Print
PDF
|
1,2-PROPYLENE OXIDE
See Occupational Exposure Standards
Human Health Effects:
Evidence for Carcinogenicity:
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Based on inadequate human data and an increased incidence of benign and malignant tumors at the site of exposure in two species of animals, when exposed by subcutaneous injection, by inhalation, and by gavage. There was also evidence of mutagenicity in a variety of test systems. Propylene oxide is structurally similar to other chemicals that demonstrate carcinogenic activity in animals.HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of propylene oxide. There is sufficient evidence in experimental animals for the carcinogenicity of propylene oxide. Overall evaluation: Propylene oxide is possibly carcinogenic to humans (Group 2B).
Human Toxicity Excerpts:
Propylene oxide is a strong irritant of the eyes, mucous membranes, ... and high concn have shown a mild CNS depression. Corneal burns and dermatitis have been reported ... .
EFFECTS OF OVEREXPOSURE: MILD DEPRESSION OF CNS, EYE, NASAL & LUNG IRRITATION, NAUSEA, VOMITING & DRUNKENNESS.
One case of human poisoning reported in Russia resulted from vapor exposure to 1500 ppm wt/vol for 10 min. Initial symptoms included lung ... irritation, headache, general asthenia & diarrhea. After 2 hr, the patient became cyanotic & collapsed. After admin of oxygen & antihistamines & treatment for shock, he regained consciousness & vomited but remained confused & weak. The pulse rate & blood pressure returned to normal in 2 hr ... recovery was complete on the following day.
A 26 YR OLD FEMALE ANALYST DEVELOPED HAND ECZEMA FROM EXPOSURE TO PROPYLENE OXIDE IN DEHYDRATION OF ANIMAL SPECIMENS FOR ELECTRON MICROSCOPY.
TWO LAB ASSISTANTS DEVELOPED CONTACT DERMATITIS FROM A DISPOSABLE SWAB FOR PREINJECTION USE, CONTAINING ISOPROPYL ALCOHOL 70% & PROPYLENE OXIDE 1%. PATCH TESTING GAVE POSITIVE ALLERGIC REACTION TO PROPYLENE OXIDE IN BOTH PATIENTS.
PROPYLENE OXIDE CAUSED INHIBITION OF UNSCHEDULED DNA SYNTHESIS AFTER OCCUPATIONAL EXPOSURE.
THE MEAN CHROMOSOME ABERRATION RATE IN WORKERS WITH GREATER THAN 20 YR EXPOSURE TO ALKYLENE OXIDES INCL ETHYLENE & PROPYLENE OXIDES SHOWED A SIGNIFICANT INCR WITH 5.7-6.4% INCL GAPS & 2.7-3.5% EXCLUDING GAPS, AS COMPARED TO 1.4 & 4% RESPECTIVELY IN THE CONTROLS.
A method for quantifying alkylated amino acids in hemoglobin involved specific splitting off of the N-terminal amino acid while not touching the rest of the protein. Ethylene oxide, propylene oxide and styrene oxide were the alkylating agents used in this study. Tests with spiked globin samples indicated that concentrations as low as 1 nanomole N-(2-hydroxyethyl)valine per gram hemoglobin were quantifiable with this method. This would be equivalent to an average exposure to 1 ppm ethylene oxide for 40 hours per week, for the lifetime of the hemoglobin. This is of sufficient detail for determining exposure to alkylating agents in occupational settings and differentiating them from the background levels found in human blood.
In humans, propylene oxide has produced corneal burns, elevated blood alkylhistidine, and chromosomal aberrations.
A technique was described which used sister chromatid exchanges in human peripheral blood lymphocyte cultures to assess the genotoxic potential of vapors. The compounds tested were methyl bromide, ethylene oxide, propylene oxide, and diesel exhaust. Heparinized human whole blood was obtained from healthy nonsmokers. Whole blood was cultured under standard conditions, with the addition of phytohemagglutinin to stimulate lymphocyte division. After 22 to 26 hours, cultures were exposed to 4.3 percent methyl bromide, 4.0 percent ethylene oxide, 2.5 percent propylene oxide, or direct diesel exhaust. Propylene oxide increased sister chromatid exchanges from 8.74 to 22.74 per cell. This system is useful for detecting volatile genotoxic agents and may have application for monitoring of workplaces where airborne genotoxic agents may exist.
ADVERSE ... EFFECTS CAN FOLLOW INHALATION OF VAPORS & FROM EYE & SKIN CONTACT WITH LIQUID OR WITH SOLN AS DILUTE AS 1%.
Commercially avail mixtures /of propylene oxide/ with carbon dioxide ... may be asphyxiant & vesicant.
Exposure of man to propylene oxide mainly occurs through inhalation at the workplace. Because of the alkylating nature of propylene oxide, the formation of DNA adducts, the positive response in vitro mutagenesis assays, the carcinogenic effects in animals at the sites of entry into the body, and the absence of adequate data on cancer in human beings - propylene oxide should be regarded as if it presented a carcinogenic risk for man, and levels in the environment should be kept as low as feasible.
Chromosomal aberrations and micronuclei in lymphocytes were measured in workers exposed to propylene oxide in a alkylated starch factory, 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 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.
Employees of plants where alkylene oxide is manufactured or processed were subjected to mutagenicity studies carried out on lymphocyte cultures in accordance with the methods of Moorhead at al, de Jong and Anders. The employees were divided into four groups, according to their periods of exposure: (1) Long-term exposure for more than 20 years; (2) exposure for less than 20 years; (3) long-term exposure and accident (ethylene oxide inhalation or skin contact); and (4) accident, ie, brief high exposure to ethylene oxide. Measurement of the concentrations in various sections of the plant yielded values of up to 3 ppm under conditions of normal operation. However, this figure rose briefly to 1900 ppm under plant breakdown hat workers were subjected to higher exposure in the past. One hundred metaphases per person were analyzed for chromosome aberrations. The results are given in Tables 1 through 4. A significant increase in the aberration rate was found only in employees in Group 1. This was confirmed by a control examination carried out one year later. The employees of groups 2, 3 and 4 displayed no significant increases. However, in evaluating these findings, it should be noted that the employees had been in contact with a wide range of substances and products in the course of their occupation, which means that the increased aberrations rate found cannot be attributed unequivocally to exposure to a particular substance.
1,2-epoxypropane has been shown to act as a direct alkylating agent in various tissues, & thus the possibility of carcinogenic potential is raised.
Skin, Eye and Respiratory Irritations:
... WHEN CONFINED TO THE SKIN ... EVEN DILUTE CONCN (10%) MAY CAUSE IRRITATION ... HIGHLY DILUTE SOLUTIONS (LESS THAN 10%) MAY BE MORE IRRITATING TO THE SKIN THAN UNDILUTED PROPYLENE OXIDE.
Propylene oxide vapors are irritating to the skin, eyes and respiratory system.
The major adverse effects ... demonstrated in humans involve burning or blistering of the skin when prolonged contact with non-volatilized chemical has occurred. This has been shown to occur even with low concentrations of propylene oxide. Corneal burns ... have also been reported.
Irritating to skin, eyes, and respiratory system.
Medical Surveillance:
The following medical procedures should be made available to each employee who is exposed to propylene oxide at potentially hazardous levels. Employees should be screened for history of certain medical conditions which might place them at an increased risk from propylene oxide exposure. Skin disease: Propylene oxide can cause dermatitis. Persons with existing skin disorders may be more susceptible to the effects of this agent. Liver disease: Although propylene oxide is not known as a liver toxin in humans, the importance of this organ in the biotransformation and detoxification of foreign substances should be considered before exposing persons with impaired liver function. Kidney disease: Although propylene oxide is not known as a kidney toxin in humans, the importance of this organ in the elimination of toxic substances justifies special consideration in persons with impaired renal function. Chronic respiratory disease: In persons with impaired pulmonary function, especially those with obstructive airway diseases, the breathing of propylene oxide may cause exacerbation of symptoms due to its irritant properties. Periodic Medical Examination: Any employee developing the above-listed conditions should be referred for further medical examination.
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/
Monitoring propylene oxide exposure by analyzing N-gamma-(2-hydroxypropyl)histidine in hemoglobin from a group of exposed workers was investigated. N-gamma-(2-hydroxypropyl)histidine values were assayed in blood samples from workers in different departments of a facility where propylene oxide was used for producing hydroxypropylated starch, from four comparisons employed at an ethylene oxide sterilization factory, and from nine comparisons from the same geographic area. Personal and stationary air concentrations of propylene oxide were also monitored during 5 work days and exposures classified as high, intermediate, or low on the basis of propylene oxide concentration and duration of worker exposure. The four workers whose propylene oxide exposure was rated high had hemoglobin alkylation ranging from 4.5 to 8.6 nanomoles N-gamma-(2-hydroxypropyl)histidine per gram hemoglobin (nmol/G). The two workers with intermediate exposure had hemoglobin alkylation of 1.0 and 1.2 nmol/g. The workers with low exposure had values of 0.85 and 0.2 nmol/g. The second worker had not been exposed over the previous year and could be considered a referent. Hemoiglobin alkylation in employees of an ethylene oxide sterilization ranged from less than 0.1 to 0.38 nmol/g. In all other comparisons hemoglobin alkylation values were less than 0.1 nmol/g. /It was/ concluded that the method is sensitive enough for dosimetry to be carried out at current exposure concentrations in some work environments. The degree of alkylation of hemoglobin gives a measure of the in vivo propylene oxide dose obtained during a period of about 4 months, the lifespan of red cells.
Populations at Special Risk:
Persons with existing skin disorders or liver, kidney or chronic respiratory diseases may be more susceptible to the effects of propylene oxide.
Probable Routes of Human Exposure:
Exposure of man to propylene oxide mainly occurs through inhalation at the workplace.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 421,140 workers (317,309 of these are female) are potentially exposed to 1,2-propylene oxide in the US(1). Occupational exposure to 1,2-propylene oxide may occur through inhalation and dermal contact with this compound at workplaces where 1,2-propylene oxide is produced or used(SRC). In a 1979 study by one USA manufacturer, the typical average daily exposure of workers to propylene oxide were 0.5-5 mg/cu m with worst-case peak exposures of 59-9000 mg/cu m (highest exposure being that of maintenance workers cleaning pumps)(2). Levels of worker exposure were reported to be 0.5 to 5.9 mg/cu m in a polymer polyol unit, not detectable to 1.2 mg/cu m in an oxide adducts unit, and not detectable in a flexible polyol unit of a large chemical manufacturing facility producing many chemical products including propylene oxide derivatives(2). A propylene oxide concn of 3.6 mg/cu m was found near an operator at a flexible polyol unit in another large chemical manufacturing facility(2). Propylene oxide has been detected in 6.2% of 1,159 consumer products that are used indoors; products found to containing the highest concentration of propylene oxide were automotive and paint products(SRC).
