Maria-Jose Lopez-Espinosa

Human exposure to endocrine-disrupting chemicals and prenatal risk factors for cryptorchidism and hypospadias: a nested case-control study

Background Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs. Objective In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations. Methods In a case–control study, nested in a mother–child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results TEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus non-detectable TEXB of 2.82 (95% CI, 1.10–7.24). More pesticides were detected in cases than in controls (9.34 ± 3.19 vs. 6.97 ± 3.93). ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p′-DDT (OR = 2.25; 95% CI, 1.03–4.89), p,p′-DDT (OR = 2.63; 95% CI, 1.21–5.72), lindane (OR = 3.38; 95% CI, 1.36–8.38), mirex (OR = 2.85; 95% CI, 1.22–6.66), and endosulfan alpha (OR = 2.19; 95% CI, 0.99–4.82). Engagement of mothers in agriculture (OR = 3.47; 95% CI, 1.33–9.03), fathers’ occupational exposure to xenoestrogens (OR = 2.98; 95% CI, 1.11–8.01), and history of previous stillbirths (OR = 4.20; 95% CI, 1.11–16.66) were also associated with risk of malformations. Conclusions We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta.

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 childrens hair, and daily fish intake was assessed by a food frequency questionnaire. The McCarthy Scales of Childrens Abilities (MSCA) were used to assess childrens 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 Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) with Age of Puberty among Children Living near a Chemical Plant

Animal studies suggest that perfluorocarbons (PFCs) may alter sexual maturation. Relationships of human PFC exposure with puberty are not clear. We conducted a cross-sectional study to investigate whether perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were associated with indicators of sexual maturation in a 2005-2006 survey of residents with PFOA water contamination from the Mid-Ohio Valley. Participants were 3076 boys and 2931 girls aged 8-18 years. They were classified as having reached puberty based on either hormone levels (total >50 ng/dL and free >5 pg/mL testosterone in boys and estradiol >20 pg/mL in girls) or onset of menarche. We estimated the odds of having reached puberty classified by these criteria and the fitted median age of reaching puberty in relation to serum PFOA and PFOS concentrations measured when puberty status was assigned. For boys, there was a relationship of reduced odds of reached puberty (raised testosterone) with increasing PFOS (delay of 190 days between the highest and lowest quartile). For girls, higher concentrations of PFOA or PFOS were associated with reduced odds of postmenarche (130 and 138 days of delay, respectively). In conclusion, our study showed a later age of puberty in this population correlated with PFC concentrations.

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 (NO2), 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. NO2 exposure was predicted by means of land use regression models. A standardised version of the McCarthy Scales of Childrens Abilities (MSCA) was used to assess childrens motor and cognitive abilities. Multivariate analyses were performed to evaluate the relation between exposure to NO2 and MSCA outcomes, adjusting for potential confounders. Results A negative effect of NO2 was found across all MSCA subscales, despite low predicted NO2 exposure levels (5–36 μg/m3). Children exposed to higher NO2 (>24.75 μg/m3) 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 NO2 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.

Serum perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) concentrations and liver function biomarkers in a population with elevated PFOA exposure.

Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported inconsistent associations between PFOA and liver enzymes. Objectives: We examined the cross-sectional association between serum PFOA and PFOS concentrations with markers of liver function in adults. Methods: The C8 Health Project collected data on 69,030 persons; of these, a total of 47,092 adults were included in the present analysis. Linear regression models were fitted for natural log (ln)-transformed values of alanine transaminase (ALT), γ-glutamyltransferase (GGT), and direct bilirubin on PFOA, PFOS, and potential confounders. Logistic regression models were fitted comparing deciles of PFOA or PFOS in relation to high biomarker levels. A multilevel analysis comparing the evidence for association of PFOA with liver function at the individual level within water districts to that at the population level between water districts was also performed. Results: ln-PFOA and ln-PFOS were associated with ln-ALT in linear regression models [PFOA: coefficient, 0.022; 95% confidence interval (CI): 0.018, 0.025; PFOS: coefficient, 0.020; 95% CI: 0.014, 0.026] and with raised ALT in logistic regression models [with a steady increase in the odds ratio (OR) estimates across deciles of PFOA and PFOS; PFOA: OR = 1.10; 95% CI: 1.07, 1.13; PFOS: OR = 1.13; 95% CI: 1.07, 1.18]. There was less consistent evidence of an association of PFOA and GGT or bilirubin. The relationship with bilirubin appears to rise at low levels of PFOA and to fall again at higher levels. Conclusions: These results show a positive association between PFOA and PFOS concentrations and serum ALT level, a marker of hepatocellular damage.

Effect of Iodine Supplementation During Pregnancy on Infant Neurodevelopment at 1 Year of Age

Iodine is the main constituent of thyroid hormones, which in turn are required for fetal brain development. However, the relation between iodine intake during pregnancy, thyroid function, and child neurodevelopment needs further evaluation. The authors assessed the association of maternal iodine intake from diet and supplements during pregnancy and of maternal and neonatal thyroid function with infant neurodevelopment. The Mental Development Index and Psychomotor Development Index (PDI) for 691 children were obtained between 2005 and 2007 using the Bayley Scales of Infant Development at age 1 year in a prebirth cohort in Valencia, Spain. In multivariate analyses, a maternal thyrotropin level >4 μU/mL was associated with an increased risk of a PDI <85 (odds ratio = 3.5, P = 0.02). Maternal intake of ≥150 μg/day, compared with <100 μg/day, of iodine from supplements was associated with a 5.2-point decrease in PDI (95% confidence interval: -8.1, -2.2) and a 1.8-fold increase in the odds of a PDI <85 (95% confidence interval: 1.0, 3.3). When analyses were stratified by sex, this association was intensified for girls but was not observed for boys. Further evidence on the safety and effectiveness of iodine supplementation during pregnancy is needed before it is systematically recommended in iodine-sufficient or mildly deficient areas.

