Testing Information

Testing Status of Agents at NTP

CAS Registry Number: 106-89-8 Toxicity Effects

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Selected toxicity information from HSDB, one of the National Library of Medicine's databases. 1

Names (NTP)

  • Epichlorhydrin
  • (CHLOROMETHYL)-OXIRANE (9CI)
  • ALPHA-EPICHLOROHYDRIN

Human Toxicity Excerpts

  • ... CASES OF SENSITIZATION WITH RESULTING INTOLERANCE TO TRIVIAL EXPOSURES ... SEVERAL CASES OF SKIN BURNS ... FROM PROLONGED CONTACT ... CONCN OF ... 25 PPM ARE REPORTED TO PRODUCE NO SERIOUS DEGREE OF EXTERNAL IRRITATION, ALTHOUGH VAPOR IS READILY DETECTABLE @ THESE LEVELS. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values for Substances in Workroom Air. Third Edition, 1971. Cincinnati, Ohio: American Conference of Governmental Industrial Hygienists, 1971. (Plus supplements to 1979), p. 99]**PEER REVIEWED**
  • VAPORS PRODUCE LACRIMATION & CORYZA IN MAN @ SUBLETHAL CONCN. ... A SINGLE HUMAN RESP EXPOSURE ... RESULT IN CHRONIC ASTHMATIC BRONCHITIS & SEVERE DIFFUSE FATTY INFILTRATION OF THE LIVER. [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984., p. II-168]**PEER REVIEWED**
  • IN ACUTE POISONING, DEATH MAY BE CAUSED BY RESPIRATORY PARALYSIS. IN CHRONIC POISONING THERE IS KIDNEY DAMAGE. INFLAMMATORY CHANGES IN THE EYES & LUNG HAVE BEEN OBSERVED. PRIMARY IRRITATION & SENSITIZATION OF SKIN HAS BEEN DESCRIBED. [Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 710]**PEER REVIEWED**
  • MUCH LOWER CONCN /THAN 20 PPM/ CAUSE CHRONIC POISONING ... SYMPTOMS ... FATIGUE, GASTROINTESTINAL PAINS, CHRONIC CONJUNCTIVITIS ... THE LIQ IS CAUSTIC, & INSTILLED INTO THE EYE IT CAN GIVE RISE TO OPACITY & NECROSIS OF CORNEA. [Lefaux, R. Practical Toxicology of Plastics. Cleveland: CRC Press Inc., 1968., p. 108]**PEER REVIEWED**
  • ... PROSPECTIVE CYTOGENIC STUDY ON 35 WORKERS ... OCCUPATIONALLY EXPOSED TO EPICHLOROHYDRIN. BLOOD SAMPLES WERE OBTAINED ... AFTER 1ST & 2ND YEAR OF EXPOSURE & CULTIVATED FOR 56-58 HR. % CELLS WITH CHROMOSOMAL ABERRATIONS ... 1.37 BEFORE EXPOSURE, 1.91 AFTER 1ST YR, & 2.69 AFTER 2ND YR. ... FREQUENT ... CHROMATID & CHROMOSOMAL BREAKS. [National Research Council. Drinking Water and Health. Volume 3. Washington, DC: National Academy Press, 1980., p. 120]**PEER REVIEWED**
  • HUMAN PERIPHERAL LYMPHOCYTES ... WERE EXPOSED TO 1X10-11 TO 1X10-4 MOLAR EPICHLORHYDRIN IN VITRO FOR 24 HR ... CHROMOSOMAL CHANGES WERE DOSE-DEPENDENT, & THE MOST COMMON TYPE OF ABERRATION PRODUCED BY EACH WERE CHROMATID BREAKS, FOLLOWED BY CHROMOSOMAL BREAKS. CHROMATID EXCHANGES WERE RARE, CHROMOSOMAL CHANGES EXTREMELY RARE. [National Research Council. Drinking Water and Health. Volume 3. Washington, DC: National Academy Press, 1980., p. 120]**PEER REVIEWED**
  • SCEs are observed in human lymphocytes exposed to epichlorohydrin in vitro. The compound produces chromosomal abnormalities in bone marrow cells and in human lymphocytes in vitro and in vivo. [De Serres FJ, Hollaender A; Chemical Mutagens Vol 8 p.302 (1983)]**PEER REVIEWED**
  • Male employees engaged in the manufacture of glycerine, who were exposed to epichlorohydrin, allyl chloride, and 1,3-dichloropropane were studied for their fertility status. The results showed no detrimental effect on fertility from exposure to the chlorinated three-carbon compounds including epichlorohydrin. [USEPA; Health Assessment Document: Epichlorohydrin p.5-9 (1983) EPA 600/8-83-032A]**PEER REVIEWED**
  • Human Reflex Response: no response: 0.2 mg/cu m; adverse response: 0.3 mg/cu m [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 612]**PEER REVIEWED**
  • ... NIOSH concluded that risks from exposure to epichlorohydrin may include carcinogenesis, mutagenesis, and sterility, as well as damage to the kidneys, liver, respiratory tract and skin. [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 613]**PEER REVIEWED**
  • Acute: Irritation of eyes, respiratory tract and skin. Effects may be delayed several hours. Chronic: Enervation, stomach troubles, disturbances in intestines and kidneys; irritation of mucous membranes of eyes and nose; dermatitis. [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 208]**PEER REVIEWED**
  • A case of toxic allergic skin reaction, secondary to accidental contact with methylenedianiline, in a cleaner at a chemical factory was reported. An extensive red, itchy, papular and vesicular rash developed on the face, neck, and wrists of a 32 year old cleaner several hours after cleaning a shallow gutter in a chemical facility with a high pressure water hose. The cleaner was wearing protective clothing including gloves, apron, safety goggles, and a cap during the cleaning operation. Among the chemicals present in the gutter, two were suspcted as the causative agent, epichlorohydrin and methylenedianiline. Patch testing revealed a strong positive reaction to methylenedianiline and epoxy resin, and a broad spectrum of reactions apparently due to cross sensitization to para groups. The patch test with epichlorohydrin was negative. The authors conclude that occupational exposure to methylenedianiline, used as a catalyst in the production of polyurethanes, as a hardener or curing agent for epoxy resins, and as an antioxidant in the manufacture of synthetic fibers, should be avoided because of its manufacture of synthetic fibers, should be avoided because of its sensitization capability and possible cross sensitization with azo dyes. [Van Joost T et al; Contact Dermatitis 16 (5): 246-8 (1987)]**PEER REVIEWED**
  • The mortality experience of 863 workers identified as having probable exposures to epichlorohydrin at two Shell Chemical facilities was examined. One of the facilities was located at Deer Park, Texas where production of epichlorohydrin started in May of 1948. The other location was at Norco, Louisiana, where production of epichlorohydrin started in April of 1955. The cohorts were followed up for the period 1948 through 1983; only two workers were lost to follow up. The standard mortality ratio for all cancer at 20 or more years after the first exposure was 112.2 and the standard mortality ratio for leukemia was 500.0 which was statistically significant. A relation to estimated levels of exposure to epichlorohydrin was noted for all cancer, leukemia, and most other causes of death except death to violence. The relationship between exposure level and heart disease was the most consistent and occurred at both facilities. The standard moratlity ratio for heart disease 20 or more years after the first exposure was 39.2 for low exposures and 105.4 for high exposures. /It was/ suggested that the use of allyl-chloride in the production of epichlorohydrin may play a part in these findings. [Enterline PE et al; Br J Ind Med 47 (40: 269-76 (1990)]**PEER REVIEWED**
