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Key value for chemical safety assessment

Effects on fertility

Description of key information
No data
Effect on fertility: via oral route
Dose descriptor:
LOAEL
3.3 mg/kg bw/day
Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
19 mg/m³
Additional information

Twenty-four male and female rats per group were given epichlorohydrin by gavage at 0, 3.3, 10, and 30 mg/kg/day. Males were dosed for 10 weeks prior to and during mating. Females were dosed from 2 weeks before mating to day 21 of lactation. At 30 mg/kg, an increase in the incidence of clinical signs (i.e., nasal discharge, soft feces, depression, and piloerection), gross necropsy findings (i.e., cystic pustule of the epididymidis and enlargement of the kidney) and the weights of heart, liver, and epididymidis, a decrease in male fertility, and an increased incidence of histopathological changes of the testis, epididymidis, and kidney were observed. At 10 mg/kg, decreased male fertility and increased kidney weight and incidence of histopathological changes of the epididymidis were found. There was a slight, but nonsignificant, reduction in the male fertility index at the dose of 3.3 mg/ kg. Under these experimental conditions, the lowest-observed-adverse-effect level of epichlorohydrin was 3.3 mg/kg/day for parent animals and their offspring. The absolute toxic dose for parent animals and their offspring was estimated to be 10 mg/kg/day.

The effects of inhaled epichlorohydrin (ECH) on the fertility of Sprague-Dawley rats were studied. Groups of 30 male rats and 30 female rats were exposed to 0, 5, 25, or 50 pprn of ECH vapor for 6 hr/day, 5 days/week for 10 weeks, and were held for a 10-week postexposure period. Exposed male rats were mated with unexposed females at several intervals during and after the exposure period. In addition, female rats which had been exposed for the 10-week period were mated with unexposed males and allowed to deliver their young. Exposure to 50 pprn of ECH vapor for 10 weeks resulted in transient infertility in the male Sprague-Dawley rats; recovery of fertility in rats occurred during the second week after termination of exposure. Male rats exposed to 25 pprn of ECH were able to impregnate unexposed females; however, fewer implantations were observed in these females than in the females mated to control males suggesting that fertility was adversely affected in this group as well. This effect also was reversed by the second week following termination of exposure. The incidence of resorptions in the unexposed female rats which were bred to the exposed males was not adversely affected. Among female rats exposed to ECH, no adverse effects were observed on estrus cycle, pregnancy rate, parturition, or the number and viability of the offspring. Histologic examination of tissues from an interim and final termination of the exposed animals indicated that the most severely affected organ following inhalation exposure to 25 or 50 pprn of epichlorohydrin in both rats was the nasal turbinates. These lesions, interpreted to be a result of irritation from the test material, were no longer present in animals which were held for the 10-week postexposure period. No adverse effects were observed among rats exposed to 5 pprn of ECH for 10 weeks.


Short description of key information:
Studies on male and female fertility have been conducted by the oral and inhalation route.

Effects on developmental toxicity

Description of key information
Developmental toxicity studies have been conducted by the inhalation route in rats and rabbits.
Effect on developmental toxicity: via inhalation route
Dose descriptor:
NOAEC
94.2 mg/m³
Additional information

Pregnant Sprague-Dawley rats were exposed to vapors of epichlorohydrin (ECH) at concentrations of 0, 2.5 or 25 pprn. Exposures were for 7 hr/day on days 6 through 15 (rats) of gestation. Maternal effects including decreased body weight and food consumption were observed among rats inhaling 25 pprn of ECH. No evidence of an adverse effect to the embryo or fetus was observed among rats following exposure to ECH. Thus, ECH was not teratogenic or embryolethal in rats following inhalation exposure to concentrations which induced effects in the maternal animals.

Toxicity to reproduction: other studies

Additional information

No data

Justification for classification or non-classification

Administration of the substance caused a reduction in male fertility, reversible when the observation period was extended post-dosing. Therefore, the substance is classified as Category 2 reproductive toxicant according to GHS.