Juan P. Arrebola

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.

Multivariate models to predict human adipose tissue PCB concentrations in Southern Spain.

The use of Polychlorinated biphenyls (PCBs) has been severely restricted due to their high toxicity and persistency in the environment. However, the presence of PCBs in human tissues nowadays is still been reported worldwide. Background exposure predictors of the human PCB body burden require more precise understanding. In the present study, PCB congeners 138, 153, and 180 were quantified in adult adipose tissue samples (n=387) from Granada Province (Southern Spain) and data on potential predictors of PCB concentrations were gathered by questionnaire. Chemical analysis of the selected congeners was done by gas chromatography and mass spectrometry, and multivariate analyses were performed stratifying by gender. PCB residues were quantified in 92% (PCB 153), 90% (PCB 180), and 86% (PCB 138) of the population. Geometric mean concentrations were 161.65+/-4.41 ng/g lipid for PCB 153, 111.62+/-6.27 ng/g lipid for PCB 180, and 38.41+/-8.61 ng/g lipid for PCB 138. Multivariate models explained 30-36% of the variability in PCB concentrations. Age and body mass index (BMI) predicted exposure in both males and females and were positively correlated with the concentration of the three PCB congeners. Occupation and diet predicted exposure in the males, whereas only dietary predictors were observed in the females. Further in-depth studies are required to investigate the influence of dietary habits on the bioaccumulation of PCBs and to evaluate the impact of policies aimed at reducing human exposure.

Predictors of concentrations of hexachlorobenzene in human adipose tissue: a multivariate analysis by gender in Southern Spain.

Hexachlorobenzene (HCB) was measured in adipose tissue intraoperatively collected from 387 subjects over 16 years old undergoing surgery in two hospitals in Granada (Southern Spain). HCB was quantified in 90.7% of subjects. The concentrations and frequencies of HCB were similar to those reported in adipose tissue samples in other recent European studies. Exposure patterns differed between females and males: higher HCB concentrations were found in females than in males (geometric mean 18.3 vs. 6.8 ng/g, p<0.001). The relationship between HCB concentrations and exposure risk factors was assessed by multivariate analysis stratifying by gender. In men, HCB concentrations were predicted (r(2)=0.45) by age, body mass index (BMI), place of residence, smoking, consumption of fish, chicken and cheese, occupation related to agriculture, and family involvement in construction activities. In women, HCB concentrations were predicted (r(2)=0.50) by age, BMI, consumption of milk and cheese, and occupation related to industry. The finding that women had three-fold higher levels of HCB than the men deserves further investigation.

Zearalenone and its metabolites in urine and breast cancer risk: a case-control study in Tunisia.

Zearalenone (ZON) is a non-steroidal estrogenic mycotoxin produced by Fusarium species. The exposure risk to humans and animals is the consumption of contaminated food and animal feeds. It has been reported that ZON and some of its metabolites promote the development of hormone-dependent tumors. The aim of this case-control study was to estimate exposure to ZON and its five metabolites (α-zearalenol [α-ZOL], β-zearalenol [β-ZOL], α-zearalanol [zeranol, α-ZAL], β-zearalanol [teranol, β-ZAL] and zearalanone [ZAN]) by measuring urinary concentrations of these compounds, and to evaluate the risk of breast cancer related to this exposure. Chemical analyses were carried out by liquid-liquid extraction (LLE) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Statistical analyses were performed in order to determine the association between exposure to these compounds and the development of breast cancer. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by unconditional logistic regression to estimate the magnitude of the associations. The obtained results (adjusted OR=1.54, 95% CI=1.10-2.77) suggest a potential role of α-ZAL in the risk of developing breast cancer.

Male specific association between xenoestrogen levels in placenta and birthweight

BACKGROUND Fetal exposure to endocrine disrupting chemicals may increase the risk for adverse health effects at birth or later in life. OBJECTIVES The objective of this study is to analyze the combined effect of xenoestrogens on reproductive and perinatal growth outcomes (child birthweight, early rapid growth and body mass index (BMI) at 14 months) using the biomarker total effective xenoestrogen burden (TEXB). METHODS 490 placentas were randomly collected in the Spanish prospective birth cohort Environment and Childhood (INMA) project. TEXB was used to assess the estrogenicity of placental samples in two fractions: that largely attributable to environmental organohalogenated xenoestrogens (TEXB-alpha), and that mostly due to endogenous estrogens (TEXB-beta), both expressed in estrogen equivalent units (Eeq) per gram of tissue. Linear or logistic regression models were performed adjusting for cohort and confounders. Sex interactions were investigated. RESULTS The median TEXB-alpha level was 0.76 pM Eeq/g (interquartile range (iqr): 1.14). In multivariate models, higher TEXB-alpha levels (third tertile, >1.22 pM Eeq/g; iqr: 1.73) were associated with increased birthweight in boys but not in girls (β=148.2 g, 95% CI: 14.01, 282.53, p(int)=0.057). Additionally, higher TEXB-alpha values in boys were related with a lower risk of early rapid growth (OR=0.37; 95% CI: 0.15, 0.88) and with a non significant association with larger BMI z-scores at 14 months of age (β=0.29; 95% CI: -0.11, 0.69). CONCLUSIONS These findings suggest that prenatal exposure to xenoestrogens may increase birthweight in boys, which might have an impact on child obesity and other later health outcomes.

