COMPARATIVE CYTOTOXICITY OF THE AQUEOUS CHLORINATION PRODUCTS OF THIOBENCARB, A THIOCARBAMATE HERBICIDE, IN CULTURED RAT HEPATOCYTES

Thiobencarb (S-4-chlorobenzyl N,N-diethylthiocarbamate) has been widel y used in the rice fields of Japan. This herbicide is reported to deco mpose in aqueous chlorination to the compounds 4-chlorotoluene, 4-chlo robenzyl chloride, 4-chlorobenzyl alcohol, 4-chlorobenzaldehyde and 4- chlorobenzoic acid. We compared their cytotoxicity and the inducibilit y of cytochrome P-450 (P450) in cultured rat hepatocytes. Of the six c ompounds including thiobencarb, 4-chlorobenzyl chloride was the most h epatotoxic (EC50: 0.17 mw), followed by thiobencarb (0.69 mM) and 4-ch lorotoluene (1.2 mM). il-Chlorobenzyl alcohol (4.6 mM) and 4-chloroben zaldehyde (4.6 mM) were less toxic than thiobencarb and 4-chlorobenzoi c acid was the least toxic (> 6.0 mM). From the results of the TEARS ( 2-thiobarbituric acid reactive substance) assay, lipid peroxidation wa s shown to be involved in the hepatotoxicity of 4-chlorobenzyl chlorid e, and less probably in that of thiobencarb and 4-chlorobenzaldehyde. 4-Chlorobenzoic acid and 4-chlorobenzaldehyde induced hepatic ethoxyre sorufin O-deethylase and pentoxyresorufin O-depentylase activities, re spectively. The induction of enzyme activities was accompanied by the increase in the corresponding P-450 apoprotein. Furthermore, 4-chlorot oluene, 4-chlorobenzaldehyde and 4-chlorobenzoic acid also induced CYP 2B1, which was not reflected in the enzyme activity. These results pro vide primary information on the toxicity of the thiobencarb degradatio n products in cultured rat hepatocytes. (C) 1997 Elsevier Science Ltd.