The developmental and neurobehavioral effects of gestational and lactational exposure to a mixture of 14 polychlorinated biphenyls (PCBs) and 11 organochlorine pesticides was examined and compared against the commercial PCB mixture Aroclor 1254. The mixture was based on blood levels reported in Canadian populations living in the Great Lakes/St. Lawrence basin. Pregnant Sprague-Dawley rats were dosed orally with 0.013, 0.13, 1.3, or 13 mg/kg of the chemical mixture or 15 mg/kg of Aroclor 1254 from gestation day (GD) 1 to postnatal day (PND) 23. The highest mixture dose decreased maternal gestation and lactation body weight, and produced high mortality rates (80% overall) and reductions in offspring weight that persisted to adulthood. Aroclor 1254 produced smaller but persistent decreases in offspring weight without affecting maternal weight or offspring mortality. Aroclor 1254 and 13 mg/kg of the mixture produced comparable decreases in maternal and offspring serum T4 levels and comparable alterations to maternal thyroid morphology. Aroclor 1254 delayed the righting reflex and ear opening, accelerated eye opening, and reduced grip strength at PNDs 10-14. The mixture at 13 mg/kg delayed negative geotaxis in addition to delaying righting reflex and ear opening and reducing grip strength but had no effect on eye opening. Lower mixture doses (0.13 and 1.3 mg/kg) also delayed ear opening but affected no other parameters. Developmental exposure to the chemical mixture was found to be more toxic than exposure to Aroclor 1254 and produced a different profile of effects on early neurodevelopment. This PCB/organochlorine pesticide mixture affects mortality, growth, thyroid function, and neurobehavioral development in rodents.
Groups of ten male and female weanling Sprague-Dawley rats were fed diet containing 0, 5, 50, 500 or 5000 ppm of a medium-chain chlorinated paraffin (C14-17, 52% chlorination) for a period of 13 weeks. Increased relative liver weight was observed at 500 and 5000 ppm in females and at 5000 ppm in males. Relative kidney weight was increased at 5000 ppm in both sexes. Serum cholesterol was increased in the females in a dose-related manner starting at 50 ppm. At 5000 ppm, animals of both sexes had elevated hepatic UDP-glucuronosyltransferase activity while only females showed increased aminopyrine N-demethylase activity. Increased urinary N-acetylglucosaminidase activity occurred at 5000 ppm in females. Increased urinary ascorbic acid excretion monitored at week 12 and a decreased hepatic vitamin A level were detected in females receiving the 500 ppm diet and male and female rats at 5000 ppm. Mild, adaptive histopathological changes were detected in the liver of rats of both sexes at 500 and 5000 ppm, and in the thyroid of males and females starting at 500 and 50 ppm respectively. Minimal changes were observed in the kidney proximal tubules of male rats fed the 5000 ppm diet and in the inner medulla tubules of female rats fed the 500 and 5000 ppm diets. These data indicate that the medium-chain chlorinated paraffin produces biochemical and histological changes at dietary levels of greater than or = 50 ppm in females and greater than or = 500 ppm in males.
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