Annalisa Abballe

Endometriosis and Organochlorinated Environmental Pollutants: A Case–Control Study on Italian Women of Reproductive Age

Background Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. Objective We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. Methods We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. Results We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs. Conclusions The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis.

Maternal exposures to endocrine disrupting chemicals and hypospadias in offspring

BACKGROUND Prenatal exposures to endocrine-disrupting chemicals (EDCs) are suspected risk factors in the etiology of hypospadias. The aim of this case-control study was to test the hypothesis of an association between maternal environmental exposures to EDCs and hypospadias in the offspring. METHODS Detailed questionnaire data on occupational and dietary exposures to EDCs in the perinatal period were collected from 80 mothers with hypospadiac infants and from 80 mothers with healthy controls within 24 months of childbirth. Maternal exposure to selected EDCs was also ascertained by measuring the concentration of dichlorodiphenyldichloroethylene, hexachlorobenzene, and several polychlorinated biphenyl congeners in the serum of primiparous mothers of 37 cases and 21 controls. RESULTS The risk to bear an hypospadiac infant was associated with perinatal maternal occupational exposures to EDCs evaluated by a job-exposure matrix: jobs with exposure to one class of EDCs (odds ratios [OR](crude), 2.83; 95% confidence intervals [CI], 1.32-6.07; OR(adjusted), 2.44; 95% CI, 1.06-5.61) and jobs with exposure to more than one group of EDCs (OR(crude), 4.27; 95% CI, 1.43-12.78; OR(adjusted), 4.11; 95%CI, 1.34-12.59). Increase in risk was also found among mothers consuming a diet rich in fish or shellfish (OR(crude), 3.41; 95% CI, 1.42-8.23; OR(adjusted), 2.73; 95%CI, 1.09-6.82). Serum hexachlorobenzene concentration above the median of all subjects was significantly associated with the risk of hypospadias (OR(adjusted), 5.50; 95% CI, 1.24-24.31). CONCLUSIONS This study, although based on a limited number of cases, for the first time provides evidence of an association between maternal exposure to EDCs, in particular elevated plasma hexachlorobenzene concentration, and the development of hypospadias in the offspring.

Placental transfer of persistent organic pollutants: a preliminary study on mother-newborn pairs.

The aim of this study was to characterize the placental transfer of some environmental pollutants, and to explore the possibility of quantitatively predicting in utero exposure to these contaminants from concentrations assessed in maternal blood. Levels of toxic substances such as pesticides (p,p’-DDE, β-HCH, and HCB), polychlorinated biphenyls (PCBs), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA) were determined in serum samples of 38 pregnant women living in Rome and in samples of cord blood from their respective newborns. The study was carried out in the years 2008–2009. PCB mean concentrations in maternal serum and cord serum ranged from 0.058 to 0.30, and from 0.018 to 0.064 ng/g·fw respectively. Arithmetic means of PFOS and PFOA concentrations in mothers and newborns were 3.2 and 1.4 ng/g·fw, and 2.9 and 1.6 ng/g·fw. A strong correlation was observed between concentrations in the maternal and the foetal compartment for PFOS (Spearman r = 0.74, p < 0.001), PFOA (Spearman r = 0.70, p < 0.001), PCB 153 (Spearman r = 0.60, p < 0.001), HCB (Spearman r = 0.68, p < 0.001), PCB 180 (Spearman r = 0.55, p = 0.0012), and p,p’-DDE (Spearman r = 0.53, p = 0.0099). A weak correlation (p < 0.1) was observed for PCBs 118 and 138.

Perfluorooctanesulfonate and perfluorooctanoic acid exposures of the Italian general population

The serum concentrations of perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) were determined in 230 subjects of the Italian general population. Participants were enrolled in 2008 in two Italian towns (Brescia, Northern Italy, and Rome, Central Italy) and belonged to the three age ranges: 20-35 years, 36-50 years, and 51-65 years. PFOS and PFOA were quantified by HPLC interfaced to a mass spectrometer operating in the electrospray negative mode. Data were acquired using multiple reaction monitoring (MRM). The isotope dilution technique was applied throughout. The median serum concentrations of all participants were 6.31 ng g(-1) and 3.59 ng g(-1) for PFOS and PFOA, respectively, and the pertinent 90th percentiles were 12.38 and 6.92. Men had higher concentrations of PFOS and PFOA than women, regardless of age. The differences were statistically significant in the 20-35 and 36-50 years groups, but not in the 51-65 group. An increase of PFOS and PFOA serum concentrations with age was observed. The Median test showed a statistically significant difference (p<<0.01) between the three age groups for both PFOS and PFOA when applied to the entire dataset (males and females). When the test was applied to the groups of males and females separately, a significant difference was observed for females (p<<0.005) but not for males (p>0.1). The observed strong correlation between PFOS and PFOA concentrations suggests same or similar exposure routes.

