DEVELOPMENTAL NEUROTOXICITY OF METALLIC MERCURY

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DESCRIPTION: (Adapted from the Investigator's Abstract) Metallic mercury, a neurotoxicant usually viewed as an occupational hazard, is a more general environmental hazard as well. Although we know a great deal about its effects in adults, our knowledge of its impact on the developing brain is fragmentary. This information gap is disquieting. (1) Many women in the work force are exposed to mercury vapor. (2) Many, perhaps most, women have dental amalgam fillings. These emit mercury vapor. Maternal tissue and fetal levels are correlated with the number of fillings. (3) Mercury is a more common contaminant of indoor environments than is generally recognized. Because of its physical properties it can lurk undetected and continue to evaporate. (4) Young children are considerably more vulnerable to mercury toxicity than adults; the syndrome of Pink Disease is a childhood affliction. (5) Organic mercury compounds are potent disrupters of brain development; some authorities believe that its conversion to the inorganic form in brain cells is the toxic mechanism responsible. (6) The experimental literature devoted to neurobehavioral effects consists of a handful of studies. To enhance our ability to evaluate the risks of metallic mercury to the developing brain, we intend to expose both pregnant rats and neonates to mercury vapor. Pregnant rats will be exposed to air, 30 ug/cubic meter, 100 ug/cubic meter, the OSHA permissible level, and 300 ug/cubic meter. Neonatal rats will be exposed to air, 10, 30, and 100 ug/cubic meter. Exposure will last two hours. The different levels are based on reports indicating widely different sensitivities between prenatal and neonatal exposures. Dam and pup blood levels will be monitored, and tissue assays, especially of brain, will be conducted at selected times. To determine the functional consequences of developmental exposure, three behavioral endpoints will be assayed: (1) The acoustic startle response, which will provide measures of habituation, sensory dysfunction, and the total neuromuscular response pattern to sound. (2) Spontaneous locomotor activity in the rats, a common index of neurotoxicity. (3) Acquisition of schedule-controlled operant behavior. Histochemical techniques will be deployed to map localization of brain mercury deposits.