Study of endocrine disruptor effects in AVP and OT mediated behavioral and reproductive processes in female rat models.

Environmental exposures may have endocrine disruptor (ED) effects, e.g., a role for halogenated hydrocarbon chlorobenzenes in increasing vasopressin (AVP), oxytocin (OT) secretion and, in association, anxiety and aggression in male rats has been shown. Our aim is to investigate whether 1,2,4-trichlorobenzenehexachlorobenzene= 1:1 (mClB) treatment of female rats also shows ED effects and reproductive biology differences, and whether AVP may have a mediator role in this? Female Wistar rats were treated (0.1; 1.0; 10.0 µg/bwkg/day) with mClB (by gastrictube) and then 30; 60; 90 days after treatment anxiety (open field test) and aggressive (resident intruder test) behaviors AVP, OT concentrations from blood plasma samples were detected by radioimmunoassay on 30; 60; 90 days. Treated female rats were mated with untreated males. Mating success, number of newborn and maternal aggression on the neonates were monitored. Results showed that AVP, OT levels; and anxiety, aggressive behaviors; and mothers' aggression towards their offspring increased significantly in relation to the duration and the dose of mClB treatment. But mating propensity and number of offspring decreased. Patterns of AVP, OT release and anxiety, aggression behaviors, and reproductive-related behaviors were correlated. Consistent with the literature, our studies confirmed the role of AVP and OT in different behavioral effects.

Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study.

BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism. METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression. RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles. CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.

Application of ensemble methods to analyse the decline of organochlorine pesticides in relation to the interactions between age, gender and time.

Organochlorine pesticides (OCPs) are toxic chemicals that persist in human tissue. Short and long term exposure to OCPs have been shown to have adverse effects on human health. This motivates studies into the concentrations of pesticides in humans. However these studies typically emphasise the analysis of the main effects of age group, gender and time of sample collection. The interactions between main effects can distinguish variation in OCP concentration such as the difference in concentrations between genders of the same age group as well as age groups over time. These are less studied but may be equally or more important in understanding effects of OCPs in a population. The aim of this study was to identify interactions relevant to understanding OCP concentrations and utilise them appropriately in models. We propose a two stage analysis comprising of boosted regression trees (BRTs) and hierarchical modelling to study OCP concentrations. BRTs are used to discover influential interactions between age group, gender and time of sampling. Hierarchical models are then employed to test and infer the effect of the interactions on OCP concentrations. Results of our analysis show that the best fitting model of an interaction effect varied between OCPs. The interaction between age group and gender was most influential for hexachlorobenzene (HCB) concentrations. There was strong evidence of an interaction effect between age group and time for ß-hexachlorocyclohexane (ß-HCH) concentrations in >60 year olds as well as an interaction effect between age group and gender for HCB concentrations for adults aged >45 years. This study highlights the need to consider appropriate interaction effects in the analysis of OCP concentrations and provides further insight into the interplay of main effects on OCP concentration trends.

Drivers of maternal accumulation of organohalogen pollutants in Arctic areas (Chukotka, Russia) and 4,4'-DDT effects on the newborns.