Emergency Medical Treatment:
Emergency Medical Treatment:
[Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2004; CCIS Volume 122, edition expires Nov, 2004.]**PEER REVIEWED**
Antidote and Emergency Treatment:
Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Provide a low-stimulus environment. Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Treat frostbite by rapid rewarming ... . /Ethers and related compounds/
Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in respiratory arrest. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors for hypotension with a normal fluid volume. Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Ethers and related compounds/
Animal Toxicity Studies:
Evidence for Carcinogenicity:
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Based on inadequate human data and an increased incidence of benign and malignant tumors at the site of exposure in two species of animals, when exposed by subcutaneous injection, by inhalation, and by gavage. There was also evidence of mutagenicity in a variety of test systems. Propylene oxide is structurally similar to other chemicals that demonstrate carcinogenic activity in animals.HUMAN CARCINOGENICITY DATA: Inadequate. ANIMAL CARCINOGENICITY DATA: Sufficient.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of propylene oxide. There is sufficient evidence in experimental animals for the carcinogenicity of propylene oxide. Overall evaluation: Propylene oxide is possibly carcinogenic to humans (Group 2B).
Non-Human Toxicity Excerpts:
... IN ACUTE /INHALATION/ EXPOSURES OF RATS, SURVIVORS EXHIBITED FOLLOWING SYMPTOMS: IRRITATION OF THE EYE AND NOSE, DIFFICULTY IN BREATHING, DROWSINESS, WEAKNESS, AND OCCASIONALLY SOME INCOORDINATION. SINGLE 4 HR EXPOSURE TO 4000 PPM RESULTED IN DEATH IN 4 OF 6 RATS.
Liquid propylene oxide dropped on rabbit eyes has caused reversible injury similar to that caused by acetone, graded 5 on scale of 1 to 10 after 24 hr. Exposure of monkeys & rabbits to 457 ppm vapor in air for 7 hr daily had no adverse effect, but in rats & guinea pigs it irritated eyes & induced lung edema. In guinea pigs & rabbits no disturbance of corneas ... was detectable by slit-lamp biomicroscope after exposure to vapor concn high enough to cause death of guinea pigs & rabbits from respiratory ... /injury/ in the course of several days, except possibly ... the incr in normal punctate staining of corneal epithelium with fluorescein.
MATCHED GROUPS OF 5 YOUNG ADULT FEMALE WHITE RATS EACH WERE FED OLIVE OIL SOLN OF PROPYLENE OXIDE BY INTUBATION 5 TIMES A WK UNTIL A TOTAL OF 18 DOSES HAD BEEN GIVEN AT LEVELS OF 0.1, 0.2, & 0.3 G/KG/DAY. ANIMALS RECEIVING A DOSAGE LEVEL OF 0.2 G/KG & 0.1 G/KG SHOWED NO EFFECT AS JUDGED BY GROSS APPEARANCE, GROWTH, BLOOD UREA NITROGEN DETERMINATIONS, ORGAN WT, & MICROPATHOLOGY OF THE VARIOUS ORGANS IN COMPARISON WITH CONTROLS RECEIVING OLIVE OIL. A DOSAGE LEVEL OF 0.3 G/KG CAUSED LOSS OF BODY WT, GASTRIC IRRITATION, & SLIGHT LIVER INJURY.
EARLY SYMPTOMS /OF ACUTE VAPOR POISONING/ INCLUDE LACRIMATION, NASAL DISCHARGE, AND SALIVATION FOLLOWED BY GASPING & LABORED BREATHING IN ALL SPECIES, & VOMITING IN DOGS. SEVERE IRRITATION IN THE LUNGS MAY PERSIST FOR SEVERAL DAYS &, IN SOME CASES, LEAD TO PNEUMONIA. ... PROPYLENE OXIDE HAS ONLY A RELATIVELY WEAK ANESTHETIC ACTION WHICH BECAME APPARENT WHEN ANIMALS WERE EXPOSED TO CONCN OF 4000 PPM OR MORE.
UPON REPEATED 7-HR EXPOSURE TO 457 PPM /BY INHALATION, THERE WAS/ ONLY ... SLIGHT DEPRESSION OF GROWTH IN GUINEA PIGS EXPOSED FOR 15-17 DAYS. NO EFFECTS WERE NOTED IN RATS. AFTER 37-39 DAYS ... DEPRESSION OF GROWTH WAS NOTED IN BOTH GUINEA PIGS & RATS. ADDITIONAL EFFECTS WERE MODERATE AND INCLUDED ALVEOLAR HEMORRHAGE & EDEMA ... WITH INTERSTITIAL EDEMA & CONGESTION OF LUNGS OF RATS & GUINEA PIGS. ... SLIGHT FATTY DEGENERATION OF LIVER IN MALE GUINEA PIGS WAS OBSERVED.
OF 12 RATS ... GIVEN TOTAL DOSES OF 1500 MG/KG BODY WT ... IN ARACHIS OIL BY SC INJECTION WITHIN 325 DAYS (DOSING SCHEDULE NOT SPECIFIED), 8 DEVELOPED LOCAL SARCOMAS AFTER 507-739 DAYS. IN SIMILAR EXPT IN WHICH TOTAL DOSES OF 1500 MG/KG BODY WT PROPYLENE OXIDE IN WATER WERE INJECTED SC, 1/12 RATS DEVELOPED LOCAL SARCOMA AFTER 158 DAYS & 2 DEVELOPED LOCAL SARCOMAS AFTER 737 DAYS.
PROPYLENE OXIDE INDUCED DOSE-DEPENDENT INCREASE IN NUMBER OF REVERTANT MUTATIONS IN HISTIDINE-DEPENDENT SALMONELLA TYPHIMURIUM STRAINS TA1535 & TA100, BUT NOT IN STRAINS TA1537 OR TA98.
INDUCTION OF BASE-SUBSTITUTION MUTATIONS WAS DEMONSTRATED IN SPOT TESTS WITH STRAINS OF S TYPHIMURIUM (TA100 & TA1535) & E COLI AT 700 UG/PLATE OF PROPYLENE OXIDE; RAT-LIVER MICROSOMES & COFACTORS (S9 MIX) WAS WITHOUT SIGNIFICANT EFFECT ON THIS RESPONSE. A MALE MOUSE DOMINANT LETHAL TEST EMPLOYING ORAL DOSES OF 50 OR 250 MG/KG/DAY FOR 14 DAYS GAVE NO EVIDENCE OF MUTAGENIC ACTION ON SPERM.
1,2-PROPYLENE OXIDE WAS ADMIN TO NMRI FEMALE MICE AT 2.5, 1.0, 0.3 & 0.1 MG IN SINGLE SC INJECTIONS ONCE/WK USING TRICAPRYLIN AS VEHICLE FOR 95 WK. TOTAL DOSE/MOUSE WAS 165.4, 72.8, 21.7 & 6.8 MG. LOCAL TUMORS DEPENDING ON DOSAGE WERE MOSTLY FIBROSARCOMAS WITH FREQUENCY BETWEEN 16 and 2%.
1,2-PROPYLENE OXIDE ADMIN INTRAGASTRICALLY BY GAVAGE AT 2 DOSAGES (60 & 15 MG/KG BODY WT) TO GROUPS OF 50 FEMALE SPRAGUE-DAWLEY RATS TWICE WEEKLY FOR A PERIOD OF NEARLY 3 YR INDUCED LOCAL TUMORS, MAINLY SQUAMOUS-CELL CARCINOMAS OF THE FORESTOMACH.
PROPYLENE OXIDE TESTED FOR MUTAGENIC ACTIVITY FOLLOWING VAPOR EXPOSURE USING 3 IN VIVO TEST SYSTEMS. RAT DOMINANT LETHAL & MOUSE SPERM-HEAD MORPHOLOGY ASSAYS WERE CONDUCTED USING MALES EXPOSED @ 300 PPM FOR 7 HR/DAY ON 5 CONSECUTIVE DAYS. A SEX-LINKED RECESSIVE LETHAL TEST IN DROSOPHILA MELANOGASTER EMPLOYED A 24 HR STATIC EXPOSURE @ 645 PPM. EVALUATION OF SPERM-HEAD MORPHOLOGY DID NOT RESULT IN AN INCR IN ABNORMAL FORMS. STATISTICALLY SIGNIFICANT INCR IN PREIMPLANTATION LOSSES & REDUCTION IN THE NUMBER OF LIVING IMPLANTS WAS OBSERVED IN RATS. A HIGHLY SIGNIFICANT INCR IN SEX-LINKED RECESSIVE LETHAL MUTATION WAS OBSERVED IN TWO GERM STAGES IN DROSOPHILA.
MALE MONKEYS WERE EXPOSED TO 0, 100, & 300 PPM PROPYLENE OXIDE FOR 6 HR/DAY, 5 DAYS/WK FOR 2 YR. BRAIN, ULNAR & SCIATIC NERVES, & SPINAL CORD TISSUE WERE EXAM HISTOLOGICALLY. NO DIFFERENCES WERE FOUND BETWEEN CONTROLS & CHEM TREATED ANIMALS. IN THE MEDULLA OBLONGATA OF THE BRAIN, PROPYLENE OXIDE EXPOSED MONKEYS HAD SIGNS OF AXONAL DYSTROPHY.
THE MUTAGENIC ACTION OF 45 EPOXIDES WAS INVESTIGATED IN LURIA & DELBRUCK'S FLUCTUATION TEST WITH KLEBSIELLA PNEUMONIAE AS THE TEST ORGANISM. IN THIS TEST 36 OF THE 45 EPOXIDES APPEARED TO BE MUTAGENIC. THE MUTAGENICITY OF 1,2-EPOXIDES DECR WITH INCR LENGTH OF C CHAIN. GENERALLY, 1,2-EPOXIDE CMPD WITH ELECTRONEGATIVE GROUPS WERE MORE MUTAGENIC THAN 1,2-EPOXYPROPANE.
AT RELATIVE HUMIDITY OF 25% & 37 DEG C, 90% OF B SUBTILIS SPORES WERE KILLED IN 40 MIN (1250 MG PROPYLENE OXIDE/L). IN COCOA POWDER, BACTERIAL COUNTS WERE REDUCED 5-70% & MOLD COUNTS 90-99%. ... IN WHEAT OF 13% MOISTURE INITIAL BACTERIAL COUNT OF 1,000,000/G WAS REDUCED TO 500/G AT 118 DEG F BY VAPOR SYSTEM CONTAINING 1.5 G/L OF PROPYLENE OXIDE.
The ability of long term exposures to inhaled propylene oxide to induce sister chromatid exchanges and chromosome aberrations in the peripheral lymphocytes of monkeys was investigated. Five groups of adult male cynomolgus monkeys were exposed to 100 or 300 ppm propylene oxide (7 hr/day, 5 days/wk) for 2 years. ... Lymphocytes from these /animals/ manifested no group differences from controls for any variable-chromatid, or chromosome type aberrations, gaps or sister chromatid exchanges (metaphase).
The chronic inhalation toxicity and carcinogenicity of ethylene oxide and propylene oxide were evaluated in a 2 yr inhalation bioassay. Five groups of male weanling Fischer 344 rats, 80/group, were exposed at 0 ppm (shared control; filtered air), 50 ppm ethylene oxide, 100 ppm ethylene oxide, 100 ppm propylene oxide, or 300 ppm propylene oxide (7 hr/day, 5 days/wk) for 104 wk. Among rats exposed to propylene oxide there was a dose-dependent increase in the incidence of complex epithelial hyperplasia in the nasal passages, and 2 adenomas were detected in the nasal passages of rats exposed at 300 ppm propylene oxide. The incidence of adrenal phenochromocytomas was elevated in both propylene oxide exposure groups, but not in a dose-related manner. All rat groups were affected by an outbreak of Mycoplasma pulmonis infection which occurred in combination with the epoxide exposures and affected the survival of rats in this study, and influenced the development of the proliferative lesions in the nasal mucosa of the propylene oxide-exposed rats. No treatment related changes in any clinical chemistry or urinalysis indices were detected. Adrenal pheochromocytomas and proliferative lesions of the nasal cavity were increased in rats exposed to propylene oxide.
