As a guide to establishing a safe exposure level for fluoride exposure in pregnancy, we applied benchmark dose modeling to data from two prospective birth cohort studies. 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. Maternal urinary fluoride concentrations (U-F, in mg/L, creatinine-adjusted) were measured in urine samples obtained during pregnancy. Children were assessed for intelligence quotient (IQ) at age 4 (n = 211) and between six and 12 years (n = 287) in the ELEMENT cohort, and three to four years (n = 407) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to assess the association of maternal U-F concentrations with children’s IQ measures. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) and benchmark concentration levels (BMCLs). No deviation from linearity was detected in the dose-response relationships, but boys showed lower BMC values than girls. Using a linear slope for the joint cohort data, the BMC for maternal U-F associated with a 1-point decrease in IQ scores was 0.31 mg/L (BMCL, 0.19 mg/L) for the youngest boys and girls in the two cohorts, and 0.33 mg/L (BMCL, 0.20 mg/L) for the MIREC cohort and the older ELEMENT children. Thus, the joint data show a BMCL in terms of the adjusted U-F concentrations in the pregnant women of approximately 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in pregnant women.
*Original abstract online at https://doi.org/10.1111/risa.13767
… The increased precision using the average maternal U-F concentration as an indicator of prenatal fluoride exposure results in stronger statistical evidence of fluoride-associated deficits, compared with using cross-sectional or retrospective studies. Still, the amount of fluoride that reaches the brain during early brain development is unknown, and even the maternal U-F concentration measurements may be considered somewhat imprecise as dose indicators. Such imprecision, likely occurring at random, will tend to underestimate fluoride neurotoxicity (Grandjean & Budtz-Jørgensen, 2010).
The prospective studies offer strong evidence of prenatal neurotoxicity, and the benchmark results should inspire a revision of water-fluoride recommendations aimed at protecting pregnant women and young children. While systemic fluoride exposure has been linked to dental health benefits in early studies (Iheozor-Ejiofor et al., 2015), these benefits occur in the oral cavity after teeth have erupted (Featherstone, 2000), thus suggesting that use of toothpaste and other topical treatment should be considered for alternative caries prevention…
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).
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*Original abstract online at https://doi.org/10.1111/risa.13767