medical surveillance for EtO must include a complete blood count (CBC) with differential leukocyte count. This requirement is based on reports of EtO associated absolute lymphocytosis and other hematologic effects. This paper describes experiences in providing EtO medical surveillance for a 300 bed hospital over a 6 year period. An apparent relative lymphocytosis which persisted over 3-4 years in sterilization workers with documented TWA personal EtO exposures averaging 0.07 ppm /was observed/. In addition three workers had a history of acutely toxic overexposure to EtO as a result of a sterilizer malfunction. These workers became symptomatic following the high accidental overexposure but did not show absolute lymphocytosis or altered patterns in the relative lymphocytosis. Finally a cross-sectional comparison of the CBC data from the EtO exposed workers to data from non-EtO exposed hospital workers showed no significant differences ruling out an association of the relative lymphocytosis with EtO exposure. These observations led us to review the basis for the inclusion of the CBC in routine EtO medical surveillance. /Such/ experience, review of the literature on EtO associated lymphocytosis and anemia, and review of the literature on the use of the CBC with differential as screening test suggest that the leukocyte differential may not be useful in routine medical surveillance for EtO exposure.
[LaMontagne AD et al; Am J Ind Med; 24 (2): 191-206 (1993)]**PEER REVIEWED**

In a study on workers in a chemical plant where ethylene oxide (EtO) is manufactured and partly used for ethylene glycol production, exposure to EtO was monitored during annual periodic health assessments In January 1988, December 1988, and March 1990 by the determination of the level of 2-hydroxyethylvaline in hemoglobin. The 2-hydroxyethylvaline levels in workers corresponded with the potential EtO exposures. The highest level was found in December 1988, in blood samples collected 1-2 months after a shut down, maintenance, and start up program. The range of adduct levels found in the three examinations indicated that average EtO exposures during the 4 months preceding blood sampling were below 0.5 ppm. It was demonstrated that the method allows for the accurate monitoring of low levels of EtO exposure and provides personalized time integrated exposure data with great discriminative power. In addition, the method may serve to identify unexpected personal exposures, which may lead to targeted exposure control measures.
[van Sittert NJ et al; Environ Health Perspect 99: 217-20 (1993)]**PEER REVIEWED**

Populations at Special Risk:

Ethylene oxide is a suspected occupational toxicant of the male reproductive system indigenous to the occupation of hospital sterilizers. /From table/
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 144]**PEER REVIEWED**

Industrial and occupational exposure is generally the result of inhalation of ethylene oxide vapor released from leaking or faulty equipment, valves, or fittings.
[O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume II. Boca Raton, FL: CRC Press, Inc., 1985. 86]**PEER REVIEWED**

/Hospital workers/ operating a defective ethylene oxide sterilizer.
[O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume II. Boca Raton, FL: CRC Press, Inc., 1985. 86]**PEER REVIEWED**

Probable Routes of Human Exposure:

Exposure to ethylene oxide is primarily occupational via inhalation. (SRC)
**PEER REVIEWED**

OSHA estimates that approximately 80,000 and 144,000 workers are directly and indirectly exposed to ethylene oxide in ethylene oxide production, chemical synthesis by ethoxylation, health care facilities (sterilization), medical products (sterilization) and miscellaneous manufacturers (e.g., spice sterilization)(1). The number of workers exposed directly (indirectly) in the various industries are: production and synthesis 3676; sterilization - health care facilities 62,370 (25,000); sterilization - medical products manufacture 14,000 (116,900); sterilization - spice manufacturers 160(1). Typical exposures are usually high during short periods in which sterilizer doors are opened, typically 5-10 ppm for 20 minutes(1). Some typical survey results are: Medical products manufactures 0.1.1-2.0 ppm 8 hr TWA; Hospital sterilizer chamber operators 2.5 ppm TWA; 121 use sites in Southern California <5 ppm (TWA) in 114/121 sites; 2 hospitals 3-6 ppm and <5 ppm resp; survey of 27 hospitals TWA exposures less than or equal to 1, <4 and >10 ppm in 9/27, 16/27 and 5/27, respectively(1). Union Carbide production plant in Texas City 5-33 ppm and 7.25 and 10.25 ppm avg in 2 control rooms and 0-56 ppm, 11.6 ppm avg throughout plant(2). In-depth survey of 2 Union Carbide production facilities in West Virginia- 2 of 48 and 4 of 41 samples positive, TWA exposure of positive samples 1.5-82 ppm(4,5). Production and maintenance workers in the 1960's avg exposure levels 0.6-60 ppm(3).
[(1) OSHA; Occupational Exposure to Ethylene Oxide; Proposed Rule. 48 FR 17283-17319 4,21 (1983) (2) Joyner RE; Arch Environ Health 8:700-10 (1964) (3) Hogstedt C et al; Brit J Ind Med 36:276-80 (1979) (4) Oser JL; In-depth Industrial Hygiene Report of Ethylene Oxide Exposure at Union Carbide Corp., WV NIOSH IWS-67.17B 47 p (1978) (5) Oser JL; In-depth Industrial Hygiene Report of Ethylene Oxide Exposure at Union Carbide Corp., South Charleston, WV NIOSH IWS-67.10 25 p (1979)]**PEER REVIEWED**

NIOSH (NOES Survey 1981-1983) has statistically estimated that 50,132 workers are exposed to ethylene oxide in the USA(2). The personal 8-hr TWA exposure in 12 hospitals ranged from ND to 6.3 ppm for sterilizer operators and ND to 6.7 ppm for folders and packers. Short term (2 to 30 min) exposure levels for sterilizer operators ranged from ND to 103 ppm(1). Lower exposure levels were correlated with effective engineering controls and good work practices, rather than with the size of the hospital, or number or location of sterilizers.
[(1) Elliot LJ et al; Appl Ind Hyg 3: 141-5 (1988) (2) NIOSH; National Occupational Exposure Survey (1989)]**PEER REVIEWED**

Emergency Medical Treatment:

Emergency Medical Treatment:

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The following Overview, *** ETHYLENE OXIDE ***, is relevant for this HSDB record chemical.

Life Support:
  o   This overview assumes that basic life support measures
      have been instituted.
Clinical Effects:
  SUMMARY OF EXPOSURE
   0.2.1.1 ACUTE EXPOSURE
     o   Early signs and symptoms of exposure to ethylene oxide
         (ETO) may include eye, nose, and throat irritation and
         noticing a sweet or peculiar taste in the mouth.
     o   Delayed effects may include headache, nausea, vomiting,
         diarrhea, abdominal pain, dyspnea, cough, weakness,
         lethargy, numbness, incoordination and vertigo.  Acute
         effects such as pneumonia, pulmonary edema, respiratory
         failure, asthma, cardiac arrhythmias, seizures,
         allergic reaction, paralysis and coma may also be seen.
     o   Direct contact with the eye can cause severe ocular
         damage.  Direct dermal contact with the gas or liquid
         ethylene oxide can cause blistering, severe chemical
         burns and tissue necrosis.  Evaporation of the liquid
         from the skin may cause frostbite.
     o   Occupational exposure to ethylene oxide may be linked
         with spontaneous abortions and other adverse
         reproductive effects.  ETO is known to cause cancer in
         laboratory animals and is a probable human carcinogen.
         Leukemia and non-Hodgkin's lymphoma have been primarily
         associated with ETO.  Cases of Hodgkin's disease,
         stomach, breast and pancreatic cancer, lymphosarcoma
         and reticulosarcoma have also been reported.
     o   CNS and musculoskeletal abnormalities have been
         reported in the offspring of  laboratory animals.
  VITAL SIGNS
   0.2.3.1 ACUTE EXPOSURE
     o   Pulmonary irritation is likely after inhalation;
         dyspnea may occur.
  HEENT
   0.2.4.1 ACUTE EXPOSURE
     o   Ocular irritation and conjunctivitis may be seen on
         splash contact with the eyes.  ETO has been implicated
         as a causal agent for the formation of cataracts.
     o   Irritation of eyes, nose and throat, as well as a
         peculiar taste, are  the early symptoms of ethylene
         oxide exposure.
  CARDIOVASCULAR
   0.2.5.1 ACUTE EXPOSURE
     o   Ethylene oxide has no appreciable effect on the
         cardiovascular system until respiratory compromise is
         serious enough to cause anoxia.
  RESPIRATORY
   0.2.6.1 ACUTE EXPOSURE
     o   Pulmonary irritation is a common symptom after
         inhalation.  Pulmonary edema may be seen with acute
         exposures.  Pneumonia may be a complication of ethylene
         oxide exposure.  A rare report of asthma has also been
         reported.
  NEUROLOGIC
   0.2.7.1 ACUTE EXPOSURE
     o   Convulsive movements, twitching, malaise, lethargy,
         headache, seizures,  and dizziness have been reported.
         Serious exposure may result in coma.   Chronic exposure
         may result in peripheral and central nervous system
         effects, including neuropsychiatric symptoms, cognitive
         dysfunction, and  polyneuropathies.
   0.2.7.2 CHRONIC EXPOSURE
     o   Various polyneuropathies, memory impairment, and mood
         changes have been reported after chronic exposure.
  GASTROINTESTINAL
   0.2.8.1 ACUTE EXPOSURE
     o   Nausea, vomiting, and diarrhea may occur.
  GENITOURINARY
   0.2.10.1 ACUTE EXPOSURE
     o   Severe cases of ethylene oxide exposure may result in
         renal damage.
  HEMATOLOGIC
   0.2.13.1 ACUTE EXPOSURE
     o   Severe cases of ethylene oxide exposure may result in
         cyanosis.
     o   Anemia developed in rats after chronic exposure.
  DERMATOLOGIC
   0.2.14.1 ACUTE EXPOSURE
     o   Pure anhydrous ETO does not injure dry skin, but
         solutions have a vesicant  action.  Exposure to the
         liquid or gas may cause irritation or burns to  moist
         skin.  ETO may also cause contact dermatitis, allergic
         contact  dermatitis, thermal burns, frostbite, edema,
         erythema, vesiculation, blebs,  and desquamation.
  REPRODUCTIVE HAZARDS
    o   Ethylene oxide has been fetotoxic and teratogenic in
        experimental animals.
  CARCINOGENICITY
   0.2.21.1 IARC CATEGORY
     o   IARC has classified ethylene oxide as Group 1
         (carcinogenic to humans),  based on limited evidence in
         humans and sufficient evidence in experimental  animals
         (IARC, 2001).
   0.2.21.2 HUMAN OVERVIEW
     o   Ethylene oxide has been linked with leukemia, stomach,
         brain and pancreatic  cancer, lymphatic cancer,
         hematopoietic cancer, non-Hodgkin lymphoma, and
         Hodgkin disease.
     o   The evidence for human and animal carcinogenicity and
         for genotoxicity  has been extensively reviewed (Their
         & Bolt, 2000).
  GENOTOXICITY
    o   MUTAGENIC effects due to ethylene oxide exposure have
        been shown in non-mammalian animals.  Many of the
        observed mutagenic effects are a result  of high
        dose/short term exposure (Sheikh, 1984).  Case studies
        indicate  ethylene oxide is fetotoxic (Sheikh, 1984).
        In man, cytogenetic studies  have shown increases in
        sister chromatid exchanges, ethylene  oxide-hemoglobin
        adducts, micronuclei, chromosomal aberrations and DNA
        strand breaks in those exposed to ethylene oxide (ACGIH,
        1991; Baselt, 2000;  Mayer et al, 1991; Schulte, 1995;
        Landrigan et al, 1984).                             
Laboratory:
  o   Chest film should be considered to evaluate the extent of
      pulmonary involvement after inhalation.                
Treatment Overview:
  ORAL EXPOSURE
    o   EMESIS - Oral exposure to ethylene oxide is unusual.
        Because of the volatility of the liquid, and the extreme
        reactivity of ethylene oxide, it is questionable whether
        emesis would be of value.  Activated charcoal may be of
        more benefit.
    o   ACTIVATED CHARCOAL:  Administer charcoal as a slurry
        (240 mL water/30 g charcoal).  Usual dose:  25 to 100 g
        in adults/adolescents, 25 to 50 g in children (1 to 12
        years), and 1 g/kg in infants less than 1 year old.
    o   CATHARTIC - Ethylene oxide is irritating and probably
        serves as its own cathartic.
  INHALATION EXPOSURE
    o   INHALATION:  Move patient to fresh air.  Monitor for
        respiratory distress.  If cough or difficulty breathing
        develops, evaluate for respiratory tract irritation,
        bronchitis, or pneumonitis.  Administer oxygen and
        assist ventilation as required.  Treat bronchospasm with
        beta2  agonist and corticosteroid aerosols.
    o   Clothing should be removed and washed thoroughly.
    o   TREATMENT - If significant amounts of ethylene oxide
        have been inhaled, immediate hospitalization and
        observation for 72 hours are recommended.  There may be
        delayed onset of pulmonary edema.
    o   ACUTE LUNG INJURY:  Maintain ventilation and oxygenation
        and evaluate with frequent arterial blood gas or pulse
        oximetry monitoring.  Early use of PEEP and mechanical
        ventilation may be needed.
  EYE EXPOSURE
    o   DECONTAMINATION:  Irrigate exposed eyes with copious
        amounts of tepid water for at least 15 minutes.  If
        irritation, pain, swelling, lacrimation, or photophobia
        persist, the patient should be seen in a health care
        facility.
  DERMAL EXPOSURE
    o   DECONTAMINATION - If liquid is spilled on the skin,
        allow ethylene oxide to vaporize before washing with
        water.  Dermal exposure should be washed with water,
        from a hose or shower.  A physician should examine the
        exposed area if irritation or pain persists after the
        area is washed.              
Range of Toxicity:
  o   30 mg/kg caused nausea, vomiting, and diarrhea for 2 hours
      in animals.  The permissible exposure limit in air is 1
      ppm as an eight hour TWA.  The OSHA action level is 0.5
      ppm.

[Rumack BH: POISINDEX(R) Information System. Micromedex, Inc., Englewood, CO, 2003; CCIS Volume 116, edition exp May, 2003. Hall AH & Rumack BH (Eds):TOMES(R) Information System. Micromedex, Inc., Englewood, CO, 2003; CCIS Volume 116, edition exp May, 2003.] **PEER REVIEWED**

Antidote and Emergency Treatment:

Treatment consists of general supportive care.
[Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988. 997]**PEER REVIEWED**

Animal Toxicity Studies:

Evidence for Carcinogenicity:

A2; Suspected human carcinogen.
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents andBiological Exposure Indices for 2002. Cincinnati, OH. 2002. 32]**QC REVIEWED**

Evaluation: There is limited evidence in humans for the carcinogenicity of ethylene oxide. There is sufficient evidence in experimental animals for the carcinogenicity of ethylene oxide. In making the overall evaluation, the Working Group took into consideration the following supporting evidence. Ethylene oxide is a directly acting alkylating agent that: (1) induces a sensitive, persistent dose-related increase in the frequency of chromosomal aberrations and sister chromatid exchange in peripheral lymphocytes and micronuclei in bone marrow cells of exposed workers; (2) has been associated with malignancies of the lymphatic and hematopoietic system in both humans and experimental animals; (3) induces a dose related increase in the frequency of hemoglobin adducts in exposed humans and dose related increases in the numbers of adducts in DNA and hemoglobin in exposed rodents; (4) induces gene mutations and heritable translocations in germ cells of exposed rodents; and (5) is a powerful mutagen and clastogen at all phylogenetic levels. Overall evaluation: Ethylene oxide is carcinogenic to humans (Group 1).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. 60 139 (1994)]**PEER REVIEWED**

Non-Human Toxicity Excerpts:

Perturbations in bone marrow and peripherial blood elements of mice exposed to ethylene oxide were evaluated. Mice exposed to 225 ppm ethylene oxide for 6 hr/day were removed for analysis 1, 2, 4, 8, and 14 days and 4, 6, 8, and 10 wk (5 day/week). Blood analysis included blood cell counts, hemoglobin determination, and hematocrit. Bone marrow evaluation included stem-cell assay (CFU-S) or flow cytometry analysis, cell cycle and B-cell analysis. Perturbations of peripheral leukocytes occurred after one exposure. After multiple exposures, hematocrit, red cell number, and hemoglobin were generally depressed, with transient compensatory bursts, and bone marrow cellularity and CFU-S were below normal. White cell numbers fluctuated dramatically during the exposure period. There was a shift in the numbers of granulocytes in the bone marrow followed by replacement and relative lymphocyte deficit, especially pronounced at 10 wk.
[Popp DM et al; J Toxicol Environ Health 18: 543-65 (1986)]**PEER REVIEWED**

Female mice of hybrid stocks (C3H x C57BL)F1 and (SEC x C57BL)F1 were exposed to 300, 1200, or 1800 ppm of ethylene oxide for various exposure periods. Exposed females were either mated before or after treatment to male mice (C3H x C57BL)F1 and killed on the 17th day after observation of a vaginal plug. Fetal abnormalities and mortality were observed in both treatment groups. Early developmental stages of the zygote appears to be more sensitive to the action of ethylene oxide than later stages.
[Generoso WM et al; Mutat Res 176: 269-74 (1987)]**PEER REVIEWED**

... REPEATED EXPOSURES OF RATS @ 400 PPM CAUSED RESP IRRITATION, WT LOSS, WEAKNESS & DEATH. ... REPEATED EXPOSURES OF DOGS, RATS & MICE @ 100 PPM FOR SIX MONTHS CAUSED NO SIGNIFICANT EFFECTS; HOWEVER, THERE WAS A SLIGHT ANEMIA IN DOGS.
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 256]**PEER REVIEWED**