The SOS umu-test has been used for the detection of DNA-damaging agents. In this system the plasmid pSK1002 carrying a fused gene umuC-lacZ was introduced into Salmonella typhimurium TA1535. The SOS function induced by genotoxic agents is detected by a colorimetric measurement of beta-galactosidase activity encoded by the lacZ gene, which is regulated by the Umu operon. This system was used with modifications to study the SOS function inducibility of volatile chemicals (propylene oxide, methyl bromide, and ethylene dibromide) and air pollutants (diesel emission, welding fumes, and cigarette smoke). Tester cells were exposed directly to the test material. The enzyme activity of the treatment cells was measured according to the established procedure. Results of the study showed that all chemicals and pollutants tested induced SOS function in a dose-related manner.
A short-term microbial method using Bacillus subtilis infected with bacteriophage phi 105 DNA was described. Wild-type bacteriophage phi 105 DNA was reacted with potential mutagens and then transfected into Bacillus subtilis carrying a mutated bacteriophage phi 105 DNA. After plating, an increase in frequency of clear plaques signified that the tested cmpd was mutagenic. Propylene oxide was mutagenic.
Sprague-Dawley rats receiving propylene oxide by stomach tube in doses of 15 or 60 mg/kg of body weight twice weekly for 109.5 weeks exhibited a dose dependent increase in forestomach tumors. ... NMRI-mice receiving 0.1, 0.3, 1.0, or 2.5 mg of propylene oxide by sc or im injection once a week for 95 weeks developed tumors at the site of injection. ... Propylene oxide has induced mutations in Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae, Neurospora crassa, Schizosaccharomyces pombe, Drosophila melanogaster, rat hepatocytes and human lymphocytes in vitro, and male CD 1 mice.
Propylene oxide inhalation by B6C3F1-mice at concentrations of 200 or 400 ppm 6 hours a day, 5 days a week, for 103 weeks caused an increase in nasal turbinate respiratory epithelium inflammation, in hemangiomas among both sexes, and in hemangiosarcomas among males. Exposure of Fischer 344 rats caused increases in inflammation, epithelial hyperplasia, and squamous metaplasia of the nasal turbinate respiratory epithelium, as well as in C-cell adenomas and carcinomas among females. Propylene oxide inhalation by Fischer 344 rats at 100 or 300 ppm 7 hours a day, 5 days a week for 104 weeks, resulted in a dose-dependent increase in inflammatory respiratory system lesions and complex nasal cavity epithelial hyperplasia, as well as in pheochromocytomas and peritoneal mesotheliomas. ...
Propylene oxide inhalation by New Zealand white rabbits at 500 ppm 7 hours a day from gestation days 1 or 7 to 19 caused a 2.8 percent resorption rate increase. Exposure of Sprague-Dawley-rats from 3 weeks before gestation to gestation day 16, from gestation day 1 to 16, or from gestation day 7 to 16 caused reduced maternal weights, copora lutea populations, implantation site numbers, live fetus counts, and fetal growth, while increasing rib dysmorphology.
The possible use of the degree of inhibition of glutathione-S-transferase activity as a biological marker for determining exposure to chemicals such as acrolein, styrene oxide, propylene oxide, ethylene dibromide, and ethylene dichloride was explored. A dose-dependent inhibition was evident in each case not only for inactivation of erythrocyte glutathione-S-tranferase in situ but for inhibition of purified erythrocyte glutathione-S-transferase as well. Concentrations inhibiting 50% of the activity ranged from around 10-3 to 10-4 molar.
The potential of vapor phase chemicals to alter susceptibility to induced respiratory infection was examined in mice. Female CD1 mice were simultaneously exposed to Streptococcus zooepidemicus aerosols and threshold limit value of ... propylene oxide. ... A pulmonary bactericidal activity assay was performed after mice inhaled aerosols of viable radioactive bacteria to determine bacterial clearance from the lung. Changes in pulmonary bactericidal activity were significant after single and multiple exposures of some compounds, but there was no consistent pattern of effects with the mortality studies.
A battery of short term tests was performed. Bacterial mutation assays conducted were: plate incorporation assay, preincubation assay, spot test, and treat and plate method. Saccharomyces gene conversion assays conducted involved treatment of stationary phase cells and treatment of log phase cells. Rat liver chromosome assays included cytotoxicity and chromosome assays. Specific compounds which indicated mutations in bacteria, gene conversion in yeast, or chromosome damage /included/ propylene oxide ... .
Propylene oxide, glycidol, epichlorohydrin, and trichloropropylene oxide were reacted with deoxyguanosine as well as deoxyadenosine and, except for the trichloro compound, with DNA. Reactivity with the purine deoxynucleosides as well as the four deoxynucleosides in DNA were quantitated by HPLC methods. Correlations for reactivity of the propylene oxides with the individual deoxynucleosides in solution and in DNA, except for deoxythymidine, were indicated for mutagenicity in TA100 in the liquid-preincubation Ames test.
37 aliphatic epoxides were tested for mutagenicity in Salmonella strains TA98, TA100, TA1535 and TA1537 and/or TA97 with and without metabolic activation using a standardized protocol. 3 of the 8 unsubstituted aliphatic epoxides and 11 of the 12 glycidyl ethers were mutagenic. /Propylene oxide was mutagenic/ in TA100 without activation and was mutagenic in TA1535 without activation.
Inhalation exposures were conducted with five water-reactive compounds: beta-propiolactone, methylmethane sulfonate, ethylchloroformate, dichloroacetyl chloride, and propylene oxide on male Sprague-Dawley rats. The hydrolysis rates of these compounds span 6 orders of magnitude. The compounds were administered for 30 days (6 hr/day X 5 days/wk) with the use of exposure concentrations that were inversely proportional to the respective hydrolysis rates. With this protocol, all compounds except propylene oxide (the slowest reacting compound) produced nasal cancer in rats.
Propylene oxide is a highly reactive, electrophilic substance, which reacts with cellular macromolecules such as RNA, DNA and proteins, by alkylating nucleophilic centers. Propylene oxide is a mutagen. It induces local tumors when inhaled or administered by subcutaneous and intragastric routes and has an adverse effect on male and female reproduction in animals (mice and rats). Propylene oxide is an allergic sensitiser.
Twenty-seven chemicals (including 1,2-propylene oxide) previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. 1,2-Propylene oxide was shown to be a potent inducer of sister chromatid exchanges and chromosomal aberrations both with and without S9.
Reproductive parameters in Fischer 344 rats were evaluated following inhalation of propylene oxide for two successive generations. Thirty male and 30 female rats were exposed to 0, 30, 100, or 300 ppm propylene oxide for 6 hr/day, 5 days/week for 14 weeks and then mated to produce the f1 litters. After weaning, 30 randomly selected f1 pups/sex/group were exposed to propylene oxide for 17 weeks and subsequently mated to produce the f2 litters. Reproductive parameters examined included fertility, litter size neonatal growth, and survival. All adults and selected weanlings were examined for gross and histologic lesions. Toxicity due to propylene oxide was demonstrated by decreased body weights of parental f0 and f1 rats at 300 ppm. No treatment-related effects on fertility (mating or conception) were observed in either f0 or f1 matings. Neonatal surival indices for f1 or f2 litters revealed no treatment-related effects. Litter size was decreased in the f1 rats exposed to 100 ppm propylene oxide. However, the litter size in the 300 ppm group was comparable to the control group, and no effect on litter size was shown in propylene oxide exposed f2 litters. Pup weights were unaffected by parental exposure to propylene oxide in either generation. Pathologic examination of adults and weanlings revealed no changes considered due to propylene oxide. Based on these results, it is concluded that inhalation exposure to propylene oxide at levels up to 300 ppm over two generations did not produce any adverse effects on reproductive function.
The developmental toxicity potential of propylene oxide was evaluated in Fischer 344 rats following inhalation exposure. Four groups of 25 mated female rats were exposed to 0, 100, 300, and 500 ppm of propylene oxide for 6 hr per day on Gestation Days 6 through 15, inclusive. Cesarean sections were performed on all females on Gestation Day 20 and the fetuses removed for morphological evaluation. Exposure to propylene oxide did not adversely affect survival, appearance, or behavior at any of the exposure levels tested. Maternal body weight gain and food consumption were reduced significantly among the females at the 500 ppm level during the exposure period. No exposure-related effects were noted with respect to maternal water consumption, organ weights, cesarean section, or fetal morphological observations with the sole excretion of increased frequency of seventh cervical ribs in fetuses at the maternally toxic exposure level of 500 ppm. In summation, the no-observable-adverse-effect level of propylene oxide, when administered to Fischer 344 rats via whole-body inhalation exposure, was considered to be 300 ppm.
Propylene oxide was tested for mutagenic activity following vapor exposure using 3 in vivo test systems. Rat dominant lethal and mouse sperm-head morphology assays were conducted using males exposed to propylene oxide at 300 ppm in a dynamic exposure chamber for 7 hr/day on 5 consecutive days. A sex linked recessive lethal test in Drosophila melanogaster employed a 24 hr static exposure to propylene oxide at 645 ppm. Male mice were killed 1, 3, 5, 7 and 9 wk post exposure for evaluation of sperm-head morphology. Propylene oxide exposure did not result in an increase in abnormal forms. Male rats were mated with 2 virgin females/wk for 6 wk following exposure. A statistically significant increase in preimplantation losses and a statistically significant reduction in the number of living implants in the 1st post exposure wk did not appear to be treatment related. A highly significant increase in sex linked recessive lethal mutations was observed in 2 germ cell stages (mature sperm and developing spermatocytes). These results warrant continued caution in potential human exposure to propylene oxide.
The ethylene oxide/propylene oxide polymers evaluated in this study have previously been shown to have a low order of toxicity and/or irritancy by ocular, dermal, or oral routes of administration. These studies evaluated the acute inhalation toxicity of respirable aerosols of three ethylene oxide/propylene oxide compounds (U-660, U-2000, and U-5100) that differ in chain length, molecular weight, and viscosity. The respective 4 hr LC50 values (95% confidence limits) for U-660, U-2000, and U-5100 in Wistar albino rats were 4670 (4090-5320), 330 (227-480), and 106 (45-245) mg/cu m. Occasionally, slight increase in respiration rate and slight hyperactivity were observed during the postexposure period. All deaths were delayed for 2-5 days postexposure. Body weight gains were transiently depresed in rats exposed to U-2000 and U-5100. Discolored lungs and livers occurred in animals which died during the 14 day postexposure period. Subsequently, a repeated-exposure study was conducted on U-5100 in F-344 rats exposed for 6 hr/day, 5 days/week, for 9 exposures at mean concentrations of 0, alveolar epithelial cells. Lung weights remained elevated after the 2 wk at concentrations as low as 5 mg/cu m.
A new protocol for testing vapors and gases in the L5178Y mouse lymphoma assay is presented. Four chemicals, propylene, 1,2-propylene oxide, 1,3-butadiene, and vinylidene chloride, were tested for their mutagenic potential. Cultures were exposed to the chemicals, which were delivered as vapors or gases, for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine, 3 ug/ml. Each chemical was tested at least twice. Significant responses were obtained with 1,2-propylene oxide and vinylidene chloride, but neither cytotoxicity nor mutagenicity was induced by 1,3-butadiene; propylene could not be classified as either mutagenic or non-mutagenic in the assay. Rat liver S9 mix was not a requirement for the mutagenic activity of 1,2-propylene oxide, whereas the liver preparation markedly enhanced both the cytotoxicity and mutagenicity of vinylidene chloride.
