As a safe exposure level for fluoride in pregnancy has not been established, we used data from two prospective studies for benchmark dose modeling. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Children were assessed for IQ at age 4 (n=211) and between 6 and 12 years (n=287) in the ELEMENT cohort and between ages 3 and 4 years (n=512) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to explore the concentration-effect function for maternal urinary fluoride with children’s IQ, including possible sex-dependence. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) of maternal urinary fluoride and benchmark concentration levels (BMCLs). No deviation from linearity was detected from the results of the two studies. Using a linear slope, the BMC for maternal urinary fluoride associated with a 1-point decrease in IQ scores of preschool-aged boys and girls was 0.29 mg/L (BMCL, 0.18 mg/L). The BMC was 0.30 mg/L (BMCL, 0.19 mg/L) when pooling the IQ scores from the older ELEMENT children and the MIREC cohort. Boys showed slightly lower BMC values compared with girls. Relying on two prospective studies, maternal urine-fluoride exposure at levels commonly occurring in the general population, the joint data showed BMCL results about 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in vulnerable populations.

PG has served as an expert on the hazards of environmental chemicals on behalf of the paintiffs in Food & Water Watch v US EPA. HH and BL served as non-retained expert witnesses (uncompensated) for the trial of Food and Water Watch v US EPA, in which they offered testimony regarding the studies their respective teams on fluoride exposure and neurobehavioral outcomes.

The ELEMENT study was supported by U.S. NIH R01ES021446, NIH R01-ES007821, NIEHS/EPA P01ES022844, NIEHS P42-ES05947, NIEHS Center Grant P30ES017885 and the National Institute of Public Health/Ministry of Health of Mexico. The MIREC study was supported by the Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research (grant # MOP-81285). PG is supported by the NIEHS Superfund Research Program (P42ES027706). CT is supported by the NIEHS (grants R21ES027044; R01ES030365-01).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ELEMENTS study was approved by the Institutional Review Boards of the National Institute of Public Health of Mexico, University of Toronto, University of Michigan, Indiana University, and Harvard School of Public Health. The MIREC study was approved by the research ethics boards at Health Canada, York University, and Indiana University. In both studies, all participating women signed informed consent forms for both mothers and children.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

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