Abstract |
Chloroform (CAS No. 67-66-3) was evaluated for clastogenicity in Chinese Hamsters (5/sex/treatment group) exposed by oral gavage to doses of 0 (solvent control), 40, 120, and 400 mg/kg bw with subsequent harvest, preparation and analysis of metaphase bone marrow cells (100 cells/animal) at 6 (high dose), 24 (all doses), and 48 (high dose) hours post-treatment. Hamsters of 400 mg/kg doses exhibited signs of toxicity including hypoactivity, closed eyes, and arrested food consumption. Slight enhancement of chromosomal aberrations was statistically significant (Mann-Whitney-U-test) 6 and 24 hours after doses of 400 mg/kg, although the rate was still within the range of historical negative controls. Further, outside the range of historical controls, no dose-response relationship was demonstrated. The study authors noted an inference of chloroform mutagenicity, however, based on the nature of marked damage (multiple aberrations, chromosomal disintegration, and exchanges) associated with oral chloroform at doses of 120 and 400 mg/kg (6-, 24-, and 48-hour assessments). In repeat study, exposing groups of hamsters to doses of 0 (solvent control), 120, and 400 mg/kg bw, 24-hour cytogenetic assay again revealed a slight but statistically significant increase in chromosome aberrations in association with 400 mg/kg doses, failing again to demonstrate a dose-response relationship for rates of damage (chromosome breaks) beyond the range of historical controls. Distinctly heavy damage (multiple aberrations and exchanges) characterized the chloroform-induced aberrations at 400 mg/kg in 6/6000 metaphase bone marrow cells. |