BACKGROUND: One of the most worrying consequence of the production and use of persistent organohalogen pollutants (POPs) is the high accumulation in Arctic populations because of long-range transport. Study of the effects in these populations may illustrate human impacts that are difficult to assess in other locations with lower exposure to these compounds and more diverse pollutant influences. OBJECTIVE: We aimed to identify the main maternal characteristics influencing on the accumulation of these compounds and the effects on the newborns in a highly exposed Arctic population (Chukotka, Russia). METHODS: Organochlorine and organobromine compounds were analysed in maternal venous serum (n = 250). The study included data on residence, educational level, age, parity and body mass index (BMI) from self-reported questionnaires and measured anthropometric characteristics of newborns. RESULTS: Concentrations of ß-hexachlorocyclohexanes, hexachlorobenzene, 4,4'-DDT and polychlorobiphenyls were high when compared with those generally found in adult populations later than year 2000. The polybromodiphenyl ethers were negligible. These POP concentrations were higher than in Alaska and Arctic Norway and similar to those in Canada. The Chukotka mothers living in inland areas showed significant lower concentrations than those living in the coast (p < 0.001) except for 4,4'-DDT. The population from the Chukotsky District, a specific coastal area, showed the highest concentrations. Residence was therefore a main concentration determinant (p < 0.001) followed by maternal age, and in some cases parity and BMI (p < 0.05). 4,4'-DDT showed an association with the anthropometric characteristics of the newborns (p < 0.05). Mothers with higher 4,4'-DDT concentrations had longer gestational ages and gave birth to infants with higher weight and length. CONCLUSIONS: The maternal accumulation patterns of POPs were mainly related with residence. Most of these compounds were found in higher concentration in women living at coastal areas except 4,4'-DDE and 4,4'-DDT which were of inland origin. This last pesticide was the pollutant showing positive associations with gestational age and newborn's weight and length. To the best of our knowledge, this is the first study reporting statistically significant associations between maternal 4,4'-DDT exposure and anthropometric characteristics of the newborns.

Prenatal and postnatal exposure to persistent organic pollutants and attention-deficit and hyperactivity disorder: a pooled analysis of seven European birth cohort studies.

Background: Attention-deficit/hyperactivity disorder (ADHD) is increasing worldwide for reasons largely unknown and environmental chemicals with neurotoxic properties, such as persistent organic pollutants (POPs), have been proposed to play a role. We investigated the association between prenatal and postnatal exposure to polychlorinated biphenyl-153 (PCB-153), p-p´-dichlorodiphenyldichloroethylene (p-p'-DDE) and hexachlorobenzene (HCB) and ADHD in childhood. Methods: We pooled seven European birth cohort studies encompassing 4437 mother-child pairs from the general population with concentrations of PCB-153, p-p´-DDE and HCB measured in cord blood, maternal blood or milk. We then calculated prenatal (birth) and postnatal (3, 6, 12 and 24 months) POP concentrations using a pharmacokinetic model. The operational definition of ADHD varied across cohorts and ranged from doctor diagnosis obtained from patient registries to maternal or teachers reports. We used multilevel (mixed) logistic regression models to estimate the associations between exposure to POPs at birth, 3, 6, 12 and 24 months and ADHD. Results: The global prevalence of ADHD in our study was 6%. The mean age at assessment of ADHD was 5.8 years (range: 3.8-9.5 years). We found no association between exposure to PCB-153, p-p´-DDE and HCB at any age point between birth and 24 months and ADHD, in the pooled analyses (pooled odds ratios ranging from 1.00 to 1.01). A number of sensitivity analyses gave basically the same results. Conclusions: In the largest study to date of 4437 children in seven European birth cohorts, we did not observe any association between either pre- or postnatal exposure (up to 24 months) to PCB-153, p-p´-DDE and HCB and the risk of ADHD before the age of 10 years.

Polychlorinated biphenyls, indicators of thyroid function and thyroid autoantibodies in the Anniston Community Health Survey I (ACHS-I).

In this study, we examined associations between serum concentrations of 35 polychlorinated biphenyl (PCB) congeners, pesticides, and indicators of thyroid function in participants of the Anniston Community Health Survey (ACHS). Study subjects lived in the vicinity of a former PCB production facility and had PCB concentrations 2 to 3 times higher than similar age and race groups from the general population. We investigated associations among serum levels of thyroid hormones (thyroxin [T4], free thyroxin [fT4], triiodothyronine [T3], thyroid stimulation hormone [TSH]) and auto-antibodies (thyroglobulin antibody [TgAb] or thyroperoxidase antibody [TPOAb]) and combined indicators of thyroid function with the sum of PCBs, varying PCB groups, individual PCB congeners, and 8 pesticides. Logistic and linear regression models were adjusted for log10 transformed total lipids, age, sex, ethnicity, BMI, smoking, and family history of thyroid disease. We also performed analyses stratified by ethnicity and sex. Linear regression showed inverse associations between TT3 and thyroid-like PCBs (sum of PCBs 28, 52, 74, 101, 105, and 118; p = .0004), two pesticides (hexachlorobenzene, and pp'-DDE), and individual congeners (PCBs 74, 105). Null associations were observed between PCBs, pesticides, TSH, TT4, and fT4. Logistic regression analyses did not provide support for TT3 findings and found no association with other thyroid hormones, antibodies, or combined indicator of thyroid function. These results suggest there is little evidence that these chemicals have any major clinical effect on thyroid function in this highly PCB exposed population.

