Our Environmental Health Perspective’s paper (Swan 2005) was awarded “Best Paper of the Year” (based on frequency of citations over a five year period). This is the editorial that accompanied that award.
Fetal exposure to antiandrogens alters androgen-sensitive development in male rodents, resulting in less male-typical behavior. Fetal phthalate exposure is also associated with male reproductive development in humans, but neurodevelopmental outcomes have seldom been examined in relation to phthalate exposure. To assess play behavior in relation to phthalate metabolite concentration in prenatal urine samples, we recontacted participants in the Study for Future Families whose phthalate metabolites had been measured in mid-pregnancy urine samples. Mothers completed a questionnaire including the Preschool Activities Inventory (PSAI), a validated instrument used to assess sexually dimorphic play behavior. We examined play behavior scores (masculine, feminine and composite) in relation to (log10) phthalate metabolite concentrations in mother’s urine separately for boys (N=74) and girls (N=71). Covariates (child’s age, mother’s age and education and parental attitude towards atypical play choices) were controlled using multivariate regression models. Concentrations of dibutyl phthalate (DBP) metabolites, mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP), and their sum, were associated with a decreased (less masculine) composite score in boys (regression coefficients -4.53, -3.61, and -4.20, p=0.01, 0.07 and 0.04 for MnBP, MiBP and their sum, respectively). Concentrations of two urinary metabolites of di(2-ethylhexyl) phthalate (DEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and the sum of these DEHP metabolites plus mono(2-ethylhexyl) phthalate were associated with a decreased masculine score (regression coefficients -3.29, -2.94, and -3.18, p=0.02, 0.04 and 0.04) for MEHHP, MEOHP, and the sum, respectively. No strong associations were seen between behavior and urinary concentrations of any other phthalate metabolites in boys, or between girls’ scores and any metabolites. These data, though based on a small sample, suggest that prenatal exposure to antiandrogenic phthalates may be associated with less male-typical play behavior in boys. Our findings suggest that these ubiquitous environmental chemicals have the potential to alter androgen-responsive brain development in humans.