In Wistar rats subjected daily to 6 hr exposure of propylene oxide at a concentration of 1,500 ppm (5 times a wk for 7 wk). ataxia developed in the hindlegs. Myelinated fibers in hindleg nerves and in the fasciculus gracilis showed axonal degeneration, sparing the nerve cell body of the first sacral dorsal root ganglion ad myelinated fibers of the first sacral dorsal and ventral roots. These pathologic findings are compatible with central-peripheral distal axonopathy. This is apparently the first animal model of propylene oxide neuropathy to be verified histologically.
The carcinogenicity of proplene oxide was investigated because of its extensive production, its potential for exposure of humans in the workplace or for exposure through food, the positive results in short term genetic assays, and the inadequacy of available animal carcinogenesis data on the material. Groups of 50 F344/N rats and (C57BL/6x3H) F1 mice were exposed to 0, 200, or 400 ppm propylene oxide for 6 hours/day, 5 days/week, for up to 103 weeks. Mean body weight decreased during the second year of exposure in mice rats exposed at the higher level. There was a decrease in survival in mice exposed to 400 ppm. Neoplastic lesions were observed in the nasal cavity of rats and mice exposed to 400 ppm. In male and female rats there was in increased incidence of papillary adenomas of the nasal epithelium, while in male and female mice there were increased incidences of hemoglomas and hemangiosarcomas of the nasal mucosa. Exposure also caused suppurative inflammation, hyperplasia, and squamous metaplasia in the nasal epithelium of rats and inflammation in mice.
Four groups of 100 Wistar rats of each sex were exposed by inhalation to 0, 30, 100 or 300 ppm propylene oxide for 6 hr/day, 5 days/wk for 28 months. After 12, 18 and 24 months ten rats/sex/group were killed to provide interim hematological, biochemical and urinary data. Mortality was increased by wk 115 in both sexes in the 300 ppm group and by wk 119 in females of the 100 ppm group. Body weights were lower than those of the controls throughout the study in males of the 300 ppm group and in females of the 300 ppm group during the first year of the study. Increased incidences of degenerative and hyperplastic changes of the nasal mucosa were observed in all exposed groups. Exposure to 300 ppm propylene oxide was associated with an increased incidence of both benign and malignant mammary tumors in females. There was no increase in the incidence of any particular type of tumor other than mammary tumors. The total number of rats bearing malignant tumors at sites other than the mamamry glands was increased in both sexes in the 300 ppm group compared with the controls.
1,2-Propylene oxide ... test results for mutagenicity in Salmonella assays ... proved positive.
Under the conditions of these studies, there was some evidence of carcinogenicity for F344/N rats, as indicated by increased incidences of papillary adenomas of the nasal turbinates in male and female rats exposed to propylene oxide at 400 ppm. For male and female B6C3Fl mice, there was clear evidence of carcinogenicity, as indicated by increased incidences of hemangiomas or hemangiosarcomas of the nasal turbinates at 400 ppm. In the respiratory epithelium of the nasal turbinates, propylene oxide also caused suppurative inflammation, hyperplasia, and squamous metaplasia in rats and inflammation in mice.
Hyperemia & edema resulted from application of 10% or 20% aqueous soln of propylene oxide to the shaved intact skin of rabbits under an occluding plastic cover when the duration of exposure was 6 min or longer. The most severe exposures resulted in scar formation.
... Propylene oxide /is/ 1/2 to 1/3 as potent as ethylene oxide based on single-exposure data. Secondary pulmonary infection followed acute inhalation exposure to propylene oxide.
When gavaged as a 10% olive oil solution, rats survived 0.3 g/kg and died at 1.0 g/kg. The dermal LD50 in rabbits was 1.3 g/kg. Four-hour inhalation LC50 of propylene oxide were 4126 mg/cu m (1740 ppm) in mice and 9486 mg/cu m (4000 ppm) in rats. At 7200 ppm in rats, deaths were 0/10, 2/10, and 5/10 after exposures of 0.25, 0.5, and 1.0 hr, respectively.
Propylene oxide is a direct-acting mutagen and rodent carcinogen. We have studied how propylene oxide modifies 2'deoxynucleosides at pH 7.0-7.5 and 37 deg C for 10 hr. Propylene oxide reacts as an SN2 alkylating agent by forming the following 2-hydroxypropyl adducts: N6-2-hydroxypropyl-dAdo (7% yield), 7-2-hydroxypropyl-Gua (37%) and 3-2-hydroxypropyl-dThd (4%). Alkylation at N-3 of dCvd resulted in conversion of the adjacent exocylic imino group at C-4 to an oxygen (hydrolytic deamination) with the formation of a dUrd adduct, 3-2-hydroxypropyl-dUrd (14%). Ultraviolet spectroscopy and mass spectrometry were used for the structural determination of these adducts. Confirmation of the unexpected 3-2-hydroxypropyl-dUrd adduct was provided by an accurate mass measurement technique where diagnostic ions in the mass spectra of 3-2-hydroxypropyl-dUrd were measured to within 0.0005 atomic mass units of the predicted mass. Propylene oxide was reacted in vitro with calf thymus DNA (pH 7.0-7.5, 37 deg C, 10 hr) and yielded N6-2-hydroxypropyl-dAdo (1 nmol/mg DNA), 3-2-hydroxypropyl-Ade (14 nmol/mg DNA), 7-2-hydroxypropyl-Gua (133 nmol/mg DNA) and 3-2-hydroxypropyl-dUrd (13 nmol/mg DNA). A mechanism for the hydrolytic deamination of 3-2-hydroxpropyl-dCyd to 3-2-hydroxypropyl-dUrd involving the hydroxide on the 2-hydroxypropyl side chain is proposed. This cytosine to uracil conversion may play a role in the mutagenic and carcinogenic activity of this epoxide.
Irritating to the eyes of animals, and liquid caused severe eye irritation in rabbits.
National Toxicology Program Studies:
The 2 year carcinogenesis studies of propylene oxide (greater than 99.9% pure) were conducted by exposing groups of 50 F344/N rats and 50 B6C3Fl mice of each sex to air containing propylene oxide at concentrations of O (chamber control), 200, or 400 ppm for 6 hours per day, 5 days per week, for 103 weeks. Under the conditions of these studies, there was some evidence of carcinogenicity for F344/N rats, as indicated by increased incidences of papillary adenomas of the nasal turbinates in male and female rats exposed to propylene oxide at 400 ppm. For male and female B6C3Fl mice, there was clear evidence of carcinogenicity, as indicated by increased incidences of hemangiomas or hemangiosarcomas of the nasal turbinates at 400 ppm. In the respiratory epithelium of the nasal turbinates, propylene oxide also caused suppurative inflammation, hyperplasia, and squamous metaplasia in rats and inflammation in mice.
Non-Human Toxicity Values:
LD50 Guinea pig /oral/ 0.69 g/kg
LC50 Mouse inhalation 1740 ppm/4 hr
LD50 Rabbit skin 1245 mg/kg
LC50 Rat inhalation 4000 ppm/ 4 hr
LD50 Rabbit percutaneous 1.5 ml/kg
LD50 Rat ip 150 mg/kg
LD50 Rat oral 380 mg/kg
LD50 Mouse ip 175 mg/kg
LD50 Guinea pig oral 660 mg/kg
Ecotoxicity Values:
LC50 Goldfish 170 mg/l/24 hr /Conditions of bioassay not specified/
LC50 Mullet 89 ppm/96 hr /Conditions of bioassay not specified/
TLm Gambusia affinis (mosquito fish) 141 mg/l/96 hr at 24 deg C, static bioassay.
TLm Bluegill 215 mg/l/96 hr at 24 deg C, static bioassasy.
TSCA Test Submissions:
Chronic toxicity and oncogenicity were evaluated in male and female SPF-reared albino rats (100/sex/group) exposed via inhalation to 0, 30, 100 and 300 ppm propylene oxide for 6 hrs/day, 5 days/week for 123 weeks (females) or 124 weeks (males). Significant increases were observed in treated animals compared to controls in the following: palpable subcutaneous masses (females at 300 ppm), mortality (both sexes at 300 ppm, females at 100 ppm), degenerative and hyperplastic changes in the nasal mucosa (all treated rats), incidence and multiplicity of mammary gland masses and benign mammary tumors (females at 300 ppm), number of mammary fibroadenomas per fibroadenoma-bearing females (all treated females), malignant mammary tumors (females at 300 ppm), and malignant non-mammary tumors (both sexes at 30 ppm). Significant decreases for treated animals was observed for the following: body weights (both sexes at 300 ppm, females only in first year of study) and incidence of pale exorbital lachrymal glands (males at 300 ppm). No significant effects were observed in the following: food intake, biochemistry or urinalysis.
The mutagenicity of propylene oxide was evaluated in Salmonella tester strain 1538 (Ames Test) and also in E. coli strains WP2 and WP2uvrA, both in the presence and absence of Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity determinations, propylene oxide was tested for mutagenicity at concentrations of 0, 0.2, 2.0, 20.0 and 500 ug/ml in two sets of tests, one set preincubated the chemical and cells for 1 hr (both with and without activation) and the other set preincubated for 4 hrs (without activation only). Tryptophan was used as the selection agent for the E coli mutants. Propylene oxide did not cause a reproducible positive response in the Salmonella tester strain TA1538. Propylene oxide did cause a reproducible positive response without metabolic activation at exposures of 1 and 4 hrs when tested at 20 ug/ml with strain WP2uvrA. With metabolic activation, a positive response occurred with WP2uvrA at 500 ug/ml after a 1 hr exposure. The lack of a positive response in WP2 at the 500 ug/ml concentration with activation was attributed to the considerable cell toxicity observed in those tests.
The ability of propylene oxide to cause chromosome aberrations was evaluated in an liver epithelial-type cell line of Carworth Farm E (CFE) rat. Cultures were treated with propylene oxide at 0, 25, 50, 75 and 100ug/ml and incubated for 24 hours, after which colcemid was added. Chromosome changes were analyzed in 100 cells from each culture. All of the treated cells exhibited increases (no statistics reported) in the frequency of chromosome aberrations relative to the controls, and a dose-response relationship was also observed.
The effect of propylene oxide (PO) on liver non-protein sulfhydryls was evaluated in male Wistar/Lewis rats (9/exposure) receiving nominal concentrations of PO at 75 (TWA 80ppm), 150 (TWA 143ppm), 225 (TWA 217ppm), 300 (TWA 284ppm) or 600ppm (TWA 904ppm) for six hours in a dynamic air flow chamber. All animals were sacrificed at the end of exposure, and blood and livers were collected for analysis. Hepatic non-protein sulfhydryls were significantly depressed in livers of animals exposed at 300ppm or greater relative to the controls, and a dose-response relation was observed. The concentration of PO in the blood was proportional to exposure concentrations, except for exposures ranging from 150ppm to 300ppm were there was a disproportionate increase concentration of PO in the blood.