Serum concentrations of beta-hexachlorocyclohexane in groups of the Italian general population: a human biomonitoring study

Because of its persistence and toxicological profile, beta-hexachlorocyclohexane (beta-HCH) has been proposed for inclusion in the Stockholm Convention on persistent organic pollutants (POPs). Although the use of technical HCH, which is the primary source of beta-HCH in the environment, has been banned in the EU in 1978 and progressively at a global level, beta-HCH is still detectable in the general environment worldwide. Human exposure mostly occurs via food and may be of concern in areas where illegal use and/or improper disposal of stockpiles occurred and locally grown food is consumed. Exposure of the Italian general population to beta-HCH has been poorly characterised. Lack of human biomonitoring data severely hinders the ability to interpret potential increases in exposure related to situations of environmental risk. We carried out a human biomonitoring study aimed to provide baseline information on background exposure of the Italian general population to this pollutant. For this purpose, we analysed 116 serum samples from groups of subjects of both sex from the general population residing in three Italian towns at different latitudes. Serum concentrations of beta-HCH resulted to be comprised between 1.64 and 300 ng/g fat, with a median value of 18.0 ng/g fat and a 90th percentile of 65.9 ng/g fat. The serum concentrations detected are in line with those detected in most Western European countries.

Biomonitoring of perfluorinated compounds in adults exposed to contaminated drinking water in the Veneto Region, Italy

In 2013 a contamination of drinking water by perfluoroalkylated substances (PFASs) was discovered in areas of the Veneto Region (northern Italy). In this study the exposure to PFASs of people living in the aforesaid areas was characterized: contaminant serum concentrations were measured and compared with those of a control population group living in neighboring areas at background exposure (based on available drinking water data). The enrolled population was also genotyped for the OATP1A2*3 allelic variant, possibly affecting PFAS excretion and hence the internal dose. The difference in PFAS concentrations between exposed and not exposed subjects was significantly larger for nine of the 12 substances analyzed, and confirmed that water contamination had resulted in an appreciable high exposure of the residing population over time. Within the group of exposed subjects, subgroups at different exposure levels were identified. The contamination of drinking water of the residence area was found to be the main factor influencing PFAS serum levels; in addition to water contamination, other relevant influencing factors were sex, the years of residence and raising own livestock. No relationship with the genetic trait for the studied renal transporter was evidenced. These results provide a baseline characterization of PFAS exposure of the monitored population groups for further studies, planned to be carried out in the near future.

A biomonitoring study on blood levels of beta-hexachlorocyclohexane among people living close to an industrial area.

BackgroundA chemical plant manufacturing pesticides has been operating since the 1950’s in the Sacco River Valley (Central Italy). In 2005, high beta-hexachlorocyclohexane (Beta-HCH) concentrations were found in milk of cows raised and fed near the river. We report the results of a biomonitoring study conducted in this region to evaluate the body burden of Beta-HCH and to identify the determinants of the human contamination.MethodsWe defined four residential areas by their distance from the chemical plant and the river, and selected a stratified random sample of 626 people aged 25–64 years. We evaluated the association, in terms of the geometric mean ratio (GMR), between several potential determinants and Beta-HCH serum concentrations using multivariate linear regression analysis.ResultsTwo hundred forty-six serum samples were analysed to assess Beta-HCH levels (mean concentration: 99 ng/g lipid; Standard Deviation: 121; Geometric Mean: 60.6; Geometric Standard Deviation: 2.65). We found a strong association between Beta-HCH and living in the area close to the river (GMR: 2.00; 95%CI: 1.36-2.94). Beta-HCH levels were also associated with age, level of education, use of private wells and consumption of local food.ConclusionsThe results suggest that people living close to the river may have been contaminated by Beta-HCH, most likely through water from private wells and privately grown food. A programme of epidemiological and clinical surveillance is on-going on this population.

Concentrations of polychlorinated dibenzodioxins, polychlorodibenzofurans, and polychlorobiphenyls in women of reproductive age in Italy: A human biomonitoring study

BACKGROUND Polychlorinated dibenzodioxins (PCDDs), polychlorodibenzofurans (PCDFs), and polychlorobiphenyls (PCBs) are persistent organic pollutants that represent a major concern for women of reproductive age because of the neurodevelopmental effects associated to perinatal exposure. OBJECTIVES This study was aimed at characterizing exposure of women of reproductive age to PCDDs, PCDFs, and PCBs as a function of residence in different Italian Regions, in areas at presumable different environmental contamination and human exposure to these pollutants. METHODS Study participants were enrolled in 2011-2012 in 6 Italian Regions representative of Northern, Central and Southern Italy; in each region, areas at presumed different exposure (rural, urban and industrial) were selected for enrolment. Each participant provided a serum sample for the analysis of PCDDs, PCDFs and PCBs. RESULTS Median concentrations of PCDDs+PCDFs, DL-PCBs, NDL6-PCBs and NDL9-PCBs in serum samples were respectively 6.0 and 3.5 pgWHO-TE05/g fat, and 75 and 93ng/g fat. Age was the variable that most affected median serum concentrations. Age adjusted concentrations were found significantly different between geographical zones: women from Northern Italy showed the highest values, followed by Central and Southern Italy. PCDDs+PCDFs concentrations were significantly higher in the group of women residing in industrial areas compared to the group residing in rural areas. A clear diminishing temporal trend was observed compared to levels reported in previous studies. CONCLUSIONS This study produced the largest dataset on serum concentrations of PCDDs, PCDFs and PCBs in women of childbearing age in Italy. RESULTS confirmed that environmental and lifestyle factors may influence exposure to these contaminants and thereby the body burden. The observed marked temporal decline in body burden during three decades is in agreement with the general trend observed worldwide.