2-chloroethanol

Carcinogenicity

Description of key information

See discussion section.

Justification for classification or non-classification

Under the conditions of 2-year dermal studies performed by NTP (TR 275, 1985), there was no evidence of carcinogenicity of 2 - chloroethanol for male and female F344/N rats given 50 or 100 mg/kg per day or for male and female Swiss CD-1 mice given 7.5 or 15 mg per animal per day.

Additional information

In NTP TR 275 a summary is given of the carcinogenicity studies in mice and rats on page 10:

"Toxicology and carcinogenesis studies of 2-chloroethanol (99% pure), an industrial chemical and an intermediate in the synthesis of ethylene oxide, were conducted by dermal application of 2chloroethanol dissolved in 70% ethanol:30% water (v/v) solutions to groups of 50 F344/N rats of each sex at

doses of 0, 50, or 100 mg/kg for 103 weeks or to groups of 50 Swiss CD-1 mice of each sex at doses of 0, 7.5, or 15 mg per animal for 104 weeks (0, 253, or 630 mg/kg at week 1; 0, 180, or 411 mg/kg at week 100). The control groups received skin applications of the vehicle; the mouse studies also included untreated control groups of 50 males and 50 females.

2-Chloroethanol solutions were applied to the clipped interscapular area of the animals once daily, 5 days per week for the test period. Rats received a volume of 0.18-0.22 ml of solution; mice received 0.10 ml of solution. In the 13-week studies, mortality was observed in male and female rats receiving 250 mgkg per day and higher and in male and female mice receiving 20 mg per day and higher. In the 104-week studies, the survival and body weights of dosed rats were unaffected by 2-chloroethanol. The survival of high dose male mice was lower (P < 0.05) than that of the vehicle controls (vehicle control, 26/50; 7.5 mg, 16/50; 15 mg, 12/50). Body weights of dosed mice were unaffected by 2-chloroethanol. The survival and body weight gain data suggest that the male and female rats and female mice could have tolerated a higher dose of 2-chloroethanol. Male mice probably could not have tolerated a higher dose than was applied to the skin. Seven high dose male mice died within 3 days of the start of dosing; all of these had inflammation at the site of dermal application. Five also had ulceration at the site of dermal application, and five had lung congestion, inflammation, or hemorrhage.

Marginal increases were found in the incidence of lymphomas or leukemias (combined) as well as in the incidence of alveolar/bronchiolar adenomas or carcinomas (combined) in low dose male mice. Since there was no dose-related trend for these tumor incidences and because the increases were observed in only one sex, the increases were not considered to be related to the dermal application of 2 - chloroethanol.

2-Chloroethanol was mutagenic in Salmonella typhimurium strains TAlOO and TA1535 (but not TA1537 or TA98) in either the presence or the absence of Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver S9. 2-Chloroethanol did not induce sex-linked recessive lethal mutations in Drosophila melanogaster.

An audit of the experimental data was conducted for these 2-year studies. No data discrepancies were found that influenced the final interpretations.

Under the conditions of these 2-year dermal studies, there was no evidence of carcinogenicity of 2 - chloroethanol for male and female F344/N rats given 50 or 100 mg/kg per day or for male and female Swiss CD-1 mice given 7.5 or 15 mg per animal per day."