  • The cytogenetic effects of epichlorohydrin exposure was evaluated among epoxy resin and glycerin production workers. Samples of blood from 76 epoxy resin workers and 93 glycerine workers were evaluated. Blood from newly hired subjects undergoing preemployment medical examinations was used for comparison. Two different culture media were used to maximize chances for sufficient lymphocytes. After incubation at 37 deg C for 69 to 71 hours, lymphocytes were harvested. Chromosomes were spread and slides were fixed. Chromosomal aberrations were scored by five technologists. Alterations in chromosomes were totaled. Repeat samples were collected from subjects with an abnormally high number of aberrations. Groups were divided by intensity and duration of exposure based on job histories. The estimated exposure to epichlorohydrin did not exceed 5 ppm. There was a significant elevation in the number of chromosome aberrations in epoxy resin workers relative to comparisons. In the repeat cultures, the number of aberrations was only slightly more than that of the comparisons. The initial differences were attributed to the differences between culture media used. No significant differences were found between glycerine workers and their comparisons. /It was/ suggested that control of critical variables during large human cytogenetic studies is needed. In light of these results, previously reported increases in chromosome aberrations due to chemical exposure should be reviewed. [Dabney BJ; Progress in Clinical and Biological Research 207: 59-73 (1986)]**PEER REVIEWED**
  • In an epoxy resin manufacturing plant, 26 of 228 (11.4%) workers had work-related eruptions; 19 were patch tested. The test series consisted of chemicals used in the manufacturing process, a standard battery and some other sensitisers. The prevalence of sensitisation to epichlorohydrin and/or epoxy resins in the whole group was 6.1%. A relatively high prevalence (3.5%) of epichlorohydrin sensitisation was found. 10 cases of sensitisation to liquid epoxy resin (MW about 385) were observed, in 7 cases combined with allergy to solid epoxy resin (MW 980). Sensitisation to Bisphenol A was not seen. [Prens EP et al; Contact Dermatitis 15 (2): 85-90 (1986)]**PEER REVIEWED**
  • A study of mortality in dye and resin manufacturing workers was conducted. The cohort consisted of 2642 males employed at a dye and resin manufacturing facility in New Jersey for at least 6 months between January 1, 1952 and January 1, 1985. A subcohort was formed of 89 subjects who had previously worked at Cincinnati Chemical Works, Cincinnati, Ohio. Cincinnati Chemical Works produced or used benzidine and beta-naphthylamine. The vital status of cohort was determinge as of December 31, 1985. Death certificates were examined. Standardized mortality ratios were calculated using the United States white male population as the reference. The data were also examined according to payroll classification (hourly, weekly, or monthly) and job area. Total mortality in the cohort was significantly decreased, standardized mortality ratios 81. The decrease was due to deficits in mortality from circulatory, respiratory, and digestive diseases, and external causes. Mortality from all cancers of specific sites was not significantly increased. The former Cincinnati Chemical Works employees had a slight excess of deaths from all causes and a significant excess of cancer deaths. The excess cancer mortality was due to increased numbers of deaths from bladder, kidney and central nervous system (CNS) cancer. By work area, maintenance workers had significantly elevated mortality from lung and liver cancer, azo dye workers an excess of CNS cancer, and epichlorohydrin workers an excess of lung cancer. The excess risk, however, were usually based on a small number of observed cases. The excess lung cancer mortality in maintenance workers increased with length of employment. Mortality generally did not vary significantly across payroll category except for an excess of esophageal cancer mortality in monthly employees. The authors note that because the study did not assess workplace exposures it is not possible to link the increases in specific cancer mortalities in some work areas with any specific chemical. Further observation of this cohort and independent evaluations of workers with similar exposures at other facilities are warranted. [Delzell E et al; J Occup Med 31 (3): 273-8 (1989)]**PEER REVIEWED**
  • Squamous cell carcinomas of the forestomach have been observed in many carcinogenicity studies in rodents, especially after oral or gavage exposure. The histopathologial diagnosis of forestomach lesions and the relevance of the data for human risk estimation can be controversial. The pathological classification may be troublesome because of the low-grade malignancy and the pseudoepitheliomatous hyperplasia that may develop after ulceration and inflammation. For human risk estimation it is important to understand the mechanism of actions; this is illustrated by examples using butylated hydroxyanisole, methyl bromide, and epichlorohydrin. Another feature that complicates risk estimation is the absence of a homolog for the forestomach in man. The potential risk from non-genotoxic forestomach carcinogens in man involves exposure of the mouth, pharynx, and esophagus at dose levels that exert irritating action. It is assumed that exposure to non-genotoxic chemicals at concentrations far below those having irritating potential is not hazardous to humans. [Wester PW, Kroes R; Toxicol Pathol 16 (2): 165-71 (1988)]**PEER REVIEWED**
  • Morbidity experience in two cohorts of workers with potential exposure to epichlorohydrin was examined. The first population (Shell cohort) contained 713 workers with industrial hygiene confirmed potential exposure to epichlorohydrin at the same two Shell manufacturing locations studied in an earlier report by Enterline. The morbidity experience of this group was examined from 1981 through 1988. Heart disease morbidity for workers who had potential exposure to both epichlorohydrin and allyl-chloride was examined. The second population consisted of a subset (Enterline cohort) of the original Enterline cohort members for whom mortality data were available from 1981 to 1988. For both cohorts, the standarized morbidity ratios for all causes and all neoplasms were similar to an internal comparison group. No increases were noted in heart disease morbidity for the Shell cohort or the Enterline cohort. The standardized morbidity ratios for heart disease in the lower exposure group of the Shell cohort were 101 and 93 for the corresponding Enterline cohort. They were 92 and 87, respectively, in the higher exposure group. Morbidity from skin and subcutaneous tissue disorders, however, was increased significantly in the Shell cohort. The standardized morbidity ratios was 98 for the lower exposure group and 195 for the higher exposure group. A review of the original morbidity reports for each case suggested that factors unrelated to exposure to epichlorohydrin such as the physical demands of a particular job, amount of time outside, and other underlying medical conditions may be of greater importance than exposure to epichlorohydrin. [Tsai SP et al; Br J Ind Med 47 (6): 392-9 (1990)]**PEER REVIEWED**
  • EPICHLOROHYDRIN CAN AFFECT THE BODY IF IT IS INHALED, IF IT COMES IN CONTACT WITH THE EYES OR SKIN, OR IF IT IS SWALLOWED. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. ]**PEER REVIEWED**

