Dose-dependent effects of dichloropropanol on liver histology and lipid peroxidation in rats.
A rare outbreak of acute hepatic damage in workers exposed to dichloropropanols (DCPs) was reported recently. The purpose of the present study is to examine the effects of DCPs on various organs, the dose dependency and the pathogenetic potential of DCP hepatotoxicity. A single intraperitoneal injection was given to six groups of rats with 0.2 ml of 20% ethanol (control), or 1/8 x, 1/4 x, 1/2 x, 1 x, and 2 x LD50 (0.11 ml/kg) of 1,3-dichloro, 2-propanol (DC2P) diluted in 20% ethanol. After blood samplings, all organs were subjected to histologic examinations with light and electron microscopes. Fresh liver tissues from further 4 control and 4 experimental rats sacrificed 6 hours after the injection of 20% ethanol and 1 x LD50 of DC2P were homogenized and subjected to evaluate lipid peroxidation, glutathione S-transferase activity and reduced glutathione contents in the liver. The rats administered with only ethanol or 1/8 and 1/4 LD50 of DC2P showed no serological or histopathological abnormalities. Marked elevation of serum glutamate pyruvate transaminase (SGPT) with a diffuse massive necrosis of the liver cells were noted in all rats of both the 1 x and 2 x LD50 groups, and irregular zonal necroses were found in 3 of 4 rats injected with 1/2 LD50. There were no serious toxic changes in other organs. Hepatic malondialdehyde level was significantly increased, associated with decreases of liver glutathione S-transferase activity and reduced glutathione content. It was concluded that the serious DC2P-toxicity was mainly found in the livers, dose dependently, and one of the causative mechanisms of this hepatotoxicity might be the lipid peroxidation.
Katoh
T
T
School of Health Sciences, University of Occupational & Environmental Health, Kitakyushu, Japan.
Haratake
J
J
Nakano
S
S
Kikuchi
M
M
Yoshikawa
M
M
Arashidani
K
K
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D020005:Propanols / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D000517:alpha-Chlorohydrin / Q000031:analogs & derivatives / Q000633:toxicity*
D020005:Propanols; D000517:alpha-Chlorohydrin; D000410:Alanine Transaminase