... THERE WAS IRRITATION OF RESP PASSAGES, INCLUDING THE LUNGS, IN ANIMALS REPEATEDLY EXPOSED TO 204, 357 & 841 PPM ... IN ADDITION THERE WERE GROWTH DEPRESSIONS, ORGAN WT CHANGES & ORGANIC INJURY TO THE LIVERS, KIDNEYS, ADRENALS, & TESTES OF RATS & GUINEA PIGS.
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 256]**PEER REVIEWED**

Exposure of animals to high concn of the gas has caused lacrimation in cats, and inflammation of the conjunctiva and clouding of the cornea in dogs, cats, rabbits, and especially guinea pigs.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 419]**PEER REVIEWED**

30 8-WK OLD FEMALE ICR/HA SWISS MICE WERE PAINTED THRICE WEEKLY ON CLIPPED DORSAL SKIN WITH APPROX 0.1 ML OF 10% SOLN ... IN ACETONE FOR LIFE. MEDIAN SURVIVAL TIME WAS 493 DAYS; NO SKIN TUMORS WERE OBSERVED.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V11 161 (1976)]**PEER REVIEWED**

12 RATS RECEIVED MAX TOTAL DOSES OF 1 G/KG BODY WT ... IN ARACHIS OIL BY SC INJECTION ... PERIOD OF TREATMENT WAS 94 DAYS. ANIMALS WERE OBSERVED FOR LIFETIME; NO LOCAL SARCOMAS WERE OBSERVED.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V11 161 (1976)]**PEER REVIEWED**

... 86 FEMALE SWISS-WEBSTER MICE, GERM-FREE & INBRED, WERE EXPOSED TO ... ETHYLENE OXIDE TREATED GROUND-CORNCOB BEDDING FOR 150 DAYS & THEN TO UNTREATED BEDDING FOR LIFESPAN (MAXIMAL, 900 DAYS); 63 MICE DEVELOPED TUMORS @ VARIOUS SITES. NO TUMORS WERE REPORTED IN 83 FEMALE MICE, 100-600 DAYS OLD, WHICH WERE NOT EXPOSED TO TREATED BEDDING ... (THIS OBSERVATION DOES NOT ALLOW AN EVALUATION OF THE CARCINOGENICITY OF ETHYLENE OXIDE).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V11 161 (1976)]**PEER REVIEWED**

EXPOSURE OF MALE LONG-EVANS RATS FOR 4 HR TO 1.83 G/CU M (1000 PPM) ETHYLENE OXIDE PRODUCED DOMINANT LETHAL MUTATIONS; CHROMOSOME ABERRATIONS WERE OBSERVED IN BONE-MARROW CELLS OF MALE LONG-EVANS RATS EXPOSED TO 0.45 G/CU M (250 PPM) ETHYLENE OXIDE FOR 7 HR PER DAY FOR 3 DAYS.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V11 163 (1976)]**PEER REVIEWED**

TERATOGENIC POTENTIAL OF IV ADMIN WAS ASSESSED IN CD-1 MOUSE @ DOSE 0, 75, & 150 MG/KG @ 4 PERIODS DURING GESTATION. RESULTS INDICATE TERATOGENICITY @ LEVELS 500-5000 TIMES ABOVE EXPOSURE LIMITS CURRENTLY PROPOSED BY FDA FOR ETO RESIDUES IN MEDICAL DEVICES.
[LABORDE JB ET AL; TOXICOL APPL PHARMACOL 56 (1): 16 (1980)]**PEER REVIEWED**

Ethylene oxide was reported positive for mutagenicity test performed on bacteria, Neurospora, Drosophila, mammalian cells.
[Fishbein L; Potential Indust Carcins & Mutagens p.31 (1977) USEPA 560/5-77-005]**PEER REVIEWED**

Statistically significant increases in mononuclear cell leukemia in female Fischer rats increased linearly with dose. Among male Fischer 344 rats in the same experiment, ethylene oxide induced peritoneal mesothelioma which originated in the testicular mesothelium.
[NIOSH; Current Intelligence Bulletin: Ethylene Oxide 35, 9, May 22 (1981) DHHS Pub. NIOSH 81-130]**PEER REVIEWED**

Rats and mice exposed to ethylene oxide had significantly increased numbers of polychromatic erythrocytes containing micronuclei.
[Appelgren LE et al; Acta Pharmacol Tox 43: 69 (1978)]**PEER REVIEWED**

/Ethylene oxide/ was injected iv on several days during organogenesis in the mouse. Skeletal malformations occurred in fetuses whose mother received 150 mg/kg which produced maternal toxicity. Doses of 75 mg/kg caused no defects. Rats /were/ exposed on days 6-15 of gestation for 6 hr daily to 10-100 ppm. At the highest dose, fetal growth retardation occurred but there was no increase in congenital defects.
[Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986. 246]**PEER REVIEWED**

Ethylene oxide was administered intragastrically by gavage at 2 dosages, 30 and 7.5 mg/kg body weight to groups of 50 female Sprague-Dawley rats twice weekly for a period of nearly 3 years using salad oil as the solvent. It induced local tumors, mainly squamous cell carcinomas of the forestomach, dependent on the dosage. The first tumor occurred in the 79th week. The following tumor rates resulted 62 and 16%. In addition carcinomata in situ, papillomas and reactive changes of the squamous epithelium of the forestomach were observed in other animals, but ethylene oxide did not induce tumors at sites away from the point of administration.
[Dunkelberg H; Br J Cancer 46 (6): 924-33 (1982)]**PEER REVIEWED**

Groups of F344 rats of each sex were exposed to either ethylene oxide vapor (concentrations of 100, 33 or 10 ppm) or to room air 6 hr daily, 5 days/wk, for up to 2 yr. Three representative sections of the brain from each rat were evaluated. Of 23 primary brain tumors which were found, 2 were in control animals. Increased numbers of brain tumors were seen in 100 ppm and 33 ppm ethylene oxide exposed male and female rats. Significant trend analyses were found for both males and females, indicating that ethylene exposure > 10 ppm was related to the development of these brain tumors.
[Garman RH et al ; Neurotoxicology 6 (1): 117-38 (1985)]**PEER REVIEWED**

In a dose-response study, male mice were exposed to inhalation of ethylene oxide for 4 consecutive days. Mice were exposed for 6 hr per day to 300 ppm, 400 ppm, or 500 ppm ethylene oxide for a daily total of 1,800, 2,400, or 3,000 ppm per hr, respectively. In the dose-rate study, mice were given a total exposure of 1,800 ppm per hr per day delivered either at 300 ppm in 6 hr, 600 ppm in 3 hr, or 1,200 ppm in 1.5 hr. Quantitation of dominant-lethal responses was made on matings involving sperm exposed as late spermatids and early spermatozoa, the most sensitive stages to ethylene oxide. In the dose-response study, a dose related increase in dominant-lethal mutations were observed, the dose-response curve proved to be nonlinear. In the dose-rate study, increasing the exposure concentrations resulted in increased dominant-lethal responses.
[Gosslee DG; Environ Mutagen 8 (1): 1-8 (1986)]**PEER REVIEWED**

The offspring of DBA/2J male mice exposed to ethylene oxide (ETO) by inhalation had an increased incidence of both dominant visible and electrophoretically detected mutations over that found in control populations. The progeny at risk were obtained from matings during the exposure period and were the products of germ cells that were exposed throughout the entire spermatogenic process. Apparently, male germ cells repeatedly exposed to ethylene oxide during spermatogenesis are susceptible to ethylene oxide induced transmissible damage.
[Lewis SE et al; Environ Mutagen 8 (6): 867-72 (1986)]**PEER REVIEWED**

Ethylene oxide at 357 ppm 35 hr/week for 12 weeks produced a sensorimotor neuropathy in rats, rabbits, and monkeys, but not guinea pigs or mice. Continued exposure resulted in paralysis and muscle atrophy of the hindlimbs. At 204 ppm, 35 hr/wk for 32 weeks, rabbits and monkeys, but not guinea pigs, rats, or mice, developed a clinical neuropathy. The monkeys had decreased tendon reflexes, loss of withdrawal from superficial pain over the hindquarters, partial paralysis, and muscle atrophy indicative of toxic axonopathy. A positive Babinski reflex in these monkeys indicated that upper motor neurons or their axons were also affected. Dogs showed occasional tremors, transient weakness, atrophy and fatty replacement of skeletal muscle following ethylene oxide exposures of 292 ppm, 30 hr/week for 6 weeks. Levels of about 100 ppm repeatedly were without neurotoxicity in rats, rabbits, guinea pigs, mice, dogs, and monkeys.
[O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume II. Boca Raton, FL: CRC Press, Inc., 1985. 87]**PEER REVIEWED**

The results of efforts to identify and quantify macromolecular adducts of ethylene oxide, to determine the source and significance of background levels of these adducts, and to generate molecular dosimetry data on these adducts are reviewed. A time-course study was conducted to investigated the formation and persistence of 7-(2-hydroxyethyl) guanine in various tissues of rats exposed to ethylene oxide by inhalation, providing information necessary for designing investigations on the molecular dosimetry of adducts of ethylene oxide. Male F344 rats were exposed 6 hr/day for up to 4 weeks (5 days/wk) to 300 ppm ethylene oxide by inhalation. Another set of rats was exposed for 4 weeks to 300 ppm ethylene oxide, and then killed 1-10 days cessation of exposures. DNA samples from control and treated rats were analyzed for 7-(2-hydroxyethyl)guanine using neutral thermal hydrolysis, HPLC separation, and fluorescence detection. The adduct was detectable in all tissues of treated rats following 1 day of ethylene oxide exposure and increased approximately linearly for 3-5 days before the rate of increase began to level off. Concentrations of 7-(2-hydroxyethyl)guanine was greatest in brain, but the extent of formation was similar in all tissues studied. The adduct disappeared slowly from DNA, with an apparent half-life of approx 7 days. The shape of the formation curve and the in vivo half-life indicate that 7-(2-hydroxyethyl)guanine will approach steady-state concentrations in rat DNA by 28 days of ethylene oxide exposure. The similarity in 7-(2-hydroxyethyl)guanine formation in target and nontarget tissues indicates that the tissue specificity for tumor induction is due to factors in addition to DNA-adduct.
[Walker VE et al; Mutat Res 233 (1-2): 151-64 (1990)]**PEER REVIEWED**

The utility of hemoglobin as a DNA monitor in cases of exposure to ethylene oxide was investigated in rats via use of an inhalation system with dynamically generated test atmospheres. Animals were exposed to atmospheres containing 1, 10, or 33 ppm radiolabeled ethylene oxide for 6 hours. After exposure, the animals were sacrificed and the organs removed for isolation of DNA. DNA hydrolysates and adducts were further analyzed by high pressure liquid chromatography. Globin was isolated from pooled erythrocytes. The relationship between inhalation doses of ethylene oxide and alkylation DNA and globin was described in terms of moles of adduct per gram of DNA or globin. Linear relationships were observed between formation of hydroxyethyl adducts in both DNA and hemoglobin and the exposure concentration of radiolabeled ethylene oxide. Alkylation frequencies of DNA were similar in all tissues studied with exception of testis; corresponding alkylation in hemoglobin was not significantly different. Results indicate that the results support the suggestion that, in the case of ethylene oxide exposure, determination of the hemoglobin dose in vivo is a valid indicator of the dose delivered to DNA.
[Potter D et al; Arch Toxicol Suppl 13: 254-7 (1989)]**PEER REVIEWED**

Exposure of female mice to ethylene oxide by inhalation 1 or 6 hr after mating produced not only multitemporal death of conceptuses but also high rates of abnormalities among surviving fetuses. In contrast, only marginal effects were observed when females were exposed 9 or 25 hr after mating. The abnormalities found among 17 day gestation live fetuses were predominated by hydrops and eye defects, which, together, constitute 54% of all anomalies. Most of the remaining anomalies were distributed among 5 other types: small size, cleft palate, and cardiac, abdominal wall, or extremity and/or tail defects. In a follow-up study the fetuses of females treated 6 hr postmating were examined at 11-15 days gestation and the progression of fetal death and of malformations was studied. Results indicate that the expression of most fetal anomalies does not become apparent until late in gestation. Several of these induced anomalies are similar to common human sporadic birth defects. This new class of experimentally induced fetal anomalies provides a new avenue for investigating zygotic biology and a system for studying the progression of aberrant development.
[Rutledge JC, Generoso WM; Teratology 39 (6): 563-72 (1989)]**PEER REVIEWED**

Wistar male and female rats were exposed to ethylene oxide at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the sex difference of anemia induced by ethylene oxide was investigated. Hemoglobin concentrations of both the male and female exposed groups were decreased when compared with each control group, and the anemia in the female exposed group was more severe than that in the male exposed group. Absolute spleen weight increased only in the female exposed group. We have already reported that a decrease of the glutathione reductase activity in the erythrocyte plays an important role in the ethylene oxide induced anemia. In the present study, the activity in both male and female exposed groups decreased when compared with each control group, and there was no sex difference in the degree of the decrease. From these observations, /it was/ concluded that there was a sex difference in the ethylene oxide induced anemia.
[Mori K et al; J Univ Occup Environ Health 12 (3): 343-8 (1990)]**PEER REVIEWED**

The effect of chronic inhalation of ethylene oxide on urinary coproporphyrin and delta- aminolevulinic acid were studies. When Wistar male rats were exposed to 500 ppm ethylene oxide three times a week, daily urine volume was increased by 200-300% from the first week to the fifth week of the experimental period. After exposure, daily coproprorphyrin excretion and urinary coproporphyrin per mg of creatinine increased by 250% and 141%, respectively. On the other hand, daily excretion of delta-aminolevulinic acid in urine tended to increase but did not increase significantly by creatinine correction. This /may be/ the first report of ethylene oxide induced experimental porphyria.
[Fugishiro K et al; Sangyo Ika Daigaku Zasshi 11 (1): 2308 (1989)]**PEER REVIEWED**

Male Wistar rats were exposed to ethylene oxide at concentrations of 50, 100, or 250 ppm for six hours a day, on five days a week for 13 weeks. Dose effect relations of inhaled ethylene oxide on spermatogenesis were evaluated from testicular and epididymal weights, histopathological changes and lactate dehydrogenase X (LDH X) activity in the testis, and sperm counts and sperm head abnormalities in the epididymis. At 250 ppm, a decrease in epididymal weights, slight degenerations in the seminiferous tubules, decreased sperm counts, and increased numbers of abnormal sperm heads in the tail of the epididymis were found; these were not seen at lower doses. When the abnormal sperm heads were classified into immature types and teratic types, the number of immature heads increased only at 250 ppm. On the other hand, the teratic type had increased at doses of 50 and 100 ppm ethylene oxide when compared with the control group. Hence, subchronic inhalation of ethylene oxide at low concentrations affects spermatogenesis in rats.
[Mori K et al; Br J Ind Med 48 (4): 270-4 (1991)]**PEER REVIEWED**

The effects of systemic toxicity including reproductive toxicity of ethylene oxide on female rats were studied. When Wistar female rats were exposed to 250 ppm of ethylene oxide for six hours a day, five days a week for ten weeks, they showed inhibition of body weight gain and paralysis of the hindlegs. Hematogological examination revealed macrocytic and normochromic anemia with high reticulocyte counts. The estrus cycle of the exposed group was prolonged and the percentage of the diestrus stage increased. There was no atrophy in the ovary or the uterus. However, the activity of glutathione reductase in the ovary decreased by 18% and that of glutathione-S-transferase increased by 30%. These results indicate that ethylene oxide has a similar effect on both female and male rats and that the female reproductive system is also affected.
[Mori K et al; Sangyo Ika Daigaku Zasshi 11 (2): 173-9 (1989)]**PEER REVIEWED**

The toxic effects of residual ethylene oxide, a frequently used gas-sterilant, on embryos either frozen for long-term purposes or stored acutely for 30 min to 9 hr in a fresh condition in 0.25 ml straw containers were evaluated. In Experiment 1, fresh embryos were frozen (using conventional technology) in straws previously aerated for 0 hr to 8 mo after ethylene oxide sterilization. With the exception of the 8 mo group in which survival and quality ratings were depressed, embryo viability was not affected significantly by short-term prefreeze and post-thaw exposure to ethylene oxide residues. Experiment 2 was conducted to analyze the influence of prefreeze exposure to ethylene oxide residues on embryo development in vitro for embryos temporarily stored in previously sterilized straws aerated for different intervals. Compared to non-ethylene oxide sterilized control straws, the development, quality, and viability of embryos exposed to ethylene oxide-treated straws were compromised (p less than 0.05) as the aeration interval decreased and the exposure interval increased. The combined results of both experiments indicate that ethylene oxide-treated straws can be used to cryopreserve gametes efficiently, but only if the aeration interval is greater than or equal to 72 hr and the prefreeze duration of exposure is less than or equal to 3 hr.
[Schiewe MC et al; Gamete Res 19 (1): 31-9 (1988)]**PEER REVIEWED**

Thirty B6C3F1 mice of both sexes that were exposed at ethylene oxide vapor concentrations of 1, 10, 50, 100, or 250 ppm, 6 hours/day, 5 days/week for 10 to 11 weeks showed no effects on survival, body weight, or histologic sections of various organs. Neuromuscular toxicity was observed at the three highest exposure levels, and both sexes in the 250 ppm exposure group had a statistically significant increase in hunched posture, reduced locomotion, and righting reflex. These symptoms were also observed in some animals of both sexes exposed at 50 or 100 ppm. Neuromuscular effects appeared to be the most sensitive indicator of exposure to ethylene oxide in this study.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 618]**PEER REVIEWED**