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Non-Human Toxicity Excerpts

  • ... POISONED ANIMALS SHOW CYANOSIS, MUSCULAR RELAXATION OR PARALYSIS, TREMOR, CONVULSIONS & DEATH IN RESPIRATORY ARREST. DEATH MAY BE DELAYED AS LONG AS 2 HR EVEN AFTER PARENTERAL ADMIN ... NO CHARACTERISTIC ORGAN PATHOLOGY ... [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-168]**PEER REVIEWED**
  • Rats failed to gain weight at a normal rate when exposed at a level of 32 ppm of the vapor for 91 days on a 7 hr/day, 5 day/wk schedule, and similar exposures at 16 ppm resulted in significant increase in kidney size. Trace amt of urinary coproporphyrins were noted at this level. ... Repeated 6 hr exposures at 120 ppm caused lung, liver and kidney injury in rats. Some respiratory distress was observed at 56 ppm, mild irritation at 27 ppm, and vague adverse effects at 17 ppm after 19 exposures. No effects were noted at 9 ppm. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 233]**PEER REVIEWED**
  • DEATH IS ATTRIBUTABLE TO EFFECTS ON CNS & RESP TRACT FROM HIGH DOSAGES. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 233]**PEER REVIEWED**
  • EPICHLOROHYDRIN MANIFESTS CUMULATIVE ACTION AS A RESULT OF ITS NEPHROTOXICITY. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 233]**PEER REVIEWED**
  • MARKEDLY IRRITATING TO EYE ON LOCAL CONTACT. VAPORS OF ABOUT 100 PPM ALSO GIVE RISE TO EYE IRRITATION. ... UNDILUTED ... IS INTENSELY IRRITATING TO THE DEPILATED SKIN OF LAB ANIMALS. REPEATED APPLICATIONS LEAD TO WIDESPREAD NECROSIS. [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 418]**PEER REVIEWED**
  • OF 50 ... MICE GIVEN 1/WK SC INJECTIONS OF 1 MG EPICHLOROHYDRIN IN 0.05 ML TRICAPRYLIN ... (580 DAYS), 6 DEVELOPED LOCAL SARCOMAS & 1 HAD LOCAL ADENOCARCINOMA. ... ONE LOCAL SARCOMA ... IN 50 TRICAPRYLIN-INJECTED CONTROLS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V11 134 (1976)]**PEER REVIEWED**
  • IN 12 WK...TEST IN RATS INJECTED IP WITH EPICHLOROHYDRIN ... DOSE-RELATED DECR IN HEMOGLOBIN VALUES; WITH DOSES OF 0.056 G/KG BODY WT AN INCR IN SEGMENTED NEUTROPHILS...REDN IN PROPORTION OF LYMPHOCYTES OCCURED AT DOSES ... @ ... 0.022 & 0.056 G/KG BODY WT ... INCR LEUKOCYTE COUNT WAS OBSERVED AFTER CHRONIC EXPOSURE ... CHRONICALLY TO VAPORS ... AT ... 2 MG/CU M. THE MAXIMUM TOLERATED DOSE IN A 13 WEEK SUBACUTE STUDY IN RATS FOLLOWING ORAL ADMIN OF EPICHLOROHYDRIN WAS 45 MG/KG BODY WEIGHT/DAY. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V11 135 (1976)]**PEER REVIEWED**
  • REPEATED ORAL ADMIN OF 15 MG/KG BODY WT EPICHLOROHYDRIN PRODUCED REVERSIBLE INFERTILITY IN MALE RATS WITHIN 7 DAYS. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V11 135 (1976)]**PEER REVIEWED**
  • TEST BY APPLICATION OF A DROP TO RABBIT EYES HAS CAUSED MILD & PRESUMABLY REVERSIBLE INJURY, GRADED 4 ON A SCALE OF 1-10 AFTER 24 HR. [Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 394]**PEER REVIEWED**
  • 5 UMOLES ADMIN TO MOUSE GAVE THESE TUMORS: 3% SKIN; 10% MALIGNANT LYMPHOMAS; 3% PULMONARY ADENOMAS. /FROM TABLE/ [Searle, C. E. (ed.). Chemical Carcinogens. ACS Monograph 173. Washington, DC: American Chemical Society, 1976., p. 174]**PEER REVIEWED**
  • ... 140 /RATS/ ... EXPOSED 30 DAYS (6 HR/DAY) TO VAPOR CONCN 100 PPM & ... UNEXPOSED FOR REST OF THEIR LIFE-SPAN, @ LEAST 15 ... DEVELOPED SQUAMOUS CELL CARCINOMA OF NASAL CAVITY & 1 ... A NASAL CAVITY PAPILLOMA. IN LIFETIME STUDY ... 30 PPM (6 HR/DAY, 5 DAY/WK) 2/100 RATS HAVE DEVELOPED TUMORS ... NASAL ... & ... LARYNX ... . [Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 420]**PEER REVIEWED**
  • Epichlorohydrin (without metabolic activation) at concn of 50 mM for an hr induced reverse mutations in Salmonella typhimurium G46 and TA100 tester strains. The mutagenic activity with TA1535 tester strain was markedly reduced in the presence of liver homogenates. Epichlorohydrin produced reverse mutations in Escherichia coli and in Neurospora crassa, recessive lethal mutations in Drosophila melanogaster, and was mutagenic in Klebsiella pneumoniae. [Fishbein L; Potential Indust Carcins & Mutagens p.45 (1977) EPA 560/5-77-005]**PEER REVIEWED**
  • Doses of 50 and 100 mg/kg of epichlorohydrin after 3 hr increased the frequency of reverse mutations using Salmonella typhimurium strains G46, TA100, and TA1950 in ICR female mice in a host-mediated assay. [Fishbein L; Potential Indust Carcins & Mutagens p.46 (1977) EPA 560/5-77-005]**PEER REVIEWED**
  • Mutagenic activity (as determined with the TA 1535 strain of Salmonella typhimurium) was detected in the urine of mice after oral administration of 200-400 mg/kg epichlorohydrin. Although an initial evaluation of 2 industrial workers exposed to a concentration in excess of 25 ppm was regarded as borderline, additional mutagenic testing revealed more definitive evidence of activity, with the active compound appearing as a conjugate. [Fishbein L; Potential Indust Carcins & Mutagens p.46 (1977) EPA 560/5-77-005]**PEER REVIEWED**
  • Epichlorohydrin induced dose-dependent chromosome abnormalities in bone marrow of ICR mice injected ip to a single dose of 1-50 mg/kg or repeated doses of five times at 5-20 mg/kg, or given po in a single dose of 5-100 mg/kg or repeated doses of five times at 20 mg/kg. Epichlorohydrin did not induce any dominant lethal mutation in ICR mice when given ip in a single dose of 5-40 mg/kg, 150 mg/kg, repeated doses of five times at 1-10 mg/kg, po in a single dose of 20 or 40 mg/kg or by repeated doses at five times at 4-20 mg/kg. [Fishbein L; Potential Indust Carcins & Mutagens p.46 (1977) EPA 560/5-77-005]**PEER REVIEWED**
  • Human peripheral lymphocytes exposed to 10-5 to 10-7 M epichlorohydrin in vitro during the last 24 hr of cultivation showed chromosomal aberrations. ... The epichlorohydrin induced changes were mainly classified as chromatid and isochromatid breaks and exchanges. [Fishbein L; Potential Indust Carcins & Mutagens p.46 (1977) USEPA 560/5-77-005]**PEER REVIEWED**
  • Epichlorohydrin has: resulted in very low mutagenic activity. [De Serres FJ, Hollaender A; Chemical Mutagens Vol 5 p.31 (1978)]**PEER REVIEWED**
  • Epichlorohydrin induces reverse mutation presumably through base-pair substitution in Salmonella strains TA1535 and TA100 without addition of S-9. The urine of exposed humans and mice also gives positive results in Salmonella without further metabolic activation. [De Serres FJ, Hollaender A; Chemical Mutagens Vol 8 p.302 (1983)]**PEER REVIEWED**
