Public health and chronic low chlordecone exposure in Guadeloupe, Part 1: hazards, exposure-response functions, and exposures.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Public health and chronic low chlordecone exposures in Guadeloupe; Part 2: Health impacts, and benefits of prevention.

BACKGROUND: Inhabitants of Guadeloupe are chronically exposed to low doses of chlordecone via local food due to its past use in banana plantations. The corresponding health impacts have not been quantified. We develop a quantitative method and present the results in two articles: 1. Hazard identification, exposure-response functions, and exposure, 2. Health impacts, and benefits of a program to reduce the exposure of the population. Here is the second article. METHODS: The exposure-response functions derived in Part 1 (for liver and prostate cancer, renal dysfunction and cognitive development) are combined with the exposure data to calculate the impacts. The corresponding costs are calculated via DALY's and VOLY. A no-effect threshold is included via the marginal fraction of the collective exposure above the reference dose. The health benefits are the impacts in 2002 (before the exposure reduction program) minus the impacts in 2006 (since the program). They are compared to the costs, namely the public annual expenditures for reducing the population exposure. RESULTS: Without threshold, estimated annual cases of liver cancer, prostate cancer and renal dysfunction are respectively 5.4, 2.8, 0.10 in 2002; and 2.0, 1.0, 0.04 in 2006. Annual IQ points lost (cognitive development) are respectively: 1 173 and 1 003. The annual cost of total impacts is 38.3 Million Euros (M€) in 2002 and 23.7 M€ in 2006. Comparing the benefit of 14.6 M€ with the 3.25 M€ spent for prevention, the program appears well justified. With threshold, the costs of the impacts are lower, respectively: 26.5 M€ in 2002 and 12.8 M€ in 2006, but the benefit is not very different: 13.7 M€. CONCLUSION: This is the first study that quantified chronic non genotoxic effects of chlordecone exposures in Guadeloupe. According to our results, preventive actions should be focused on pregnant women because of the high social cost of development impairment and also because their exposures decreased less rapidly than others. Prevention effort should be sustained as long as chlordecone remains in soils. Additional toxicological and epidemiological research would also be required for health endpoints that could not be taken into account (neurotoxicity of adults, autoimmune diseases and other developmental effects).