When ethylene oxide/saline solutions of varied concentrations (0.1% to > 20%) were applied repeatedly over a 6-hour period to the eyes of rabbits, a dose-dependent increase in congestion, swelling, discharge, iritis, and corneal cloudiness was observed. These effects were an indication of the irritating effect of ethylene oxide on mucous membranes and corneal epithelium. The 0.1% ethylene oxide concentration was the maximum, nondamaging concentration of this chemical for the 6 hour exposure period.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 618]**PEER REVIEWED**

Infusion of ethylene oxide into the aorta of rats caused a significant decrease (approximately 30%) in kidney glomerular filtration rates, resulting in kidney dysfunction.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 617]**PEER REVIEWED**

Pathological examination of tissues from mice, rats, and guinea pigs that died after lethal exposure to ethylene oxide revealed adverse effects that included lung congestion, hyperemia of the liver and kidneys, and gray discoloration of the liver. Animals that experienced delayed death had emphysema of the lungs, fatty degeneration of the liver, cloudy swelling of the kidney tubules, and congestion of the spleen and brain, all believed to be a cause or contributing to these deaths.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 617]**PEER REVIEWED**

Mice, rats, guinea pigs, rabbits, and dogs exposed to lethal concentrations of ethylene oxide had symptoms of mucous membrane irritation, central nervous system (CNS) depression, lacrimation, nasal discharge, salivation, nausea, vomiting, diarrhea, respiratory irritation, incoordination, and convulsions. Surviving animals showed subsequent bronchitis, pneumonia, and loss of appetite with delayed symptoms of apathy, dyspnea, vomiting, paralysis (particularly of the hindquarters), and periodic convulsions, followed eventually by death. Rapid deaths were usually associated with lung edema; delayed deaths frequently resulted from secondary infections in the lungs, although general systemic intoxication is also believed to be associated with these delayed deaths.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 617]**PEER REVIEWED**

... Fischer 344 rats, 120 rats/sex/group, /were exposed/ at 10, 30, or 100 ppm ethylene oxide vapor, 6 hours/day, 5 days/week for 2 years. Two groups of controls were exposed to untreated air under similar conditions. Ten animals each at 6 and 12 months and 20 animals at 18 months were sacrificed to determine possible treatment-related effects. Both interim and terminal evaluations included hematology, serum clinical chemistry, urinalysis, body weight, organ weight, bone marrow cytogenicity studies, and gross and histologic examinations. Histopathologic examinations of rat tissue from the 100 ppm ethylene oxide exposed animals and the control group were performed at 6, 12, and 18 month necropsy intervals. At the 24 month sacrifice, histopathologic examination was made on all tissues of the 100 ppm exposed rats as well as controls and on potential target tissues, other selected tissues, and tissues with gross lesions in the 10 and 33 ppm exposed animals. The six types of tumors found in the ethylene oxide exposed rats that appear to be treatment related are subcutaneous fibroma, peritoneal mesothelioma, pancreatic adenoma, pituitary adenoma, brain neoplasm, and mononuclear cell leukemia. In this 2-year study, a dose-related increased incidence of mononuclear cell leukemia was found in both sexes. It was significant in the 100 and 33 ppm exposed females from the 18th or 19th month onward. A trend test revealed a treatment-related response in both sexes. An increased incidence of peritoneal mesotheliomas originating from the testicular mesothelium was found in males exposed at 33 and 100 ppm from the 23rd month onwards and an increased incidence of subcutaneous fibroma in males surviving the 24-month, 100 ppm exposures. There was no increased incidence of pituitary tumors, although they appeared earlier in the 100 ppm exposed group.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 618]**PEER REVIEWED**

No specific testicular damage was seen in test animals exposed at nontoxic doses of ethylene oxide. When maternally toxic doses of ethylene oxide were administered intravenously in mice, embryo and fetal toxicity were found. Pregnant rats inhaling ethylene oxide had a reduction in fetal weight but no teratogenic effects.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 619]**PEER REVIEWED**

Earlier studies ... revealed that ethylene oxide or ethyl methanesulfonate induced high frequencies of midgestation and late fetal deaths and of malformations among some of the surviving fetuses when female mice were exposed at the time of fertilization of their eggs or during the early pronuclear stage of the zygote. Effects of the two mutagens are virtually identical. Thus ln investigating the mechanisms responsible for the dramatic effects ln the early pronuclear zygotes the two compounds were used interchangeably in the experiments. First a reciprocal zygote-transfer study was conducted in order to determine whether the effect is directly on the zygotes or Indirectly through maternal toxicity. And second cytogenetic analyses of pronuclear metaphases early cleavage embryos and midgestation fetuses were carried out. The zygote transplantation experiment rules out maternal toxicity as a factor ln the fetal maldevelopment. Together with the strict stage specifically observed in the earlier studies this result points to a genetic cause for the abnormalities. However the cytogenetic studies failed to show structural or numerical chromosome aberrations. Since intragenic base changes and deletions may also be ruled out it appears that the lesions in question induced In zygotes by the two mutagens are different from conventional ones and therefore could be a novel one ln experimental mammalian mutagenesis.
[Katoh M et al; Mutat Res 210 (2): 337-44 (1989)]**PEER REVIEWED**

A ... 2-year carcinogenic study involved male Fischer 344 rats (80 in each group) and 12 Cynomolgus-monkeys per group exposed at either 50 or 100 ppm ethylene oxide 7 hours/day, 5 days/week for 24 months. Rats exposed at 50 ppm had a significantly increased incidence of mononuclear cell leukemia. The absence of a dose-response relationship was attributed to an increased mortality rate for the rats exposed at 100 ppm. Peritoneal mesotheliomas originating from the testicular mesothelium and mixed cell gliomas in the brain were found in a dose related increased incidence that was statistically significant for the 100 ppm exposure group. Exposures at the 50 and 100 ppm concentrations also reduced body weight gain and had an adverse effect upon the survival rate of the rats compared to the controls. Mortality was dose-dependent. Peritoneal mesotheliomas and gliomas are tumor types that can be found in humans. The 50 or 100 ppm exposed monkeys did not show any significant changes in hematological, clinical or urine chemistry, or ophthalmological parameters. At 100 ppm, nerve conduction velocities were decreased, and evidence of neurotoxicity and demyelination was noted in the 50 ppm and 100 ppm exposure groups. Sperm counts and motility were also reduced, and both exposure concentrations caused significant increases in the incidence of sister-chromatid exchanges (SCE) and chromosomal aberrations.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 618]**PEER REVIEWED**

... Monkeys /were exposed/ at 50 or 100 ppm ethylene oxide for 7 hours/day, 5 days/week for 2 years. ... Data /were collected/ in 1987 for sister chromatid exchanges (SCE) in peripheral blood lymphocytes and compared these data with those generated immediately prior to cessation of the 2 year exposure in 1981. Ethylene oxide induced SCE persisted at levels significantly higher than those of the nonexposed controls. These findings indicate that long lived lymphocytes may not be efficient with repair of the ethylene oxide induced lesions which produce SCE.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 619]**PEER REVIEWED**

Male mice were exposed to ethylene oxide for 6 hours/day on 4 consecutive days at 300, 400, or 500 ppm for a daily total of 1800, 2400, or 3000 ppm hours (total exposures of 7200, 9600, and 12,000 ppm hours), respectively. A dose related increase in dominant-lethal mutations was observed; the dose response curve proved to be nonlinear. In a dose rate study, mice were given a total exposure of 1800 ppm hours per day for 4 consecutive days. This exposure was delivered at 300 ppm for 6 hours, 600 ppm for 3 hours, or 1200 ppm for 1.5 hours. Increasing the exposure concentrations resulted in increased dominant lethal responses even when the total dose was the same.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 619]**PEER REVIEWED**

When freshly prepared aqueous solutions (2 to 5 percent) were injected intravenously into dogs, the LD50 was found to be about 125 mg/kg. A dose of 30 mg/kg or more usually caused vomiting and defecation for about 2 hr, followed by weakness and flaccidity, usually apparent in the hind limbs first. Doses up to 100 mg/kg in dogs under barbiturate anesthesia caused no apparent changes in blood pressure or cardiac rate. Respiration is adequate until terminal stages, when it becomes labored and cyanosis develops. Tonic extensor spasm may precede respiratory cessation. Since the heart usually beats after all reflexes disappear, death is believed due to respiratory failure .
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2172]**PEER REVIEWED**

... In aqueous solution the maximum concentration that could be applied externally to the ... /eyes of rabbits/, one drop every 10 minutes for 6 hours, without causing damage to the conjunctiva was 0.1%, to the cornea was 1%, and to the lens or retina was 20%. ... /Also/ if the aqueous humor was replaced once with an aqueous solution of ethylene oxide the maximum nondamaging concentration for the iris and lens was 0.1%, and for the cornea was 1%. At higher concentrations, damage consisted of irreversible opacities of cornea and lens.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 100]**PEER REVIEWED**

Ethylene oxide is a classical mutagen and a carcinogen based on evidence from studies in experimental animals. Chinese hamster V79 cells were treated for 2 hr with gaseous ethylene oxide, in sealed treatment chambers, and assayed for survival and mutagenic response by analysis of induced resistance to 6-thioguanine or ouabain. Significant numbers of mutants were produced at both genetic markers by 1,250-7,500 ppm ethylene oxide. Similarly, primary Syrian hamster embryo cells were treated for 2 or 20 hr with gaseous ethylene oxide in sealed treatment chambers and subsequently assayed for survival and increased sensitivity to SA7 virus transformation. Treatment concentrations extended from toxic to several nontoxic concentrations. After 2 hr ethylene oxide treatment at 625-2,500 ppm a significant enhancement of virus transformation was observed. At 20 hr after treatment no enhancement was observed. Treatment of hamster cells with ethylene oxide in both bioassay systems yielded concentration-related, quantitative results.
[Hatch GG et al; Environ Mutagen 8 (1): 67-76 (1986)]**PEER REVIEWED**

In mice exposed by inhalation for 5 hr/day, 5 days/week, for 10 weeks to 250, 100, 50, 10, or 0 ppm epoxyethane in air, clinical significant pathological findings were limited to the group exposed to 250 ppm. These findings included minimal decreases in red blood cell count, packed cell volume, and hemoglobin; decreased testicular and spleen weights; and increased liver weight. Abnormal pinch and righting reflexes, posture, and locomotion were also observed in mice exposed to 250 ppm. However, histological sections of the liver, testis, bone marrow, brain, and spleen taken from these mice were normal.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 664]**PEER REVIEWED**

Groups of 120 male and 120 female Fischer 344 rats, eight weeks of age, were exposed by inhalation to ethylene oxide (purity, > 99.9%) vapor at 10, 33 or 100 ppm (18, 59 or 180 mg/cu m) for 6 hr per day on five days per week for two years. Two control groups, each of 120 male and 120 female rats, were exposed in inhalation chambers to room air. All animals that died or were killed when moribund and those killed at scheduled intervals of 6, 12, 18 an 24-25 months were examined. During month 15 of exposure, mortality increased in both treated and control groups due to a viral sialodacryoadenitis. Mortality was higher in the groups inhaling 33 and 100 ppm ethylene oxide than in the other groups and was more frequent in females than in males near the fifteenth month. Up to 18 months of exposure, no significant increase in tumor incidence was observed. In treated rats killed after 18 months, the incidence of tumors in the brain classified as gliomas, malignant reticulosis and granular-cell tumors was increased for animals of each sex. The incidences of glioma among rats killed at 18 and 24-25 months were: males: 1/181 (controls), 0/92 (10 ppm), 3/86 (33 ppm) and 6/87 (100 ppm) (p < 0.05, trend analysis and Fisher's exact test for high dose versus control); and females: 0/187 (controls), 1/94 (10 ppm), 2/90 (33 ppm) and 2/78 (100 ppm) (p < 0.05, trend analysis). In females killed after 24 months of exposure mononuclear-cell leukaemia was found in 5/60 (control I), 6/56 (control II), 11/54 (10 ppm), 14/48 (33 ppm) and 15/26 (100 ppm) animals; the incidence of leukaemia was reported ... to be significantly increased in the 100 ppm group (p < 0.001) and in a mortality adjusted trend test (p < 0.005). In males, mononuclear-cell leukaemia was found in 5/48 (control I), 8/49 (control II), 9/51 (10 ppm), 12/39 (33 ppm) and 9/30 (100 ppm) animal (p < 0.05 in a mortality adjusted trend test). Peritoneal mesotheliomas originating in the testicular serosa were found in 1/48 (control I), 1/49 (control II), 2/51 (10 ppm), 4/39 (33 ppm) and 4/30 (100 ppm) males (p < 0.005 trend test). The incidence of subcutaneous fibromas in male rats of the high-dose group was also significantly increased: 1/48 (control I) 2/49 (control II), 9/51 (10 ppm), 1/39 (33 ppm) and 11/30 (100 ppm) (p < 0.001).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V60 102 (1994)]**PEER REVIEWED**

The effects of repeated exposure to ethylene oxide on lipid peroxidation and glutathione metabolism in both rat liver and brain were examined. Increased levels of malondialdehyde in the liver were observed after 6 and 13 weeks of exposure to ethylene oxide. The increased level of malondialdehyde observed in the hepatic homogenates of the treated rats reflected that of the microsomal fraction. On the other hand, no change in the level of malondialdehyde was detected in the brain of rats either at a 6- or 13-week treatment. Glutathione reductase activity was found to decrease at 6 or 13 weeks in liver and brain of treated rats. Both reduced and oxidized forms of glutathione in homogenates of liver and brain obtained from treated rats were, however, similar to those of the control at 40 hr after the last exposure in individual experiments. To elucidate the cause of lipid peroxidation, the time course of glutathione content after exposure with ethylene oxide were studied in more detail. Significant decreases in both GSH and GSSG content in these organs were detected shortly after exposure to ethylene oxide and their levels recovered gradually with time and reached the control values at 40 hr in the liver, although the changes were less significant in the brain as compared with those in the liver. These results suggest that enhancement of lipid peroxidation in the microsomal fraction of the liver after repeated exposure to ethylene oxide may possibly arise from repeated depletions of glutathione to certain critical levels and less removal of lipid peroxidation.
[Katoh T et al; Toxicol 58 (1): 1-9 (1989)]**PEER REVIEWED**

This paper describes a dominant neurological mutation identified among the progeny of a male parent treated with ethylene oxide. The defects observed in the heterozygous mutant include: head tossing, poor limb coordination, and corneal clouding. Both the behavior and ocular manifestations of the mutant syndrome worsen progressively as the affected animals grow older. The mutant animals swim poorly, although they do orient themselves in reference to the surface of the water. Breeding in general is poor. Very small litter sizes result when heterozygous animals of either sex are mated to normal mice. Many male carriers are functionally sterile. All mutant animals had abnormal karyotypes. The original carrier mouse had a translocation between chromosomes 4 and 17, which was also present in all but one mutant animal. The exceptional animal, which showed all mutant behavior characteristics, had 41 chromosomes, which included two normal 4 and 17 homologs and the small 417 translocation chromosome. Karyotypes of unaffected siblings of mutants were normal. ...
[Lewis SE et al; Mutat Res 229 (2): 135-40 (1990)]**PEER REVIEWED**

Male Fischer and B6C3Fl mice (10/species/group) were exposed to ethylene 6 hr/day, 5 days/week, for 4 weeks. The ethylene target concentrations were 0, 40, 1000, and 3000 ppm. An ethylene oxide (EO) control group for each species was exposed under the same conditions at a target concentration of 200 ppm. Bone marrow was collected approximately 24 hr after the final exposure. Polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) ratios were determined and 2000 PCE/animal were scored for the presence of micronuclei. Ethylene did not produce statistically significant, exposure-related increases in the frequency of micronucleated PCE (MNPCE) in the bone marrow of either rats or mice when compared to air exposed control animals. As expected, EO exposure resulted in significant increases in the frequencies of MNPCE in both species.
[Vergnes JS, Pritts IM; Mutat Res 324 (3): 87-91 (1994)]**PEER REVIEWED**

... Conclusions: Under the conditions of these 2 yr inhalation studies, there was clear evidence of carcinogenic activity for B6C3F1 mice as indicated by dose related incr incidences of benign or malignant neoplasms of the lung and benign neoplasms of the harderian gland in both male and female B6C3F1 mice following exposure to ethylene oxide vapors at 50 and 100 ppm. In female mice, ethylene oxide caused additional malignant neoplasms of the uterus, mammary gland, and hematopoietic system (lymphoma).
[Toxicology & Carcinogenesis Studies of Ethylene Oxide in B6C3F1 Mice (Inhalation Studies). Technical Report Series No. 326 (1987) NIH Publication No. 88-2582 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**QC REVIEWED**

National Toxicology Program Studies:

... Toxicology and carcinogenesis studies of ethylene oxide (greater than 99% pure) were conducted by exposing groups of 50 B6C3F1 mice of each sex to air containing 0, 50, or 100 ppm ethylene oxide, 6 hours per day, 5 days per week for 102 wk. ... Conclusions: Under the conditions of these 2 yr inhalation studies, there was clear evidence of carcinogenic activity for B6C3F1 mice as indicated by dose related incr incidences of benign or malignant neoplasms of the lung and benign neoplasms of the harderian gland in both male and female B6C3F1 mice following exposure to ethylene oxide vapors at 50 and 100 ppm. In female mice, ethylene oxide caused additional malignant neoplasms of the uterus, mammary gland, and hematopoietic system (lymphoma).
[Toxicology & Carcinogenesis Studies of Ethylene Oxide in B6C3F1 Mice (Inhalation Studies). Technical Report Series No. 326 (1987) NIH Publication No. 88-2582 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709]**QC REVIEWED**

Ethylene oxide (ETO) ... was evaluated for toxic and teratogenic effects in artificially inseminated New Zealand white (NZW) rabbits which were matched for body weight across treatment groups on gestational day (gd) 0. Ethylene oxide in 5% dextrose was administered daily in a volume of 1 ml/kg of body weight on gestational day 6 through 14 at dosages of 0, 9, 18 or 36 mg/kg/day, iv, or on gestational day 6 through 9 at dosages of 0, 18 or 36 mg/kg/day, iv. ... Administration of ethylene oxide (0, 9, 18 or 36 mg/kg/day, iv) on gestational days 6-14 resulted in mortality rates of 0% (0/27), 8.3% (2/24), 4.2% (1/24) and 22.2% (6/27), for the control through high-dose groups, respectively. Measures of maternal body weight (gestational days 14 and 30), maternal weight gain (i.e., weight gain during gestation, weight gain during treatment and absolute weight gain) and gravid uterine weight were each decreased in a dose-related manner. Examination of uterine contents on gestational day 30 revealed significant dose-related increases in the percentage of resorptions, nonlive and affected fetuses per litter. Average live litter size was decreased in a dose-related manner, as was the percentage of males per litter. No evidence of a treatment-related teratogenic effect observed, even at dosages which produced maternal and fetal toxicity. Maternal toxicity related to ethylene oxide (0, 18 or 36 mg/kg/day, iv) administered on gestational days 6-9 was limited to localized inflammation at the injection site for 1/23 confirmed-pregnant females in the high-dose group. Maternal weight gain during treatment and during gestation were reduced in a dose-related manner, but absolute maternal weight gain was not affected. At sacrifice on gestational day 30, examination of the uterine contents failed to reveal any evidence of a fetotoxic or teratogenic effect. In conclusion, no evidence for a teratogenic effect of ethylene oxide was observed when the compound was administered intravenously to NZW rabbits on gestational days 6-14 or gestational days 6-9 of gestation.
[Department of Health & Human Services/National Institute of Environmental Health Sciences, National Toxicology Program; Teratologic Evaluation of Ethylene oxide (CAS No. 75-21-8) in New Zealand White Rabbits, NTP Study No. TER82078 (April 18, 1983) available at http://ntp-server.niehs.nih.gov/htdocs/pub-TT0.html as of August 16, 2002]**QC REVIEWED**

Non-Human Toxicity Values:

LC50 Rat 1460 ppm (Exposure: 882-2298 ppm/4 hr). Effects were ocular and respiratory irritation, diarrhea, increased activity. /From table/
[O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume II. Boca Raton, FL: CRC Press, Inc., 1985. 88]**PEER REVIEWED**

LC50 Mouse 835 ppm (Exposure: 533-1365 ppm/4 hr). Effects were ocular and respiratory irritation, increased activity. /From table/
[O'Donoghue, J.L. (ed.). Neurotoxicity of Industrial and Commercial Chemicals. Volume II. Boca Raton, FL: CRC Press, Inc., 1985. 88]**PEER REVIEWED**

LD50 Rat oral 330 mg/kg
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

LC50 Rat inhalation 1462 ppm/4 hr
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

LC50 Mouse inhalation 836 ppm/4 hr
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

LC50 Dog inhalation 973 ppm/4 hr
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

LD50 Guinea pig oral 270 mg/kg
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

Ecotoxicity Values:

LC50 Goldfish 90 mg/l/24 hr modified ASTM D 1345
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 654]**PEER REVIEWED**

TSCA Test Submissions:

Chronic toxicity was evaluated in rats from the Army Chemical Center's Chemical Corps Medical Laboratories colony (20 animals) exposed to 100 ppm ethylene oxide via inhalation for 6 hrs/day for 6 months. The exposed animals showed no toxic signs. No significant effects were observed in weight gain, rectal temperature, EKG's, blood calcium and urea, or bilirubin. Mortalities for exposed and control rats were 3 out of 20 and 3 out of 20, respectively.
[Army Chemical Center; The Chronic Toxicity of Inhaled Ethylene Oxide. (1955), EPA Document No. 878211697, Fiche No. 205856] **UNREVIEWED**

Chronic toxicity was evaluated in mice from the Army Chemical Center's Chemical Corps Medical Laboratories colony (30 animals) exposed to 100 ppm ethylene oxide via inhalation for 6 hrs/day for 6 months. The exposed animals showed no toxic signs. No significant effects were observed in weight gain, rectal temperature, EKG's, blood calcium and urea, or bilirubin. Mortalities for exposed and control mice were 8 out of 30 and 4 out of 30, respectively.
[Army Chemical Center; The Chronic Toxicity of Inhaled Ethylene Oxide. (1955), EPA Document No. 878211697, Fiche No. 205856] **UNREVIEWED**

In a one-generation teratology study, pregnant female Fischer 344 rats (21-22/group) were exposed to ethylene oxide by inhalation at nominal concentrations of 0, 10, 33 or 100 ppm for 6 hrs on gestation days (GD) 6-15. The only treatment-related effect noted was a significant decrease in male and female fetal body weight relative to fetuses in control groups. No significant differences between treated and control animals were observed in the following: maternal and fetal survival, number of implantation and resorption sites, number of preimplantation losses, crown-to-rump length, the results of examination of all the fetuses for gross external abnormalities and half of each litter for visceral abnormalities and the other half for skeletal abnormalities.
[Carnegie-Mellon University; Ethylene Oxide Teratology Study. (1979), EPA Document No. 878213864, Fiche No. OTS0206333] **UNREVIEWED**

Chronic toxicity and oncogenicity were evaluated in groups of male and female Fischer 344 rats (120/sex/group) exposed to ethylene oxide via inhalation at 0, 10, 33 and 100 ppm for 6 hrs/day, 5 days/week for approximately 2 yrs. There was a statistically significant difference between treated animals and controls in the following: mortality (increased for both sexes at 100 ppm), body weight (decreased in males at 100 ppm and females at 100 and 33 ppm), mononuclear cell leukemia (increased in all treated female groups), peritoneal mesothelioma (increased in males at 100 and 33 ppm), cumulative percentage of pituitary adenoma (increased in females at 100 ppm), number of neoplasms/neoplasm bearing rats (increased for all treated rats, especially females), and number of rats with malignant neoplasms (increased in females at 100 and 33 ppm). There were no statistically significant differences in the following: chromosomal aberrations, ophthalmic lesions, urinalysis, hematology, serum clinical chemistry, or histopathology of the testes in males.
[Bushy Run Research Center; Ethylene Oxide Two-Year Inhalation Study on Rats, Final Report. (1981), EPA Document No. 878212152, Fiche No. 206028 ] **UNREVIEWED**

As part of a chronic inhalation study, the ability of ethylene oxide to cause chromosome aberrations was evaluated in bone marrow cells of Fischer 344 rats receiving nominal concentrations of the test material at 0 or 100ppm in a dynamic air flow chamber for 6hours/day, 5days/week for 12 months [also see OTS0206201; final report]. After exposure, a minimum of 5 animals/sex/group were sacrificed and at least 50 bone marrow cells/animal were collected. No statistically significant (Wilcoxon Sum of Ranks Test) increase in the frequency of chromosome aberrations was observed in bone marrow cells of rats exposed to 100ppm of ethylene oxide compared to the controls.
[Bushy Run Research Center; Report on Cytogenetic Studies of Bone Marrow Cells: 12-Month Sacrifice Interval, (1980), EPA Document No. 878212057, Fiche No. OTS0206060 ] **UNREVIEWED**

The fate of ethylene oxide (EO) was evaluated in preexposed male Fischer 344 rats and their respective controls (2 preexposed to 100ppm EO for 8 weeks plus 2 controls/ 2 preexposed to 100ppm EO for 10 weeks plus two controls) receiving a nominal concentration of 14C-EO at 100ppm for six hours in a closed cycle, recirculating inhalation chamber. Urine, feces and expired air were collected during and 18 hours after exposure to 14C-EO. There were no significant differences between the non-preexposed or preexposed animals in the routes of elimination or in metabolic profiles. There were no significant differences in the concentration of radioactivity in either group of animals, except that the radioactivity associated with the RBC was 1.3 times greater in the non-preexposed animals. The data indicates that prolonged exposure of rats to EO has little effect on the metabolism of the chemical.
[Carnegie-Mellon Institute of Research; Metabolism Study on Ethylene Oxide (EO) in Rats, (1978), EPA Document No. 878212054, Fiche No. OTS0206060 ] **UNREVIEWED**

The disposition of ethylene oxide (EO) was evaluated in male Fischer 344 rats (4/exposure) receiving nominal concentrations of 14C-EO at 10, 100 or 1000ppm for six hours in a closed cycle, recirculating, inhalation metabolism chamber. Urine, feces and carbon dioxide was collected during exposure and in Roth metabolism cages for 18 hours following exposure. The mean estimated absorbed dose was 2.7, 20.2 and 106.8mg EO/kg body weight for the 10, 100 and 1000ppm exposure, respectively. For all exposures the primary route of elimination was urine (mean value of 59% recovered 14C-activity), followed by CO2 (12%), feces (4.5%), and expired EO (1%). The highest concentrations of 14C-activity was found in the urinary bladder, liver, packed blood cells and adrenal glands, with the lowest concentration found in the fat. The increase in radioactivity concentration in tissue associated with increased exposure level of EO appeared to have a non-linear component. Analysis of urine obtained 18 hours post exposure was characterized by four radioactive metabolites. A significant increase in radioactivity was observed in two metabolites, a significant decrease in one and no difference in the fourth metabolite at 1000ppm relative to urinary metabolites in the other exposed rats.
[Bushy Run Research Center; Dose Dependent Disposition of 14-Labeled Ethylene Oxide in Rats, (1982), EPA Document No. 878212056, Fiche No. OT0206060 ] **UNREVIEWED**

Metabolism/Pharmacokinetics:

Metabolism/Metabolites:

... ABSORBED INTO THE CELL WHERE IT UNDERGOES HYDROLYSIS TO ETHYLENE GLYCOL ...
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2179]**PEER REVIEWED**

In adult male Sprague-Dawley rats, male Swiss CD-1 mice, and male rabbits, 20 or 60 mg/kg ethylene oxide as a solution in distilled water was injected into the caudal vein in rats and mice or in the marginal vein in rabbits. Some animals were exposed to 200 ppm ethylene oxide in inhalation chambers. The animals were housed in metabolism cages, and urine samples were collected at 0-6 hr and 6-24 hr. The urine samples were analyzed for 2-hydroxyethylmercapturic acid, N-acetyl-S-carboxy-methyl-L cysteine, S-(2-hydroxyethyl)-L-cysteine, S-carboxymethyl-L-cysteine, and ethylene glycol. Species-related differences in the metabolic disposition of ethylene oxide were observed. Excretion product patterns did not differ significantly between injected doses. Rats (n= 5) eliminated 37% of ethylene oxide as 2-hydroxyethylmercapturic acid (31%) and ethylene glycol (6%); mice (n= 10) converted 19.3% of the ethylene oxide to 2-hydroxyethylmercapturic acid (8.3%), S-2-hydroxyethyl-L-cysteine (5.8%), S-carboxymethyl-L-cysteine (1.9%), and ethylene glycol (3.3%). The rabbits (n= 3) excreted only 2% of the ethylene oxide, primarily as ethylene glycol. In rats, larger amounts of 2-hydroxyethylmercapturic acid were excreted in the 6-24 hr period, and larger amounts of ethylene glycol were excreted in the 0-6 hr period. In mice, equal amounts of 3-hydroxyethylmercapturic acid were excreted in the two collection periods and larger amounts of ethylene glycol were excreted in the 6-24 hr period. No urine was voided by the rabbits in the 0-6 hr period. No qualitative differences in urinary metabolite excretion of ethylene oxide were observed relative to the method of exposure.
[Tardif R et al; Fundam Appl Toxicol 9 (3): 448-53 (1987)]**PEER REVIEWED**

After fumigation of coca powder with ethylene oxide, several derivatives were isolated. Using IR and MS, these compounds have been identified as N,N-bis-(di-ethoxy-O-hydroxyethyl)isoleucylalanyl-cysteine, and N-(ethoxy-O-hydroxyethyl)tyrosine.
[Menzie, C.M. Metabolism of Pesticides-Update III. Special Scientific Report- Wildlife No. 232. Washington, DC: U.S.Department of the Interior, Fish and Wildlife Service, 1980. 292]**PEER REVIEWED**

Absorption, Distribution & Excretion:

AFTER EXPOSURE OF MICE TO MIXT OF 1,2-(3)H-ETHYLENE OXIDE VAPOR IN AIR FOR 75 MIN, 90-95% OF RADIOACTIVITY WAS ELIMINATED IN 24 HR. HIGHEST CONCN OF RESIDUAL RADIOACTIVITY WERE FOUND IN PROTEIN FRACTIONS OF SPLEEN; SMALLER AMT OCCURRED IN LIVER, KIDNEY, LUNG & TESTIS.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V11 162 (1976)]**PEER REVIEWED**

Iv injection of (14)C-labeled ethylene oxide indicated that (14)C concn in the testicle, epididymis and other organs were higher than those in the blood when measured 20 min to 4 hr after exposure. Radioactivity was still present in the epididymis 24 hr after exposure had ended.
[Appelgren LE et al; Europ Soc Toxicol 18: 315 (1977)]**PEER REVIEWED**

Biological monitoring of ethylene oxide exposure by analysis of alveolar air and blood was studied in 10 workers employed in a hospital sterilizer unit. Environmental air, alveolar air, and venous blood were sampled during and at the end of an 8-hr workshift. The mean environmental concentration of ethylene oxide was 5.4 mg/cu m air and the mean alveolar ethylene oxide concentration was 1.2 mg/cu m alveolar air. Regression analysis showed that blood ethylene oxide concentrations were higher than environmental ethylene oxide concentrations by a mean ratio of 3 and higher than alveolar ethylene oxide concentrations by a mean ratio of 12.
[Brugnone F et al; Int Arch Occup Environ Health 58: 105-12 (1986)]**PEER REVIEWED**

... Rats /were exposed/ for 6 hours at airborne concentrations of 1800, 180, or 18 ug/l of (14)C labeled ethylene oxide. The assimilated doses of ethylene oxide were 107 20, and 2.7 mg/kg, respectively.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I,II, III. Cincinnati, OH: ACGIH, 1991. 619]**PEER REVIEWED**

The distribution of radioactivity following the incubation of human blood with radio-labelled ethylene oxides was investigated in vitro. After incubation, the individual blood samples were separated into lymphocytes and high (Mr greater than 10,000) and low (Mr less than 10,000) molecular fractions of erythrocyte cytoplasm and blood plasma. The radioactivity was determined in each sample by liquid scintillation counting. In erythrocyte cytoplasm, the distribution of radioactivity showed marked interindividual differences and two distinct groups could be distinguished. The coincidence of these groups with conjugators and non-conjugators, in terms of the enzymatic conjugation of methyl halides to glutathione in erythrocytes, suggests a common principle, such as enzyme polymorphism. Such polymorphism has been described for glutathione S-transferase mu in the human liver, an enzyme that efficiently conjugates epoxides. In the other blood compartments, the interindividual differences were either less significant or were not detectable. Binding products with various macromolecules in blood, such as hemoglobin or lymphocyte DNA, are being discussed as biological monitors for occupational exposure to ethylene oxide. The observation that erythrocytes exhibit interindividual differences as described above make binding products with hemoglobin less suitable for biological monitoring of ethylene oxide exposure than, for example, DNA adducts in lymphocytes.
[Fost U et al; Hum Exp Toxicol 10 (1): 25-31 (1991)]**PEER REVIEWED**

Inhaled epoxyethane is well absorbed. The absorption of inhaled epoxyethane was limited by alveolar ventilation in resting rats and mice. In mice, the highest concn of radioactivity were found in the liver and kidneys following a 75-min inhalation exposure to 2.2 ppm 14(C) epoxyethane. Concentrations of radioactivity in the testes, spleen, lungs, and brain were approximately equal to level expected if 14(C) epoxyethane was evenly distributed in the body. The radioactivity was rapidly cleared from the tissue and eliminated in the urine.
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 664]**PEER REVIEWED**

Ethylene oxide is readily taken up by the lungs. A study on workers exposed to ethylene oxide revealed an alveolar retention of 75-80%, calculated from hourly determinations of ethylene oxide concentrations in environmental air ranging from 0.2 to 22.5 mg/cu m (0.11-12.3 ppm) and in alveolar air from 0.05 to 7 mg/cu m (0.03-3.8 ppm). At steady state, therefore, 20-25% of inhaled ethylene oxide reaching the alveolar space is exhaled as unchanged compound and 75-80% is taken up by the body and metabolized. Blood samples taken from workers 4 hours after the work shift and later gave venous blood:alveolar air coefficients of 12-17 and venous blood:environmental air coefficients of 2.5-3.3. The difference from the value of 90 determined from the blood:air partition coefficient in vitro was explained by incomplete saturation of tissues and limitation of the metabolic rate by the lung uptake rate.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V60 104 (1994)]**PEER REVIEWED**