  • Forward mutations are produced in Neurospora in the absence of exogenous activation. [De Serres FJ, Hollaender A; Chemical Mutagens Vol 8 p.302 (1983)]**PEER REVIEWED**
  • Primary DNA damage tests using repair-proficient and deficient bacteria show largely positive results in the presence of activation. [De Serres FJ, Hollaender A; Chemical Mutagens Vol 8 p.302 (1983)]**PEER REVIEWED**
  • The 14 day LC50 value of epichlorohydrin to the guppy (Poecilia reticulata) was determined. These data were investigated through the construction of a quantitative structure-activity relationship (QSAR). Both hydrophobicity and alkylating potency of the compound were found to be necessary parameters for the satisfactory description of the LC50 data. The log LC50 experimental data for epichlorohydrin was 0.85 umol/l as compared to the calculated QSAR value of 1.08 umol/l. [Deneer JW et al; Aquatic Toxicol 13 (3): 195-204 (1988)]**PEER REVIEWED**
  • The Drosophila wing somatic mutation and recombination test was applied to a series of chemicals to determine its suitability in genotoxicity screening. Epichlorohydrin was weakly positive in the sex linked recessive lethal test, but only after injection. Inhalation testing of 3 day old larvae for 1 hour showed inconclusive results for the lowest exposure (1 ul liquid injected into 1150 ml air), positive for small and large single spots and inconclusive for twin spots at the intermediate exposure (2 ul), and positive for all three mutations at the highest exposure (4 ul). [Graf U et al; Mutat Res 222 (4): 359-73 (1989)]**PEER REVIEWED**
  • A study was conducted using a combined testing protocol, to determine whether short-term biological end-points, singly or in combination, are sufficiently sensitive to identify damage induced by exposure to ambient levels of industrial chemicals. A small-scale inhalation set-up which is both economical and easy to assemble was designed. Mice were exposed to 4 concentratons of a custom-blend mixture of benzene, chloroprene, epichlorohydrin and xylene in a ratio of 2:2:1:2, respectively. The concentrations for benzene, chloroprene and xylene 0, 0.1, 1.0 and 10 ppm each. Concentrations for epichlorohydrin were half those for the other components. Groups of 22 males and 22 female mice were exposed to each concentration of the mixture for 3 and 6 weeks. Selected biological end-points including urine mutagenesis, bone marrow cell aberrations and micronuclei, spleen lymphocyte aberrations and liver and enzyme induction were monitored. The spleen lymphocyte aberrations and liver and enzyme induction were the most sensitive end-points. The lymphocytes showed a significant induction of chromosome aberrations from exposure for 3 weeks to all 3 concentrations of the mixtures. After 6 weeks of exposure, significant induction of aberrations was observed after exposure to low and medium concentrations but not to the high concentration. This lack of response at the high concentration after 6 weeks exposure, appeared to correlate with a significant induction of glutathione S-transferase in the liver. Since this enzyme is known to detoxify 3 of the 4 chemicals in our mixture, it may indicate a detoxification mechanism after enzyme induction. The present study indicates that the combined testing protocol is sufficiently sensitive to identify toxicological effects after exposure to ambient levels of a gas mixture. [Au WW et al; Mutat Res 203 (2): 103-15 (1988)]**PEER REVIEWED**
  • A multiple end-point approach to assessing genetic toxicity (the combined testing protocol) was evaluated in male and female CD-1 mice exposed subacutely (3 and 6 weeks) to low levels of a custom blended gas mixture (epichorohydrin, benzene, chloroprene and xylene, at 50, 100, 100, and 100 ppb, respectively, as the low dose, with concentration levels 10 fold and 100 fold higher as the intermediate and high doses, or 0.1, 1 and 10 ppm of benzene). Urine mutagenicity was tested in the Salmonella/microsome assay, chromosome aberrations were examined in bone marrow and spleen lymphocytes, micronuclei were measure in bone marrow and peripheral erythrocytes, and cytochrome p450 and glutathione S-transferases were measured in the liver. Structural aberrations in alveolar macrophages and speratocytes, and thioguanine resistance in spleen lymphocytes were examined for their suitability for incorporation into the overall protocol. Spleen lymphocytes were the most sensitive indicator cells, and showed a dose-related increase (P< 0.01) in structural chromosome aberrations and in cytotoxicity after 6 weeks of exposure. Analysis of micronucleus formation and metaphase aberrations in the bone marrow, and icronucleus in peripheral erythrocytes showed an overall statistically non-significant but positive trend at the high dose. No mutagenicity was detected in pooled urine samples. Liver microsomal cytochrome p450 was not increased, but cytosolic glutathione S-transferases were significantly increased in a dose-related manner. Since the probability of detecting a genotoxic effect increases with the number of endpoints and tissues examined, this approach should be applicable to many situations without having to perform separate experiments for each tissue examined. [Harper BL et al; J Appl Toxicol 9 (2): 97-102 (1989)]**PEER REVIEWED**
  • The use of cytogenetic assays in genotoxic investigations was discussed and in vivo cytogenetic investigations conducted in mice and rats were reviewed. An inhalation investigation of the effects of a 1:1:0.5:1 mixture of benzene, chloroprene, epichlorohydrin, and xylene in CD-1 mice at concentrations up to 10 ppm, using induction of chromosome aberrations in splenic lymphocytes as the endpoint, revealed that low and medium doses increased the frequency of chromosome aberrations, whereas high doses decreased it. [Au WW et al; Teratogenesis, Carcinogenesis, & Mutagenesis 10 (2): 125-34 (1990)]**PEER REVIEWED**