Blood Concentrations of Persistent Organic Pollutants and Unhealthy Metabolic Phenotypes in Normal-Weight, Overweight, and Obese Individuals.

Factors underlying metabolic phenotypes, such as the metabolically healthy but obese phenotype, remain unclear. Differences in metabolic phenotypes-particularly, among individuals with a similar body mass index-could be related to concentrations of persistent organic pollutants (POPs). To our knowledge, no studies have analyzed POPs and metabolic phenotypes in normal-weight persons. We investigated the relationships between serum concentrations of POPs and metabolic phenotypes in 860 normal-weight, overweight, and obese participants in the 2002 Catalan Health Interview Survey (Spain). POP concentrations were significantly higher in metabolically unhealthy than in metabolically healthy individuals. In models adjusting for body mass index and other confounders, hexachlorobenzene, ß-hexachlorocyclohexane, and polychlorinated biphenyls were associated with the unhealthy metabolic phenotype and metabolic syndrome. Among normal-weight individuals, the adjusted prevalence ratio of having an unhealthy phenotype for the upper category of the sum of orders of the 6 mentioned POPs (all individually associated with metabolic phenotypes) was 4.1 (95% confidence interval: 1.7, 10.0). Among overweight and obese individuals, the corresponding prevalence ratio for the sum of polychlorinated biphenyls was 1.4 (95% confidence interval: 1.0, 1.8). Our results supported the hypothesis that POP concentrations are associated with unhealthy metabolic phenotypes, not only in obese and overweight individuals but also (and probably more strongly) in normal-weight individuals.

Transplacental transfer characteristics of organochlorine pesticides in paired maternal and cord sera, and placentas and possible influencing factors.

Organochlorine pesticides (OCPs), including dichlorodiphenyltrichloroethane (DDT) and its metabolites [dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane], hexachlorocyclohexanes (HCHs), and hexachlorobenzene (HCB), are widely detected in humans despite the considerable decline in environmental concentrations. To understand the placental transfer of OCPs and the possible maternal influence on them, we measured the concentrations of DDTs, HCHs, and HCB in 102 paired samples of maternal and cord sera, and placentas collected in Shanghai, China. The median concentrations of DDTs and HCHs were the highest in maternal sera (601, 188 ng g-1 lipid), followed by umbilical cord sera (389, 131 ng g-1 lipid), and placentas (65, 37 ng g-1 lipid). 4,4'-DDE, ß-HCH, and HCB were the predominant contaminants in the three matrices. The ubiquitous existence of OCPs, and the significant concentration relationships of DDTs, HCHs, and OCPs in the three matrices suggested placental transfer from mother to fetus. The lipid-based concentration ratios of 4,4'-DDE, ß-HCH, and HCB in umbilical cord serum to those in maternal serum (F/M), and ratios of placenta to maternal serum (P/M) ranged from 0.66 to 1.01, and 0.12 to 0.25, respectively. Maternal variables affected the levels of fetal contamination. For primiparous women, significant correlations between maternal age and maternal HCHs, and between pre-pregnancy body mass index (BMI) and maternal HCHs were found. The negative effect of parity, and the positive effect of food consumption on maternal OCP concentrations were also observed, although there were no significant differences. The possible influence of parity on F/M and P/M of 4,4'-DDE suggested borderline significant differences between primiparous and multiparous women. Also, slight group differences were observed between elder and younger women, and between overweight and normal/underweight women. Parity seems to have a potential influence on transfer ratios of some OCP pollutants.

Levels and profiles of organohalogenated contaminants in human blood from Egypt.

Concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and some organochlorine pesticides (OCPs) were determined in serum of Egyptian colorectal cancer patients (n = 35) and compared to a healthy control group (n = 32). p,p'-DDE (the major metabolite of DDT) was the most frequently detected contaminant with the highest concentration (median = 131 ng/g lw) in all studied serum samples. BDE-209 was the least frequently detected contaminant with a median concentration <0.3 ng/g lw. The contamination profile in patients and controls was almost identical with p,p'-DDE showing the highest median contribution (77%) and oxychlordane the lowest (1%). The low p,p'-DDT/p,p'-DDE ratio (3.7%) in serum implies bioaccumulation and past exposure to DDT (c.f. recent and ongoing intake). Statistical analysis revealed no significant differences (P > 0.05) between the levels of target contaminants in serum of patients and the control group. Gender, age and body mass index (BMI) were investigated as potential factors influencing serum contaminant levels. ΣDDT, hexachlorobenzene and pentachlorophenol concentrations showed significant positive associations with age and/or BMI of the participants. Comparison with other countries revealed concentrations of PBDEs and PCBs in Egyptian serum among the lowest reported worldwide.

Organochlorine pesticide concentrations in pooled serum of people in different age groups from five Chinese cities.

Organochlorine pesticides (OCPs) were determined in human serum samples pooled by donor age (≥60, 50-59, 40-49, 30-39, and 20-29y). The pooled samples were supplied by hospitals in five Chinese cities, Yitong (Jilin Province), Weifang (Shandong Province), Ganzi (Sichuan Province), Huaihua (Hunan Province), and Lingshui (Hainan Province). p,p'-Dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), ß-hexachlorocyclohexane (HCH), and endosulfan I were the dominant OCPs in the serum samples. The total OCP concentrations and individual concentrations of p,p'-DDE, HCB, and ß-HCH were relatively high compared with concentrations that have been found in other parts of the world. The total OCP, p,p'-DDE, and ß-HCH concentrations decreased as age decreased but the HCB and endosulfan I concentrations were slightly higher in the samples from younger donors than in samples from older donors. HCB must be currently used and have new sources to people to cause this. Chinese government policies and the characteristics of the OCPs have led to OCP concentrations in serum decreasing with decreasing age. Different OCP usage patterns in different Chinese cities have led to the inhabitants of different cities having different OCP distributions in their serum.

Concentrations of organochlorine pesticides in pooled human serum by age and gender.

Organochlorine pesticides (OCPs) have been used for many decades in Australia with cessation of selected persistent and bioaccumulative OCPs ranging from the 1970s to as recently as 2007. The specific aims of this study were to use samples representative of an Australian population to assess age and gender differences in the concentration of OCPs in human blood sera and to investigate temporal trends in these chemicals. Serum was collected from de-identified, surplus pathology samples over five time periods (2002/03, 2006/07, 2008/09, 2010/11 and 2012/13), with 183 serum pools made from 12,175 individual samples; 26 pools in 2002/03, 85 pools in 2006/07 and 24 pools each in 2008/09, 2010/11 and 2012/13. Samples were analyzed for hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), γ -hexachlorocyclohexane (lindane) (γ-HCH), oxy-chlordane, trans-nonachlor, p,p'-DDE, o,p'-DDT, p,p'-DDT and Mirex. Stratification criteria included gender and age (0-4; 5-15; 16-30; 31-45; 46-60; and >60 years) with age additionally stratified by adults >16 years and children 0-4 and 5-15 years. All pools from all collection periods had detectable concentrations of OCPs with a detection frequency of >60% for HCB, ß-HCH, trans-nonachlor, p,p'-DDT and p,p'-DDE. The overall OCP concentrations increased with age with the highest concentrations in the >60 years groups. Females did not have higher mean OCP concentrations than males except for HCB concentrations (p=0.0006). Temporal trends showed overall decreasing serum concentrations by collection period with the exception of an increase in OCP concentrations between 2006/07 and 2008/09. Excluding this data point, HCB decreased from year to year by 7-76%; ß-HCH concentrations decreased by 14 - 38%; trans-nonachlor concentrations decreased by 10 - 65%; p,p'-DDE concentrations decreased by 6 - 52%; and p,p'-DDT concentrations decreased by 7 - 30%. The results indicate that OCP concentrations have decreased over time as is to be expected following the phase out of these chemicals in Australia.