Mechanism of Action:

Ethylene oxide is a carcinogenic compound which is also an ethylene metabolite. Ethylene oxide forms macromolecular adducts with proteins and nucleic acids. Targets in proteins are the amino acids cysteine, histidine and valine (if N-terminal, as in hemoglobin). The major DNA adduct is 7-(2-hydroxyethyl)-guanine.
[Bolt HM et al; Int Arch Occup Environ Health 60 (3): 141-4 (1988)]**PEER REVIEWED**

Mechanisms underlying the production of fetal anomalies subsequent to exposure of zygotes to ethylene oxide or ethyl methanesulfonate were investigated in (C3HxC57BL)F1-mice. Female mice were injected with ethyl methanesulfonate ip at 250 mg/kg, 6 hours after mating, or were exposed to ethylene oxide at 1,200 ppm for 1.5 hours, starting 6 hours after mating. A reciprocal zygote transfer study was conducted to determine if the induced response was direct property of exposed zygotes or an indirect effect due to maternal toxicity. Cytogenetic analyses of pronuclear metaphases, early cleavage embryos, and midgestation fetuses were also carried out to explore the nature of the genetic damage. The zygote transplantation experiment ruled out maternal toxicity as a factor in fetal maldevelopment and pointed to a genetic cause for the abnormalities. The cytogenetic studies, however, failed to uncover structural or numerical chromosome aberrations. The authors conclude that while the lesions induced in zygotes by the two mutagenic compounds are likely to be genetic in nature, they are different from conventional ones; they could be novel lesions in experimental mammalian mutagenesis, or the mechanisms responsible for their production could involve a nonmutational imprinting process that causes changes in gene expression.
[Katoh M et al; Mutat Res 210 (2): 337-44 (1989)]**PEER REVIEWED**

Interactions:

Cell transformation in vitro of C3H/10T1/2 cells, using gamma-radiation and ethylene oxide, in both the absence and presence of the cancer promoter, 12-O-tetradecanoylphorbol-13- acetate, was studied. 12-O-tetradecanoylphorbol-13-acetate promotes transformation of C3H/10T1/2 cells to the same extent. In the dose ranges studied the average enhancement of the transformation frequency was 2.4 and 2.5 for ethylene oxide and gamma-radiation, respectively. The rad-equivalence of ethylene oxide in the presence of 12-O-tetradecanoylphorbol-13-acetate was calculated to be 75 + or - 52 rad/mMh (95% confidence interval) which is consistent with the value 78 + or - 14 rad/mMh (95% confidence interval) obtained without 12-O-teradecanoylphorbol-13-acetate treatment.
[Kolman A et al; Toxicol Lett 53 (3): 307-13 (1990)]**PEER REVIEWED**

Pharmacology:

Therapeutic Uses:

MEDICATION (VET): SPORICIDAL, VIRUCIDAL
[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974. 209]**QC REVIEWED**

Interactions:

Cell transformation in vitro of C3H/10T1/2 cells, using gamma-radiation and ethylene oxide, in both the absence and presence of the cancer promoter, 12-O-tetradecanoylphorbol-13- acetate, was studied. 12-O-tetradecanoylphorbol-13-acetate promotes transformation of C3H/10T1/2 cells to the same extent. In the dose ranges studied the average enhancement of the transformation frequency was 2.4 and 2.5 for ethylene oxide and gamma-radiation, respectively. The rad-equivalence of ethylene oxide in the presence of 12-O-tetradecanoylphorbol-13-acetate was calculated to be 75 + or - 52 rad/mMh (95% confidence interval) which is consistent with the value 78 + or - 14 rad/mMh (95% confidence interval) obtained without 12-O-teradecanoylphorbol-13-acetate treatment.
[Kolman A et al; Toxicol Lett 53 (3): 307-13 (1990)]**PEER REVIEWED**

Environmental Fate & Exposure:

Environmental Fate/Exposure Summary:

Ethylene oxide will primarily enter the atmosphere in association with its production and use as a chemical intermediate as well as its relatively minor use as a sterilant and fumigant. From its industrial use, some ethylene oxide will be discharged into water. Once in the atmosphere it will degrade very slowly by reaction with hydroxyl-radicals (estimated half-life 211 days). Releases into water will be removed by volatilzation, hydrolysis and to a lesser extent, biodegradation. The volatilization half-lives for its removal from a model river and model lake are 5.9 hr and 3.8 days, respectively. Ethylene oxide will not adsorb strongly to soil or bioconcentrate in fish, although its presence in some food items may result from its use as a fumigant and sterilant. Major human exposure will be from occupational atmospheres. (SRC)
**PEER REVIEWED**

Probable Routes of Human Exposure:

Exposure to ethylene oxide is primarily occupational via inhalation. (SRC)
**PEER REVIEWED**

OSHA estimates that approximately 80,000 and 144,000 workers are directly and indirectly exposed to ethylene oxide in ethylene oxide production, chemical synthesis by ethoxylation, health care facilities (sterilization), medical products (sterilization) and miscellaneous manufacturers (e.g., spice sterilization)(1). The number of workers exposed directly (indirectly) in the various industries are: production and synthesis 3676; sterilization - health care facilities 62,370 (25,000); sterilization - medical products manufacture 14,000 (116,900); sterilization - spice manufacturers 160(1). Typical exposures are usually high during short periods in which sterilizer doors are opened, typically 5-10 ppm for 20 minutes(1). Some typical survey results are: Medical products manufactures 0.1.1-2.0 ppm 8 hr TWA; Hospital sterilizer chamber operators 2.5 ppm TWA; 121 use sites in Southern California <5 ppm (TWA) in 114/121 sites; 2 hospitals 3-6 ppm and <5 ppm resp; survey of 27 hospitals TWA exposures less than or equal to 1, <4 and >10 ppm in 9/27, 16/27 and 5/27, respectively(1). Union Carbide production plant in Texas City 5-33 ppm and 7.25 and 10.25 ppm avg in 2 control rooms and 0-56 ppm, 11.6 ppm avg throughout plant(2). In-depth survey of 2 Union Carbide production facilities in West Virginia- 2 of 48 and 4 of 41 samples positive, TWA exposure of positive samples 1.5-82 ppm(4,5). Production and maintenance workers in the 1960's avg exposure levels 0.6-60 ppm(3).
[(1) OSHA; Occupational Exposure to Ethylene Oxide; Proposed Rule. 48 FR 17283-17319 4,21 (1983) (2) Joyner RE; Arch Environ Health 8:700-10 (1964) (3) Hogstedt C et al; Brit J Ind Med 36:276-80 (1979) (4) Oser JL; In-depth Industrial Hygiene Report of Ethylene Oxide Exposure at Union Carbide Corp., WV NIOSH IWS-67.17B 47 p (1978) (5) Oser JL; In-depth Industrial Hygiene Report of Ethylene Oxide Exposure at Union Carbide Corp., South Charleston, WV NIOSH IWS-67.10 25 p (1979)]**PEER REVIEWED**

NIOSH (NOES Survey 1981-1983) has statistically estimated that 50,132 workers are exposed to ethylene oxide in the USA(2). The personal 8-hr TWA exposure in 12 hospitals ranged from ND to 6.3 ppm for sterilizer operators and ND to 6.7 ppm for folders and packers. Short term (2 to 30 min) exposure levels for sterilizer operators ranged from ND to 103 ppm(1). Lower exposure levels were correlated with effective engineering controls and good work practices, rather than with the size of the hospital, or number or location of sterilizers.
[(1) Elliot LJ et al; Appl Ind Hyg 3: 141-5 (1988) (2) NIOSH; National Occupational Exposure Survey (1989)]**PEER REVIEWED**

Natural Pollution Sources:

Since ethylene oxide is a product of combustion of hydrocarbon fuels, it is likely that ethylene oxide would be produced during the combustion of naturally-occurring hydrocarbons.(SRC)
**PEER REVIEWED**

Artificial Pollution Sources:

In vent gas and fugitive emission from its production and use as a chemical intermediate in the manufacture of ethylene glycol, ethoxylates, glycol ethers and ethanolamines(1). Aqueous effluent associated with its production and use as a chemical intermediate. Fugitive emissions from its use as a fumigant and sterilant of food, cosmetics and hospital supplies(1,3-4); auto and diesel exhaust - combustion product of hydrocarbon fuels(1,2); tobacco smoke(1). While its use as a fumigant and sterilant constitute only 2% of its use, emissions from these uses are proportionately higher than other uses and result in greater exposure(3,4).
[(1) Bogyo DA et al; Investigations of Selected Potential Environmental Contaminants. Epoxides USEPA-560/11-80-005 p. 60-9 (1980) (2) Graedel TE; Chemical Compounds in the Atmosphere Academic Press, NY p. 272 (1978) (3) Chemical & Engineering News p. 12 (1983) (4) Cawse JN et al; in Kirk-Othmer Encycl Chem Tech 3rd ed. NY,NY: Wiley-Interscience 9: 432-71 (1980)]**PEER REVIEWED**

Environmental Fate:

TERRESTRIAL FATE: When released on land, ethylene oxide would tend to volatilize rapidly. It is miscible in water and poorly adsorbed to soil so leaching is likely to occur. Although experimental data are lacking, hydrolysis in soil is probable. (SRC)
**PEER REVIEWED**

AQUATIC FATE: When released into water ethylene oxide will primarily be lost by three processes: volatilization, hydrolysis and biodegradation in that order of importance. Volatilization will depend on wind and mixing conditions and would be expected to occur in hours to days. The volatilization half-lives of ethylene oxide in a model river and lake are 5.9 hr and 3.8 days, respectively. The half-life for hydrolysis is 9-14 days leading to biodegradable products. Because of the limited data, it is difficult to estimate the rate of biodegradation; the available data would suggest that the biodegradation rate is slower than the volatilization and hyrdrolysis rates. Ethylene oxide would not tend to adsorb to sediment. In groundwater, ethylene oxide will degrade due to hydrolysis. (SRC)
**PEER REVIEWED**

ATMOSPHERIC FATE: Ethylene oxide will degrade in the atmosphere primarily by reaction with photochemically produced hydroxyl radicals. Assuming a hydroxyl radical concn of 5X10+5 radicals/cu cm, the half-life of ethylene oxide in the atmosphere will be 211 days(1,SRC). Data suggests that neither rain out nor adsorption into aqueous aerosols in the air should remove much of this compound(2).
[(1) Atkinson R; J Chem Phys Ref Data Monograph 1 (1989) (2) Cupitt LT; Atmospheric persistence of eight air tosics. USEPA-600/S3-87/004 (1987)]**PEER REVIEWED**

Environmental Biodegradation:

Based on limited data, ethylene oxide biodegrades at a reasonable rate after a period of acclimation. In a dilution bottle test, there was 3-5% degradation after 5 days and 52% degradation after 20 days(1,2). Since ethylene oxide hydrolyzes to ethylene glycol which is readily biodegraded, there is a fair amount of uncertainty in the biodegradability measurements(2). In a river die-away test, the rate of degradation was not significantly different than for hydrolysis(2). Ethylene oxide biodegradation rate constants measured at a full-scale wastewater treatment plant were 0.38 and 0.59 ug/min-g biomass(3). These rate constants would imply that a system with a 6 day residence time operated with mixed liquor suspended solids of 2500 mg/L would effectively biodegrade 8.2 and 12.7 mg/L of ethylene oxide, respectively(SRC).
[(1) Bridie AL et al; Water Res 13:627-30 (1979) (2) Conway RA et al; Environ Sci Technol 17:107-12 (1983) (3) Green D, Eklund B; Field assessment of the fate of volatile organics in aerated wastewater systems. pp. 478-86 in USEPA/9-87-015. (1987)]**PEER REVIEWED**

Environmental Abiotic Degradation:

Ethylene oxide hydrolyzes slowly in fresh and salt water to give ethylene glycol and ethylene chlorohydrin(1). The half-life for this reaction is 12-14 days for pH's between 5-7 in fresh water(1,2,3) and 9-11 days in salt water(1). The ratio of chlorohydrin to glycol formed was found to be 0.11 and 0.23 in 1% and 3% sodium chloride solutions respectively(1). The hydrolysis rate is increased considerably in acidic or basic solutions(2). In the atmosphere, ethylene oxide reacts with photochemically-produced hydroxyl radicals with a rate constant of 7.6X10-14 cu cm/molecule-s at(1). Assuming a hydroxyl radical concn of 5X10+5 radicals/cu cm, the half-life of ethylene oxide in the atmosphere would be 211 days(SRC). Earlier smog chamber experiments with both natural and artificial illumination are consistent with a slowly degrading compound(6). In one of these, 20% of the ethylene oxide degraded in 5.3 hr(4).
[(1)Conway RA et al; Environ Sci Technol 17:107-12 (1983) (2) Bogyo DA et al; Investigation of selected environmental contaminants: Epoxides. USEPA-560/11-80-005 p 69-96 (1980) (3) Mabey W, Mill T; J Phys Chem Ref Data 7:383-415 (1978) (4) Joshi SB et al; Atmos Environ 16: 1301-10 (1979) (5)Atkinson R; J Chem Phys Ref Data Monograph 1 (1989) (6) Cupitt LT; Atmospheric persistence of Eight Air Toxics. USEPA-600/S3-87/004 (1987)]**PEER REVIEWED**

Environmental Bioconcentration:

Although no studies of bioconcentration for ethylene oxide were found in the literature, one would not expect it to bioconcentrate due to its low octanol/water partition coefficient (log Kow= -0.3)(1).(SRC)
[(1) Hansch C, Leo AJ; Substituent Constants for Correlation Analysis in Chemistry and Biology. NY: John Wiley & Sons p. 339 (1979)]**PEER REVIEWED**

Soil Adsorption/Mobility:

No data could be found concerning the adsorption of ethylene oxide to soil. One would not expect a very high adsorptivity due to its low octanol/water partition coefficient (log Kow = -0.3)(1). Based on a regression analysis with the log octanol/water partition coefficient(2), one would calculate a KOC of 16(SRC).
[(1) Hansch C, Leo AJ; Substituted Constants for Correlation Analysis in Chemistry and Biology. NY: John Wiley & Sons p. 339 (1979) (2) Kenaga EE, Going CAI; Aquatic Toxicology, Proceedings of the Third Annual Symp on Aquatic Toxicology, ASTM, Philadelphia, PA (1980)]**PEER REVIEWED**

Volatilization from Water/Soil:

The half-life for evaporation of ethylene oxide from water is 1 hr with no wind and 0.8 hr with a 5 m/sec wind as determined in a laboratory experiment(1). The Henry's law constant for ethylene oxide is 1.48X10-4 atm-cu m/mole(1). Using this value of the Henry's Law constant, one would estimate a volatilization half-life of 5.9 hr for ethylene oxide from a model river 1 m deep with a 1 m/s current and a 3 m/s wind(3,SRC). Similarly, its half-life from a model lake 1 m deep with a 0.05 m/s current and 0.5 m/s wind is 3.8 days. Although no data on the volatilization of ethylene oxide from soil could be found, a study of the dissipation of ethylene oxide from fumigated commodities gave half-life values of 4 hr to 17.5 days(2).
[(1) Conway RA et al; Environ Sci Technol 17:107-112 (1983) (2) Bogyo DA et al; Investigations of Selected Potential Environmental Contaminants: Epoxides. USEPA-560/11-80-005 p 70-90 (1980) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods, NY: McGraw-Hill Chapt 15 (1982)]**PEER REVIEWED**

Effluent Concentrations:

Detected, not quantified in an effluent sample in Brandenburg, KY in Feb 1974, at a production facility(1,2). It is estimated that in ethylene oxide production, between 0.25 and 47.5 kg of ethylene oxide is emitted to the air for each kg produced(3).
[(1) Shalkelford WM, Keith LH; Frequency of Organic Compounds Identified in Water. USEPA-600/4-76-062 p 129 (1976) (2) Bogyo DA et al; Investigation of Selected Potential Environmental Contaminants: Epoxides. USEPA-560/11-80-005 p 17 (1980) (3) Carpenter CE et al; Toxic Subst J 10: 323-71 (1990)]**PEER REVIEWED**

Food Survey Values:

1970-76 FDA Monitoring Program - detected, not quantified in 1 out of 2372 samples of eggs in 1975(1).
[(1) Duggan RE et al; Pesticide residue levels in foods in the US from July 1 to June 30, 1976. Food and Drug Admin. page 10-18 (1983)]**PEER REVIEWED**

Fish/Seafood Concentrations:

1970-1976 FDA Food Monitoring Program - detected, not quantified in 1 out of 3262 samples of fish (1975), not found in 443 samples of shellfish for this period(1).
[(1) Duggan RE et al; Pesticide Residue Levels in Foods in the US from July 1 to June 30, 1976. Food and Drug Administration p 10-18 (1983)]**PEER REVIEWED**

Environmental Standards & Regulations:

FIFRA Requirements:

A tolerance is established for residues of the antimicrobial agent and insecticide ethylene oxide, when used as a postharvest fumigant in or on the following raw agricultural commodities: black walnut meats, copra, whole spices.
[40 CFR 180.151 (7/1/92)]**PEER REVIEWED**