  • The genotoxicity of monofunctional alkylating agents and their carcinogenicity potency in rodents were examined. Epichlorohydrin, was one several compounds which was tested for its genotoxic potential in a specially designed Escherichia coli assay system (Escherichia coli multitest). The multitest consisted of a set of Escherichia coli mutants created by fusing the cI and cro region and gal operon of two strains, MT103 and MT119. The endpoints were increases in mutation and recombination frequency and RecA-dependent protease activity (SOS induction). Increases in mutation and recombination frequency and numbers of SOS induction colonies induced by the alkylating agents were compared with previously published data obtained in carcinogenesis studies in rats. When analyzed separately, increases in mutant and recombinant frequencies and SOS induction colonies induced by the compounds did not correlate well with their carcinogenic potencies. When product of the mutant and recombinant frequencies were analyzed, it correlated well the in vivo carcinogenic potencies, correlation coefficient 0.95. Escherichia coli multitest is a rapid, simple test for assessing the correlation between carcinogenicity and genotoxicity of DNA damaging agents. [Quinto I et al; Mutat Res 228 (2): 177-85 (1990)]**PEER REVIEWED**
  • Measurements were taken of fertility rates, litter sizes, and pup weights during development for female Long-Evans hooded rats exposed to epichlorohydrin prior to ovulation through fertilization and gestation. Epichlorohydrin treatment prior to fertilization and gestation was initiated for the purpose of studying possible effects on the hormonal regulation of the estrous cycle and to study changes in copulatory behavior as a manifestation of an adverse effect on the central nervus system. Male rats were dosed with 12.5, 25, or 50 mg/kg/day orally for 21 days. Females were treated similarly with 25, 50, or 100 mg/kg/day. The animals were paired with untreated mates. Fertility at the high dose male group was totally impaired. Female reproduction was unchanged. Treated males showed normal copulatory behavior. No statistical differences were noted for either sperm morphology or percentage motile sperm in both ejaculated and cauda epididymal samples from treated males. At the 50 mg/kg dose level, the number of sperm in ejaculates was normal while cauda epididymal sperm count was slightly decreased. At 12.5 mg/kg/day dose levels and above the man curvilinear velocity, straight line velocity, and amplitude of lateral head displacement or cauda epididymal sperm were significantly reduced. A reduction was also noted in sperm track linearity, but only at the 50 mg/kg/day dose level. A significant increase was noted in beat/cross frequency of sperm at 12.5 mg/kg/day and above. Dose dependent trends were noted in all of the above sperm motion parameters. [Toth GP et al; Fund and Appl Toxicol 13 (1): 16-25 (1989)]**PEER REVIEWED**
  • Trichloroethylene is a high production volume chemical frequently stabilized with oxiranes. These oxiranes may be responsible for the mutagenic activity of trichloroethylene in Salmonella, which has been occasionally, but not consistently, reported. High purity and oxirane-stabilized trichloroethylene samples were tested for their mutagenic potential in Slmonella typhimurium strains TA 1535, TA 98, and TA 100. Stabilized trichloroethylene was tested using a preincubation protocol up to a dose level of 10,000 ug per plate, but no mutagenic response was observed in either the presence or absence of a supplementary metabolic activation system (S9 mix) derived from Aroclor 1254-induced male rat liver. Trichloroethylene without oxirane stabiliers also was nonmutagenic when tested in a vapor delivery system at nominal concentrations of up to 20% and using S9 mix derived from either rat or hamster. Trichloroethylene containing 0.5-0.6% 1,2-epoxybutane did induce mutagenic responses from strains TA 1535 and TA 100 in the presence and absence of S9 mix. The lowest effective dose was about 0.63% in TA 1535 in the absence of S9 mix. Vapor-phase tests with 1,2-epoxybutane showed that an atmospheric concentration of 0.009% could induce 12-fold and 3-fold increases, respectively, in strains TA 1535 and TA 100. These increases would account for the mutagenic activity of the stabilized trichloroethylene sample. Epichlorohydrin (another commonly used stabilizer) induced similar increases in mutant numbers at an atmospheric concentration of 0.0009%. The absence of a significant response caused by unstabilized trichloroethylene in the presence of S9 mix is probably due to a lack of assay sensitivity, since chloral, a metabolite of trichloroethylene, is a mutagen in TA 100. [McGregor DB et al; Environ Mol Mutagen 13 (3): 197-202 (1989)]**PEER REVIEWED**
  • Deuterated and non-deuterated N-nitrosodimethylamine, epichlorohydrin and dimethyl sulfate were evaluated for the ability to iduce DNA single-strand breaks in rat hepatocytes as measured by alkaline elution. Non-deuterated nitrosodimethylamine induced twice the amount of DNA-strand breaks as the deuterated form. No evidence of a deuterium isotone effect was seen for the direct-acting alkylating agents epichlorohydrin and dimethyl sulfate. [Sargent EV et al; Mutat Res 263 (1): 9-12 (1991)]**PEER REVIEWED**
  • The effect of inhaled epichlorohydrin on rat sperm motility characteristics was evaluated. Male F-344 rats were exposed to 100 ppm epichlorohydrin via inhalation for 4 hrs on the morning of day 0 and killed immediately and on day 1, 2, 6 and 14 postexposure. Videotapes of cauda epididymal sperm were analyzed (300-350 sperm/sample) with a Hamilton Thorn Motility Analyzer. Epichlorohydrin did not affect the percentage of motile sperm at any time. However, transient changes in sperm velocity were found. On day 1 postexposure mean progressive (straight-line) and mean path (smoothed curvilinear) velocity were significantly decreased to 80% and 85% of control, respectively. The progressive velocities of sperm from both control and treated rats were normally distributed, indicating a general effect of epichlorohydrin on all sperm as opposed to a more severe effect on a spsecific sperm subpopulation. Both velocities remained slightly but significantly decreased on day 2 (92% and 93% of control for progressive and path velocity, respectively), and were unaffected at later timepoints. Other endpoints (testis and epididymis weights, testicular spermatid counts adn cauda epididymal sperm reserves) were unaltered by epichlorohydrin. Thus, inhaled epichlorohydrin produced specific, transient decreases in rat sperm velocity. [Slott VL et al; Govt Reports Announcements & Index (GRA&I) Issue 9, NTIS/PB91-149732 (1991)]**PEER REVIEWED**
  • There is evidence that epichlorohydrin may have adverse reproductive effects in animals, including testicular damage, estrous-cycle changes, intrauterine growth retardation, intrauterine death, congenital malformation, and alterations in postnatal development. [Marzulli, F.N., H.I. Maibach. Dermatotoxicology 4th ed. New York, NY: Hemisphere Publishing Corp., 1991., p. 706]**PEER REVIEWED**