Risk profile and health vulnerability of female workers who pick cotton by organanochlorine pesticides from southern Punjab, Pakistan.

The present study was conducted to highlight the existing level of organochlorine-pesticides (OCPs) from human milk (n = 45) and blood serum (n = 40) of female workers who pick cotton in Khanewal District, southern Punjab, Pakistan. Source apportionment, congener-specific analysis, and risk surveillance of OCPs are reported from human milk and blood samples. Levels of OCPs in milk and blood serum samples ranged from 15.7 ppb to 538.3 ppb and from 16.4 ppb to 747.1 ppb, respectively, and were lower than previously published reports from other regions of the globe. Congener-specific analysis revealed that DDTs were predominant, followed by hexachlorocyclohexane, chlordane, and hexachlorobenzene. Calculated results for source apportionment analysis suggested that contamination load was a new input of DDTs as well as the historic use of lindane in the study area. Levels of OCPs in milk and blood serum were significantly (p < 0.05) correlated with age, time period of picking cotton, and number of children. Health risk revealed that female workers had risk of cancer among 1 per million; however, noncarcinogenic risks were not considerable. Environ Toxicol Chem 2017;36:1193-1201. © 2016 SETAC.

Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: a Scandinavian case-cohort study.

BACKGROUND: The associations between prenatal exposure to endocrine disruptive chemicals (EDCs) and fetal growth are inconsistent, and few studies have considered small-for-gestational-age (SGA) birth as an outcome. Our current study of Scandinavian parous women aimed to address these inconsistencies and gaps in the literature. METHODS: This case-cohort study included 424 mother-child pairs who participated in a prospective, multi-center study of parous women in Norway (Trondheim and Bergen) and Sweden (Uppsala). We used linear and logistic regression with 95% confidence intervals (CIs) to analyze the associations between two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) from early second trimester and indices of fetal growth. RESULTS: Among Swedish women, prenatal exposure to perfluorooctanoate (PFOA), polychlorinated biphenyl (PCB) 153 and hexachlorobenzene (HCB) were associated with higher odds for SGA birth. We found stronger associations among Swedish male offspring. In the Norwegian cohort, we found no significant associations between EDC exposure and indices of fetal growth. CONCLUSIONS: Some populations may be more vulnerable to EDCs, possibly due to differences in exposure levels, exposure sources and/or modifiable lifestyle factors. Male offspring may be more vulnerable to endocrine disruption.

Untargeted metabolomic analysis of human serum samples associated with exposure levels of Persistent organic pollutants indicate important perturbations in Sphingolipids and Glycerophospholipids levels.

Persistent organic pollutants (POPs) are distributed globally and are associated with adverse health effects in humans. A study combining gas chromatography-mass spectrometry (GC-MS), high resolution mass spectrometry (UPLC-QTof-MS) and chemometrics for the analysis of adult human serum samples was undertaken. Levels of serum POPs found were in the low range of what has been reported in similar populations across Europe (median 33.84 p, p'-DDE, 3.02 HCB, 83.55 ß-HCH, 246.62 PCBs ng/g lipids). Results indicated that compounds concentrations were significantly different between the two groups of POPs exposure (high vs low) and classes (DDE, ß-HCH, HCB, PCBs). Using orthogonal partial last-squares discriminant analysis (OPLS-DA), multivariate models were created for both modes of acquisition and POPs classes, explaining the maximum amount of variation between sample groups (positive mode R2 = 98-90%; Q2 = 94-75%; root mean squared error of validation (RMSEV) = 12-20%: negative mode R2 = 98-91%; Q2 = 94-81%; root mean squared error of validation (RMSEV) = 10-19%. In the serum samples analyzed, a total 3076 and 3121 ions of interest were detected in positive and negative mode respectively. Of these, 40 were found to be significantly different (p < 0.05) between exposure levels. Sphingolipids and Glycerophospholipids lipids families were identified and found significantly (p < 0.05) different between high and low POPs exposure levels. This study has shown that the elucidation of metabolomic fingerprints may have the potential to be classified as biomarkers of POPs exposure.