A subchronic inhalation toxicity study was conducted with group of male and female Wistar rats receiving whole body exposure to propylene oxide at nominal concentration of 0, 75, 150, 300 or 600ppm in a dynamic air flow chamber. At each concentration, groups of 20 rats (10 male & 10 female) were exposed 6 hours a day, 5 days a week, for 13 weeks. The treatment produced no signs of toxicity in any of the animals as indicated by mortality, hematological values, major biochemical and urinary values, gross and histopathologic observations relative to controls. There was a depression in body weight gain in males and females at the high dose level.
As part of a two-generation reproduction study, the neurotoxic potential of propylene oxide was evaluated in male Fischer 344 rats (F0 generation). Thirty animals per group received whole body exposure to propylene oxide at nominal concentrations of 0, 30, 100 or 300ppm for 6 hours per day, 5 days per week, for approximately 24 weeks. Observational battery tests were performed on all rats from each dose level at approximately 8, 16 and 24 weeks of exposure. Also preformed prior to sacrifice were hindlimb grip strength test and an open-field activity test. After sacrifice an extensive histopathologic examination of the central and peripheral nervous system was conducted. There were no differences in the test results between the treated groups and control groups. Mild neuroaxonal dystrophy (eosinophilic spheroids) in the region of the nucleus gracilis was present in the majority of control and treated animals, however, the incidence and severity of the condition was more prevalent in the controls than the high dose animals.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
PROPYLENE OXIDE REACTS WITH DNA AT NEUTRAL PH TO YIELD TWO PRINCIPAL PRODUCTS, N-7-(2-HYDROXYPROPYL)GUANINE & N-3-(2-HYDROXYPROPYL)ADENINE.
Chromosomal aberrations and micronuclei in lymphocytes were measured in workers exposed to propylene oxide in a factory 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 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.
The pharmacokinetics of propylene and its reactive metabolite, propylene oxide, were assessed in rats to examine purported differences in carcinogenicity between the two compounds. Groups of Sprague-Dawley rats were exposed in closed exposure systems to propylene or propylene oxide. Pharmacokinetic parameters were determined by a two compartment model which was used to calculate the body burden of propylene oxide resulting from inhaled propylene. The thermodynamic equilibrium constant for the whole body to air ratio was dependent on the physical properties of the substances and was determined to be 1.6 for propylene and 45 for propylene oxide. Saturation kinetics according to the Michaelis Menten constant were found for propylene; in contrast, no saturation kinetics were observed for propylene oxide up to initial concentrations of 3000 ppm in the atmosphere of the exposure chambers. By means of pharmacokinetic parameters, the body burden of propylene oxide was calculated for different conditions of continous exposure either to propylene oxide or to propylene. The maximum body burden of propylene oxide did not exceed a concentration of 71 nanoliters propylene oxide gas per milliter tissue if rats were exposed to propylene even at very high concentrations.
Absorption, Distribution & Excretion:
THE RESPIRATORY SYSTEM IS THE PRIMARY ROUTE OF ABSORPTION, ALTHOUGH THE SKIN ALSO REPRESENTS A ROUTE BY WHICH PHYSIOLOGICALLY SIGNIFICANT AMT ... MAY ENTER THE BODY ... .
Biological Half-Life:
... The half-life of inhaled propylene oxide in rats is 40 min.
Mechanism of Action:
Thymidine was reacted in methanol with 4 epoxides of varying mutagenicities: propylene oxide, glycidol, epichlorohydrin, and trichloropropylene oxide. A single product was detected with each epoxide, and these products had the same retention times on silica HPLC. UV spectra of the products identified them as 3-alkylthymidines, and this was confirmed by IR and NMR spectra. Mass spectra analysis showed that the attachment was at the least substituted C of the epoxide. Formation of alkylthymidines correlated to Taft sigma electron withdrawing values for the substituents on the epoxides and mutagenicities in strain TA100 of the Ames assay.
Interactions:
WHEN ... /IT IS MIXED WITH CARBON DIOXIDE/ SMALL DOSES ARE MORE EFFECTIVE & A QUICKER KILL IS EFFECTED THROUGH STIMULATION OF INSECT RESP.
Pharmacology:
Interactions:
WHEN ... /IT IS MIXED WITH CARBON DIOXIDE/ SMALL DOSES ARE MORE EFFECTIVE & A QUICKER KILL IS EFFECTED THROUGH STIMULATION OF INSECT RESP.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
1,2-Propylene oxide's production and its use as a chemical intermediate in polymer synthesis and as a food additive (fumigant), may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 538 mm Hg at 25 deg C indicates 1,2-propylene oxide will exist solely as a vapor in the ambient atmosphere. Vapor-phase 1,2-propylene oxide will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 30 days. If released to soil, 1,2-propylene oxide is expected to have very high mobility based upon an estimated Koc of 25. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 6.96X10-5 atm-cu m/mole. 1,2-Propylene oxide may volatilize from dry soil surfaces based upon its vapor pressure. 1,2-Propylene oxide, present at 100 mg/l, reached 95% of its theoretical BOD in 3 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test, suggesting biodegradation will be an important fate process. If released into water, 1,2-propylene oxide is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 12 hours and 6 days, respectively. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Propylene oxide will hydrolyze at half-life rates of 11.6 days (at pH's 7-9) and 6.6 days (at pH 5) at 25 deg C. The presence of chloride ion accelerates the degradation in water and the chemical degradation half-lives in seawater are estimated to be 4.1 days (at pH's 7-9) and 1.5 days (at pH 5) at 25 deg C. Reaction of propylene oxide with Cl ion in water yields approximately 90% 1-chloro-2-propanol and 10% 2-chloro-1-propanol as products under neutral pH conditions. Occupational exposure to 1,2-propylene oxide may occur through inhalation and dermal contact with this compound at workplaces where 1,2-propylene oxide is produced or used. Propylene oxide has been detected in 6.2% of 1,159 consumer products that are used indoors; products found to containing the highest concentration of propylene oxide were automotive and paint products. (SRC)
Probable Routes of Human Exposure:
Exposure of man to propylene oxide mainly occurs through inhalation at the workplace.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 421,140 workers (317,309 of these are female) are potentially exposed to 1,2-propylene oxide in the US(1). Occupational exposure to 1,2-propylene oxide may occur through inhalation and dermal contact with this compound at workplaces where 1,2-propylene oxide is produced or used(SRC). In a 1979 study by one USA manufacturer, the typical average daily exposure of workers to propylene oxide were 0.5-5 mg/cu m with worst-case peak exposures of 59-9000 mg/cu m (highest exposure being that of maintenance workers cleaning pumps)(2). Levels of worker exposure were reported to be 0.5 to 5.9 mg/cu m in a polymer polyol unit, not detectable to 1.2 mg/cu m in an oxide adducts unit, and not detectable in a flexible polyol unit of a large chemical manufacturing facility producing many chemical products including propylene oxide derivatives(2). A propylene oxide concn of 3.6 mg/cu m was found near an operator at a flexible polyol unit in another large chemical manufacturing facility(2). Propylene oxide has been detected in 6.2% of 1,159 consumer products that are used indoors; products found to containing the highest concentration of propylene oxide were automotive and paint products(SRC).
Natural Pollution Sources:
Propylene oxide is not known to occur as a natural product.
Artificial Pollution Sources:
1,2-Propylene oxide's production and its use as a chemical intermediate in polymer synthesis(1) and as a food additive (fumigant)(1,2), may result in its release to the environment through various waste streams(SRC).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 25(SRC), determined from an measured log Kow of 0.03(2) and a regression-derived equation(3), indicates that 1,2-propylene oxide is expected to have very high mobility in soil(SRC). Volatilization of 1,2-propylene oxide from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.96X10-5 atm-cu m/mole(SRC), calculated from its vapor pressure, 538 mm Hg(4), and water solubility, 5.9X10+5 mg/l(5). The potential for volatilization of 1,2-propylene oxide from dry soil surfaces may exist (SRC) based upon a vapor pressure of 538 mm Hg(4). The aqueous hydrolysis of propylene oxide occurs at an environmentally important rate; therefore, hydrolysis in moist soil is likely to be important (5). 1,2-Propylene oxide, present at 100 mg/l, reached 95% of its theoretical BOD in 3 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(6), suggesting biodegradation will be an important fate process(SRC).
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 25(SRC), determined from an measured log Kow of 0.03 and a regression-derived equation(3), indicates that 1,2-propylene oxide is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 6.96X10-5 atm-cu m/mole (SRC), based upon its vapor pressure, 538 mm Hg(4), and water solubility, 5.9X10+5 mg/l(5). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 12 hours and 6 days, respectively(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression- derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). In freshwater, propylene oxide will hydrolyze with estimated half-lives of 11.6 days (pH's 7-9) and 6.6 days (pH 5) at 25 deg C(5). 1,2-Propylene oxide, present at 100 mg/l, reached 95% of its theoretical BOD in 3 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(8), suggesting biodegradation will be an important fate process(SRC).
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 1,2-propylene oxide, which has a vapor pressure of 538 mm Hg at 25 deg C(2) is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 1,2-propylene oxide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 30 days(SRC), calculated from its rate constant of 5.2X10-12 cu cm/molecule-sec at 25 deg C(3).
Environmental Biodegradation:
AEROBIC: 1,2-Propylene oxide, present at 100 mg/l, reached 95% of its theoretical BOD in 3 weeks using an activated sludge inoculum at 30 mg/l and the Japanese MITI test(1); therefore, this compound is expected to biodegrade rapidly. In another study, using the standard dilution method, a 5 day theoretical BOD of 8% was measured for propylene oxide using a filtered effluent seed from a biological sanitary waste treatment plant while a 5 day theoretical BOD of 9% was measured using an adapted seed(2).
Environmental Abiotic Degradation:
The rate constant for the gas-phase reaction of propylene oxide with photochemically produced hydroxyl radicals in the atmosphere has been experimentally determined to be 5.2X10-13 cu cm/molecule-sec at 25 deg C(1); assuming an average atmospheric hydroxyl radical concn of 5X10+5 molecules/cu cm, a half-life of 30 days can be calculated for this reaction(SRC). The anticipated products of the atmospheric reaction with hydroxyl radicals have been cited as oxomethyl acetate, propanedial, formaldehdye, and diformyl ether(2). Ozone is not expected to react with propylene oxide in the atmosphere(3). The hydrolysis half-life of propylene oxide in fresh water at 25 deg C has been estimated to be 11.6 days at pH 7-9 and 6.6 days at pH 5(4). The half-life of propylene oxide in seawater (3% NaCl concn) at 25 deg C has been estimated to be 4.1 days at pH 7-9 and 1.5 days at pH 5(4) with the formation of chloropropanols. The rate constant for the reaction of propylene oxide with photochemically produced hydroxyl radicals in water at room temperature has been experimentally determined to be 2.4X10+8/m-sec(5); assuming an average hydroxyl radical concentration of 1X10-17M in natural water(6), a half-life of 9.15 years can be calculated indicating no environmental significance(SRC).
Environmental Bioconcentration:
An estimated BCF of 3 was calculated for 1,2-propylene oxide(SRC), using a log Kow of 0.03(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
Soil Adsorption/Mobility:
The Koc of 1,2-propylene oxide is estimated as 25(SRC), using a measured log Kow of 0.03(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 1,2-propylene oxide is expected to have very high mobility in soil(SRC).
