Bondy Genevieve, Armstrong Cheryl, Coady Laurie, Doucet Josée, Robertson Patrick, Feeley Mark, Barker Michael
Toxicology Research Division, Postal Locator 2204D2, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Ontario, Canada K1A 0L2.
Food Chem Toxicol. 2003 Feb;41(2):291-301. doi: 10.1016/s0278-6915(02)00229-6.
Due to widespread usage of the pesticide chlordane until the 1980's, this toxic and persistent mixture has accumulated in the food chain. The Arctic acts as a global sink for these and other persistent organic pollutants, which bioaccumulate in the marine and freshwater food chains. As a result, humans consuming diets high in Arctic fish and marine mammal fat can ingest higher levels of chlordane contaminants than humans consuming "southern" diets. The most abundant constituents of the chlordane mixture are trans-chlordane, cis-chlordane, trans-nonachlor, cis-nonachlor and heptachlor; oxychlordane is the major metabolite of the chlordanes and nonachlors. In humans the predominant chlordane-related contaminants detected in breast milk and adipose tissues are trans-nonachlor and oxychlordane. The present studies were undertaken to provide toxicological data on oxychlordane for the purpose of clarifying target organ toxicity and risks to human health associated with ingesting contaminated foods. Female rats were gavaged with oxychlordane at doses ranging from 0.01 to 10 mg/kg body weight/day for up to 28 days. In terms of general toxicity oxychlordane had a steep dose-response curve: 10 mg/kg oxychlordane was acutely toxic and 1 mg/kg oxychlordane caused no measurable effects. Weight loss, reduced feed consumption and thymic atrophy were the hallmarks of acute oxychlordane toxicity. At lower doses rats showed signs of hepatic changes indicative of microsomal enzyme induction. Oxychlordane was more bioaccumulative and was toxic at levels approximately 8 times lower than trans-nonachlor and cis-nonachlor. Thus, ingestion of trans-nonachlor and related chlordane contaminants in foods results in the formation of a metabolite that is more toxic and bioaccumulative than the parent contaminants.
直到20世纪80年代，由于杀虫剂氯丹的广泛使用，这种有毒且持久的混合物已在食物链中累积。北极充当了这些及其他持久性有机污染物的全球汇，这些污染物在海洋和淡水食物链中生物累积。因此，食用富含北极鱼类和海洋哺乳动物脂肪的饮食的人类，摄入的氯丹污染物水平可能高于食用“南方”饮食的人类。氯丹混合物中最主要的成分是反式氯丹、顺式氯丹、反式九氯、顺式九氯和七氯；氧氯丹是氯丹和九氯的主要代谢产物。在人类中，母乳和脂肪组织中检测到的与氯丹相关的主要污染物是反式九氯和氧氯丹。开展本研究是为了提供氧氯丹的毒理学数据，以阐明靶器官毒性以及与摄入受污染食物相关的人类健康风险。给雌性大鼠灌胃氧氯丹，剂量范围为0.01至10毫克/千克体重/天，持续28天。就一般毒性而言，氧氯丹具有陡峭的剂量反应曲线：10毫克/千克的氧氯丹具有急性毒性，而1毫克/千克的氧氯丹未产生可测量的影响。体重减轻、饲料消耗减少和胸腺萎缩是氧氯丹急性毒性的特征。在较低剂量下，大鼠表现出肝脏变化的迹象，表明微粒体酶诱导。氧氯丹的生物累积性更强，其毒性水平比反式九氯和顺式九氯低约8倍。因此，食物中摄入反式九氯及相关氯丹污染物会导致形成一种代谢产物，其毒性和生物累积性比母体污染物更强。