Temporal variation in circulating concentrations of organochlorine pollutants in a pelagic seabird breeding in the high Arctic.

The present study explored short-term temporal variations in circulating concentrations of 3 legacy organochlorines with different physicochemical properties (polychlorinated biphenyl 153 [PCB-153], p,p'-dichlorodiphenyldichloroethylene [DDE], and hexachlorobenzene [HCB]) in breeding kittiwakes (Rissa tridactyla) in a colony in Svalbard (78°N), Norwegian Arctic. Concentrations were measured in blood of a large number (n = 412-521 blood samples, depending on the data analyses) of prebreeding, incubating, and chick-rearing birds over a period of 5 yr (2007-2011). The PCB-153 concentrations were equal in male and female blood in the prebreeding period, whereas females had significantly lower concentrations during incubation and chick rearing, probably because of their ability to eliminate organochlorines through egg laying. A similar temporal pattern was observed with DDE, although the lower concentrations in incubating females were not significant. Males and females had similar concentrations of HCB over all reproductive stages. The concentrations of all 3 compounds varied greatly between years. The concentrations of PCB-153 tended to decline over the study period, whereas concentrations of HCB showed an increasing trend, especially among chick-rearing males late in the season. Concentrations of PCB-153 increased approximately 2.5 times from the prebreeding to the chick-rearing period, concurrent with mobilization of body lipids (reduced body mass). A similar, but less pronounced trend was found for HCB. For DDE, however, kittiwakes had the highest concentrations in the prebreeding period, suggesting relatively high exposure in their winter areas. The present study documented large variations in circulating concentrations of legacy organochlorines among and within breeding seasons in kittiwakes, but the alterations within seasons were relatively consistent from year to year. Environ Toxicol Chem 2017;36:442-448. © 2016 SETAC.

Prenatal exposure to persistent organic pollutants in association with offspring neuropsychological development at 4years of age: The Rhea mother-child cohort, Crete, Greece.

BACKGROUND: Persistent Organic Pollutants (POPs) are highly-resistant compounds to environmental degradation and due to fat solubility they bioaccumulate through the food chain. As they cross the placenta, in utero exposure to POPs could disrupt child neurodevelopment as they are considered to be neurotoxic. AIMS: We examined whether in utero exposure to levels of different POPs is associated with offspring cognitive and behavioral outcomes at 4years of age in a mother-child cohort in Crete, Greece (Rhea study). METHODS: We included 689 mother-child pairs. Concentrations of several polychlorinated biphenyls (PCBs) and other organochlorine compounds (dichlorodiphenyl dichloroethene [DDE], hexachlorobenzene [HCB]) were determined in maternal serum collected in the first trimester of pregnancy by triple quadrupole mass spectrometry. Neurodevelopment at 4years was assessed by means of the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for potential confounders. RESULTS: Children with "high" HCB concentrations (≥90th percentile) in maternal serum, demonstrated decreased scores in perceptual performance (adjusted ß=-6.07; 95% CI: -10.17, -1.97), general cognitive (adjusted ß=-4.97; 95% CI: -8.99, -0.96), executive function (adjusted ß=-6.24; 95% CI: -10.36, -2.11) and working memory (adjusted ß=-4.71; 95% CI: -9.05, -0.36) scales at 4years of age. High exposure to PCBs (≥90th percentile) during pregnancy was associated with a 4.62 points reduction in working memory score at 4years of age (95% CI: -9.10, -0.14). Prenatal exposure to DDE, HCB and PCBs was not associated with child behavioral difficulties. CONCLUSIONS: The findings suggest that prenatal exposure to HCB and PCBs may contribute to reduced cognitive development at preschool age. Our results raise the possibility that exposure to HCB may play a more important role in child cognition than previously considered.

Diabetes in Native Americans: elevated risk as a result of exposure to polychlorinated biphenyls (PCBs).

