Occurrence of toxicity and cell proliferation after a single gavage administration of chloroform to male F344 rats.
Chloroform, an industrial solvent and one of the most common environmental contaminants which produces carcinogenic effects in the liver and kidney of rodents, is not genotoxic in most traditional bacterial and mammalian test systems. Its carcinogenic potential appears attributable to the sustained cell turnover (regenerative hyperplasia) which results from chronic chloroform toxicity. In this present study, cell proliferation (replicative DNA synthesis, RDS) and histopathological changes in hepatocytes and renal tubular epithelial cells were assessed in male F344 rats following a single gavage chloroform exposure (50, 150 or 500 mg/kg). In addition, biochemical parameters (BUN, GOT, LDH and NAG) were examined using plasma and urine samples. Cell proliferation and histopathological changes (e.g. hypertrophy, necrosis, vacuolation) were only seen at the dose of 500 mg/kg in the liver and kidney. At the same dose, all biochemical markers were increased at the 24 to 48 hr time points. These results obtained are thus in line with earlier findings pointing to epigenetic carcinogenicity.
Miyagawa
M
M
Kashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., Ibaraki, Japan.
Katsuta
O
O
Chida
T
T
Toyota
N
N
Tsuchitani
M
M
Yoshikawa
K
K
Fujii
O
O
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002725:Chloroform / Q000008:administration & dosage / Q000633:toxicity*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000008:administration & dosage / Q000633:toxicity*
D002273:Carcinogens; D012997:Solvents; D002725:Chloroform