Volatilization from Water/Soil:
The Henry's Law constant for 1,2-propylene oxide is estimated as 6.96X10-5 atm-cu m/mole(SRC) based upon its vapor pressure, 538 mm Hg(1), and water solubility, 5.9X10+5 mg/l(2). This Henry's Law constant indicates that 1,2-propylene oxide is expected to volatilize from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 12 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 6 days(SRC). The potential for volatilization of 1,2-propylene oxide from dry soil surfaces may exist(SRC) based upon a vapor pressure of 538 mm Hg(1).
Effluent Concentrations:
A propylene oxide concentration of 0.047 mg/l was detected in a water effluent from Olin Corporation's Brandenberg, KY chemical production facility on Feb 2, 1974(1). Atmospheric emissions of propylene oxide from propylene oxide manufacturing processes during 1978 were estimated to be about 1.16 million lb(2). Atmospheric emissions resulting from the use of propylene oxide in the production of urethane polyols, propylene glycol, surfactant polyols, di- and tripropylene glycols, glycol ethers and miscellaneous applications during 1978 were estimated to be about 147.7, 13.9, 15.8, 2.9, 1.2 and 3.8 thousand lb, respectively(2). It has been suggested that proplyene oxide may be emitted to the atmosphere from automobile exhaust and from combustion exhausts of stationary sources that burn hydrocarbons(3).
Atmospheric Concentrations:
SOURCE DOMINATED: Propylene oxide has been detected in 6.2% of 1,159 consumer products that are used indoors. Products containing the highest concentration of propylene oxide were automotive (0.3% w/w) and paint products (0.3% w/w)(1). Propylene oxide was tentatively identified in unspecified atmospheric air samples in the US(2).
Food Survey Values:
TREATED WHEAT HAD EPOXIDE RESIDUE OF 300 PPM, BUT AFTER IT WAS MILLED FLOUR CONTAINED LESS. /PROPYLENE OXIDE/
WHEN FOODS WERE TREATED WITH PROPYLENE OXIDE, 1-CHLOR-2-PROPANOL WAS FORMED.
Environmental Standards & Regulations:
FIFRA Requirements:
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. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA, as amended in 1988, were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Propylene oxide is found on List B. Case No: 2560; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): Propylene oxide; 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.
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, methyl is included on this list.
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 100 lb or 45.4 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).
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. Propylene oxide is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered for and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... .
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. Propylene oxide is produced, as an intermediate or a final product, by process units covered under this subpart.
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. 1,2-Propylene oxide is included on this list.
Clean Water Act Requirements:
Propylene oxide is designated as a hazardous substance under section 311(b)(2)(A) of the Federal Water Pollution Control Act and further regulated by the Clean Water Act Amendments of 1977 and 1978. These regulations apply to discharges of this substance. This designation includes any isomers and hydrates, as well as any solutions and mixtures containing this substance.
State Drinking Water Guidelines:
(FL) FLORIDA 5,000 ug/l
Chemical/Physical Properties:
Molecular Formula:
C3-H6-O
Molecular Weight:
58.08
Color/Form:
Colorless liquid ... [Note: A gas above 94 degrees F.]
Odor:
ODOR IS SWEET, ALCOHOLIC, & LIKE ETHER OR BENZENE
In foods, propylene oxide has no residual odor.
Ethereal odor
... Benzene-like odor ...
Taste:
In foods, propylene oxide has no residual taste.
Boiling Point:
34.23 deg C
Melting Point:
-112.13 deg C
Corrosivity:
NONCORROSIVE TO METALS
Critical Temperature & Pressure:
Critical temperature: 209.1 deg C at 48.6 atm
Density/Specific Gravity:
0.8304 @ 20/20 deg C
Heat of Combustion:
-13,000 BTU/LB = -7,221 CAL/G = -302.3X10+5 JOULES/KG
Heat of Vaporization:
LATENT HEAT OF VAPORIZATION: 205 BTU/LB+ 114 CAL/G+ 4.77X10+5 JOULES/KG
Octanol/Water Partition Coefficient:
log Kow= 0.03.
Solubilities:
40.5 wt% water @ 20 deg C
MISCIBLE WITH ACETONE, BENZENE, CARBON TETRACHLORIDE, METHANOL, & ETHER
Soluble in alcohol and ether.
In water, 590,000 mg/l @ 25 deg C
Spectral Properties:
IR: 15270 (Sadtler Research Laboratories IR Grating Collection)
NMR: 32 (Varian Associates NMR Spectra Catalogue)
MASS: 31 (Atlas of Mass Spectral Data, John Wiley & Sons, New York)
MASS: 3980 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63)
Index of refraction: 1.3670 @ 20 degrees C/D
Surface Tension:
24.5 dynes/cm
Vapor Density:
2.0 (Air= 1)
Vapor Pressure:
538 mm Hg @ 25 deg C
Viscosity:
0.28 centipoise at 25 deg C
Other Chemical/Physical Properties:
Solubility of water in propylene oxide is 12.8% by wt at 20 deg C.
LIQ SURFACE TENSION: 24.5 DYNES/CM= 0.0245 NEWTON/M @ 15 DEG C; HEAT OF SOLN (EST): -19 BTU/LB= -11 CAL/G= -0.45X10+5 JOULES/KG
Ratio of Specific Heats of Vapor (gas): 1.113
SADTLER REFERENCE NUMBER: 387, 2211, 2212 (IR, PRISM) INDEX OF REFRACTION: 1.3607 AT 20 DEG C/D /DL-FORM/
Hydroxyl radical reaction rate constant= 5.20X10-13 cu cm/molecule-sec @ 25 deg C
Chemical Safety & Handling:
DOT Emergency Guidelines:
Fire or explosion: HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Those substances designated with a "P" may polymerize explosively when heated or involved in a fire. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water. /Propylene oxide/
Health: Inhalation or contact with material may irritate or burn skin and eyes. Fire may produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control may cause pollution. /Propylene oxide/
Public safety: CALL Emergency Response Telephone Number ... . Isolate spill or leak area immediately for at least 25 to 50 meters (80 to 160 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate closed spaces before entering. /Propylene oxide/
Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Structural firefighters' protective clothing will only provide limited protection. /Propylene oxide/
Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. /Propylene oxide/
Fire: CAUTION: All these products have a very low flash point: Use of water spray when fighting fire may be inefficient. Small fires: Dry chemical, CO2, water spray or alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam. Use water spray or fog; do not use straight streams. Move containers from fire area if you can do it without risk. Fire involving Tanks or Car/Trailer loads: 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. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn. /Propylene oxide/
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. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. A vapor suppressing foam may be used to reduce vapors. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. Use clean non-sparking tools to collect absorbed material. Large spills: Dike far ahead of liquid spill for later disposal. Water spray may reduce vapor; but may not prevent ignition in closed spaces. /Propylene oxide/
First aid: Move victim to fresh air. Call 911 or emergency medical service. Apply artificial respiration if victim is not breathing. 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. Wash skin with soap and water. Keep victim warm and quiet. Ensure that medical personnel are aware of the material(s) involved, and take precautions to protect themselves. /Propylene oxide/
Odor Threshold:
Inasmuch as the detectable odor concn of propylene oxide is reported to be as high as 200 ppm, its odor cannot be reliably used as a warning.
Odor detection in air= 9.90x10+0 ppm /Purity not specified/
Odor recognition in air= 3.50x10+1 ppm /Purity not specified/
Low: 24.7500 mg/cu m; High: 500.000 mg/cu m
Odor thresholds of 35 ppm, 44 ppm, and 200 ppm have been reported.
Skin, Eye and Respiratory Irritations:
... WHEN CONFINED TO THE SKIN ... EVEN DILUTE CONCN (10%) MAY CAUSE IRRITATION ... HIGHLY DILUTE SOLUTIONS (LESS THAN 10%) MAY BE MORE IRRITATING TO THE SKIN THAN UNDILUTED PROPYLENE OXIDE.
Propylene oxide vapors are irritating to the skin, eyes and respiratory system.
The major adverse effects ... demonstrated in humans involve burning or blistering of the skin when prolonged contact with non-volatilized chemical has occurred. This has been shown to occur even with low concentrations of propylene oxide. Corneal burns ... have also been reported.
Irritating to skin, eyes, and respiratory system.
Fire Potential:
FLAMMABLE, DANGEROUS FIRE RISK
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.
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.
Reactivity: 2. 2= This degree includes materials that are normally unstable and readily undergo violent chemical change, but are not capable of detonation. This includes materials that can undergo chemical change with rapid release of energy at normal temperatures and pressures and materials that can undergo violent chemical changes at elevated temperatures and pressures. This also includes materials that may react violently with water or that may form potentially explosive mixtures with water. In advanced or massive fires involving these materials, fire fighting should be done from a safe distance or from a protected location.
Flammable Limits:
Lower flammable limit: 2.3% by volume; Upper flammable limit: 36% by volume
Flash Point:
-35 deg F (closed cup); -20 deg F (open cup)
Autoignition Temperature:
Ignition temp 449 deg C, 840 deg F
Fire Fighting Procedures:
If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as a fog. Solid streams of water may be ineffective. Cool all effective containers with flooding quantities of water. Apply water from as far away as possible. Use "alcohol" foam, dry chemical or carbon dioxide.
Evacuation: If fire becomes uncontrollable or container is exposed to direct flame, evacuate for a radius of 1 mile.
Use flooding quantities of water as fog. May use water spray, dry chemical, "alcohol resistant" foam, or carbon dioxide. Use water spray to keep fire exposed containers cool. Fight fire from protected location or maximum possible distance.
Explosive Limits & Potential:
A VERY DANGEROUS FIRE AND EXPLOSION HAZARD WHEN EXPOSED TO HEAT OR FLAME.
LOWER 2.1%; UPPER 38.5%
Explosive reaction with epoxy resin and sodium hydroxide. Forms explosive mixtures with oxygen. Reacts with ethylene oxide + polyhydric alcohol to form the thermally unstable polyether alcohol.
Hazardous Reactivities & Incompatibilities:
No acetylide-forming metals such as copper or copper alloys should be in contact with propylene oxide.
A polyether-alcohol, prepared by co-condensation of ethylene oxide and propylene oxide with a polyhydric alcohol, was stored at above 100 deg C and exposed to air via a vent line. After 10-15 hr, violent decompostion occurred, rupturing the vessel.
... PROPYLENE OXIDE MAY REACT WITH INORG CHLORIDES PRESENT IN FOODSTUFFS TO FORM TOXIC CHLOROHYDRINS.
Mixing propylene oxide and epoxy resin in a waste bottle led to an explosion, probably owing to the polymerization of the oxide catalysed by the amine accelerator in the resin.
The transition of deflagration to detonation in /propylene oxide and oxygen/ mixtures was studied with respect to mixing ratio, pressure, and spark energy.
A drum of crude product containing unreacted propylene oxide & sodium hydroxide catalyst exploded & ignited, probably owing to base-catalyzed exothermic polymerization of the oxide.
Anhydrous metal chlorides; iron; strong acids, caustics & peroxides. [Note: polymerization may occur due to high temperatures or contamination with alkalis, aqueous acids, amines & acidic alcohols.]
Can react vigorously with oxidizing materials.
Hazardous Decomposition:
When heated to decomposition it emits acrid smoke and fumes.
