Martine Bellanger

Estimating Burden and Disease Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union

CONTEXT Rapidly increasing evidence has documented that endocrine-disrupting chemicals (EDCs) contribute substantially to disease and disability. OBJECTIVE The objective was to quantify a range of health and economic costs that can be reasonably attributed to EDC exposures in the European Union (EU). DESIGN A Steering Committee of scientists adapted the Intergovernmental Panel on Climate Change weight-of-evidence characterization for probability of causation based upon levels of available epidemiological and toxicological evidence for one or more chemicals contributing to disease by an endocrine disruptor mechanism. To evaluate the epidemiological evidence, the Steering Committee adapted the World Health Organization Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group criteria, whereas the Steering Committee adapted definitions recently promulgated by the Danish Environmental Protection Agency for evaluating laboratory and animal evidence of endocrine disruption. Expert panels used the Delphi method to make decisions on the strength of the data. RESULTS Expert panels achieved consensus at least for probable (>20%) EDC causation for IQ loss and associated intellectual disability, autism, attention-deficit hyperactivity disorder, childhood obesity, adult obesity, adult diabetes, cryptorchidism, male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median cost of €157 billion (or

Neurobehavioral Deficits, Diseases and Associated Costs of Exposure to Endocrine Disrupting Chemicals in the European Union

209 billion, corresponding to 1.23% of EU gross domestic product) annually across 1000 simulations. Notably, using the lowest end of the probability range for each relationship in the Monte Carlo simulations produced a median range of €109 billion that differed modestly from base case probability inputs. CONCLUSIONS EDC exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those EDCs with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.

Childhood lead exposure in France: benefit estimation and partial cost-benefit analysis of lead hazard control

CONTEXT Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. OBJECTIVE The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. DESIGN An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients and Participants, and Intervention: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. RESULTS The panel identified a 70-100% probability that polybrominated diphenyl ether and organophosphate exposures contribute to IQ loss in the European population. Polybrominated diphenyl ether exposures were associated with 873,000 (sensitivity analysis, 148,000 to 2.02 million) lost IQ points and 3290 (sensitivity analysis, 3290 to 8080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis, €1.58 billion to €22.4 billion). Organophosphate exposures were associated with 13.0 million (sensitivity analysis, 4.24 million to 17.1 million) lost IQ points and 59 300 (sensitivity analysis, 16,500 to 84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis, €46.8 billion to €194 billion). Autism spectrum disorder causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis, 126-631) attributable cases at a cost of €199 million (sensitivity analysis, €79.7 million to €399 million). Attention-deficit hyperactivity disorder causation by multiple EDCs was assigned a 20-69% probability, with 19 300 to 31 200 attributable cases at a cost of €1.21 billion to €2.86 billion. CONCLUSIONS EDC exposures in Europe contribute substantially to neurobehavioral deficits and disease, with a high probability of >€150 billion costs/year. These results emphasize the advantages of controlling EDC exposure.

Burden of disease and costs of exposure to endocrine disrupting chemicals in the European Union: an updated analysis.

BackgroundLead exposure remains a public health concern due to its serious adverse effects, such as cognitive and behavioral impairment: children younger than six years of age being the most vulnerable population. In Europe, the lead-related economic impacts have not been examined in detail. We estimate the annual costs in France due to childhood exposure and, through a cost benefit analysis (CBA), aim to assess the expected social and economic benefits of exposure abatement.MethodsMonetary benefits were assessed in terms of avoided national costs. We used results from a 2008 survey on blood-lead (B-Pb) concentrations in French children aged one to six years old. Given the absence of a threshold concentration being established, we performed a sensitivity analysis assuming different hypothetical threshold values for toxicity above 15 μg/L, 24 μg/L and 100 μg/L. Adverse health outcomes of lead exposure were translated into social burden and economic costs based on literature data from literature. Direct health benefits, social benefits and intangible avoided costs were included. Costs of pollutant exposure control were partially estimated in regard to homes lead-based paint decontamination, investments aiming at reducing industrial lead emissions and removal of all lead drinking water pipes.ResultsThe following overall annual benefits for the three hypothetical thresholds values in 2008 are: €22.72 billion, €10.72 billion and €0.44 billion, respectively. Costs from abatement ranged from €0.9 billion to 2.95 billion/year. Finally, from a partial CBA of lead control in soils and dust the estimates of total net benefits were € 3.78 billion, € 1.88 billion and €0.25 billion respectively for the three hypothesized B-Pb effect values.ConclusionsPrevention of childhood lead exposure has a high social benefit, due to reduction of B-Pb concentrations to levels below 15 μg/L or 24 μg/L, respectively. Reducing only exposures above 100 μg/L B-Pb has little economic impact due to the small number of children who now exhibit such high exposure levels. Prudent public policies would help avoiding future medical interventions, limit the need for special education and increase future productivity, and hence lifetime income for children exposed to lead.

