Some Biochemical and Histological Effects of 2-Chloroethanol in Rats

Abstract

The effects of 2-chloroethanol(2-CE) on rat tissue following in vitro and in vivo exposure were studied. At concentrations as low as 2.5 mg/ml, protein synthesis in liver slices was inhibited; at concentrations of 25 mg/ml and above, RNA synthesis and respiration were also impaired. Single oral doses of 2-CE to young adult rats at levels of 15-40 mg/kg body weight depressed liver nonprotein sulfhydryl (GSH) concentration and liver protein but not RNA synthesis. Liver lipid was increased by 7 hr after a single oral dose of 30 mg/kg. The time courses and dose-response relationship for GSH depletion and restoration and for protein synthesis inhibition and recovery were similar. The livers of female rats were more sensitive than the livers of male rats to the effects of 2-CE. Protein synthesis was also depressed in kidneys of 2-CE-treated male rats but at higher doses than those needed for this effect to occur in livers of the same animals. Liver polysome disaggregation also occurred after oral 2-CE doses of 20 mg/kg and greater. The effects of 2-CE on ribosome profiles and protein synthesis were at least partially reversed by concurrent intraperitoneal administration of cysteine. The possible relationship of these findings to a role of GSH in protein synthesis is discussed. Downloaded from FRIEDMAN ET AL. kidney, and lung), but no histopathological changes in rats given 2-CE ip at 12.8 mg/kg of body weight three times a week for 3 months. Oser et u/. (~) found similar effects in rats administered 2-CE by oral gavage at the level of 67.5 mg/kg of body weight and reported that some fatty changes occurred in the livers of these animals; growth depression was also demonstrated in dogs and monkeys treated in this manner. Mason et a/.,(') however, could demonstrate no effect on weight gain, mortality, or histology in rats given 2-CE subcutaneously (sc) at doses up to 10 mg/kg twice a week for 1 year.Dietary ingestion of 2-CE at levels of 0.32, 0.64, and 1.28% for 220 days produced high mortality in rats and growth depression at levels of 0.16% or higher, but no gross pathological or histological changes were noted."' also failed to note any histological changes in a small number of rats administered 2-CE at doses up to 16 mg/kg of body weight by oral gavage daily for 24 months. Repeated short exposures of rats to 2.5-5.0 ppm of 2-CE by inhalation resulted in several pathological changes, including renal hemorrhages, renal tubular necrosis, and fatty degeneration and necrosis of the liver.('') Several cases of human toxicity apparently resulting from cutaneous or respiratory exposure to 2-CE have been reported.'10~11~'2~'31 The liver, lungs, and kidneys appeared to be target organs in many of these cases.2-CE is destructive to the ophthalmic, mucosal, muscular, and subcutaneous tissues of rabbit^,''^' and causes teratogenic effects in the developing chick embryo (M. J. Verrett, personal communication, cited in ref. 15). Rosenkranz and Wlodkowski'l6) reported that 2-CE is mutagenic for Sulmonetta typhimurium at levels as l...

2‐Chloroethanol [MAK Value Documentation, 1993]

“…The metabolites form conjugates with glutathione [11,13]. In animals given oral doses of 2-chloroethanol, the glutathione level [11,14,15] and the level of protein biosynthesis [15] have been shown to decrease. The toxicity of 2-chloroethanol is ascribed at least in part to the action of toxic metabolites such as 2-chloroacetaldehyde [11,16].…”