RESUMO
BACKGROUND: Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF). OBJECTIVE: To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain). METHODS: BPA concentrations were quantified by LC-MS/MS in spot urine samples from boys aged 9-11 years, normalized by creatinine and log-2 transformed. At adolescence (15-17 years), blood and urine specimens were collected, and serum and urinary BDNF protein levels were measured using immunoassays. DNA methylation levels at 6 CpGs in Exon IV of the BDNF gene were also assessed in peripheral blood using bisulfite-pyrosequencing. Adolescent's behavior was parent-rated using the Child Behavior Checklist (CBCL/6-18) in 148 boys. Adjusted linear regression and mediation models were fit. RESULTS: Childhood urinary BPA concentrations were longitudinally and positively associated with thought problems (ß = 0.76; 95% CI: 0.02, 1.49) and somatic complaints (ß = 0.80; 95% CI: -0.16, 1.75) at adolescence. BPA concentrations were positively associated with BDNF DNA methylation at CpG6 (ß = 0.21; 95% CI: 0.06, 0.36) and mean CpG methylation (ß = 0.10; 95% CI: 0.01, 0.18), but not with total serum or urinary BDNF protein levels. When independent variables were categorized in tertiles, positive dose-response associations were observed between BPA-thought problems (p-trend = 0.08), BPA-CpG6 (p-trend ≤ 0.01), and CpG6-thought problems (p-trend ≤ 0.01). A significant mediated effect by CpG6 DNA methylation was observed (ß = 0.23; 95% CI: 0.01, 0.57), accounting for up to 34% of the BPA-thought problems association. CONCLUSIONS: In line with toxicological studies, BPA exposure was longitudinally associated with increased BDNF DNA methylation, supporting the biological plausibility of BPA-behavior relationships previously described in the epidemiological literature. Given its novelty and preliminary nature, this effect biomarker approach should be replicated in larger birth cohorts.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Exposição Ambiental , Adolescente , Compostos Benzidrílicos , Criança , Cromatografia Líquida , Exposição Ambiental/análise , Humanos , Masculino , Fenóis , Estudos Prospectivos , Espectrometria de Massas em TandemRESUMO
INTRODUCTION: Bisphenol A (BPA) is a well-known endocrine disrupting compound. Although several studies have investigated the effect of BPA exposure and reproductive hormones in humans, results have been inconsistent. OBJECTIVE: To explore the cross-sectional relationship between bisphenol A (BPA) exposure and reproductive hormones/cortisol among peripubertal boys. MATERIAL AND METHODS: Urinary BPA and serum hormones were assessed in 172 boys belonging to the INMA "Environment and Childhood" Granada birth cohort in their follow-up at 9-11years of age. BPA concentrations were quantified by liquid chromatography-mass spectrometry, and levels of serum total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol were measured by electrochemiluminescence immunoassay. RESULT(S): After adjustment for confounders, linear regression models showed that each natural-log unit increase in urinary BPA concentrations was associated with a 19% increase in geometric mean (GM) serum TT levels, and a 16% decrease in GM serum cortisol levels. When urinary BPA concentrations were categorized in tertiles, boys in the 3rd tertile showed 49% higher TT levels and 23% lower cortisol concentrations compared to boys in the 1st tertile. Additionally, urinary BPA concentrations were also significantly associated with higher TT:LH and TT:cortisol ratios, but not with serum LH or FSH levels. CONCLUSION(S): Our results suggest the possible endocrine disrupting potential of BPA during this important period of development. Although action at the testis or pituitary cannot be ruled out, our findings are compatible with a possible involvement of BPA at the adrenal gland, resulting in a differential production of androgens/cortisol. However, given the cross-sectional design of our study, the heterogeneous results reported in the literature, and the scant experimental research on BPA effects at the adrenal gland, the present findings should be interpreted with caution.
Assuntos
Compostos Benzidrílicos/urina , Hormônio Foliculoestimulante/sangue , Hidrocortisona/sangue , Hormônio Luteinizante/sangue , Fenóis/urina , Testosterona/sangue , Glândulas Suprarrenais/efeitos dos fármacos , Criança , Estudos Transversais , Exposição Ambiental/análise , Humanos , Masculino , EspanhaRESUMO
This study examined the potential association of maternal serum levels of o,p'-DDT and p,p'-DDE with gestation time and with anthropometric measurements and thyroid-stimulating hormone (TSH) levels of newborns in a Bolivian birth cohort. Two hundred mothers were consecutively recruited between January and March 2013 at the "Hospital de la Mujer Dr. Percy Boland" in Santa Cruz de la Sierra. Potential confounders were derived from an ad hoc questionnaire. o,p'-DDT and p,p'-DDE were quantified in cord serum by high-resolution gas chromatography coupled with mass spectrometry. Multivariable linear regression analyses were performed, with POP concentrations as independent variables and log-transformed newborn birth outcomes (newborn weight, gestational age, head circumference, birth height, ponderal index, and TSH levels) as dependent variables. o,p'-DDT was detected in 82.5% of samples at median concentration of 0.22ng/mL and p,p'-DDE in 86.5% of samples at median concentration of 1.01ng/mL. Opposite associations with birth weight were found for p,p'-DDE (ß=0.012, p=0.006) and o,p'-DDT (ß=-0.014, p=0.039), and these associations were stronger when both chemicals were entered in the same model. p,p'-DDE was negatively associated with gestation time (ß=-0.004, p=0.012), and o,p'-DDT was borderline negatively associated with newborn head circumference (ß=-0.004, p=0.054). We observed no relevant changes in the magnitude of the coefficients or in statistical significance after adjustment for newborn TSH levels. This study indicates a possible impact of prenatal exposure to o,p'-DDT and p,p'-DDE on newborn anthropometric measurements in a population showing evidence of recent exposure to the pesticide DDT.