Evaluation of full costs of care for patients with Alzheimer's disease in France: the predominant role of informal care.

A previous report documented that endocrine disrupting chemicals contribute substantially to certain forms of disease and disability. In the present analysis, our main objective was to update a range of health and economic costs that can be reasonably attributed to endocrine disrupting chemical exposures in the European Union, leveraging new burden and disease cost estimates of female reproductive conditions from accompanying report. Expert panels evaluated the epidemiologic evidence, using adapted criteria from the WHO Grading of Recommendations Assessment, Development and Evaluation Working Group, and evaluated laboratory and animal evidence of endocrine disruption using definitions recently promulgated by the Danish Environmental Protection Agency. The Delphi method was used to make decisions on the strength of the data. Expert panels consensus was achieved for probable (>20%) endocrine disrupting chemical causation for IQ loss and associated intellectual disability; autism; attention deficit hyperactivity disorder; endometriosis; fibroids; childhood obesity; adult obesity; adult diabetes; cryptorchidism; male infertility, and mortality associated with reduced testosterone. Accounting for probability of causation, and using the midpoint of each range for probability of causation, Monte Carlo simulations produced a median annual cost of €163 billion (1.28% of EU Gross Domestic Product) across 1000 simulations. We conclude that endocrine disrupting chemical exposures in the EU are likely to contribute substantially to disease and dysfunction across the life course with costs in the hundreds of billions of Euros per year. These estimates represent only those endocrine disrupting chemicals with the highest probability of causation; a broader analysis would have produced greater estimates of burden of disease and costs.

Calculation of Mercury's Effects on Neurodevelopment

OBJECTIVE It is crucial that the cost of Alzheimers disease be evaluated, from a societal perspective, since the number of patients is expected to increase dramatically in the coming decades. This assessment of the full cost of care for community-dwelling patients with Alzheimers disease in France also addresses the factors associated with informal care, its predominant component. DATA AND METHODS From 2009 to 2010, 57 patient/informal caregiver pairs were interviewed using the Resource Utilization in Dementia questionnaire, adapted to provide a micro-costing approach of the overall care process. Both the opportunity cost method and the proxy good method were used to value informal care. Ordinary least square regression was performed to determine factors associated with informal care. RESULTS Average total monthly costs were €2450 with the proxy good method and €3102 with the opportunity cost method. Living with the patient, severity of dementia and hours spent on formal care were significantly associated with informal care time. POLICY IMPLICATIONS Since French allowance cannot cover all formal and informal non-medical costs, the choice for policy makers is either to spend more on formal care or to develop family care by investing in supportive programmes for informal caregivers.

Economic evaluation of health consequences of prenatal methylmercury exposure in France