Ethylene oxide may be safely used as a fumigant for the control of microorganisms and insect infestation in ground spices and other processed natural seasoning materials, except mixt to which salt has been added ... Tolerances are established for residues of ethylene oxide in ground spices from both postharvest application to the raw agricultural commodity whole spices and application to the ground spices.
[40 CFR 185.2850 (7/1/92)]**PEER REVIEWED**

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Ethylene oxide is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA, as amended in 1988. Case No: 2275; Pesticide type: insecticide, fungicide, rodenticide, antimicrobial; Case Status:In Pre-Special Review. The pesticide is in or has completed the reregistration process and, meanwhile, is also the subject of an in-depth Special Review.; Active ingredient (AI): Ethylene oxide; Data Call-in (DCI) Date(s): 05/24/91; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.
[USEPA/OPP; Status of Pesticides in Registration, Reregistration and Special Review p.182 (Spring, 1998) EPA 738-R-98-002]**QC REVIEWED**

TSCA Requirements:

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Oxirane is included on this list.
[40 CFR 716.120 (7/1/92)]**PEER REVIEWED**

Section 8(a) of TSCA requires manufacturers of this chemical substance to report preliminary assessment information concerned with production, use, and exposure to EPA as cited in the preamble of the 51 FR 41329.
[40 CFR 712.30 (7/1/92)]**PEER REVIEWED**

CERCLA Reportable Quantities:

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 10 lb or 4.54 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).
[40 CFR 302.4 (7/1/92)]**PEER REVIEWED**

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Ethylene Oxide is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 1,000 lbs.
[40 CFR 355 (7/1/97)]**QC REVIEWED**

RCRA Requirements:

U115; As stipulated in 40 CFR 261.33, when ethylene oxide, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).
[40 CFR 261.33 (7/1/92)]**PEER REVIEWED**

Atmospheric Standards:

This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Ethylene oxide is produced, as an intermediate or a final product, by process units covered under this subpart.
[40 CFR 60.489 (7/1/92)]**PEER REVIEWED**

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Ethylene oxide is included on this list.
[Clean Air Act as amended in 1990, Sect. 112 (b) (1) Public Law 101-549 Nov. 15, 1990]**QC REVIEWED**

State Drinking Water Guidelines:

(FL) FLORIDA 10 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)] **QC REVIEWED**

Allowable Tolerances:

A tolerance of 50 ppm is established for residues of the antimicrobial agent and insecticide ethylene oxide, when used as a postharvest fumigant in or on the following raw agricultural commodities: Black walnut meats, copra, whole spices.
[40 CFR 180.151 (7/1/92)]**PEER REVIEWED**

Residues of ethylene oxide in ground spices from both postharvest application to the raw agricultural commodity whole spices and application to the ground spices shall not exceed the established tolerance of 50 ppm for residues in whole spices.
[40 CFR 185.2850(c) (7/1/92)]**PEER REVIEWED**

Chemical/Physical Properties:

Molecular Formula:

C2-H4-O
**PEER REVIEWED**

Molecular Weight:

44.06
[U.S. Department of Health and Human Services, Public Health Service, Center for Disease Control, National Institute for Occupational Safety Health. Registry ofToxic Effects of Chemical Substances (RTECS). National Library of Medicine's current MEDLARS file.,p. 87/8704]**PEER REVIEWED**

Color/Form:

COLORLESS GAS @ ORDINARY ROOM TEMP & PRESSURE; LIQUID BELOW 12 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 559]**PEER REVIEWED**

Colorless gas or liquid (below 51 degrees F) ...
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

Odor:

Sweet
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

ETHER-LIKE ODOR
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 49-68]**QC REVIEWED**

Reminiscent of bruised apples
[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982. 562]**PEER REVIEWED**

... Ether-like odor.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

Boiling Point:

10.7 DEG C @ 760 MM HG
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 599]**PEER REVIEWED**

Melting Point:

-111 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 599]**PEER REVIEWED**

Critical Temperature & Pressure:

Critical temperature = 469.15 K; Critical pressure = 7.1941X10+6 Pa
[Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.]**PEER REVIEWED**

Density/Specific Gravity:

0.882 @ 10 DEG C/10 DEG C
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 599]**PEER REVIEWED**

Heat of Combustion:

1280.9 kJ/mol (liquid); 1306.1 kJ/mol (gas)
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 75th ed. Boca Raton, Fl: CRC Press Inc., 1994-1995.,p. 5-76]**PEER REVIEWED**

Heat of Vaporization:

24.75 kJ/mol @ 25 deg C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 75th ed. Boca Raton, Fl: CRC Press Inc., 1994-1995.,p. 6-114]**PEER REVIEWED**

Octanol/Water Partition Coefficient:

log Kow= -0.30
[Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995. 4]**QC REVIEWED**

Solubilities:

... Miscible in all proportions with water, alcohol, ethers, and most organic solvents
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present. 916]**PEER REVIEWED**

SOL IN BENZENE, ACETONE
[Lide, D.R. (ed). CRC Handbook of Chemistry and Physics. 72nd ed. Boca Raton, FL: CRC Press, 1991-1992.,p. 3-243]**PEER REVIEWED**

MISCIBLE WITH CARBON TETRACHLORIDE
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2167]**PEER REVIEWED**

Spectral Properties:

MAX ABSORPTION (GAS): 169 NM (LOG E= 3.58); 171 NM (LOG E= 3.57)
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979.,p. C-293]**PEER REVIEWED**

INDEX OF REFRACTION: 1.3597 @ 7 DEG C/D
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 599]**PEER REVIEWED**

IR: 1109 (Sadtler Research Laboratories Prism Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 627]**PEER REVIEWED**

MASS: 12 (Atlas of Mass Spectral Data, John Wiley & Sons, New York)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985.,p. V1 627]**PEER REVIEWED**

Surface Tension:

Liquid: 24.3 dynes/cm= 0.0243 N/m at 20 deg C.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Vapor Density:

1.49
[Celanese Chemical Co Inc, Product Bulletin Sheet 1978 as cited in Environment Canada; Tech Info for Problem Spills: Ethylene oxide p.3 (1982)]**PEER REVIEWED**

Vapor Pressure:

1314 MM HG AT 25 DEG C (calculated from experimentally derived coefficients)
[Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.]**PEER REVIEWED**

Viscosity:

9.45x10-3 mPa.s (25 deg C, gas) and 0.254 mPa.s (10 deg C, liquid)
[Matheson Gas Prod; Tech Info for Problem Spills: Ethylene oxide p.4 (1982)]**PEER REVIEWED**

Other Chemical/Physical Properties:

LIQ IS LIGHTER THAN WATER, VAPOR IS HEAVIER THAN AIR
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 49-68]**QC REVIEWED**

Heat of solution in water: 142.57 kJ/kg @ 25 deg C
[Gerhartz, W. (exec ed.). Ullmann's Encyclopedia of Industrial Chemistry. 5th ed.Vol A1: Deerfield Beach, FL: VCH Publishers, 1985 to Present.,p. VA10 118]**PEER REVIEWED**

CAN REACT WITH OXIDIZING MATERIALS
[Sax, N.I. Dangerous Properties of Industrial Materials. 4th ed. New York: Van Nostrand Reinhold, 1975. 741]**PEER REVIEWED**

Ratio of specific heats of vapor (gas): 1.212
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Chemical oxygen demand: 1.74 Nederlands norm (dutch standard test method) 3235 - 5.3 sublimation: 24.9 K/mole at 25 deg C
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 654]**PEER REVIEWED**

Heat of fusion: 28.07 cal/g
[Weast, R.C. (ed.) Handbook of Chemistry and Physics. 67th ed. Boca Raton, FL: CRC Press, Inc., 1986-87.,p. C-689]**PEER REVIEWED**

Ionization potential: 10.56 eV
[Krassig VR et al; Tech Info for Problem Spills: Ethylene Oxide p.4 (1982)]**PEER REVIEWED**

Standard Enthalpy of Formation: -77.8 kJ/mol /liquid/; -52.6 kJ/mol (gas)
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 75th ed. Boca Raton, Fl: CRC Press Inc., 1994-1995.,p. 5-28]**PEER REVIEWED**

Heat of fusion: 5.1714 J/k mol
[Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989.]**PEER REVIEWED**

Coefficient of thermal expansion: 1.51x10-3/deg C
[Celanese Chem Corp, Inc; Tech Info for Problem Spills: Ethylene Oxide p.5 (1982)]**PEER REVIEWED**

Chemical Safety & Handling:

DOT Emergency Guidelines:

Health: TOXIC; may be fatal if inhaled or absorbed through skin. Contact with gas or liquefied gas may cause burns, severe injury and/or frostbite. Fire will produce irritating, corrosive and/or toxic gases. Runoff from fire control may cause pollution.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

Fire or explosion: Flammable; may be ignited by heat, sparks or flames. May form explosive mixtures with air. Those substances designated with a "P" may polymerize explosively when heated or involved in a fire. Vapors from liquefied gas are initially heavier than air and spread along ground. Vapors may travel to source of ignition and flash back. Some of these materials may react violently with water. Containers may explode when heated. Ruptured cylinders may rocket. Runoff may create fire or explosion hazard.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

Public safety: CALL Emergency Response Telephone Number ... . Isolate spill or leak area immediately for at least 100 to 200 meters (330 to 660 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Many gases are heavier than air and will spread along ground and collect in low or confined areas (sewers, basements, tanks). Keep out of low areas. Ventilate closed spaces before entering.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing which is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

Evacuation: Spill: ... Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 1600 meters (1 mile) in all directions; also, consider initial evacuation for 1600 meters (1 mile) in all directions.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

Fire: DO NOT EXTINGUISH A LEAKING GAS FIRE UNLESS LEAK CAN BE STOPPED. Small fires: Dry chemical, CO2, water spray or alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam. FOR CHLOROSILANES, DO NOT USE WATER; use AFFF alcohol-resistant medium expansion foam. Move containers from fire area if you can do it without risk. Damaged cylinders should be handled only by specialists. Fire involving tanks: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Cool containers with flooding quantities of water until well after fire is out. Do not direct water at source of leak or safety devices; icing may occur. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

Spill or leak: ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area). All equipment used when handling the product must be grounded. Fully encapsulating, vapor protective clothing should be worn for spills and leaks with no fire. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Do not direct water at spill or source of leak. Use water spray to reduce vapors or divert vapor cloud drift. Avoid allowing water runoff to contact spilled material. FOR CHLOROSILANES, use AFFF alcohol-resistant medium expansion foam to reduce vapors. If possible, turn leaking containers so that gas escapes rather than liquid. Prevent entry into waterways, sewers, basements or confined areas. Isolate area until gas has dispersed.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

First aid: Move victim to fresh air. Call 911 or emergency medical service. Apply artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; induce artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. In case of contact with liquefied gas, thaw frosted parts with lukewarm water. Keep victim warm and quiet. Keep victim under observation. Effects of contact or inhalation may be delayed. Ensure that medical personnel are aware of the material(s) involved, and take precautions to protect themselves.
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. G-119]**QC REVIEWED**

Initial Isolation and Protective Action Distances: Small Spills (from a small package or small leak from a large package): First, ISOLATE in all Directions 60 meters (200 feet); then, PROTECT persons Downwind during DAY 0.2 kilometers (0.1 miles) and NIGHT 0.3 kilometers (0.2 miles). LARGE SPILLS (from a large package or from many small packages): First, ISOLATE in all Directions 125 meters (400 feet); then, PROTECT persons Downwind during DAY 0.3 kilometers (0.2 miles) and NIGHT 1.0 kilometers (0.6 miles). /Ethylene oxide; Ethylene oxide with nitrogen/
[U.S. Department of Transportation. 2000 Emergency Response Guidebook. RSPA P 5800.8 Edition. Washington, D.C: U.S. Government Printing Office, 2000,p. TABLE]**QC REVIEWED**

Odor Threshold:

50 ppm
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Recognition: 1.5 mg/cu m= 0.8 ppm, mean detection concn: 700 ppm; absolute perception limit: 260 ppm; 50% recognition: 500 ppm; 100% recognition: 500 ppm
[Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 654]**PEER REVIEWED**

Low: 520 mg/cu m; High: 1400 mg/cu m
[Ruth JH; Am Ind Hyg Assoc J 47: A-142-51 (1986)]**PEER REVIEWED**

300 ppm in air
[Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 663]**PEER REVIEWED**

Skin, Eye and Respiratory Irritations:

Ethylene oxide is irritating to the eyes, respiratory tract, and skin.
[Rom, W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 1992. 1034]**PEER REVIEWED**

Aqueous solutions of ethylene oxide or solutions formed when the anhydrous cmpd comes in contact with moist skin are irritating and may lead to a severe dermatitis with blisters, blebs and burns. It is also absorbed by leather and rubber and may produce burns or irritation. Allergic eczematous dermatitis has also been reported. Exposure to the vapor in high concn leads to irritation of the eyes. Severe eye damage may result if the liquid is splashed in the eyes. Large amounts of ethylene oxide evaporating from the skin may cause frostbite.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985. 433]**PEER REVIEWED**

Fire Potential:

Flammable liquid
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 49-68]**QC REVIEWED**

NFPA Hazard Classification:

Health: 3. 3= Materials that, on short exposure, could cause serious temporary or residual injury, including those requiring protection from all bodily contact. Fire fighters may enter the area only if they are protected from all contact with the material. Full protective clothing, including self-contained breathing apparatus, coat, pants, gloves, boots, and bands around legs, arms, and waist, should be provided. No skin surface should be exposed.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 325-51]**QC REVIEWED**

Flammability: 4. 4= This degree includes flammable gases, pyrophoric liquids, and Class IA flammable liquids. The preferred method of fire attack is to stop the flow of material or to protect exposures while allowing the fire to burn itself out.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 325-51]**QC REVIEWED**

Reactivity: 3. 3= This degree includes materials that, in themselves, are capable of detonation, explosive decomposition, or explosive reaction, but require a strong initiating source or heating under confinement. This includes materials that are sensitive to thermal and mechanical shock at elevated temperatures and pressures and materials that react explosively with water. Fires involving these materials should be fought from a protected location.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 325-51]**QC REVIEWED**

Flammable Limits:

Lower flammable limit: 3%; Upper flammable limit: 100%
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

Flash Point:

<0 deg F (Open cup)
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Autoignition Temperature:

804 DEG F
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 1347]**PEER REVIEWED**

Fire Fighting Procedures:

Fire extinguishing agents: water.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Stop flow of gas if possible. Combat fires from behind barrier, with unmanned hose holder or monitor nozzle. Flood discharge area with water. Cool exposed containers and protect men effecting shut off with water.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Carbon dioxide and dry-chemical extinguishers are useful against small fire.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 238]**PEER REVIEWED**

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical or carbon dioxide.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads,Bureau of Explosives, 1992. 434]**PEER REVIEWED**

Evacuation: If fire is prolonged and material is confined in the container consider evacuation of one (1) mile radius. If fire becomes uncontrollable or container is exposed to direct flame, consider evacuation of one (1) mile radius.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads,Bureau of Explosives, 1992. 434]**PEER REVIEWED**

Toxic Combustion Products:

Irritating vapors generated when heated.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Firefighting Hazards:

Vapor is heavier than air and may travel considerable distance to a source of ignition and flash back.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Explosive Limits & Potential:

LOWER EXPLOSIVE LIMIT: 3.0%, UPPER EXPLOSIVE LIMIT: 100%. EXPLOSION HAZARD: SEVERE, WHEN EXPOSED TO FLAME.
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 1347]**PEER REVIEWED**

GAS IS EXPLOSIVE IN CONCN ABOVE 3% & MUST BE MIXED WITH CARBON DIOXIDE OR FLUOROCARBONS.
[Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 972]**PEER REVIEWED**

Decompostion products are explosive.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 666]**PEER REVIEWED**

VAPOR FORMS EXPLOSIVE MIXTURES WITH AIR OVER A WIDE RANGE.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 49-68]**QC REVIEWED**

Hazardous Reactivities & Incompatibilities:

Metal fittings containing copper, silver, mercury, or magnesium should not be used in ethylene oxide service, since traces of acetylene could produce explosive acetylides capable of detonating ethylene oxide vapor.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990 272]**PEER REVIEWED**

INCOMPATIBILITIES: BECAUSE OF HIGH CHEMICAL REACTIVITY ... IT REACTS WITH MANY PHARMACEUTICAL SUBSTANCES & WITH VITAMINS, AMINO ACIDS, & OTHER FOOD CONSTITUENTS. ...
[Osol, A. (ed.). Remington's Pharmaceutical Sciences. 16th ed. Easton, Pennsylvania: Mack Publishing Co., 1980. 1101]**PEER REVIEWED**

Accidental contamination of a large ethylene oxide feed-cylinder by reaction liquor containing trimethylamine caused the cylinder to explode 18 hr later. Contamination was possible because of a faulty pressure gauge and suck-back of froth above the liquid level.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990 276]**PEER REVIEWED**

Highly reactive! Hazardous polymerization may occur especially if contaminated. Reacts with acids, alkalies, salts, combustible materials. Ethylene oxide and water may form stratified layers. May undergo runaway reaction with water. Many materials may accelerate this reaction.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997.,p. 49-68]**QC REVIEWED**

It reacts with chloride and water to produce two active germicides, 2-chloroethanol and ethylene glycol.
[American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994. 1620]**PEER REVIEWED**

Strong acids, alkalis & oxidizers; chlorides of iron, aluminum & tin; oxides of iron & aluminum; water.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

Hazardous Decomposition:

Liquid ethylene oxide is not detonable, but the vapor may be readily initiated into explosive decomposition.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990 272]**PEER REVIEWED**

