A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children

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  • Philippe Grandjean
  • Howard Hu
  • Christine Till
  • Rivka Green
  • Morteza Bashash
  • David Flora
  • Martha Maria Tellez-Rojo
  • Peter X.K. Song
  • Bruce Lanphear
  • Budtz-Jørgensen, Esben

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.

OriginalsprogEngelsk
TidsskriftRisk Analysis
Vol/bind42
Udgave nummer3
Sider (fra-til)439-449
Antal sider11
ISSN0272-4332
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The authors gratefully acknowledge: Nicole Lupien, Stéphanie Bastien, and Romy‐Leigh McMaster and the MIREC Study Coordinating Staff for their administrative support, Dr. Jillian Ashley‐Martin for providing feedback on the manuscript, as well as the MIREC study group of investigators and site investigators; Alain Leblanc from the INSPQ for measuring the urinary creatinine; Dr. Angeles Martinez‐Mier, Christine Buckley, Dr. Frank Lippert and Prithvi Chandrappa for their analysis of urinary fluoride at the Indiana University School of Dentistry; Linda Farmus for her assistance with statistical modeling. This MIREC Biobank study was funded by a grant from the National Institute of Environmental Health Science (NIEHS) (grant #R21ES027044). 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).

Funding Information:
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).

Publisher Copyright:
© 2021 Society for Risk Analysis

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