We have studied rates of diabetes in 601 members of the Mohawk Nation at Akwesasne, ages 18-84 years, in relation to serum concentrations of 101 polychlorinated biphenyl (PCB) congeners and three chlorinated pesticides [dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and mirex]. Diabetes was determined from either a diagnosis by a physician or by having a fasting glucose concentration of >125 mg/dL. Rates of diabetes are high in this community. Three models were used. In the first model rate ratios (RR) were determined for quartiles of total PCBs after adjustment for age, sex, body mass index (BMI) and total serum lipids. For total PCBs RR=2.21 (1.2-4.2), while for total pesticides RR=3.75 (1.3-10.7). When the total PCB results were also adjusted for total pesticides and the total pesticide results were also adjusted for total PCBs (Model 2) the RRs were somewhat reduced. In Model 3 we considered subgroups of PCBs based on numbers of chlorines on the molecule (tri-/tetra, penta-/hexa, hepta plus) and numbers of ortho chlorines (non-/mono; di-, tri-/tetra-), and considered each of the pesticides individually after adjustment for all other contaminants as well as age, sex, BMI and serum lipids. We found a highly significant association between diabetes and PCBs with only three or four chlorines (RR=5.02), but no significant association with those with greater chlorination. When evaluating PCBs based on numbers of ortho chlorines only, those with no or one ortho chlorine showed significant associations. As mono-ortho PCBs include some with dioxin-like activity, we compared those with and without a TEF, and found that the association with diabetes was exclusively with the non-dioxin-like congeners. Of the pesticides only hexachlorobenzene showed a small but significant association with diabetes. Because lower chlorinated PCBs are more volatile and do not greatly accumulate in fish, these results suggest that inhalation is the major route of exposure to those PCBs that increase risk of diabetes.

The metabolic fingerprint of p,p'-DDE and HCB exposure in humans.

BACKGROUND: Dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p'-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown. OBJECTIVES: We investigated the associations between p,p'-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS: HCB and p,p'-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of- flight mass spectrometry (UPLC-TOFMS). Association analyses were performed using multivariate linear regression. RESULTS: We found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p'-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides. CONCLUSIONS: Our findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to human lipid metabolism.

Environmental hexachlorobenzene exposure and human male reproductive function.

Hexachlorobenzene (HCB) is a persistent environmental fungicide that may disrupt androgen regulation. The aim of this study was to investigate associations between HCB levels and biomarkers of male reproductive function. 589 Spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men provided semen and blood samples and were interviewed. HCB was measured in serum by gas chromatography. The mean serum concentrations of HCB were higher in Ukraine (182.3ng/g lipid) and Greenland (79.0ng/g lipid) compared to Poland (14.2ng/g lipid). Sex hormone binding globulin (SHBG) and free androgen index (FAI) were associated with HCB in men from Ukraine and Poland. This study spanning large differences in environmental HCB exposure levels shows a positive association for SHBG and negative association for FAI with high serum levels of HCB in fertile men, but without major consequences for semen quality and the Inuit study population.

Prepubertal Serum Concentrations of Organochlorine Pesticides and Age at Sexual Maturity in Russian Boys.

BACKGROUND: Few human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development. OBJECTIVE: We evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ßHCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)] with age at attainment of sexual maturity among boys. METHODS: From 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ≥ 20 mL in either testis. RESULTS: In adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ≥ 20 mL a mean of 3.1 months (95% CI: -1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: -3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: -1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of ßHCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6-9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), ßHCH (trend p = 0.01), and p,p´-DDE (p trend = 0.04). No associations were observed between p,p´-DDE and Tanner stage 5 for genitalia growth or TV ≥ 20 mL. CONCLUSIONS AND RELEVANCE: Higher prepubertal serum HCB and ßHCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p,p´-DDE was associated with later pubic hair maturation. CITATION: Lam T, Williams PL, Lee MM, Korrick SA, Birnbaum LS, Burns JS, Sergeyev O, Revich B, Altshul LM, Patterson DG Jr, Hauser R. 2015. Prepubertal serum concentrations of organochlorine pesticides and age at sexual maturity in Russian boys. Environ Health Perspect 123:1216-1221; http://dx.doi.org/10.1289/ehp.1409022.