TOXICOLOGICAL EVALUATION OF MIXTURES OF 10 WIDELY USED PESTICIDES

Toxicities of pesticidal mixtures in biological systems have not been explored adequately. Therefore, mixtures of ten widely used pesticides were evaluated for their toxicity in ICR male mice (21-24 g). Mice were given four mixtures of alachlor, aldrin, atrazine, 2,4-dichlorophenoxyacetic acid, DDT, dieldrin, endosulfan, lindane, parathion and toxaphene, at 0.01, 0.1, 1.0 and 10 ppm of each of these pesticides, in drinking water for 90 days ad-libitum. Also, two mixtures at 2.5 and 5 mg kg-1 of each pesticide in 7.5% Tween-80 in water were administered to additional groups of mice by oral intubation daily for up to 14 days. In relation to the control, the 90-day exposure caused a dose-dependent increase in the liver/body weight ratio (3-44%), a decrease in the pentobarbital (60 mg kg-1, i.p.)-induced sleep time (I 1-79%) and an increase in the metabolism of aniline (233-399%), amidopyrine (79-231%), phenacetin (127-318%) and benzo[a]pyrene (286-1633%) in the 9000 g hepatic supernatants from the mixture-treated mice. Proliferation, dilatation and fragmentation of the endoplasmic reticulum and scattering of ribosomes were noticed with mixture livers. In the 5 mg kg-1 group, 90% of the animals died by Day 8; incidence of death was considerably less in the 2.5 mg kg-1 group. The serum cholinesterase activity was inhibited by ca. 50% in the 2.5 and 5 mg kg-1 groups on either one or both of Days 8 and 15; the liver/body weight ratio increased by 24-79% and the pentobarbital-induced sleep time decreased by 80-96%. On Days 8 and 15, the in vitro hepatic metabolism of amidopyrine, phenacetin and benzo[a]pyrene in the 2.5 or 5 mg kg-1 group was considerably increased (100-1478%). Findings from this study suggest that these mixtures have the potential to induce the xenobiotic-metabolizing enzymes in liver; thus, exposures to the pesticidal mixtures might cause deleterious effects in other species, including humans, by enhancing the metabolism of xenobiotics.