Early developmental neurotoxicity of a PCB/organochlorine mixture in rodents after gestational and lactational exposure.
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.
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D020111:Chlorodiphenyl (54% Chlorine) / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D007306:Insecticides / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D007774:Lactation / Q000187:drug effects* / Q000502:physiology; D008136:Longevity / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D009420:Nervous System / Q000187:drug effects* / Q000503:physiopathology; D038081:Organogenesis / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology; D013974:Thyroxine / Q000097:blood
D004338:Drug Combinations; D007306:Insecticides; D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls; D013974:Thyroxine