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The 2017–2018 U.S. PFAS exposure burden calculator was designed to provide a summary exposure score for per - and polyfluoroalkyl substances (PFAS) mixtures using targeted PFAS analyte data. Its aim was to place PFAS burden score estimates onto a common scale based on nationally representative U.S. reference ranges from 2017 to 2018, enabling comparisons of overall PFAS burden scores across studies even if they did not measure the same set of PFAS analytes. To use the U.S. PFAS exposure burden calculator for comparing the same mixture of PFAS compounds in similarly aged adolescents and their associations with cardiometabolic outcomes in the HOME Study and NHANES between 2015 and 2018. We applied the PFAS burden calculator to 8 PFAS analytes measured in the serum of adolescents from the HOME Study (Cincinnati, Ohio; age range 11–14 years; years: 2016–2019; n = 207) and NHANES (US; age range 12–14 years; years 2015–2018; n = 245). We used the non-parametric Mann-Whitney U test and chi-squared test to compare the two study samples. In both studies, we examined associations of PFAS burden scores with the same cardiometabolic outcomes, adjusted for the same core set of covariates using regression analyses. We conducted sensitivity analyses to verify robustness of exposure-outcome associations, by accounting for measurement error of PFAS burden scores. PFAS burden scores were significantly different (p = 0.004) between the HOME Study (median: 0.00, interquartile range − 0.37, 0.34) and the NHANES samples (median: 0.04, IQR -0.11, 0.54), while no significant difference was found for PFAS summed concentrations (p = 0.661). In the HOME Study, an interquartile (IQR) increase in PFAS burden score was associated with higher total cholesterol [7.0 mg/dL, 95% CI: 0.6, 13.4]; HDL [2.8 mg/dL, 95% CI: 0.4, 5.2]; LDL [5.9 mg/dL, 95% CI: 0.5, 11.3], insulin [0.1 log(mIU/L), 95% CI: 0.01, 0.2], and HOMA-IR [0.1, 95% CI: 0.01, 0.2]. In NHANES, an IQR increase in PFAS burden score was associated with higher diastolic blood pressure [2.4 mmHg, 95% CI: 0.4, 4.4] but not with other outcomes. Sensitivity analyses in the HOME Study and NHANES were consistent with the main findings. Performance of the U.S. PFAS exposure burden calculator was similar in a local versus national sample of adolescents, and may be a useful tool for the assessment of PFAS mixtures across studies. • A PFAS exposure burden calculator estimate a person's overall exposure burden to PFASs. • In the NHANES sample, adolescent PFAS exposure burden was associated with higher cholesterol and insulin resistance. • In the HOME Study sample, adolescent PFAS exposure burden was associated with higher diastolic blood pressure. • A standardized PFAS exposure burden metric can be useful for cross-study comparisons. [ABSTRACT FROM AUTHOR]

Associations between lead (Pb) and neurodevelopment have been studied widely in the context of global measures of cognitive function, such as IQ. Operant test batteries consist of behavioral tasks that can be used to target discrete cognitive and behavioral mechanisms, which contribute to global cognitive faculties. The goals of this study were to identify Pb-associated deficits in cognitive development and determine the underlying mechanisms involved, utilizing an operant test battery. We evaluated effect modification by child sex. This study utilized data from a prospective cohort in Mexico City. We included 549 participants aged 6-to-7 years with complete data on prenatal blood Pb measurements, Operant Test Battery (OTB) tasks, and demographic covariates. General linear models were used to examine the association of Pb levels at each prenatal timepoint and OTB performance. Effect modification by child sex was evaluated using 2-way interaction terms. In three of the operant tasks, we observed that higher late-pregnancy blood Pb concentrations were associated with greater response latencies. In the temporal processing task, we observed that higher late-pregnancy Pb exposure was associated with worse overall task performance. Further, in two operant tasks, the effects of Pb were dependent on the sex of the child, such that the effects of Pb were more pronounced in females in the condition position responding task, but stronger in males in the temporal processing task. Our results suggest that prenatal Pb concentrations yield broad dysregulation of executive functions, which can be attributed to dysregulation of temporal processing. In addition, we observed sex differences in two operant tasks suggesting that some Pb effects on neurocognitive function may be sexually dimorphic. • Operant testing procedures were used to attribute lead-associated deficits to discrete cognitive mechanisms • Higher prenatal lead (Pb) concentrations yield broad dysregulation of executive functions • Prenatal Pb concentrations dysregulations can be, in part, attributed to dysregulation of temporal processing • Sex differences were observed in two operant tasks suggesting that some Pb effectsmay be sexually dimorphic [ABSTRACT FROM AUTHOR]

Toxicological studies have raised concerns regarding the neurotoxic effects of per - and polyfluoroalkyl substances (PFAS). However, observational evidence from human studies investigating the association between childhood PFAS and neurobehavior is limited and remains unclear. To examine whether childhood PFAS concentrations are associated with neurobehavior in children at age 8 years and whether child sex modifies this relationship. We used data from 208 mother-child dyads in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort (Cincinnati, OH, USA). We quantified PFAS in child serum at 3 and 8 years. We assessed neurobehavioral domains using the Behavior Assessment System for Children-2 at 8 years. We used multiple informant models to estimate score changes per ln-increase in repeated PFAS concentrations. Childhood PFAS were not associated with Externalizing or Internalizing Problems at 8 years. However, we noted effect measure modification by sex, with higher scores in Externalizing Problems among males per ln-unit increase in perfluorononanoate (PFNA) at 3 years (β = 4.3 points, 95% CI: 1.0, 7.7) while females had lower scores (β = −2.8 points, 95% CI: −4.7, −1.0). More Internalizing Problems were observed among males per ln-unit increase in concurrent PFNA concentrations (β = 3.7 points, 95% CI: 0.7, 6.8), but not in females (β = −1.7 points, 95% CI: −4.6, 1.2). Childhood PFNA concentrations were associated with lower scores for attention problems and activity of daily living. While findings do not consistently support an association between childhood PFAS serum concentrations and neurobehavior, child sex may play a role in this relationship. • Childhood PFAS were not associated with externalizing or internalizing behaviors at 8 years. • Sex modified the relationship between childhood PFAS and neurobehavior, with males having worse scores. • Childhood PFNA was associated with poorer scores for activity of daily living and lower attention problems. • Prenatal PFAS were associated with more externalizing and internalizing problems even after adjustment for childhood PFAS. [ABSTRACT FROM AUTHOR]