Response to the Letter by Middlebeek and Veuger Free

Our estimates are a first of a kind; we quantified the burden of disease and costs that are likely attributable to endocrine-disrupting chemicals (EDCs) in the European Union (1–4). As regulatory agencies develop new methods to protect public health from classes of chemicals that interfere with hormone actions, it is essential to consider both the cost of action and the cost of inaction. To accomplish this, we leveraged consistent dose/response relationships of organophosphate (OP) pesticide exposures in pregnancy with intellectual quotient (IQ) across two carefully conducted longitudinal birth cohorts (5, 6). Prenatal OP exposure has been associated with magnetic resonance imaging findings in children, including frontal and parietal cortical thinning (7), and undermines any suggestion of spuriousness by Middlebeek and Veuger. That Engel et al (6) were vastly underpowered in the white population (n = 38) did not reduce validity of combined results across ethnic groups. In contrast to the claim they make without citation, human data confirm predictable outcomes of thyroid disruption produced by OP exposure, including global IQ deficits, autism spectrum disorder, and attention-deficit hyperactivity disorder (8–10). These findings are consistent with those from the laboratory, and represent realities that we must not ignore.

The claim that “due to the nature of these observational studies, excluding all other possible confounders, such as other EDCs, is most likely impossible” merits further consideration. The assumptions behind that statement are: 1) that EDC exposures are so tightly correlated as to prevent overestimating effect size; and 2) that confounding is positive. Indeed, had Middlebeek and Veuger more carefully considered their line of argument, they would have recognized that Bouchard et al (5) controlled for multiple other EDCs including polybrominated diphenyl ethers, polychlorinated biphenyls, p,ṕ-dichlorodiphenyltrichloroethane, p,ṕ-dichlorodiphenyldichloroethylene, and lead. Engel et al (6) also controlled for polychlorinated biphenyls. Indeed, none of these neurotoxicants confounded the OP-IQ relationship.

Middlebeek and Veuger question the range of costs computed across the 13 exposure-outcome relationships and fail to recognize the substantial, >99% probability that ≥ one EDC effect is causal. Our work represents a substantial underestimate of actual EDC-attributable disease, given its focus on <5% of EDCs, examination of a subset of health effects, and exclusion of human suffering and other societal costs of EDC-attributable diseases. The cost-of-illness approach also underestimates costs of early mortality due to phthalate-induced T disruption.

Yes, indeed, assessing EDC-associated costs is not easy, but we have quantified these costs in Europe in a straightforward and transparent methodology grounded on work first conducted by the Intergovernmental Panel on Climate Change and the World Health Organization. This work was assessed by a group of internationally recognized experts in epidemiology, toxicology, economics, EDCs, and neurodevelopment. The comments presented by Middlebeek and Veuger do not diminish the impact of our conservatively formulated findings for policymakers considering methods to reduce exposure to the EDCs of greatest concern. The economic rewards of doing so are likely to be in the billions of euros and accrue annually insofar as alternatives free of health effects are used.

Abbreviations

 
• EDC

  endocrine-disrupting chemical

 
• IQ

  intellectual quotient

 
• OP

  organophosphate.

References