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Human Toxicity Values

  • None found

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Non-Human Toxicity Values

  • LD50 Guinea pig intraperitoneal 118 mg/kg [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 612]**PEER REVIEWED**
  • LD50 Guinea pig oral 0.178 g/kg [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 612]**PEER REVIEWED**
  • LD50 Rat oral 0.04 g/kg [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 612]**PEER REVIEWED**
  • LD50 Mouse oral 0.238 g/kg [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 612]**PEER REVIEWED**
  • LC50 Rat inhalation 250 ppm/8 hr [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 613]**PEER REVIEWED**
  • LC50 Rat inhalation 500 ppm/4 hr [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 613]**PEER REVIEWED**
  • LC50 Rabbit inhalation 445 ppm/4 hr [Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983., p. 613]**PEER REVIEWED**
  • LD50 Rabbit skin 300 mg/kg [ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 208]**PEER REVIEWED**
  • LD50 Rat oral 90 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Rat ip 133 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Rat sc 150 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Rat iv 154 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Mouse oral 195 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Mouse skin 250 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Rabbit oral 345 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Rabbit skin 515 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Rabbit ip 118 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Guinea pig oral 280 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**
  • LD50 Guinea pig ip 118 mg/kg [Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1470]**PEER REVIEWED**

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Absorption, Distribution and Excretion

  • RATS SHOWED RAPID ABSORPTION FROM GI TRACT WITH PEAK TISSUE LEVELS @ 2 HR IN MALES & 4 HR IN FEMALES. KIDNEYS, LIVER, PANCREAS, ADRENALS, & SPLEEN CONTAINED HIGHEST AMT. [WEIGEL, WW ET AL, RES COMMUN CHEM PATHOL PHARMACOL 20 (2): 275 (1978)]**PEER REVIEWED**
  • WITH EXCEPTION OF PANCREAS, A CORRELATION OBSERVED BETWEEN TISSUE DISTRIBUTION & TARGET ORGAN TOXICITY. EXCRETION MAINLY IN URINE. 21 & 18% OF DOSE EXCRETED AS CO2 IN MALE & FEMALE RATS. PEAK TISSUE LEVELS IN FEMALES LOWER. [WEIGEL WW ET AL, RES COMMUN CHEM PATHOL PHARMACOL 20 (2): 275 (1978)]**PEER REVIEWED**
  • EPICHLOROHYDRIN MAY BE: ABSORBED THROUGH THE SKIN. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. ]**PEER REVIEWED**
  • The absorption of chemical vapors by the upper respiratory tract was studied in rats. The upper respiratory tarcts of male Fischer F344 rats were surgically isolated and connected to a specially designed flow system. The tracheal connection of the upper respiratory tract and the lower respiratory tract was interrupted. The upper respiratory tract was exposed to propylene-glycol- monomethyl ether, propylene glycol monomethyl ether acetate, epichlorohydrin, cmpd which include vapors while the rat spontaneously breathed from a stream of air. Intact rats were exposed nose only to the same compound and the percentages of vapor absorbed were determined for comparison purposes. Attempts were made to correlate the results with the water solubility of the compounds. The data were compared to predictions of two compartment mathematical models. More than 50 to 70% of the epichlorohydrin, vapors passing through the isolated upper respiratory tacts were absorbed. With the exception of styrene and methylene chloride, the percentage of vapors absorbed by the upper respiratory tract approximated that observed in the lower respiratory tract and nose only exposed animals. There was no correlation between absorption in the URT and water solubility. The mathematical models generally predicted the absorption of vapors by the lower respiratory tract and intact animals accurately. The models seriously underestimated absorption of epichlorohydrin, by the upper respiratory tract. /Results indicate/ that blood air partitioning can account for absorption of chemicals by the upper respiratory tract, but only if other metabolic and physiological parameters are considered. [Stott Wt et al; Toxicology of the Nasal Passages p.191-210 (1986)]**PEER REVIEWED**

