Biochemical effects of chloral hydrate on male rats following 7-day drinking water exposure

The biochemical and toxicological effects of chloral hydrate were investiga ted. Four groups (n = 7 per group) of male Sprague-Dawley rats (161-170 g) were administered chloral hydrate in drinking water at concentrations of 20 , 200 or 2000 ppm for 7 days. The control group received phosphate-buffered water only. There were no treatment-related changes in the body weight gai ns, relative weights of major organs or haematological parameters. Trichlor oacetic acid was significantly (P < 0.05) elevated in the serum of high-dos e animals (7.75 +/- 5.14 mg dl(-1), mean +/- SD). In the high-dose animals there was a 36% increase in protein level in the liver homogenates;but not in the corresponding 9000 g supernatants. Concurrently, there was a threefo ld increase in the activity of the hepatic peroxisomal enzyme palmitoyl CoA oxidase (PCO). A prominent change was the dose-related suppression in hepa tic aldehyde dehydrogenase (ALDH) activity observed in all treatment groups , with the decrease ranging from 15% at 20 ppm to 68% at 2000 ppm. There we re no significant decreases in the activity of hepatic enzymes ethoxyresoru fin O-deethylase (EROD), benzyloxyresorufin O-dealkylase (BROD) and UDP-glu curonosyl-transferase (UDPGT). In the high-dose group there was a 30% incre ase in hepatic glutathione-S transferase (GST) activity, accompanied by a 1 3% increase in glutathione (GSH). Significant effects on lipids were observ ed in the liver of the high-dose animals, with a 15% decrease in hepatic ch olesterol and triglyceride levels. There were no treatment-related changes in serum chemistry parameters, including cholesterol and triglyceride level s. Although in vitro assays showed chloral hydrate to be an inhibitor of se rum pseudocholinesterase activity, with a 50% inhibition concentration (IC5 0) of <similar to>0.7 mM at 5 mM butyrylthiocholine, no decrease in serum p seudocholinesterase activity was found in the treated animals. It was concl uded that the liver is the target organ for chloral hydrate, with suppressi on of ALDH as the most sensitive endpoint followed by alteration in the GSH level and GST activity. Changes observed in the high-dose animals, such as increased peroxisomal PCO activity in the liver and perturbation of lipid homeostasis in the liver and blood, were likely to be associated with trich loracetic acid, the major metabolite of chloral hydrate. Copyright (C) 2000 John Wiley & Sons, Ltd.