Hazardous Polymerization:

Precautions designed to prevent explosive polymerization of ethylene oxide are discussed, including rigid exclusion of acids, covalent halides such as aluminium, iron (III), and tin (IV) chloride, basic materials like alkali hydroxides, ammonia, amines, metallic potassium, and catalytically active solids such as aluminium or iron oxides or rust.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990 274]**PEER REVIEWED**

POLYMERIZATION IS CATALYZED BY A NUMBER OF MATERIALS, SUCH AS ACIDS, ALKALIS, SOME CARBONATES, OXIDES OF IRON & ALUMINUM, & CHLORIDES OF IRON, TIN, ALUMINUM, & BORON. NO ACETYLIDE-FORMING METALS SUCH AS COPPER OR COPPER ALLOYS SHOULD BE IN CONTACT WITH ETHYLENE OXIDE.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 2166]**PEER REVIEWED**

Accidental contamination of an ethylene oxide feed tank by ammonia caused violently explosive polymerization.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990 273]**PEER REVIEWED**

Prior History of Accidents:

A Chessie System freight train derailed in a wooded, rural area near Woodland Park, Michigan in February 1978. Four tank cars were damaged, spilling approx 300,000 lb of vinylidene chloride, 330,000 lb of phenol, and 125,000 lb of ethylene oxide. Most of the phenol, which had solidified on the surface, was removed by a cleanup contractor although residual phenol remained in the soil. The ethylene oxide vaporized, posing no groundwater contamination problems. The vinylidene chloride percolated through the sandy soils into the groundwater about 50 ft below the ground surface. Vinylidene chloride concentrations as high as 300 mg/l were found in monitoring wells near the derailment site. The groundwater cleanup program was completed over a three yr period. ...
[Posthuma AR et al; 1983 Nat Conf Environ Engin p.775-82 (1983)]**PEER REVIEWED**

Immediately Dangerous to Life or Health:

NIOSH considers ethylene oxide to be a potential occupational carcinogen.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

Protective Equipment & Clothing:

AIR-SUPPLIED MASK; GOGGLES OR FACE SHIELD; RUBBER SHOES & COVERALLS.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Wear neoprene gloves, safety glasses, plastic protective clothing and self-contained breathing apparatus.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 8]**PEER REVIEWED**

A study was conducted to evaluate protective clothing garment materials used by emergency response personnel and to determine their effectiveness when combating ammonia or ethylene oxide in gaseous form. Data were collected using an automated permeation test system for 13 garment materials representing 11 types of total encapsulating suit materials and two glove materials. For the study neat (100%) and 2000 ppm (0.2%) gas were chosen as challenge concentrations. A closed loop test system was chosen for the study using an infrared detector. Breakthrough times and steady state permeation rates were determined. The results indicated suitable garment materials were found to protect workers against 100% anhydrous ammonia for an extended time period and there was also a large selection of materials for 0.2% ammonia. Surgical latex was not recommened for protection against ammonia. While several materials offered resonable working time protection against 100% ethylene oxide, only two of the 17 materials were useful for extended time periods. The semiautomated test system expedited chemical permeation resistance testing and proved to be effective in securing the needed data.
[Berardinelli SP et al; Govt Reports Announcements & Index (GRA&I) Issue (NTIS/PB90-131368) (1990)]**PEER REVIEWED**

Wear appropriate personal protective clothing to prevent skin contact. /Liquid/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Wear appropriate eye protection to prevent eye contact. /Liquid/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [Note: It is intended that these facilities provide a sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, a deluge shower should be readily available, whereas in others, the availability of water from a sink or hose could be considered adequate.] /Liquid/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Recommendations for respirator selection. Max concn for use: 5 ppm. Respirator Class(es): Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted canister providing protection against the compound of concern. End of service life indicator (ESLI) required. Any self-contained breathing apparatus with a full facepiece. Any supplied-air respirator with a full facepiece.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Recommendations for respirator selection. Condition: Emergency or planned entry into unknown concn or IDLH conditions: Respirator Class(es): Any self-contained breathing apparatus that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode. Any supplied-air respirator that has a full facepiece and is operated in a pressure-demand or other positive-pressure mode in combination with an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive-pressure mode.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Recommendations for respirator selection. Condition: Escape from suddenly occurring respiratory hazards: Respirator Class(es): Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted canister providing protection against the compound of concern. End of service life indicator (ESLI) required. Any appropriate escape-type, self-contained breathing apparatus.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Preventive Measures:

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue personnel hazard. Use water spray to disperse vapors and dilute standing pools of liquid.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads,Bureau of Explosives, 1992. 434]**PEER REVIEWED**

Personnel protection: Avoid breathing vapors. Keep upwind. Avoid bodily contact with the material. Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads,Bureau of Explosives, 1992. 434]**PEER REVIEWED**

Contact lenses should not be worn when working with this chemical.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.
**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 8]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 8]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 8]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 9]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab also apply to microbiological & cell-culture labs ... Special consideration should be given to route of admin. ... Safest method of administering volatile carcinogen is by injection of a soln. Admin by topical application, gavage, or intratracheal instillation should be performed under hood. If chem will be exhaled, animals should be kept under hood during this period. Inhalation exposure requires special equipment. ... unless specifically required, routes of admin other than in the diet should be used. Mixing of carcinogen in diet should be carried out in sealed mixers under fume hood, from which the exhaust is fitted with an efficient particulate filter. Techniques for cleaning mixer & hood should be devised before expt begun. When mixing diets, special protective clothing &, possibly, respirators may be required. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 9]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms & sides & fitted with a filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 10]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 10]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 10]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... A prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 11]**PEER REVIEWED**

Substantial quantities of ethylene oxide may remain in treated materials after gas sterilization. Consequently,, safe use of ethylene oxide in hospitals and health instrument manufacture requires an aeration phase, the length of which depends on the material being treated.
[Rom, W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 1992. 1034]**PEER REVIEWED**

The worker should immediately wash the skin when it becomes contaminated. /Liquid/
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Work clothing that becomes wet should be immediately removed due to its flammability hazard.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 139]**QC REVIEWED**

Stability/Shelf Life:

HYDROLYZES SLOWLY IN AQ SOLN
[Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969. 517]**PEER REVIEWED**

STABLE IN WATER
[Worthing, C. R. (ed.). Pesticide Manual. 6th ed. Worcestershire, England: British Crop Protection Council, l979. 236]**PEER REVIEWED**

Shipment Methods and Regulations:

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
[49 CFR 171.2 (7/1/96)]**QC REVIEWED**

The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.
[IATA. Dangerous Goods Regulations. 38th ed. Montreal, Canada and Geneva, Switzerland: International Air Transport Association, Dangerous Goods Board, January, 1997. 148]**QC REVIEWED**

The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.
[IMDG; International Maritime Dangerous Goods Code; International Maritime Organization p.2060 (1988)]**QC REVIEWED**

Storage Conditions:

Temperature: ambient
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

Protect containers against physical damage, check for leakage intermittently. Store in distant outdoor tank or container protected from direct sunlight, lined with insulating material, equipped with an adequate refrigeration and water system. Indoor storage should be restricted to small quantities. Place material in a combustible liquid cabinet which is fireproof in conformity with regulations.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988. 237]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 13]**PEER REVIEWED**

Cleanup Methods:

Shut off ignition sources and call fire dept. Stop /flow/ if possible. Stay upwind and use water spray to "knock down" vapor. Isolate and remove discharged material. Notify local health and pollution control agencies.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 15]**PEER REVIEWED**

Disposal Methods:

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U115, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.
[40 CFR 240-280, 300-306, 702-799 (7/1/91)]**PEER REVIEWED**

A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 deg C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 deg C and residence times of seconds for liquids and gases, and longer for solids.
[USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-13 (1981) EPA 68-03-3025]**PEER REVIEWED**

Evaporation & open burning: A) Place on ground in an open area. Evaporate or burn by igniting from a safe distance. B) Dissolve in benzene, petroleum ether or higher alcohol such as butanol. Dispose by burning the soln. Recommendable method: Incineration. Peer review: Ethylene oxide boils @ 11 deg C, therefore burning in an incinerator can cause difficulties unless a gas feed can be arranged. It is soluble in water or alcohol and these soln can be burned. (Peer-review conclusions of an IRPTC expert consultation (May 1985))
[United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland: United Nations Environmental Programme, Dec. 1985. 180]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 14]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 15]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 15]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as saturated soln of potassium permanganate in acetone, which appears to be a suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 16]**PEER REVIEWED**

PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/
[Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 17]**PEER REVIEWED**

Occupational Exposure Standards:

OSHA Standards:

The employer shall ensure that no employee is exposed to an airborne concentration of ethylene oxide in excess of 1 ppm as an 8-hr TWA. The employer shall ensure that no employee is exposed to an airborne concentration of ethylene oxide in excess of 5 ppm as averaged over a sampling period of 15 min.
[29 CFR 1910.1047(c) (7/1/98)]**QC REVIEWED**

Threshold Limit Values:

8 hr Time Weighted Avg (TWA): 1 ppm.
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents andBiological Exposure Indices for 2002. Cincinnati, OH. 2002. 32]**QC REVIEWED**

A2; Suspected human carcinogen.
[American Conference of Governmental Industrial Hygienists. TLVs & BEIs: Threshold limit Values for Chemical Substances and Physical Agents andBiological Exposure Indices for 2002. Cincinnati, OH. 2002. 32]**QC REVIEWED**

NIOSH Recommendations:

Recommended Exposure Limit: 10 Hr Time-Weighted Avg: <0.1 ppm (<0.18 mg/cu m).
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

Recommended Exposure Limit: 10 min/day ceiling value: 5 ppm (9 mg/cu m).
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

NIOSH considers ethylene oxide to be a potential occupational carcinogen.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible concn.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

Immediately Dangerous to Life or Health:

NIOSH considers ethylene oxide to be a potential occupational carcinogen.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997. 138]**QC REVIEWED**

Other Occupational Permissible Levels:

Germany: 5 ppm; USSR: 0.5 ppm.
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 257]**PEER REVIEWED**

Emergency Response Planning Guidelines (ERPG): ERPG(1) Not appropriate; ERPG(2) 50 ppm (without serious, adverse effects) for up to 1 hr exposure; ERPG(3) 500 ppm (not life threatening) up to 1 hr exposure.
[American Industrial Hygiene Association. The AIHA 1999 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook.American Industrial Hygiene Association. Fairfax, VA 1999. 25]**QC REVIEWED**

Manufacturing/Use Information:

Major Uses:

For Ethylene oxide (USEPA/OPP Pesticide Code: 042301) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./
[U.S. Environmental Protection Agency/Office of Pesticide Program's Chemical Ingredients Database on Ethylene oxide (75-21-8). Available from the Database Query page at http://www.cdpr.ca.gov/docs/epa/epamenu.htm as of October 24, 2002.]**QC REVIEWED**

RIPENING AGENT FOR FRUITS, FUNGISTAT
[Furia, T.E. (ed.). CRC Handbook of Food Additives. 2nd ed. Volume 2. Boca Raton, Florida: CRC Press, Inc., 1980. 270]**PEER REVIEWED**

INACTIVATES KREB'S ASCITES TUMOR CELLS
[Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974. 209]**PEER REVIEWED**

ROCKET PROPELLANT
[Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 490]**PEER REVIEWED**

FUMIGANT FOR FOODSTUFFS & TEXTILES; IN ORGANIC SYNTHESIS; STERILIZE SURGICAL INSTRUMENTS; AGRICULTURAL FUNGICIDE
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 559]**PEER REVIEWED**

STARTING MATERIAL FOR MFR OF ACRYLONITRILE AND NONIONIC SURFACTANTS.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 559]**PEER REVIEWED**

... USEFUL FOR FUMIGATING INSECTS IN PACKAGED CEREALS, BAGGED RICE, TOBACCO, & CLOTHING & FURS IN VAULTS. ... IT IS ALSO USED IN VAULTS FOR FUMIGATING VALUABLE PACKAGED DOCUMENTS.
[The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 12202]**PEER REVIEWED**

... FOR TREATMENT BY FUMIGATION OF BOOKS; DENTAL, PHARMACEUTICAL, MEDICAL & SCIENTIFIC EQUIPMENT & SUPPLIES, ... DRUGS; LEATHER; MOTOR OIL; PAPER; SOIL; BEDDING FOR EXPERIMENTAL ANIMALS; ... FURNITURE; & TRANSPORTATION VEHICLES ... .
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V11 159 (1976)]**PEER REVIEWED**

Formation of diethylene glycol, the cellosolves and carbitols, dioxane, ethylene chlorohydrin and polymer (carbowax); intermediate for polyethylene terephthalate polyester fiber.
[Fishbein L; Potential Indust Carcins & Mutagens p.43 (1977) USEPA 560/ 5-77-005]**PEER REVIEWED**

STERILANT & SPOROCIDE-EG, IN HEALTH CARE INDUST
[SRI]**PEER REVIEWED**

Used as a fumigation agent on ... beehives (empty and diseased), beekeeping equipment ... .
[Purdue University; National Pesticide Information Retrieval System (1987)]**PEER REVIEWED**

Used on hospital equipment including: hypodermic needles/syringes, surgical prosthetic parts, heart and lung machines, dental, hospital and laboratory instruments, heat labile materials, moisture labile materials, oral and inhalation equipment, diagnostic instruments/equipment, hospital critical rubber, plastic items, hospital critical equipment, thermometers, laboratory equipment, pharmaceutical equipment, stainless steel surfaces; and on hospital fabrics, materials, paper products, sheeting, grooming instruments.
[Purdue University; National Pesticide Information Retrieval System (1987)]**PEER REVIEWED**

Chemical intermediate for ethylene glycols, ethanolamines, glycol ethers & surfactants.
[CHEMICAL PRODUCTS SYNOPSIS. Ethylene Oxide, 1985]**PEER REVIEWED**

MEDICATION (VET)
**QC REVIEWED**

Manufacturers:

BASF Corp, Hq, 8 Campus Drive, Parsippany, NJ 07054, (201) 397-2700; Consumer Products and Life Science Division, 100 Cherry Hill Road, Parsippany, NJ 07054, (201) 316-3000; Automotive Products; Industrial Organics Business; Production site: Geismar, LA 70734
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Dow Chemical USA, Hq, 2020 Dow Center, Midland, MI 48674, (517) 636-1000; Production site: Plaquemine, LA 70764
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Eastman Chemical Co, Hq, PO Box 511, Kingsport, TN 37662, (615) 229-2000; Texas Eastman Div; Production site: Longview, TX 75607
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Hoechst Celanese Corp, Hq, Route 202-206 N, Somerville, NJ 08876, (908) 231-2000; Chemical Group, Commodity Chemicals, 1601 West LBJ Freeway, Dallas, TX 75381-9005, (214) 277-4000; Production site: Clear Lake, TX 77058
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Occidental Petroleum Corp, Hq, 10889 Wilshire Blvd, Suite 1500, Los Angeles, CA 90024, (213) 879-1700; Petrochemicals, Ethylene oxide % Derivatives Division; Production site: Bayport, TX 77000
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

PD Glycol, Hq, Gulf States Rd, Beaumont, TX 77707, (409) 838-4521; Production site: Beaumont, TX 77704
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Shell Chemical Co, Hq, One Shell Plaza, PO Box 2463, Houston, TX 77252-2463, (713) 241-6161; Production site: Geismar, LA 70734
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Sun Company Inc (R&M), Hq, 1801 Market Street, Philadelphia, PA 19103, (215) 977-3451; Production site: Bradenburg, KY 40108
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Union Carbide Corp, Hq, Old Ridgeway Road, Danbury, CT 06817, (203) 794-2000; Industrial Chemicals Division; Production sites: Seadrift, TX 77983; Taft, LA 70057
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Texaco Chemical Co, Hq, 3040 Post Oak Blvd, P.O. Box 27707, Houston, TX 77056, (713) 961-3711; Production site: Port Neches, TX 77651
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Formosa Plastics Corporation U.S.A., Hq, 9 Peach Tree Road, Livingston, NJ 07039, (201) 992-2090; Production site: Point Comfort, TX 77978
[SRI. 1994 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1994. 595]**PEER REVIEWED**

Methods of Manufacturing:

CATALYTIC OXIDATION OF ETHYLENE; PREPARED FROM ETHYLENE CHLOROHYDRIN & POTASSIUM HYDROXIDE.
[Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989. 599]**PEER REVIEWED**

Direct oxidation ... utilizes the catalytic oxidation of ethylene with oxygen over a silver-based catalyst ... .
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V9 924]**PEER REVIEWED**

The process involves the reaction of ethylene with hypochlorous acid followed by dehydrochlorination of the resulting chlorohydrin with lime .... . /Chlorohydrin process/
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V9 923]**PEER REVIEWED**

General Manufacturing Information:

A variety of new process concepts for ethylene oxide-ethylene glycol are being developed based on such raw materials as synthesis gas and ethanol.
[CHEMICAL PRODUCTS SYNOPSIS: Ethylene Oxide, 1985]**PEER REVIEWED**

The compatibility of polycarbonate with ethylene oxide was studied. The polycarbonate devices can be safely exposed to 3 ethylene oxide cycles. Polycarbonates are compatible with ethanol at 73-158 deg F.
[Miller-Mizia R; Med Device Diagn 8 (11): 36-7 (1986)]**PEER REVIEWED**