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Metabolism/Metabolites

  • ... WISTAR RATS DOSED ORALLY OR IP WITH ... EPICHLOROHYDRIN YIELD ... URINARY METABOLITES ... 2,3-DIHYDROXYPROPYL-S-CYSTEINE & ITS N-ACETATE. SINCE EPICHLOROHYDRIN IS A STRONG ELECTROPHILE THAT IS CAPABLE OF REACTING WITH CELLULAR NUCLEOPHILES, IT IS PROBABLE THAT SOME EPICHLOROHYDRIN METABOLITES ARE ALSO COVALENTLY BOUND TO VARIOUS TISSUE MACROMOLECULES. [National Research Council. Drinking Water and Health. Volume 3. Washington, DC: National Academy Press, 1980., p. 113]**PEER REVIEWED**
  • Rats given oral (14)C labeled epichlorhydrin and sacrificed after 3 days: 38% exhaled as carbon dioxide; 50% excreted as metabolites in urine; 3% excreted in the feces; and the remainder was found in the tissues - liver, kidney, and forestomach. [Gingell R etal; Drug Metb Dispos 13 (3): 333-41 (1985)]**PEER REVIEWED**
  • The major urinary metabolite of (14)C-epichlorohydrin, after oral administration to rats, was identified previously to be N-acetyl-S-(3-chloro-2-hydroxypropyl)-L-cysteine at 36% of the administered dose. In a similar study reported here, 1,2-dibromo-3- chloropropane was metabolized to at least 20 radioactive urinary metabolites. N-acetyl-S-(3-chloro-2-hydroxypropyl)-L-cysteine was only a minor metabolite (4%) of 1,2-dibromo-3-chloropropane. Epichlorohydrin was metabolized in vitro by rat liver microsomes to alpha-chlorohydrin, but 1,2-dibromo-3-chloroproane was not metabolized to epichlorohydrin or alpha-chlorohydrin under similar conditions. Covalent binding of radioactivity to liver microsomal proteins occurred for both substrates, but was less for (14)C-epichlorohydrin than for (14)C-1,2-dibromo-3-chloropropane. Addition of 3,3,3-trichloropropylene oxide, an inhibitor of epoxide hydrolase, increased the extent of protein binding of epichlorohydrin, but decreased the amojnt of (14)C-1,2-dibromo-3-chloropropane which was bound. The data indicate the epichlorohydrin is not a significant in vivo nor in vitro metabolite of 1,2-dibromo-3-chloropropane in the rat, and is unlikely to be responsible for the toxicity of 1,2-dibromo-3-chloropropane. [Gingell R et al; Xenobiotica 17 (2): 229-40 (1987)]**PEER REVIEWED**