Thyroid Function and Perfluoroalkyl Acids in Children Living Near a Chemical Plant

Background: Animal studies suggest that some perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) may impair thyroid function. Epidemiological findings, mostly related to adults, are inconsistent. Objectives: We investigated whether concentrations of PFAAs were associated with thyroid function among 10,725 children (1–17 years of age) living near a Teflon manufacturing facility in the Mid-Ohio Valley (USA). Methods: Serum levels of thyroid-stimulating hormone (TSH), total thyroxine (TT4), and PFAAs were measured during 2005–2006, and information on diagnosed thyroid disease was collected by questionnaire. Modeled in utero PFOA concentrations were based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We performed multivariate regression analyses. Results: Median concentrations of modeled in utero PFOA and measured serum PFOA, PFOS, and PFNA were 12, 29, 20, and 1.5 ng/mL, respectively. The odds ratio for hypothyroidism (n = 39) was 1.54 [95% confidence interval (CI): 1.00, 2.37] for an interquartile range (IQR) contrast of 13 to 68 ng/mL in serum PFOA measured in 2005–2006. However, an IQR shift in serum PFOA was not associated with TSH or TT4 levels in all children combined. IQR shifts in serum PFOS (15 to 28 ng/mL) and serum PFNA (1.2 to 2.0 ng/mL) were both associated with a 1.1% increase in TT4 in children 1–17 years old (95% CIs: 0.6, 1.5 and 0.7, 1.5 respectively). Conclusions: This is the first large-scale report in children suggesting associations of serum PFOS and PFNA with thyroid hormone levels and of serum PFOA and hypothyroidism.

Nonylphenol and octylphenol in adipose tissue of women in Southern Spain

Alkylphenols (APs) and AP ethoxylates are environmental contaminants with endocrine disrupting activities in wildlife and humans. They have been largely used in industrial, agricultural, and domestic applications. Despite strong concerns about the consequences of human exposure to endocrine disrupters, little information is available on the presence in humans of compounds such as APs. The aim of the present study was to determine 4-nonylphenol (NP) and 4-octylphenol (OP) residues in adipose tissue of non-occupationally exposed women living in Southern Spain. NP was detected in 100% (n=20/20) and OP in 23.5% (n=4/20) of samples, with median levels of 57 and 4.5 ng g(-1) adipose tissue, respectively. Body mass index emerged as a determinant of exposure since it was associated with NP levels (p=0.041). Adipose tissue NP and OP levels are similar to the few data previously published in other countries. This is the first report on NP and OP levels in a population in Southern Spain. Further research is needed to determine trends in human exposure to these compounds and to investigate their consequences.

Oestrogenicity of paper and cardboard extracts used as food containers

Bisphenol-A (BPA), dibutyl phthalate (DBP), and di-2-ethylhexyl phthalate (DEHP), which are common chemical residues in food-packaging materials, were investigated in paper and cardboard containers used for take-away food. The oestrogenicity of aqueous extracts was tested in E-Screen bioassay and analysis carried out by high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC/MS). Oestrogenicity was demonstrated in 90% of extracts (geometric mean [GM] = 11.97 pM oestradiol equivalents g−1). DEHP, DBP, and BPA (GM = 341.74, 37.59, and 2.38 ng g−1 of material) were present in 77.50, 67.50, and 47.50% of samples, respectively. In bivariate analyses, no significant association was found between the levels of these chemicals and oestrogenicity in cardboard/paper extracts. A close-to-significant association was found between oestrogenicity and DBP (β = 1.25; p = 0.06) in paper extracts, which reached statistical significance in multivariate analysis (β = 1.61; p = 0.03). Paper and cardboard used in food packaging may contribute to the inadvertent exposure of consumers to endocrine-disrupting chemicals.

Gender differences in the neurotoxicity of metals in children

Gender-related differences in susceptibility to chemical exposure to neurotoxicants have not received sufficient attention. Although a significant number of epidemiological studies on the neurodevelopmental effects of metal exposure has been published in the last twenty years, not many of them have considered the possible gender-specific effects of such exposure. This review is focused on studies where the gender differences in pre- and/or postnatal exposure/s to five metals (mercury, lead, manganese, cadmium, and arsenic) and neurodevelopment were evaluated. We conducted a PubMed search in December 2012 and retrieved 20 studies that met the inclusion criteria. A large body of literature on potential neurodevelopment effects in children due to mercury exposure is available, but, a clear pattern regarding gender differences in neurotoxicity is not elucidated. There is also abundant available information on the gender-specific health effects of lead, and exposure to this metal seems to affect boys more than girls. Information regarding gender differences in susceptibility of manganese, cadmium, and arsenic is still too scarce to draw any definite conclusion. More research is highly warranted about this matter. Environmental epidemiological studies should be designed to quantify differential gender-based exposures and outcomes, and this may provide new insights into prevention strategies.