Determination of endocrine-disrupting chemicals in human milk by dispersive liquid-liquid microextraction.

AIM: Human populations are widely exposed to numerous so-called endocrine-disrupting chemicals, exogenous compounds able to interfere with the endocrine system. This exposure has been associated with several health disorders. New analytical procedures are needed for biomonitoring these xenobiotics in human matrices. A quick and inexpensive methodological procedure, based on sample treatment by dispersive liquid-liquid microextraction, is proposed for the determination of bisphenols, parabens and benzophenones in samples. RESULTS: LOQs ranged from 0.4 to 0.7 ng ml(-1) and RSDs from 4.3 to 14.8%. CONCLUSION: This methodology was satisfactorily applied in the simultaneous determination of a wide range of endocrine-disrupting chemicals in human milk samples and is suitable for application in biomonitoring studies.

Prenatal exposure to mixtures of xenoestrogens and genome-wide DNA methylation in human placenta.

BACKGROUND: In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation. MATERIALS & METHODS: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas. RESULTS: No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B. CONCLUSION: Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated.

Hair mercury levels, fish consumption, and cognitive development in preschool children from Granada, Spain .

The main source of human exposure to mercury is the consumption of fish contaminated with methylmercury, which may adversely affect early neurodevelopment. This study assessed mercury levels in hair of preschoolers in Spain, where fish consumption is elevated, with the aim of investigating the influence of their fish intake and other factors on mercury exposure, and evaluating their association with cognitive development. A population-based birth cohort from Granada (Spain) was studied at the age of 4yr. Total mercury (T-Hg) levels were determined in children's hair, and daily fish intake was assessed by a food frequency questionnaire. The McCarthy Scales of Children's Abilities (MSCA) were used to assess children's motor and cognitive abilities. Complete data were gathered on 72 children, and multivariate analyses were performed to evaluate the influence of mercury exposure and fish intake on MSCA outcomes. Mean concentration of T-Hg in hair was 0.96 microg/g (95% confidence interval=0.76; 1.20 microg/g). T-Hg levels were associated with higher frequency of oily fish consumption, place of residence, maternal age, and passive smoking. After adjustment for fish intake, T-Hg levels > or =1microg/g were associated with decrements in the general cognitive (-6.6 points), memory (-8.4 points), and verbal (-7.5 points) MSCA scores. Higher mercury exposure in children from this Mediterranean area was associated with cognitive development delay. Studies on the putative benefits of fish intake during early development should consider mercury exposure from different fish species.

Association of traffic-related air pollution with cognitive development in children.

BACKGROUND: Air pollution from traffic has been associated with cardiorespiratory diseases in children and adults, but there is little information on its potential neurotoxic effects. This study aimed to investigate the association between exposure to nitrogen dioxide (NO(2)), as a marker of traffic-related air pollution, and cognitive development in children. METHODS: A population-based birth cohort from southern Spain was followed from the age of 4 years for 1 year. Complete data for analyses were gathered on 210 children living in urban and rural areas. NO(2) exposure was predicted by means of land use regression models. A standardised version of the McCarthy Scales of Children's Abilities (MSCA) was used to assess children's motor and cognitive abilities. Multivariate analyses were performed to evaluate the relation between exposure to NO(2) and MSCA outcomes, adjusting for potential confounders. RESULTS: A negative effect of NO(2) was found across all MSCA subscales, despite low predicted NO(2) exposure levels (5-36 microg/m(3)). Children exposed to higher NO(2) (>24.75 microg/m(3)) showed a decrease of 4.19 points in the general cognitive score and decreases of 6.71, 7.37 and 8.61 points in quantitative, working memory and gross motor areas, respectively. However, except for gross motor function, associations were not statistically significant. CONCLUSION: Although results were not statistically significant, the associations found between exposure to NO(2) and cognitive functions suggest that traffic-related air pollution may have an adverse effect on neurodevelopment, especially early in life, even at low exposure levels.

Steroid receptor profiling of vinclozolin and its primary metabolites.

Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERalpha and ERbeta). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR>>PR>GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.