Nedellec Vincent, Rabl Ari, Dab William
Consultant on Environmental risks and health safety, 23, rue André Masséna, 83000, Toulon, France.
Retired from Ecole des Mines/ARMINES, Paris, Consultant on Environmental Impacts, 6 av. Faidherbe, 91440, Bures sur Yvette, France.
Environ Health. 2016 Jul 12;15(1):75. doi: 10.1186/s12940-016-0160-x.
Inhabitants of Guadeloupe are chronically exposed to low dose of chlordecone via local food. The corresponding health impacts have not been quantified. Nevertheless the public authority implemented an exposure reduction program in 2003. We develop methods for quantifying the health impacts of chlordecone and present the results in 2 articles: 1. hazard identification, exposure-response functions (ERF) and exposure in Guadeloupe, 2. Health impacts and benefits of exposure reduction. Here is the first article.
Relevant data are extracted from publications searched in Medline and Toxline. Available knowledges on mode of action and key-event hazards of chlordecone are used to identify effects of chlordecone that could occur at low dose. Then a linear ERF is derived for each possible effect. From epidemiological data, ERF is the delta relative risk (RR-1) divided by the corresponding delta exposure. From animal studies, ERF is the benchmark response (10 %) divided by the best benchmark dose modeled with BMDS2.4.0. Our goal is to obtain central values for the ERF slopes, applicable to typical human populations, rather than lower or upper bounds in the most sensitive species or sex.
We derive ERFs for 3 possible effects at chronic low chlordecone dose: cancers, developmental impairment, and hepatotoxicity. Neurotoxicity in adults is also a possible effect at low dose but we lack quantitative data for the ERF derivation. A renal toxicity ERF is derived for comparison purpose. Two ERFs are based on epidemiological studies: prostate cancer in men aged >44y (0.0019 per μg/Lblood) and altered neurodevelopment in boys (-0.32 QIpoint per μg/Lcord-blood). Two are based on animal studies: liver cancer (2.69 per mg/kg/d), and renal dysfunction in women (0.0022 per mg/kg/d).
The methodological framework developed here yields ERFs for central risk estimates for non-genotoxic effects of chemicals; it is robust with regard to models used. This framework can be used generally to derive ERFs suitable for risk assessment and for cost-benefit analysis of public health decisions.
瓜德罗普岛居民长期通过当地食物接触低剂量的十氯酮。相应的健康影响尚未量化。尽管如此,公共当局在2003年实施了一项减少接触的计划。我们开发了量化十氯酮健康影响的方法,并在两篇文章中呈现结果:1. 危害识别、暴露-反应函数(ERF)及瓜德罗普岛的暴露情况;2. 减少暴露的健康影响和益处。以下是第一篇文章。
从在Medline和Toxline中检索到的出版物中提取相关数据。利用关于十氯酮作用模式和关键事件危害的现有知识来识别低剂量下可能发生的十氯酮效应。然后为每种可能的效应推导线性暴露-反应函数。从流行病学数据来看,暴露-反应函数是相对风险增量(RR - 1)除以相应的暴露增量。从动物研究来看,暴露-反应函数是基准反应(10%)除以用BMDS2.4.0建模的最佳基准剂量。我们的目标是获得适用于典型人群的暴露-反应函数斜率的中心值,而非最敏感物种或性别的下限或上限。
我们推导了慢性低剂量十氯酮下3种可能效应的暴露-反应函数:癌症、发育障碍和肝毒性。成人神经毒性在低剂量下也是一种可能的效应,但我们缺乏用于推导暴露-反应函数的定量数据。为作比较推导了肾毒性暴露-反应函数。两个暴露-反应函数基于流行病学研究:44岁以上男性的前列腺癌(每升血液中0.0019)和男孩神经发育改变(每升脐血中-0.32智商点)。两个基于动物研究:肝癌(每毫克/千克/天2.69)和女性肾功能障碍(每毫克/千克/天0.0022)。
此处开发的方法框架产生了用于化学品非遗传毒性效应中心风险估计的暴露-反应函数;在所用模型方面具有稳健性。该框架可普遍用于推导适用于风险评估以及公共卫生决策成本效益分析的暴露-反应函数。