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 widely used in the rice fields of Japan. This herbicide is reported to decompose in aqueous chlorination to the compounds 4-chlorotoluene, 4-chlorobenzyl chloride, 4-chlorobenzyl alcohol, 4-chlorobenzaldehyde and 4-chlorobenzoic acid. We compared their cytotoxicity and the inducibility of cytochrome P-450 (P450) in cultured rat hepatocytes. Of the six compounds including thiobencarb, 4-chlorobenzyl chloride was the most hepatotoxic (EC(50): 0.17 mm), followed by thiobencarb (0.69 mm) and 4-chlorotoluene (1.2 mm). 4-Chlorobenzyl alcohol (4.6 mm) and 4-chlorobenzaldehyde (4.6 mm) were less toxic than thiobencarb, and 4-chlorobenzoic acid was the least toxic ( > 6.0 mm). From the results of the TBARS (2-thiobarbituric acid reactive substance) assay, lipid peroxidation was shown to be involved in the hepatotoxicity of 4-chlorobenzyl chloride, and less probably in that of thiobencarb and 4-chlorobenzaldehyde. 4-Chlorobenzoic acid and 4-chlorobenzaldehyde induced hepatic ethoxyresorufin O-deethylase and pentoxyresorufin O-depentylase activities, respectively. The induction of enzyme activities was accompanied by the increase in the corresponding P-450 apoprotein. Furthermore, 4-chlorotoluene, 4-chlorobenzaldehyde and 4-chlorobenzoic acid also induced CYP2B1, which was not reflected in the enzyme activity. These results provide primary information on the toxicity of the thiobencarb degradation products in cultured rat hepatocytes.
Jinno
H
H
Division of Environmental Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158, Japan.
Hanioka
N
N
Takahashi
A
A
Nishimura
T
T
Toyo'oka
T
T
Ando
M
M