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2L (1) - Immunotoxicity - genotoxicity - ED (TH8/5) Effects of PCB metabolites 4-OH-CB 107 and 4-OH-CB 187 on development and endocrine status of the rat. Buitenhuis, Christian1, Cenijn, Peter1, Bergman, Ake2, Gutleb, Arno1, Legler, Juliette1, Brouwer, Abraham1, 1 Institute for Environmental Studies (IVM), Vrije Universiteit, Amsterdam, The Netherlands, The Netherlands2 Department of Environmental Chemistry, Stockholm University, Stockholm, Sweden, Sweden ABSTRACT- Possible human health effects from low-level exposure to environmental chemicals are an issue that has attracted much attention. Environmental compounds that may play a role are those that may disrupt endocrine function. Organohalogenated compounds (OCs), and in particular their hydroxylated metabolites, show a striking resemblance to steroid hormones. The major aim of this study is to investigate the neuronal uptake and localization of hydroxylated OCs, as well as to determine their long-term consequences on brain development, reproduction and endocrine status of the rat. An in vivo experiment is currently underway in which pregnant rats were orally dosed to (hydroxylated) PCBs during gestation day 10-16. The major human plasma PCB metabolites 4-OH-CB 107 and 4-OH-CB 187 were chosen as test compounds. Starting on postnatal day 1, offspring were scored for onset of hair grow, pinna detachment, bilateral eye opening, vaginal opening and preputial separation. After vaginal opening, smears are taken daily and the stage and length of the estrous cycle were determined. Vaginal estrous cyclicity was monitored for 40 days and no differences were found. Vaginal smears will be taken at different periods up to 230 days of age to determine possible delayed effects of prenatal exposure to hydroxylated OCs on reproductive cycle. Biochemical and toxicological endpoints were measured, such as thyroid hormone- and estrogen levels. Preliminary results indicate reductions in plasma thyroid hormone levels in both mothers and offspring. Ongoing behavioral studies will determine if decreased thyroid hormone levels result in neurodevelopmental effects. These behavioral studies include an open-field test (for locomotor function), a catalepsy test (for habituation) and an auditory test. This work has been supported by the EU, contract no. QLK4 2000-00261. Key words: development, PCBs, endocrine status, neural uptake |