Urinary levels of bisphenol A, benzophenones and parabens in Tunisian women: A pilot study

Bisphenol A (BPA), benzophenones and parabens are commonly used in the production of polycarbonate plastics, as UV-filters and as antimicrobial preservatives, respectively, and they are thought to exhibit endocrine disrupting properties. Exposure to these compounds remains poorly characterized in developing countries, despite the fact that certain behaviors related to westernization have the potential to influence exposure. The aim of this pilot study was to measure urinary concentrations of BPA, six different benzophenones and four parabens in 34 Tunisian women. In addition, we identified some socio-demographic and dietary predictors of exposure to these compounds. Chemical analyses were carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Detection frequencies of methylparaben (MP), ethylparaben (EP) and propylparaben (PP) ranged between 67.6 and 94.1%. Butylparaben (BP) was found in 38.2% of the analyzed samples; BPA in 64.7%; and benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 91.2 and 64.7% of the analyzed samples, respectively. Urinary geometric mean concentrations of MP, EP, PP, and BP were 30.1, 1.4, 2.0 and 0.5ngmL(-1), respectively. Geometric mean concentrations of BPA, BP-1, and BP-3 were 0.4, 1.3 and 1.1ngmL(-1), respectively. Our results suggest that Tunisian women are widely exposed to BPA, parabens and some benzophenones. Further studies on the general Tunisian population are needed in order to assess the levels of exposure to these compounds and to identify sources of exposure and population groups at higher risk.

Bisphenol A and other phenols in human placenta from children with cryptorchidism or hypospadias

Embryo-foetal exposure to low doses of endocrine disrupting chemicals (EDCs) has been related to reproductive tract diseases in experimental animals but not convincingly in human populations. The aim of this case-control study was to explore the relationship between exposure to non-persistent EDCs during pregnancy and male genital development. Exposure to bisphenol-A (BPA), benzophenones (BPs) [BP-1, BP-2, BP-3, BP-6, BP-8 and 4-hydroxybenzophenone (4-OH-BP),] and parabens (PBs) [methyl-, ethyl-, propyl- and butyl-PB] was analyzed by means of ultra-high performance liquid chromatography-tandem mass spectrometry in placenta samples from a subsample of 28 cases and 51 healthy controls nested in a cohort of newborns recruited between 2000 and 2002. The multivariable regression analyses indicated a statistically significant association between exposure to BPA and propyl-PB and the risk of malformations [adjusted odd ratio (95% CIs) in the third tertile of exposure: 7.2 (1.5-35.5) and 6.4 (1.2-35.5) for BPA and propyl-PB, respectively].

Historical exposure to persistent organic pollutants and risk of incident hypertension

The aim of this study was to assess the influence of adipose tissue concentrations of a group of persistent organic pollutants (POPs) on the risk of hypertension in an adult cohort of residents of Granada (Southern Spain) over a 10-year follow-up. No chemical was significantly associated with the risk of hypertension in the overall population or when models were stratified by sex or median age. However, we found positive associations between log-transformed POP concentrations and hypertension risk in participants with body mass index (BMI) above the median value of 26.3kg/m(2), which were statistically significant for hexachlorobenzene (HR=1.26, 95% CI=1.03-1.56), β-hexachlorocyclohexane (HR=1.25, 95% CI=1.03-1.51), and polychlorinated biphenyl congeners -138 (HR=1.32, 95% CI=1.04-1.69) and -153 (HR=1.36, 95% CI=1.00-1.84). Inverse associations were observed in the subgroup with BMI≤26.3kg/m(2), but none was statistically significant. More research and a longer follow-up period are warranted to verify these associations and elucidate the role of obesity as a potential effect modifier. Given the elevated worldwide frequency of POP exposure and hypertension, the public health impact of this relationship may be substantial.

Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: Preliminary data from year 9 of the follow-up

There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01-1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort.

Sonographic quantification of a hepato-renal index for the assessment of hepatic steatosis in comparison with 3T proton magnetic resonance spectroscopy.

Context Nonalcoholic fatty liver disease is the most frequent hepatic disorder in the developed world. Currently, liver biopsy and proton magnetic resonance spectroscopy (1H-MRS) are considered the gold standard methods for the quantification of liver fat deposits. Objective To determine whether a Sonographic Hepato-Renal Index (SHRI) calculated using a standard workstation, without a specifically designed software, is an adequate alternative to 1H-MRS for the quantification of fat liver content and diagnosis of steatosis in the general population. Methods A total of 121 volunteers (mean age=46 years, range=21–77 years) were recruited at three medical centers in Granada (Southern Spain) from among individuals attending routine general checkups. All participants were examined by ultrasound and by 1H-MRS 3T, which served as a reference for the diagnosis of steatosis. The SHRI was calculated as the ratio between the echogenicity of the liver and that of the right renal parenchyma. The validity of the methodology was assessed by receiver operating characteristic curves and correlation tests. Results The quantitative SHRI showed a strong correlation (Spearman’s coefficient=0.89, P<0.001) with the 1H-MRS 3T. The optimal SHRI cutoff points of 1.21, 1.28, and 2.15 yielded 100% sensitivity for the diagnoses of steatosis greater than 5, 25, and 50%, respectively, with a specificity greater than 70%. Conclusion This study shows that the SHRI is a valid, simple, reliable, and cost-effective screening tool for the identification, assessment, and quantification of hepatic steatosis in the general population.