Assuntos
Peso ao Nascer , DDT/sangue , Diclorodifenil Dicloroetileno/sangue , Efeitos Tardios da Exposição Pré-Natal , Tireotropina/sangue , Adulto , Antropometria , Bolívia , Estudos de Coortes , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Masculino , Gravidez , Adulto JovemRESUMO
The smoke-free legislation implemented in Spain in 2006 imposed a partial ban on smoking in public and work places, but the result did not meet expectations. Therefore, a more restrictive anti-smoking law was passed five years later in 2011 prohibiting smoking in all public places, on public transport, and the workplace. With the objective of assessing the impact of the latter anti-smoking legislation on children's exposure to second-hand smoke (SHS), we assessed parent's smoking habits and children's urine cotinine (UC) concentrations in 118 boys before (2005-2006) and after (2011-2012) the introduction of this law. Repeated cross-sectional follow-ups of the "Environment and Childhood Research Network" (INMA-Granada), a Spanish population-based birth cohort study, at 4-5 years old (2005-2006) and 10-11 years old (2011-2012), were designed. Data were gathered by ad-hoc questionnaire, and median UC levels recorded as an objective indicator of overall SHS exposure. Multivariable logistic regression was used to examine the association between parent's smoking habits at home and SHS exposure, among other potential predictors. An increase was observed in the prevalence of families with at least one smoker (39.0% vs. 50.8%) and in the prevalence of smoking mothers (20.3% vs. 29.7%) and fathers (33.9% vs. 39.0%). Median UC concentration was 8.0ng/mL (interquartile range [IQR]: 2.0-21.8) before legislation onset and 8.7ng/mL (IQR: 2.0-24.3) afterwards. In the multivariable analysis, the smoking status of parents and smoking habits at home were statistically associated with the risk of SHS exposure and with UC concentrations in children. These findings indicate that the recent prohibition of smoking in enclosed public and workplaces in Spain has not been accompanied by a decline in the exposure to SHS among children, who continue to be adversely affected. There is a need to target smoking at home in order to avoid future adverse health effects in a population that has no choice in the acceptance or not of SHS exposure-derived risk.
Assuntos
Poluição do Ar em Ambientes Fechados/análise , Exposição por Inalação , Fumar/legislação & jurisprudência , Poluição por Fumaça de Tabaco/análise , Poluição do Ar em Ambientes Fechados/legislação & jurisprudência , Criança , Pré-Escolar , Cotinina/urina , Estudos Transversais , Seguimentos , Humanos , Exposição por Inalação/legislação & jurisprudência , Masculino , Prevalência , Fumar/epidemiologia , Espanha/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Poluição por Fumaça de Tabaco/legislação & jurisprudênciaRESUMO
Organochlorine pesticide p,p'-dichlorodiphenyltrichloroethane (DDT) is still used for vector control in several tropical and subtropical areas of South America and there is evidence of recent illegal use in agriculture. Its main breakdown product in the environment and living organisms is p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), which is considered a marker of past exposure to DDT. The aim of the present study was to assess human exposure to p,p'-DDE in a sample of agricultural farmers from three rural communities in eastern Bolivia. In addition, o,p'-DDT was analyzed as a surrogate of a potential ongoing exposure to the pesticide. Face-to-face questionnaires were performed, and serum samples were analyzed by high-resolution gas chromatography with mass spectrometry. p,p'-DDE was found in 100% of the samples, with a median concentration of 19.7ngmL(-1) (4788.7ng/g lipid), while o,p'-DDT was detected in 3 samples (4.3%). Serum p,p'-DDE concentrations were associated with time of residence in the study area, personal hygiene after work, and body mass index in adjusted multinomial logistic regression models with tertiles of p,p'-DDE as the dependent variable. The present results revealed high levels of exposure to p,p'-DDE, which might be derived from a heavily polluted local environment and past occupational exposure. These findings deserve further attention due to the potential associated health risks and point to the need for the continuous monitoring of these populations.