Hazardous Polymerization:
An investigation into the hazards associated with the base catalyzed polymerization reactions to which ethylene oxide and propylene oxide are subjected was conducted. The overall goal was to determine if propylene oxide undergoes a polymerization process which is as exothermic as that of ethylene oxide. In particular, the temperature dependence of these polymerizations, along with the contaminant initiations were compared for the two monomers. The polymerization studies were performed in an accelerating rate calorimeter. Both monomers were reacted in this vessel with varying amounts of an aqueous sodium hydroxide catalyst. The energy required to initiate the polymerization of propylene oxidee was higher. The activation energy for the polymerization of ethylene oxide was 81.1 kj/mol while that of propylene oxide was 83.6 kJ/mol. This meant that ethylene-oxide is about 10 to 20 times easier to polymerize at 20 degrees C. Ethylene oxide was much more likely to autoignite, with an ignition temperature of 429 degrees compared to 550 degrees for propylene oxide. The authors conclude that ethylene oxide is significantly more reactive than propylene oxide to alkali catalyzed polymerizations. The controls required for ethylene oxide handling and storage are probably too severe for propylene oxide.
Polymerizes in the presence of aqueous sodium hydroxide.
Hazardous polymerization may occur when in contact with highly active catalytic surfaces, acids, and bases.
Immediately Dangerous to Life or Health:
NIOSH considers propylene oxide to be a potential occupational carcinogen. /SRP: No IDLH value specified/.
Protective Equipment & Clothing:
/When handling/ wear rubber gloves, large & heavy face shields (body shields are also recommendable) & self-contained breathing apparatus.
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/
Wear appropriate personal protective clothing to prevent skin contact.
Wear appropriate eye protection to prevent eye contact.
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.]
Recommendations for respirator selection. Condition: At concentrations above the NIOSH REL, or where there is no REL, at any detectable concentration. 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 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.
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. Any appropriate escape-type, self-contained breathing apparatus.
Wear special protective clothing and positive pressure self-contained breathing apparatus.
Preventive Measures:
Employees should be provided with and required to use splash-proof safety goggles where liquid propylene oxide may contact the eyes. Where there is any possibility of exposure of an employee's body to liquid propylene oxide, facilities for quick drenching of the body should be provided within the immediate work area for emergency use. Any clothing which becomes contaminated with liquid propylene oxide should be removed immediately and such clothing should not be reworn until the propylene oxide is removed from the clothing. Clothing wet with liquid propylene oxide should be placed in closed containers for storage until it can be discarded or until provision is made for the removal of the propylene oxide. If the clothing is to be laundered or otherwise cleaned to remove the propylene oxide, the person performing the operation should be informed of propylene oxide's hazardous properties.
Smoking, eating, and drinking before washing should be absolutely prohibited when any pesticide ... is being handled or used. /Pesticides/
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.
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.
Contact lenses should not be worn when working with this chemical.
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/
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/
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/
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/
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/
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/
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/
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/
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/
The worker should immediately wash the skin when it becomes contaminated.
Work clothing that becomes wet should be immediately removed due to its flammability hazard.
Stability/Shelf Life:
It polymerizes exothermically.
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)./
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.
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.
PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/
Storage Conditions:
Use glass or metal containers sealed with nitrogen.
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/
Store in a cool, dry, well-ventilated location. Outside or detached storage is preferred. Separate from acids, alkalies, salts, combustible material, clay-based absorbents.
Cleanup Methods:
Evacuation: If material leaking (not on fire) consider evacuation from downwind area based on amount of material spilled, location and weather conditions.
1. REMOVE ALL IGNITION SOURCES. 2. VENTILATE AREA OF SPILL OR LEAK. 3. FOR SMALL QUANTITIES, ABSORB ON PAPER TOWELS. EVAPORATE IN A SAFE PLACE (SUCH AS A FUME HOOD). ALLOW SUFFICIENT TIME FOR EVAPORATING VAPORS TO COMPLETELY CLEAR THE HOOD DUCTWORK. BURN THE PAPER IN A SUITABLE LOCATION AWAY FROM COMBUSTIBLE MATERIALS. LARGE QUANTITIES MAY BE COLLECTED, DISSOLVED IN ALC OF GREATER MOL WT THAN BUTYL ALC, & ATOMIZED IN A SUITABLE COMBUSTION CHAMBER.
Land spill: Dig a pit, pond, lagoon, or holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, cement powder, sawdust, or commercial sorbents. Apply "universal" gelling agent to immobilize spill.
Water spill: Use natural barriers or oil spill control booms to limit spill. Use surface active agent (eg detergent, soaps, alcohols) to compress and thicken spilled material. Inject "universal" gelling agent to solidify encircled spill and increase effectiveness of booms. If dissolved, apply activated carbon at ten times the spilled amount in region of 10 ppm or greater concentration. Use mechanical dredges or lifts to remove immobilized masses of pollutants and precipitates.
Air spill: Apply water spray or mist to knock down vapors.
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/
Eliminate all ignition sources. Approach release from upwind. Stop or control the leak, if it can be done without undue risk. Use water spray to cool and disperse vapors, protect personnel, and dilute spills to form nonflammable mixtures. Do not use clay-based absorbents. Control runoff and isolate discharged material for proper disposal.
Disposal Methods:
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
Propylene oxide is a waste chemical stream constituent which may be subjected to ultimate disposal by controlled incineration. Concentrated waste containing no peroxides; discharge liquid at a controlled rate near a pilot flame. Concentrated waste containing peroxides; perforation of a container of waste from a safe distance followed by open burning.
PROPYLENE OXIDE MAY BE DISPOSED OF BY DISSOLVING IN PENTYL OR HIGHER CARBON NUMBER ALC & ATOMIZING IN A SUITABLE COMBUSTION CHAMBER.
Concentrated waste containing no peroxides-discharge liquid at a controlled rate near a pilot flame. Concentrated waste containing peroxides-perforation of a container of the waste from a safe distance followed by open burning. Recommendable methods: Incineration, open burning & evaporation. Peer review: Very volatile (bp 33 deg C) may make it difficult to feed to incinerator with safety. Open burning and evaporation are recommendable for small amounts. (Peer-review conclusions of an IRPTC expert consultation (May 1985))
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/
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/
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/
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/
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/ Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit: Table Z-1 8-hr Time Weighted Avg: 100 ppm (240 mg/cu m).
Vacated 1989 OSHA PEL TWA 20 ppm (50 mg/cu m) is still enforced in some states.
Threshold Limit Values:
8 hr Time Weighted Avg (TWA) 20 ppm
Excursion Limit Recommendation: Excursions in worker exposure levels may exceed three times the TLV-TWA for no more than a total of 30 min during a work day, and under no circumstances should they exceed five times the TLV-TWA, provided that the TLV-TWA is not exceeded.
A3: Confirmed animal carcinogen with unknown relevance to humans.
Notice of Intended Change for 2000: These substances, with their corresponding values and notations, comprise those for which a limit has been proposed for the first time or for which a change in the Adopted listing has been proposed. In each case, the proposed values should be considered trial values for the year following ratification by the ACGIH Board of Directors. If, during the year, no evidence comes to light that questions the appropriateness of these proposals, the value will be reconsidered for adoption as TLVs. Time Weighted Avg (TWA): 2 ppm; Carcinogenicity, A3; Sensitizer.
NIOSH Recommendations:
NIOSH considers propylene oxide to be a potential occupational carcinogen.
NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible concentration.
Immediately Dangerous to Life or Health:
NIOSH considers propylene oxide to be a potential occupational carcinogen. /SRP: No IDLH value specified/.
Other Occupational Permissible Levels:
Emergency Response Planning Guidelines (ERPG): ERPG(1) 50 ppm (no more than mild, transient effects) for up to 1 hr exposure; ERPG(2) 250 ppm (without serious, adverse effects) for up to 1 hr exposure; ERPG(3) 750 ppm (not life threatening) up to 1 hr exposure.
Australia: 20 ppm, Category 2, probable human carcinogen, substance under review; Federal Republic of Germany: no MAK, Group A2 unmistakable carcinogenic in animal experimentation only, Technical Exposure Limits (TRK) 2.5 ppm; Sweden: 5 ppm, short-term value 10 ppm, 15 min; United Kingdom: 20 ppm, 10 min STEL 100 ppm.
Manufacturing/Use Information:
Major Uses:
For 1,2-propylene oxide (USEPA/OPP Pesticide Code: 042501) 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./
Chemical intermediate in prepn of polyethers to form polyurethanes; in prepn of urethane polyols and propylene and dipropylene glycols; in prepn of lubricants, surfactants, oil demulsifiers. Also as a solvent; fumigant; soil sterilant.
Isopropanol amines, synthetic elastomer (homopolymer)
STERILIZATION OF PACKAGED FOOD PRODUCTS IN FUMIGATION CHAMBERS.
HERBICIDE
FDA has approved use of propylene oxide as a direct & indirect food additive for 1) use as an etherifying agent in prodn of modified food starch (at use levels of 25% max or less); & 2) use as a package fumigant for certain fruit products & as a fumigant for bulk quantities of several food products, provided residues of propylene oxide & propylene glycol do not exceed specified limits
In detergent manufacture and as a component in brake fluids
Microbicide, insecticide and miticide. ... Bacteriostat, fungicide.
Manufacturers:
Dow Chemical U.S.A., 2030 Dow Center, Midland, MI 48674, (517) 636-1000; Production sites: Freeport, TX 77541; Plaquemine, LA 70765
Huntsman ICI Chemicals LLC, 500 Huntsman Way, Salt Lake City, UT 84108, (801) 584-5700. Huntsman Polyurethanes; Production site: Port Neches, TX 77651
Lyondell Chemical Co., 1221 McKinney St., Suite 700, Houston, TX 77010, (713) 652-7200; Production sites: Bayport, TX 77062; Channelview, TX 77530
Methods of Manufacturing:
Propylene oxide was 1st prepared in 1860 ... by the reaction of propylene chlorohydrin with potassium hydroxide. Until 1969, essentially all the propylene oxide produced in USA was made by the so-called chlorohydrin process in which propylene is treated with hypochlorous acid (chlorine & water) to produce propylene chlorohydrin; this is converted to propylene oxide using calcium hydroxide or sodium hydroxide. A plant using a version of the peroxidation process was started in USA in 1969. Peroxidation processes use an oxidant such as an organic hydroperoxide (tert-butyl hydroperoxide or ethylbenzene hydroperoxide) or peracetic acid to convert propylene to propylene oxide. Currently, about 1/2 of USA propylene oxide-production capacity is based on the chlorohydrin process, & the other half is based on the peroxidation process ...
Arco produces propylene oxide ... with propylene and isobutane. The first step is isobutane hydroperoxidation to t-butyl hydroperoxide. The second is epoxidation of propylene with t-butyl hydroperoxide, forming propylene oxide and tert-butyl alcohol.
Results from the action of KOH (aq) on propylene chlorohydrin.
(1) Chlorohydration of propylene followed by saponification with lime, (2) peroxidation of propylene, (3) epoxidation of propylene by a hydroperoxide complex with molybdenum catalyst.
General Manufacturing Information:
FUMIGATION IS EFFECTIVE AT LOW TEMP BECAUSE OF LOW BOILING POINT.
UNDER CONDITION USED FOR FUMIGATION OF FOODSTUFF PROPYLENE OXIDE CAN COMBINE WITH MOISTURE TO FORM GLYCOL; IN PRESENCE OF INORGANIC CHLORIDE FROM FOODSTUFFS, CORRESPONDING CHLOROHYDRINS WERE FORMED.