The chlorohydrin process is not economically competitive, and was quickly replaced by the direct oxidation process as the dominant technology. At the present time, all ethylene oxide production in the world is achieved by the direct oxidation process.
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V9 923]**PEER REVIEWED**

Formulations/Preparations:

/ETHYLENE OXIDE/ IS MIXED WITH EITHER CARBON DIOXIDE OR FLUOROCARBON 12 ... TO ELIMINATE FLAMMABILITY ... . CARBOXIDE IS NONFLAMMABLE MIXTURE OF 10% BY WT ETHYLENE OXIDE IN CARBON DIOXIDE ... STERILANT 12 IS NONFLAMMABLE MIXT OF 12% BY WT ... IN FLUOROCARBON 12 ... .
[Farm Chemicals Handbook 1981. Willoughby, Ohio: Meister, 1981.,p. C-141]**PEER REVIEWED**

Grades or purity: commercial: 100% must contain no acetylene.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

GRADES: TECHNICAL; PURE (99.7%).
[Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 490]**PEER REVIEWED**

Specifications: 0.002 wt % acidity, max (calculated as acetic acid), 0.003 wt % aldehydes, max (calculated as acetaldehyde), 0.03 wt % water, max.
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V9 945]**PEER REVIEWED**

Consumption Patterns:

CHEM INT FOR ETHYLENE GLYCOL, 60.5%; CHEM INT FOR NONIONIC SURFACTANTS (ACYCLIC), 7.1%; CHEM INT FOR NONIONIC SURFACTANTS (CYCLIC), 4.6%; CHEM INT FOR GLYCOL ETHERS, 7.2%; CHEM INT FOR ETHANOLAMINES, 7.1%; CHEM INT FOR DIETHYLENE GLYCOL, 5.1%; CHEM INT FOR TRIETHYLENE GLYCOL, 2.1%; CHEM INT FOR POLYETHYLENE GLYCOL, 1.6%; OTHER, 4.7% (1981)
[SRI]**PEER REVIEWED**

Monoethylene glycol, 59%; higher glycols, 15%; ethoxylates, 10%; ethanolamines, 6%; glycol ethers, 5%; miscellaneous, 5% (1984)
[CHEMICAL PRODUCTS SYNOPSIS: Ethylene Oxide, 1985]**PEER REVIEWED**

CHEMICAL PROFILE: Ethylene oxide. Ethylene glycol, 59%; nonionic surfactants, 14%; ethanolamines, 8%; glycol ethers, 6%; diethylene glycol, 6%, triethylene glycol, 2%; miscellaneous, including polyethylene glycol, urethane polyols and exports, 5%.
[Kavaler AR; Chemical Marketing Reporter 231 (10): 54 (1987)]**PEER REVIEWED**

CHEMICAL PROFILE: Ethylene oxide. Demand: 1986: 5.7 billion lb; 1987: 5.8 billion lb; 1991 /projected/: 6.4 billion lb.
[Kavaler AR; Chemical Marketing Reporter 231 (10): 54 (1987)]**PEER REVIEWED**

CHEMICAL PROFILE: Ethylene oxide. Ethylene glycol, 59%; nonionic surfactants, 13%; ethanolamines, 8%; glycol ethers, 6%; diethylene glycol, 6%, triethylene glycol, 2%; miscellaneous, including polyethylene glycol, urethane polyols and exports, 6%.
[Kavaler AR; Chemical Marketing Reporter 237 (7): 54 (1990)]**PEER REVIEWED**

CHEMICAL PROFILE: Ethylene oxide. Demand: 1989: 5.8 billion lb; 1990 /projected/: 5.9 billion lb; 1994 /projected/: 6.4 billion lb. (Imports and exports are negligible, each on the order of 25 million lb per year.)
[Kavaler AR; Chemical Marketing Reporter 237 (7): 54 (1990)]**PEER REVIEWED**

U. S. Production:

(1977) 2.03X10+12 G
[SRI]**PEER REVIEWED**

(1982) 2.26X10+12 G
[SRI]**PEER REVIEWED**

(1986) 2.49X10+12 g /Estimated/
[CHEMICAL PRODUCTS SYNOPSIS: Ethylene Oxide, 1985]**PEER REVIEWED**

(1985) 2.58X10+12 g
[Chem Eng News 64 (40): 13 (1986)]**PEER REVIEWED**

(1988) 5.95X10+9 lb
[United States International Trade Commission. Synthetic Organic Chemicals- United States Production and Sales, 1988. USITC Publication 1989. Washington,DC: United States International Trade Commission, 1989.,p. 15-8]**PEER REVIEWED**

(1986) 2.49x10+12 g
[Chem Eng News 64 (40): 13 (1986)]**PEER REVIEWED**

(1990) 5.36 billion lb
[Chem & Engineering News 70 (15): 17 (4/13/92)]**PEER REVIEWED**

(1991) 5.25 billion lb
[Chem & Engineering News 71 (15): 11 (4/12/93)]**PEER REVIEWED**

(1992) 5.83 billion lb
[Chem & Engineering News 72 (15): 13 (4/11/94)]**PEER REVIEWED**

(1993) 5.68 billion lb
[Chem & Engineering News 72 (15): 13 (4/11/94)]**PEER REVIEWED**

1992 Production: 2,643,813,000 kg; 1992 Sales: 254,452,000 kg
[United States International Trade Commission. Synthetic Organic Chemicals - United States Production and Sales, 1992. USITC Publication 2720, Feb. 1994Washington, D.C.: United States Trade Commission, 1994.,p. 3-55]**PEER REVIEWED**

U. S. Imports:

(1977) 1.15X10+10 G
[SRI]**PEER REVIEWED**

(1982) 4.30X10+9 G
[SRI]**PEER REVIEWED**

(1985) 1.03X10+10 g
[BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1985 p. 1-583]**PEER REVIEWED**

U. S. Exports:

(1978) 3.46X10+10 G
[SRI]**PEER REVIEWED**

(1983) 6.27X10+9 G
[SRI]**PEER REVIEWED**

(1985) 2.82X10+10 g
[BUREAU OF THE CENSUS. U.S. EXPORTS, SCHEDULE E, 1985 p.2-76]**PEER REVIEWED**

Laboratory Methods:

Clinical Laboratory Methods:

... Methods were developed using capillary gas chromatography. Gas chromatography with mass spectrometry for determining S-methylcysteine, N(r)(2-hydroxyethyl)histidine and N(r)(2-hydroxypropyl)histidine in hemoglobin, allowing the monitoring of in vivo exposure of laboratory animals and humans to methylating agents, ethylene oxide and propylene oxide, respectively. ... An alternative method of dose monitoring of some methylating agents by the measurement of the urinary N-7-methylated guanine derived from alkylated DNA break-down products was also investigated.
[Bailey E et al; Arch Toxicol 60 (1-3): 187-91 (1987)]**PEER REVIEWED**

Analytic Laboratory Methods:

NIOSH Method 3702. Analyte: Ethylene oxide. Procedure: Gas chromatography (portable) with photoionization detector. For ethylene oxide this method has an estimated detection limit of 2.5 pg/injection @ .001 ppm/ml injection. The precision/RSD is less than 0.07 @ 0.05 to 0.02 ppm. Applicability: The working range is 0.001 to 1000 ppm in relatively non-complex atmospheres (eg, sterilization facilities). Interferences: Freon 12, carbon dioxide and alcohols do not interfere.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSHManual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984.,p. 3702-1]**PEER REVIEWED**

NIOSH Method 1614. Analyte: Ethylene oxide. Matrix: Air. Procedure: Gas chromatography electron capture detector. For ethylene oxide this method has an estimated detection limit of 1 ug ethanol/sample. The precision/RSD is 0.028 @ 18 to 71 ug ethanol/sample. Applicability: The working range is 0.05 to 4.6 ppm (0.08 to 8.3 mg/cu m) for a 24 liter air sample. Interferences: 2-Bromoethanol, if present in the sample, interferes.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSHManual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984.,p. 1614-1]**PEER REVIEWED**

Analyte: Ethylene oxide. Procedure: Gas chromatography/Electron capture detector. Carrier gas flow: 25 ml/min. Sample size: 1 ml. The working range is 0.04 to 0.98 ppm (24 liter sample). Overall precision: 0.13 and detection limit of 1 ug/sample. Interference: 2-Bromoethanol.
[Royal Society of Chemistry. Measurement Techniques for Carcinogenic Agents in Workplace Air. Publ. No. EUR 11897, Commission of the EuropeanCommunities/Scientific and Technical Communication Unit, Luxembourg. Great Britian: St. Edmundsbury Press Ltd, 1989. 21]**PEER REVIEWED**

Ethylene oxide can be determined by spectrophotometry and by colorimetry or volumetrically. Gas chromatography of air samples and residues from fumigated materials has been used for foodstuffs, pharmaceuticals and surgical equipment. It can also be found in cigarette smoke by gas chromatography or mass spectrometry ... and also in mixtures of lower olefin oxides and aldehydes. Limits of detection by spectrophotometry and gas chromatography were generally of the order of 1 mg/kg.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V11 160 (1976)]**PEER REVIEWED**

A field evaluation study was conducted to determine the effectiveness of 12 commercially available monitoring devices designed to detect exposure levels to ethylene oxide. These passive dosimeters were exposed to four different ethylene oxide concentration levels.
[Puskar MA, Hecker LH; Am Ind Hyg Assoc J 50 (1): 30-6 (1989)]**PEER REVIEWED**

OSHA Method 49. Gas chromatography using an electron capture detector, target concn 1 ppm (1.8 mg/cu m), reliable quantitation limit 0.7 ppb (1.3 ug/cu m).
[OSHA Method 49, Ethylene oxide, issued 11/84]**PEER REVIEWED**

OSHA Method 50. Gas chromatography using an electron capture detector, target concn 1 ppm (1.8 mg/cu m), reliable quantitation limit 3.0 ppb (5.4 ug/cu m).
[OSHA Method 50, Ethylene oxide, issued 1/85]**PEER REVIEWED**

OSHA Method 30. Gas chromatography using an electron capture detector, target concn 1 ppm (1.8 mg/cu m), reliable quantitation limit 52.2 ppb (94.0 ug/cu m)
[OSHA Method 30, Ethylene oxide, issued 8/81]**PEER REVIEWED**

OSW Method 8240A. Volatilie organics by gas chromatography/mass spectroscopy (GC/MS): Packed column technique. No detection limit.
[USEPA/Office of Solid Waste (OSW); Test Methods for Evaluating Solid Waste, Physical/Chemical Methods SW846 Methods (1986)]**PEER REVIEWED**

Sampling Procedures:

NIOSH Method 3702. Analyte: Ethylene oxide. Sampler: Ambient air or bag sample. Flow Rate: Greater or equal to 0.07 l/min; spot samples possible. Shipment: Calibration and carrier gas shipment must comply with hazardous materials shipment regulations. Sample Stability: Bag samples stable 24 hrs @ 25 deg C.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSHManual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984.,p. 3702-1]**PEER REVIEWED**

NIOSH Method 1614. Analyte: Ethylene oxide. Matrix: Air. Sampler: Solid sorbent tube (hydrogen bromide-coated petroleum charcoal, 100 mg/50 mg) Flow Rate: 0.05 to 0.15 l/min: Sample Size: 24 liters. Shipment: Routine. Sample Stability: 90% recovery after 17 days @ 25 deg C in the dark.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSHManual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984.,p. 1614-1]**PEER REVIEWED**

Analyte: Ethylene oxide. Procedure: Trapping on solid adsorber. Sample flow: 0.05 to 1.15 l/min. Sample Size: 11 (at 5 ppm) to 24 liters.
[Royal Society of Chemistry. Measurement Techniques for Carcinogenic Agents in Workplace Air. Publ. No. EUR 11897, Commission of the EuropeanCommunities/Scientific and Technical Communication Unit, Luxembourg. Great Britian: St. Edmundsbury Press Ltd, 1989. 21]**PEER REVIEWED**

The method uses a hydrobromic acid-coated charcoal tube to collect ethylene oxide as its 2-bromoethanol reaction product. Similar high recoveries were obtained for 4 hr samples collected at a sampling rate of 0.1 l/min from test atmospheres in the concentration range of 0.1 to 16 ppm ethylene oxide at high humidity (80%) and ambient temperature (22 deg to 25 deg C). Samples collected under these same conditions and stored for a minimum of 2 weeks resulted in average recoveries that ranged from 84% to 101%. Average recoveries of 97% were obtained for 2 ppm air samples collected at low humidity with no storage; however, storage of these samples at 22 deg C to 25 deg C resulted in an approximated loss of 5% per week.
[Cummins KJ et al: Am Ind Hyg Assoc J 48 (6): 563-73 (1987)]**PEER REVIEWED**

Special References:

Special Reports:

TSCA CHIPs present a preliminary assessment of ethylene oxide's potential for injury to human health & the environment (available at EPA's TSCA Assistance Office: (202) 554-1404

Kercher et at; Appl Ind Hyg 2 (1): 7-12 (1987). Before and after an evaluation of engineering controls for ethylene oxide sterilization in hospitals.

USEPA; Office of Air Quality and Planning Standards EPA-450/4-84-007L (1986).

DHHS/ATSDR; Toxicological Profile for Ethylene Oxide (1990) ATSDR/TP-90/16

DHHS/NTP; Toxicology & Carcinogenesis Studies of Ethylene Oxide in F344/N Rats and B6C3F1 Mice (Inhalation Studies) Technical Report Series No. 326 (1987) NIH Publication No. 88-2582

Kimmel GL et al; Toxicologist 10 (1): (1990) ... Reproductive and developmental toxicity risk assessment for ethylene oxide.

Florack EIM, Zielhuis GA; 62 (4): 273-77 (1990). This review /details/ the evidence for reproductive toxicity of ethylene oxide gathered through animal studies and epidemiological /data/.

Govt Reports Announcements & Index (GRA&I) 13: (1994). Hazards of ethylene oxide exposure. NTIS/PB94-878576. A bibliography is available that contains abstracts concerning ethylene oxide exposure.

Dellarco VL et al; Environ Mol Mutagen 16 (2): 85-103 (1990). Review of the mutagenicity of ethylene oxide.

USEPA/OPP; Pesticide Fact Sheet Number 234: Ethylene Oxide (EtO) EPA/540/FS-92/195 (1992). This document contains current information on ethylene oxide which includes regulatory data.

U.S. Department of Health & Human Services/National Toxicology Program; 9th Report on Carcinogens. National Institute of Environmental Health Sciences, Research Triangle Park, NC. (2000)

Synonyms and Identifiers:

Synonyms:

EO
**PEER REVIEWED**

AETHYLENOXID (GERMAN)
**PEER REVIEWED**

AI3-26263
**PEER REVIEWED**

Amprolene
**PEER REVIEWED**

ANPROLENE
**PEER REVIEWED**

Anproline
**PEER REVIEWED**

Caswell no 443
**PEER REVIEWED**

DIHYDROOXIRENE
**PEER REVIEWED**

DIMETHYLENE OXIDE
**PEER REVIEWED**

ENT-26263
**PEER REVIEWED**

Pesticide Code: 042301
**QC REVIEWED**

EPA pesticide chemical code 042301
**PEER REVIEWED**

Epoxyethane
**PEER REVIEWED**

1,2-EPOXYETHANE
**PEER REVIEWED**

ETO
**PEER REVIEWED**

ETYLENU TLENEK (POLISH)
**PEER REVIEWED**

Fema no 2433
**PEER REVIEWED**

T-GAS
**PEER REVIEWED**

NCI-C50088
**PEER REVIEWED**

OXACYCLOPROPANE
**PEER REVIEWED**

OXANE
**PEER REVIEWED**

OXIDOETHANE
**PEER REVIEWED**

ALPHA,BETA-OXIDOETHANE
**PEER REVIEWED**

OXIRAAN (DUTCH)
**PEER REVIEWED**

OXIRAN
**PEER REVIEWED**

OXIRANE
**PEER REVIEWED**

OXIRENE, DIHYDRO-
**PEER REVIEWED**

OXYFUME
**PEER REVIEWED**

OXYFUME 12
**PEER REVIEWED**

Formulations/Preparations:

/ETHYLENE OXIDE/ IS MIXED WITH EITHER CARBON DIOXIDE OR FLUOROCARBON 12 ... TO ELIMINATE FLAMMABILITY ... . CARBOXIDE IS NONFLAMMABLE MIXTURE OF 10% BY WT ETHYLENE OXIDE IN CARBON DIOXIDE ... STERILANT 12 IS NONFLAMMABLE MIXT OF 12% BY WT ... IN FLUOROCARBON 12 ... .
[Farm Chemicals Handbook 1981. Willoughby, Ohio: Meister, 1981.,p. C-141]**PEER REVIEWED**

Grades or purity: commercial: 100% must contain no acetylene.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.]**PEER REVIEWED**

GRADES: TECHNICAL; PURE (99.7%).
[Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 490]**PEER REVIEWED**

Specifications: 0.002 wt % acidity, max (calculated as acetic acid), 0.003 wt % aldehydes, max (calculated as acetaldehyde), 0.03 wt % water, max.
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V9 945]**PEER REVIEWED**

Shipping Name/ Number DOT/UN/NA/IMO:

UN 1040; Ethylene oxide

IMO 2.3; Ethylene oxide

Standard Transportation Number:

49 201 08; Ethylene oxide

EPA Hazardous Waste Number:

U115; A toxic waste when a discarded commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate.

RTECS Number:

NIOSH/KX2450000

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