Sex-specific neurotoxic effects of early-life exposure to fluoride: A review of the epidemiologic and animal literature.

Purpose of review: A growing body of evidence suggests adverse neurodevelopmental effects of early-life exposure to fluoride that may differ depending on timing of exposure and sex of the exposed. We conducted a literature search to identify the animal and human epidemiologic studies that examined sex-specific neurodevelopmental differences in response to prenatal and postnatal exposure to fluoride.

Recent findings: Six of 138 animal studies and 15 of 106 human epidemiologic studies tested for sex-specific effects. Prenatal exposure to fluoride was associated with a male susceptibility to adverse behavioural effects in four of six animal studies and lower IQ in one of three prospective cohort studies. The body of evidence examining sex-effects associated with postnatal fluoride exposure was scarce, and many animal and cross-sectional human studies were considered to have a high risk of bias.

Summary: Compared to females, male offspring appear to be more sensitive to prenatal, but not postnatal, exposure to fluoride. We discuss several sex-specific mechanisms and emphasize the need for future research.