Propylene oxide was 1st produced commercially in USA in 1925. ... /It was being/ produced by 6 companies /in USA in 1979/. ... /It is/ produced by 1 company in Canada & 1 in Brazil. It is produced by 4 companies in Federal Republic of Germany, 2 in the Netherlands & 1 each in France, Italy & Spain. ... Propylene oxide is also produced at 2 plants in Romania & at 1 plant each in Bulgaria, the German Democratic Republic, Poland, the USSR & Yugoslavia. Commercial prodn started in Japan in 1959. Five Japanese companies currently mfr it at 6 plants. ... /It is also/ produced by 1 company in Taiwan & at 1 plant in India.
... DESTRUCTION OF 90% OR MORE OF BACTERIA, YEAST AND MOLDS IN COCOA /WAS NOTED/. TOTAL COUNTS AS HIGH AS 200,000-300,000/G COULD BE REDUCED TO 10,000. IN DRIED EGG YOLK ORIGINAL COUNT OF 20,000/G WERE REDUCED TO 200. ... WITH DRIED WHOLE EGG SOLIDS ... BUT REFRACTIVE ANAEROBES AND SALMONELLAE WERE REDUCED BELOW DETECTION LEVELS. IN SPLIT GREEN PEAS COUNTS OF 11,000-16,000 WERE REDUCED TO 40 OR LESS. FINAL COUNTS WERE MADE FOR YEASTS, MOLDS, FLAT SOURS AND THERMOPHILES. IN DRIED YEAST, PROPYLENE OXIDE AFFECTED TOTAL COUNT, AEROBIC SPORE FORMERS AND COLIFORMS. ...
Commercial production is from chlorine and propylene using a chlorohydrin process or from alternate raw materials using peroxidation processes.
Propylene oxide has been found as a trace level impurity in poly(propylene oxide)(1).
Formulations/Preparations:
/IT IS/ OFTEN MIXED WITH CARBON DIOXIDE TO REDUCE FLAMMABILITY AS WELL AS ABSORPTION OF OXIDE BY FUMIGATED MATERIALS.
PROPYLENE OXIDE IS AVAIL ... AS PRODUCT OF 99.99% PURITY /BY ONE PRODUCER/. ANOTHER ... GIVES FOLLOWING SPECIFICATIONS: ACETIC ACID, 0.005%; WATER, 0.01%; PROPIONALDEHYDE, 0.05% ...
Propylene oxide is avail in USA with following specifications: water, 500 mg/kg max; total aldehydes, 100 mg/kg max; chlorides (as chlorine), 40 mg/kg max ...
Propylene oxide is avail in western Europe with following specifications: purity, 99.9% min; water, 200 mg/kg max; aldehydes (as propionaldehyde), 100 mg/kg max; & chlorine, 50 mg/kg max.
A ready to use soln from Jefferson Chemical Co Inc, has 99.9999% active ingredient propylene oxide. /Former/
Pressurized gas, from Union Carbide Corp, has 8.00% active ingredient propylene oxide. A ready to use soln available from Union Carbide Corp Chemicals and Plastics has 99.99% active ingredient propylene oxide.
A ready to use soln available from Aberco, Inc has 99.99% active ingredient propylene oxide.
Impurities:
Acetaldehyde & propionaldehyde are produced in small amt as by-products of the peroxidation processes.
Consumption Patterns:
CHEM INTERMED FOR POLYURETHANE POLYOLS, 64%; PROPYLENE GLYCOL, 19%; DIPROPYLENE GLYCOL, 2%; GLYCOL ETHERS, 2%; OTHER USES (INCL MINOR QUANTITIES USED IN NONINTERMEDIATE APPLICATIONS), 13% (1982)
Polyurethane- flexible foams, 40%; - rigid foams, 7%; - non-cellular, 10%; - coatings & adhesives, 7%; polyols for specialty surfactants, 4%; propylene glycol, 22%; detergents, 4%; other, 6% (1984)
CHEMICAL PROFILE: Propylene Oxide. Urethane polyether polyols (75% for flexible foams, 15% for rigid foams, 10% for non-foam uses), 60%; propylene glycol, 20%; glycol ethers, 3%; dipropylene glycol, 2%; miscellaneous, including industrial polyglycols, surfactants and isopropanolamines, 6%; exports, 9%.
CHEMICAL PROFILE: Propylene oxide. Demand: 1986: 2.2 billion lb; 1987: 2.3 million lb; 1991 /projected/: 2.6 million lb.
CHEMICAL PROFILE: Propylene oxide. Urethane polyether polyols, 60% (75% for flexible foams, 15% for rigid foams, 10% for non-foam uses); propylene glycol, 20%; glycol ethers, 3%; miscellaneous, including industrial polyglycols, surfactants and isopropanolamines, 5%; exports, 12%.
CHEMICAL PROFILE: Propylene oxide. Demand: 1989: 2,655 million lb; 1990 /projected/: 2,700 million lb; 1994 /projected/: 3,100 million lb. (Includes exports, but not imports, which are negligible.)
Urethane polyether polyols, 60 % (flexible foams, 53 %; rigid foams, 6 %; non-foam use, 1 %); propylene glycols, 25 %; P-series glycol ethers, 4 %; miscellaneous, including polyalkylene glycols, allyl alcohol and isopropanolamines, 11 %.
U. S. Production:
(1977) 8.62X10+11 G
(1982) 7.62X10+11 G (EST)
(1983) 8.35X10+11 g
(1990) 3.20 billion lb
(1991) 2.50 billion lb
(1992) 2.70 billion lb
(1993) 2.73 billion lb
(1995) 35th highest-volume chemical produced in U.S.
(1997) 3.1 million pounds; (1998) 3.2 million pounds; (2002) 3.5 million pounds.
U. S. Imports:
(1977) 1.60X10+10 G
(1982) 2.31X10+10 G
(1983) 1.45X10+10 g
(1985) 1.08X10+10 g
Imports are negligible.
U. S. Exports:
(1977) 4.50X10+10 G
(1982) 6.64X10+10 G
(1983) 7.53X10+10 g
(1985) 6.13X10+9 g
Exports of major PO derivatives, primarily urethane polyether polyols and propylene glycols, are significant.
Laboratory Methods:
Clinical Laboratory Methods:
A GAS CHROMATOGRAPHY-MASS SPECTROMETRIC METHOD IS DESCRIBED FOR DETERMINATION IN HEMOGLOBIN OF S-METHYLCYSTEINE IN FOLLOWING EXPOSURE TO PROPYLENE OXIDE.
Analytic Laboratory Methods:
Analytical methods include spectrophotometry, gas chromatography, electron impact spectroscopy, and colorimetric methods. A multigas analyzer utilizing microwave spectroscopy has also been developed to monitor propylene oxide in air.
The method is based on the hydrolysis of propylene oxide to form propylene glycol, which is then oxidized to formaldehyde with periodic acid and determined photometrically following reaction with chromotropic acid. The detection limit of the method is 1 ug, and the minimum measurable concentration is 0.5 mg/cu m.
Gas chromatography may be used to determine the levels of propylene oxide in food, cellulose, and plastic products.
NIOSH Method 1612. Analyte: Propylene oxide. Matrix: Air. Procedure: Gas chromatography, hydrogen-air flame ionization detector. For propylene oxide this method has an estimated detection limit of 0.01 mg/sample. The precision/RSD is 0.029 @ 0.6 to 2.4 mg/sample. Applicability: The working range is 8 to 295 ppm (20 to 700 mg/cu m) for a 5 liter air sample. Interferences: None found.
Propylene oxide is analysed by gas chromatograph for analysis. Recovery is 100 + or - 3 percent for samples analyzed up to 3 weeks after collection. This technique is most appropriate for concentrations of less than 100 ppm in a 1 liter air sample, and has a sensitivity of approximately 1 ppb.
Sampling Procedures:
... Sampling tubes are packed with a porous polymer gas chromatographic adsorbent (Porapak N) to collect the propylene oxide.
NIOSH Method 1612. Analyte: Propylene oxide. Matrix: Air. Sampler: Solid sorbent tube (coconut shell charcoal, 100 mg/50 mg). Flow Rate: 0.01 to 0.2 l/min: Sample Size: 5 liters. Shipment: Refrigerated. Sample Stability: Not determined.
Special References:
Special Reports:
FLORES GH; CHEM ENG PROG 79 (3): 39-43 (1983). REVIEW OF OCCUPATIONAL EXPOSURE TO ALKYLENE OXIDES.
Summary Health Assessment Document For 1,2-Propylene Oxide (Draft) (1985) EPA Contract No 68-02-4030.
Meylan W et al; Chemical of Current Interest Propylene Oxide Health and Environmental Effects Profile; Toxicol Ind Health 2 (3): 219-60 (1986).
DHHS/NTP; Toxicology & Carcinogenesis Studies of Propylene Oxide in F344/N Rats and B6C3F1 Mice (Inhalation Studies) Technical Report Series No. 267 (1985) NIH Publication No. 85-2527
U.S. Department of Health & Human Services/National Toxicology Program; Tenth Report on Carcinogens. National Institutes of Environmental Health Sciences. The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. 1,2-Propylene Oxide (75-56-9) was first listed in the Sixth Annual Report on Carcinogens (1991) as reasonably anticipated to be a human carcinogen.
Synonyms and Identifiers:
Synonyms:
AD 6 (Suspending agent)
AI3-07541
Caswell No 713A
Pesticide Code: 042501.
EPA Pesticide Chemical Code 042501
EPOXYPROPANE
1,2-Epoxypropane
ETHYLENE OXIDE, METHYL-
METHYL ETHYLENE OXIDE
Methyloxirane
NCI-C50099
OXIRANE, METHYL-
OXYDE DE PROPYLENE (FRENCH)
PROPANE, EPOXY-
PROPANE, 1,2-EPOXY-
PROPENE OXIDE
PROPYLENE EPOXIDE
PROPYLENEOXIDE
Formulations/Preparations:
/IT IS/ OFTEN MIXED WITH CARBON DIOXIDE TO REDUCE FLAMMABILITY AS WELL AS ABSORPTION OF OXIDE BY FUMIGATED MATERIALS.
PROPYLENE OXIDE IS AVAIL ... AS PRODUCT OF 99.99% PURITY /BY ONE PRODUCER/. ANOTHER ... GIVES FOLLOWING SPECIFICATIONS: ACETIC ACID, 0.005%; WATER, 0.01%; PROPIONALDEHYDE, 0.05% ...
Propylene oxide is avail in USA with following specifications: water, 500 mg/kg max; total aldehydes, 100 mg/kg max; chlorides (as chlorine), 40 mg/kg max ...
Propylene oxide is avail in western Europe with following specifications: purity, 99.9% min; water, 200 mg/kg max; aldehydes (as propionaldehyde), 100 mg/kg max; & chlorine, 50 mg/kg max.
A ready to use soln from Jefferson Chemical Co Inc, has 99.9999% active ingredient propylene oxide. /Former/
Pressurized gas, from Union Carbide Corp, has 8.00% active ingredient propylene oxide. A ready to use soln available from Union Carbide Corp Chemicals and Plastics has 99.99% active ingredient propylene oxide.
A ready to use soln available from Aberco, Inc has 99.99% active ingredient propylene oxide.
Shipping Name/ Number DOT/UN/NA/IMO:
IMO 3.1; Propylene oxide
UN 1280; Propylene oxide
Standard Transportation Number:
49 066 20; Propylene oxide
|