Bellinger (2012) recently estimated the loss of cognitive function in terms of Full-Scale intelligence quotient (IQ) in children exposed to certain environmental chemicals. To ascertain pre-natal exposures of methyl-mercury (MeHg) in children, he used exposure data on mercury (Hg) concentrations in hair of U.S. women of childbearing age (16–49 years) from NHANES (National Health and Nutrition Examination Survey) 1999–2000 (McDowell et al. 2004). Bellinger applied a regression coefficient of –0.18 IQ points per microgram per gram increase in maternal hair as calculated by Axelrad et al. (2007). However, the results of Axelrad et al. (2007) relied on incomplete data from a prospective study in the Faroe Islands and on non-adjusted results from the Seychelles study, later found to be confounded by nutrients from seafood (Strain et al. 2008). Bellinger (2012) then applied the regression coefficient to hair Hg levels > 1.11 µg/g (90th percentile), because this level corresponds to the reference dose of MeHg established many years ago. Assuming a concentration of 1.73 µg/g (95th percentile) as the midpoint (rather than the average, which is higher) for the hair Hg levels of the 10% of U.S. women with a level > 1.11 µg/g, he estimated a total IQ loss of 284,580 points. We believe that Bellinger’s general approach is sound but that the dose–response information is outdated, a caveat that Bellinger noted, although it was not reflected in the summary table. We therefore wish to complement these calculations using updated dose–response data. Prospective data justify a lower threshold Hg level of 0.58 µg/g hair corresponding to 50% of the reference dose (Grandjean and Budtz-Jorgensen 2007). In addition, a 1-µg/g increase in hair Hg concentration is more likely associated with an average adverse impact of 0.465 IQ points, as discussed by Pichery et al. (2012). Assuming a log- normal exposure distribution, a 75th percentile hair Hg concentration of 0.42 µg/g, and a 90th percentile of 1.11 µg/g as reported by McDowell et al. (2004), we estimate that 18.5% of women exceed a threshold of 0.58 µg/g hair Hg and that the average concentration for 0.58–1.11 µg/g is approximately 0.8 µg/g. For the sake of comparing these values with Bellinger’s calculations (Bellinger 2012), we used a median concentration of 1.73 µg/g as the average hair Hg level of the 10% of U.S. women with a level > 1.11 µg/g. On the basis of these assumptions, we calculated a total IQ loss for the U.S. population of children 0–5 years of age (n = 25.5 million) to be 1,590,000 IQ points, or 264,000 IQ points per year. We recently used similar calculations to estimate the annual costs of Hg pollution in France (Pichery et al. 2012), a country one-fifth the size of the United States. At slightly higher exposure levels, the annual loss in IQ points was estimated to be 157,000. Greater losses were obtained using a log-scale effect (Pichery et al. 2012). With an estimated value of each IQ point of

Economic inequality caused by feedbacks between poverty and the dynamics of a rare tropical disease: the case of Buruli ulcer in sub-Saharan Africa

18,000 in terms of life-time earnings, the current loss of IQ points associated with MeHg exposure represents a very substantial value to society.

Calculation of the disease burden associated with environmental chemical exposures: application of toxicological information in health economic estimation

BackgroundEvidence of a dose–response relationship between prenatal exposure to methylmercury (MeHg) and neurodevelopmental consequences in terms of IQ reduction, makes it possible to evaluate the economic consequences of MeHg exposures.ObjectiveTo perform an economic evaluation of annual national benefits of reduction of the prenatal MeHg exposure in France.MethodsWe used data on hair-Hg concentrations in French women of childbearing age (18–45 years) from a national sample of 126 women and from two studies conducted in coastal regions (n = 161and n = 503). A linear dose response function with a slope of 0.465 IQ point reduction per μg/g increase in hair-Hg concentration was used, along with a log transformation of the exposure scale, where a doubling of exposure was associated with a loss of 1.5 IQ points. The costs calculations utilized an updated estimate of €2008 17,363 per IQ point decrement, with three hypothetical exposure cut-off points (hair-Hg of 0.58, 1.0, and 2.5 μg/g).ResultsBecause of higher exposure levels of women in coastal communities, the annual economic impacts based on these data were greater than those using the national data, i.e. € 1.62 billion (national), and € 3.02 billion and € 2.51 billion (regional), respectively, with the linear model, and € 5.46 billion (national), and € 9.13 billion and € 8.17 billion (regional), with the log model, for exposures above 0.58 μg/g.ConclusionsThese results emphasize that efforts to reduce MeHg exposures would have high social benefits by preventing the serious and lifelong consequences of neurodevelopmental deficits in children.

Cost-Effectiveness of Capping Freeways for Use as Parks: The New York Cross-Bronx Expressway Case Study

Neglected tropical diseases (NTDs) have received increasing attention in recent years by the global heath community, as they cumulatively constitute substantial burdens of disease as well as barriers for economic development. A number of common tropical diseases such as malaria, hookworm or schistosomiasis have well-documented economic impacts. However, much less is known about the population-level impacts of diseases that are rare but associated with high disability burden, which represent a great number of tropical diseases. Using an individual-based model of Buruli ulcer (BU), we demonstrate that, through feedbacks between health and economic status, such NTDs can have a significant impact on the economic structure of human populations even at low incidence levels. While average wealth is only marginally affected by BU, the economic conditions of certain subpopulations are impacted sufficiently to create changes in measurable population-level inequality. A reduction of the disability burden caused by BU can thus maximize the economic growth of the poorest subpopulations and reduce significantly the economic inequalities introduced by the disease in endemic regions.