Abstract
BACKGROUND: Exposure to phthalates and non-phthalate plasticizers as well as bisphenols may be relevant to the development of behavioural symptoms in childhood with sex-specific effects, although the results of existing studies are not consistent. The aim of the study was to evaluate the cross-sectional association between childhood exposure to these compounds and behavioral outcomes in the REPRO_PL cohort (Poland). METHODS: Behavioral assessments were performed at the age of 7-9 years by parents using the Strengths and Difficulties Questionnaire (SDQ). HPLC-MS/MS was used for the quantification of BPA and 21 phthalate metabolites corresponding to 11 phthalate compounds (n = 400) and their replacement alternatives BPF, BPS, three metabolites of diethylhexyl terephthalate (DEHTP) and three metabolites of di-isononyl-cyclohexane-1,2-dicarboxylate (DINCH) (n = 150). Multivariable linear regression models accounting for sex-specific effects as well as sex-adjusted models were applied, using both separate models for each metabolite (or sum of metabolites) and joint models. In addition, mixtures models adjusted by the three chemical groups studied were also performed. RESULTS: Median concentrations of several phthalate metabolites and bisphenols were of 42 µg/L (MEP), 4.5 µg/L (MMP), 3.5 µg/L (ΣDiDP), 2 µg/L (BPA) and 1 µg/L (BPF). For ΣDEHTP and ΣDINCH, the median concentrations were 35 µg/L and 3.1 µg/L, respectively. Exposure to phthalates was related to behavioral problems in girls, and bisphenols and DEHTP in boys. Among girls, DiBP was associated with mental health problems (total difficulties: β = 4.84; 95% CI 0.72;8.96, emotional: β = 2.14; 95% CI 0.33;4.0, hyperactivity/inattention: β = 2.52; 95% CI 0.55;4.49, externalizing behavior: (β = 2.95; 95% CI 0.36;5.53) and DiDP with hyperactivity/inattention scores (β = 2.46; 95% CI 0.30;4.63). BPF was associated with emotional problems and internalizing behavior among boys in both main and sensitivity models (main model: β = 1.03; 95% CI -0.16;2.21 and β = 1.71; 95% CI -0.14;3.56 respectively). CONCLUSIONS: This study shows that children's exposure to several replacement compounds of BPA and phthalates, such as BPF and DEHTP, are associated with adverse effects on school-age children's behavior, with a divergent sex-specific effect. In any case, mixture models did not provide any further insight on the aforementioned cross-sectional associations and further methodological approaches are needed to explore adverse neurodevelopmental outcomes in children and teenagers.