STRATEGY TO IDENTIFY NONADDITIVE RESPONSE TO CHEMICAL

识别化学品非添加剂反应的策略

• 批准号: 2732021
• 负责人: JOHN S VOGEL
• 金额: $ 24.26万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-15 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2732021
• 关键词: biomarker; diisopropylfluorophosphate; dosage; environmental toxicology; esterase; laboratory mouse; mass spectrometry; neurons; neurotoxicology; occupational hazard; organophosphorus insecticide; parathion; pesticide interaction; pyrethroid; pyridostigmine; radionuclides; toxicant screening

DESCRIPTION Low level exposures to organophosphate (OP) esters are suspected to impact the health of agricultural workers, soldiers, and the general population. Current techniques of study require extrapolation of imprecise data from high dose exposures to the low doses of usual exposures. Biochemical markers of analyses are the most promising indicators of response to the effects of multiple chemical exposures at environmentally relevant doses. Accelerator mass spectrometry (AMS) has the sensitivity and precision to quantify attomole levels of tissue doses or biomarkers of isotopically labeled compounds to precisions of <5%. AMS will quantify the nerve cell membrane binding of an isotope labeled OP pesticide marker at sub-ppm exposures. Chemical mixtures of other esters, also at environmentally realistic doses, will be concurrently applied to determine if these multiple exposures to different esters cause non-additive effects in the binding of the marker OP. Mice will be exposed to up to four compounds in multiples, and OP binding in nerves will be assayed for up to three days. The overall goal is to demonstrate a new strategy for identifying chemical mixtures that have non-additive biochemical response at relevant low exposures in order to eliminate the current strategies that depends on uncertain extrapolation of high dose, single compound data. If the strategy proves useful, more rapid and meaningful screening of chemical mixture exposures can be implemented to provide better health advisories and regulations for the general public and for specific occupations.

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