Nephrotoxicity of 1,3-dichloropropene in vitro and effects of metabolism modifiers

1,3-Dichloropropene (1,3-D) is largely used in agriculture as a soil fumigant. The few reports on toxicological effects show that liver and kidney are the main targets. The current research assesses the effects caused by 1,3-D dissolved in ethanol (0.2-1.6 mmoles/incubation) in male and female rats, related to metabolism modifiers, by means of renal cortical slice technique. The accumulation of the organic anion p-aminohippurate (PAH) was used as an index of toxicity. Groups of rats were also pretreated with DL-buthionine [S,R]-sulfoximine (BSO), inhibitor of GSH content, or ß-naphthoflavone (NF), activator of the CYP-450 A family. After pretreatment with BSO (500 mg/kg b.w. 4 h before sacrifice), or NF (80 mg/kg b.w., once a day fro three days before sacrifice), renal cortical slices were prepared and treated in vitro with 1.2 mmoles/incubation (toxic dose for female also) of 1,3-D. A dose-dependent decrease in PAH accumulation was observed in male and female rats, but the female rats were susceptible to the higher dose only, and the decrease was significantly lower than males. NF ameliorates the loss of PAH uptake caused by 1,3-D in the male rat, whereas BSO had an additive effect on the loss of PAH uptake caused by 1,3-D in the female rat. These results show that PAH accumulation is more susceptible in male than in female rats to the effects of 1,3-D and induction of A subfamilies of CYP-450 significantly prevents the loss of PAH accumulation induced by 1,3-D in male rats, but not in female rats. On the contrary, GSH depletion increases 1,3-D toxicity in female, but not in male rats. In conclusion, sex differences of 1,3-D toxicity may be explained by difference in metabolic pathways where GSH appears to play a pivotal role in the detoxification of 1,3-D in female rats, but not in males.