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TSCA Test Submissions

  • The effects of acute oral exposure to epichlorohydrin (ECH) by gavage in male Wistar rats (20 in control group (water), 5/treated group, number of treated groups not reported) were determined. ECH (single doses of 0, 25 and 50 mg/kg) was administered and the rats were necropsied on the 11th day following dosing. There were differences between treated and control animals in the following: increase in incidence of abnormal sperm (high-dose level group), and decreased total sperm head counts (low-dose group). There were no significant differences between treated and control animals in the following: clinical observations, histopathology of the testes, and testes weights.[Shell Oil Co.; The Effects of Acute Exposure of Dimethoxyethyl Phthalate, Glycerol Alpha-monochlorohydrin, Epichlorohydrin, Formaldehyde and Methylmethanesulfonate Upon Testicular Sperm in the Rat. (1982), EPA Document No. 878210077, Fiche No. OTS0206200 ]**UNREVIEWED**
  • The effects of exposure to epichlorohydrin by inhalation on the fertility of male New Zealand white rabbits (10/group) exposed at nominal concentrations of 0, 5, 25 or 50 ppm for 6 hrs/day, 5 days/week for 10 weeks and held for a recovery period of 10 weeks were evaluated. Semen from male rabbits was examined during the exposure and recovery periods. The exposed male rabbits were mated with unexposed females. There were significant differences observed between treated and control F0 males in the following: excessive nasal exudation (50 ppm group), decreased body weight and weight gain (50 ppm), numbers of non-motile sperm (increased in 25 ppm males at 10th week of exposure), low sperm motility (decreased at 25 pm during 18th week, increased at 25 and 50 ppm during 16th week (recovery period)), increased pre-implantation losses (50 and 5 ppm groups), decreased absolute brain weight, nasal turbinate inflammation (50 and 25 ppm, at 10th week interim sacrifice), and increased rhinitis and sinusitis (50 and 25 ppm group, final sacrifice). One male in each treatment group died prematurely with observed pathology including suppurative rhinitis (50 and 5 ppm), a pulmonary abscess extensively filling the thoracic cavity (25 ppm), or external otitis and mucoid enteritis (5 ppm). There were no significant differences observed between treated and control males in the following: sperm concentration or volume per ejaculate, viability or number of live sperm, percentages of intact sperm, average number of implantations, corpora lutea in non-exposed females mated with exposed males, fertility index, hematology or clinical chemistry values, relative or absolute weights of heart, liver, kidney, testes or epididymides, final sacrifice relative or absolute organ weights,[Dow Chemical USA; The Effects of Inhaled Epichlorohydrin on the Semen of Rabbits and on the Fertility of Male and Female Rats. (1979), EPA Document No. 878210082, Fiche No. OTS0206200 ]**UNREVIEWED**
  • The effects of exposure to epichlorohydrin by inhalation on the fertility of male and female Sprague Dawley rats (30/sex/group) exposed at nominal concentrations of 0, 5, 25 or 50 ppm for 6 hrs/day, 5 days/week for 10 weeks and held for a recovery period of 10 weeks were evaluated. The male rats were mated with unexposed females and the exposed females were mated with unexposed males. There were significant differences observed between treated and control F0 animals in the following: decreased body weight and weight gain (50 ppm females and males), increased white blood counts (all exposed rats), decreased red blood cell count (males at 50 ppm), and at interim sacrifice (10th week), increased relative and absolute weight of kidney and degenerative change in nasal turbinates (both sexes at 50 ppm and 25 and 50 ppm, respectively). There were significant differences observed in the following exposed male reproductive parameters: marked decreased in number of fertile males (50 ppm group, all 4 exposure mating periods; recovery of fertility was observed as early as 1st recovery mating in 2nd week of recovery), decreased number of implantations in unexposed females (mated to 25 and 50 ppm males during exposure period), decreased number of corpora lutea (exposure period, all matings at 50 ppm, 2nd mating at 25 ppm), decreased number of resorptions (1st recovery mating at 50 ppm), increase in preimplantation losses (exposure matings at 25 and 50 ppm, recovery mating at 50 ppm), and resorption rate (50 ppm, increased for last exposure mating and decreased for 1st recovery mating). There were no significant differences observed in the following exposed female reproductive parameters: percentage of impregnated females, length of gestation period, litter size or survivability and sex ratio of neonates. There were no significant differences observed between treated and control animals in the following: maternal or paternal mortality, final sacrifice relative or absolute organ weights, and final sacrifice histopathology.[Dow Chemical USA; The Effects of Inhaled Epichlorohydrin on the Semen of Rabbits and on the Fertility of Male and Female Rats. (1979), EPA Document No. 878210082, Fiche No. OTS0206200 ]**UNREVIEWED**
  • Teratogenicity was evaluated in pregnant female Sprague Dawley rats (43-46/group) exposed by inhalation to epichlorohydrin at nominal concentrations of 0, 2.5 or 25 ppm for 7 hrs/day during gestation days (GD) 6-15. There were significant differences observed between treated and control animals in the following: decreased maternal body weights and food consumption (25 ppm group). There were no significant differences observed between treated and control animals in the following: absolute or relative liver weight, gravid uterus weights, maternal survival, percentage of pregnant dams, number of implantation sites/dam, live fetuses/litter, fetal sex ratio, fetal body measurements, number of resorptions, total or particular external and soft tissue alterations, or skeletal variations.[Dow Chemical USA; Epichlorohydrin - Subchronic Studies, IV. The Effects of Maternally Inhaled Epichlorohydrin on Rat and Rabbit Embryonal and Fetal Development. (1979), EPA Document No. FYI-AX-0280-0061, Fiche No. 0000061-0 ]**UNREVIEWED**
  • Teratogenicity was evaluated in pregnant female New Zealand white rabbits (20/treated group, 25/control group) exposed by inhalation to epichlorohydrin at nominal concentrations of 0, 2.5 or 25 ppm for 7 hrs/day during gestation days (GD) 6-18. There were significant differences observed between treated and control animals in the following: decreased incidence of foramen of the skull and incidence of extra ribs in fetuses (25 ppm group). There were no significant differences observed between treated and control animals in the following: maternal body weights, weight gain, absolute or relative liver weights, gravid uterus weights, maternal survival, percentage of pregnant dams, number of implantation sites/dam, live fetuses/litter, fetal sex ratio, fetal body measurements, number of resorptions, or total or particular external and soft tissue alterations.[Dow Chemical USA; Epichlorohydrin - Subchronic Studies, IV. The Effects of Maternally Inhaled Epichlorohydrin on Rat and Rabbit Embryonal and Fetal Development. (1979), EPA Document No. FYI-AX-0280-0061, Fiche No. 0000061-0 ]**UNREVIEWED**
  • The ability of epichlorohydrin to cause chromosome aberrations was evaluated in the bone marrow cells of male and female Fischer 344 rats (10/sex/group) exposed by inhalation to epichlorohydrin at concentrations of 0, 5, 25 or 50 ppm for the males and 0 or 50 ppm for the females for 6 hrs/day, 5 days/week for 4 weeks. The rats were sacrificed on the day following the last exposure and 200 cells/animal were scored for chromosome aberrations. The frequency of aberrations found in all groups was quite low. Male rats exposed to 25 and 50 ppm exhibited a doubling of the frequency over the controls (0.3% to 0.15%), but there was no consistent dose-response effect observed. Statistical analysis by Fischer's exact test indicated the differences in the males was not significant. There were no differences observed between treated and control females with respect to the frequency of chromosome aberrations in bone marrow cells.[Dow Chemical U.S.A.; III. Cytogenic Evaluation of Bone Marrow Cells From Rats Exposed by Inhalation to Epichlorohydrin for Four Weeks. (1979), EPA Document No. 878210084, Fiche No. OTS0206200 ]**UNREVIEWED**
  • The mutagenicity of epichlorohydrin was evaluated in Salmonella tester strains TA98, TA100, TA1535 and TA1537 (Ames Test), both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on the results of preliminary bacterial toxicity determinations, epichlorohydrin, diluted with DMSO, was tested for mutagenicity at concentrations of 0.001, 0.01, 0.1, 1.0, and 5.0 micromoles/plate using the plate incorporation method. Epichlorohydrin caused a reproducible positive response at 1.0 and 5.0 micromoles/plate in tester strains TA1535 and TA100, both in the presence and absence of metabolic activation, and at 5.0 micromoles/plate in tester strain TA98 in the absence of activation.[Rohm and Haas Co.; Epichlorohydrin Microbial Mutagen Test. (1978), EPA Document No. 878212036, Fiche No. OTS0205978 ]**UNREVIEWED**
  • The fate of 2-14C-epichlorohydrin (ECH) was studied in five male Fischer 344 rats exposed by gavage to an aqueous solution of ECH (approximately 6 mg/kg, 25 uCi/animal). Urine, feces and exhaled air were monitored for radioactivity. The animals were sacrificed 3 days after dosing and selected tissues were analyzed for radioactivity. Within 3 days, 50% of the administered radioactivity was recovered in the urine, 3% in the feces, and 38% as exhaled CO2. Total radioactivity recovered in the muscle (4.83% of dose), liver (2.82%), kidney (0.41%), and fatty tissue (0.47%). Activity (as radioactivity/g of tissue) was high in liver, kidney, and forestomach, but was below blood levels in other tissues. Unextractable radioactivity was highest in the kidney, while the level in the testis was approximately the same as that in the blood.[Shell Westhollow Research Center; Biochemistry of Three-Carbon Halogenated Compounds: Disposition of (2-14C)- Epichlorohydrin After Oral Administration to Rats. (1982), EPA Document No. 878210087, Fiche No. OTS0206200 ]**UNREVIEWED**
  • The fate of 1,3-14C-epichlorohydrin (1,3-14C-Epi) was studied using male Fischer 344 rats exposed either by inhalation in a head-only chamber to nominal doses of 1 (3 rats) or 100 ppm (4 rats) for 6 hrs or by gavage to a single dose of 1 or 100 mg/kg. The rats were immediately transferred to Roth-type glass metabolism cages following exposure, and samples of plasma, urine, feces, and expired air were collected at 8 hr intervals for 72 hrs. By 72 hrs, 79-89% of the dose had been recovered from urine (46-54%) and as 14CO2 in expired breath (25-42%) regardless of the dose level or route. At 72 hrs, 1-4% of the dose was found in the skin and 4-5% in the carcass. Very little of the excreted 14C was parent Epi. Urinary metabolites showed 9 peaks (gavage) and 8 peaks (inhalation) by ion-exclusion chromatography. Separate experiments in which rats were exposed by gavage to 100 mg 3-14C-Epi indicate that if any C-C bond is broken the molecule is metabolized completely to CO2. A 4 to 5 times greater concentration was seen in the target organ for toxicity (nasal turbinates) than in the lung immediately following inhalation. Similar results were not observed at any time after oral exposure.[Dow Chemical USA; Pharmacokinetics of Epichlorohydrin (EPI) Administered to Rats by Gavage or Inhalation. (1979), EPA Document No. FYI-AX-0185-0022, Fiche No. OTS0000022-1 ]**UNREVIEWED**

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Footnotes

1 Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.

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Web page last updated on May 14, 2008