Neurobehavioral deficits, diseases, and associated costs of exposure to Endocrine-disrupting chemicals in the European Union

Bellanger et al (1) recently reported on the estimated costs of endocrine-disrupting chemicals (EDCs) causing neurobehavioral deficits in the European Union (EU), as part of a larger effort estimating the overall costs of EDC exposure in the EU (2). Although EDCs may well have adverse health effects, we question the authors’ high economic cost estimates. Because over 90% of the full estimated cost (€146 billion out of €157 billion) derives from the effects of organophosphates (OPs) on IQ alone, our comments here focus on that specific component.

To reach their €146 billion cost estimate, the authors combine toxicological data documenting adverse effects of certain chemicals in a controlled and observed setting with longitudinal, epidemiological data to produce a “probability of causation” of a specific effect of OPs on IQ in humans. They arrive at an estimated probability of 70–100%, or near certainty, although both methodologies have their own inherent problems, including, but not limited to, sample selection, sample variation, outcome selection, and confounding bias.

But is assessing EDC-associated costs, even conditional on demonstrated causality, straightforward? First, only two studies were selected to establish the exposure-response relationship between OPs and IQ: one involving Spanishspeaking women who were born in Mexico, lived in farmworker households, did not complete high school, and had a family income below the US poverty threshold (3); and another showing an association between OP exposure and IQ in certain ethnic groups, but not among whites (4), raising significant external validity and precision concerns. Second, a possible toxicological effect of OPs on thyroid hormone action has not consistently been measured in the human observational studies used to establish exposure-response relationships between OPs and IQ. Finally, due to the nature of these observational studies, excluding all possible confounders, such as other EDCs, is most likely impossible.

Producing cost estimates to shape policy may be helpful in promoting certain causes, but it should be done with caution. The current range of annual cost estimates spans two orders of magnitude (€2.5 billion to 239 billion) and underscores the high levels of uncertainty that arise around each of the decision points in the analysis. The authors’ median cost estimate of €157 billion (over 1% of EU gross domestic product) annually seems implausibly high if it is indeed just the “tip of the iceberg” (5).

References
1. Bellanger M, Demeneix B, Grandjean P, Zoeller RT, Trasande L. Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European union. J Clin Endocrinol Metab. 2015;100(4):1256–1266.

2. Trasande L, Zoeller RT, Hass U, et al. Estimating burden and disease costs of exposure to endocrine-disrupting chemicals in the European union. J Clin Endocrinol Metab. 2015;100(4):1245–1255.

3. Bouchard MF, Chevrier J, Harley KG, et al. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect. 2011;119(8):1189–1195.

4. Engel SM, Wetmur J, Chen J, et al. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ Health Perspect. 2011;119(8):1182–1188.

5. Woodruff TJ. Making it real–the environmental burden of disease. What does it take to make people pay attention to the environment and health? J Clin Endocrinol Metab. 2015;100(4):1241–1244.

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