Polychlorinated biphenyls in prospectively collected serum and Parkinson's disease risk.

Evidence suggests possible Parkinson's disease (PD)-relevant neural effects of exposure to polychlorinated biphenyls. Limited epidemiological evidence suggests that polychlorinated biphenyl exposure may increase PD risk, but no studies have involved biomarkers of polychlorinated biphenyl exposure before PD onset. We examined the prospective association between serum polychlorinated biphenyls and PD. We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey with serum samples collected during 1968-1972 and analyzed in 2005-2007 for polychlorinated biphenyls. Incident PD cases were identified through the Social Insurance Institution's registry and were confirmed by medical record review (n = 101). Controls (n = 349) were matched on age, sex, municipality, and vital status. We used logistic regression to estimate adjusted odds ratios. There was no evidence of increasing risk of PD with increasing polychlorinated biphenyl exposure in adjusted analyses. Instead, there was a trend toward lower odds of PD with increasing serum polychlorinated biphenyl concentrations, which was most pronounced for the sum of all measured polychlorinated biphenyl congeners and the sum of dioxin-like congeners. Compared with that of those in the lowest quintile, the odds ratio of PD among those in the highest quintile of total polychlorinated biphenyls was 0.29 (95% confidence interval, 0.12-0.70; P trend = .02) and for dioxin-like congeners was 0.34 (95% confidence interval, 0.13-0.90; P trend = .05). These results do not support an increased risk of PD from polychlorinated biphenyl exposure and instead suggest a possible protective effect of polychlorinated biphenyl exposure.

Dioxin and polychlorinated biphenyl concentrations in mother's serum and the timing of pubertal onset in sons.

BACKGROUND: Animal studies have demonstrated that timing of pubertal onset can be altered by prenatal exposure to dioxins or polychlorinated biphenyls (PCBs), but studies of human populations have been quite limited. METHODS: We assessed the association between maternal serum concentrations of dioxins and PCBs and the sons' age of pubertal onset in a prospective cohort of 489 mother-son pairs from Chapaevsk, Russia, a town contaminated with these chemicals during past industrial activity. The boys were recruited at ages 8 to 9 years, and 4 years of annual follow-up data were included in the analysis. Serum samples were collected at enrollment from both mothers and sons for measurement of dioxin and PCB concentrations using high-resolution mass spectrometry. The sons' pubertal onset--defined as pubertal stage 2 or higher for genitalia (G) or pubic hair (P), or testicular volume >3 mL--was assessed annually by the same physician. RESULTS: In multivariate Cox models, elevated maternal serum PCBs were associated with earlier pubertal onset defined by stage G2 or higher (4th quartile hazard ratio = 1.7 [95% confidence interval = 1.1- 2.5]), but not for stage P2 or higher or for testicular volume >3 mL. Maternal serum concentrations of dioxin toxic equivalents were not consistently associated with the sons' pubertal onset, although a dose-related delay in pubertal onset (only for G2 or higher) was seen among boys who breast-fed for 6 months or more. CONCLUSIONS: Maternal PCB serum concentrations measured 8 or 9 years after sons' births--which may reflect sons' prenatal and early-life exposures--were associated with acceleration in some, but not all, measures of pubertal onset.

Serum PCB levels and congener profiles among teachers in PCB-containing schools: a pilot study.

BACKGROUND: PCB contamination in the built environment may result from the release of PCBs from building materials. The significance of this contamination as a pathway of human exposure is not well-characterized, however. This research compared the serum PCB concentrations, and congener profiles between 18 teachers in PCB-containing schools and referent populations. METHODS: Blood samples from 18 teachers in PCB-containing schools were analyzed for 57 PCB congeners. Serum PCB concentrations and congener patterns were compared between the teachers, to the 2003-4 NHANES (National Health and Nutrition Examination Survey) data, and to data from 358 Greater Boston area men. RESULTS: Teachers at one school had higher levels of lighter (PCB 6-74) congeners compared to teachers from other schools. PCB congener 47 contributed substantially to these elevated levels. Older teachers (ages 50-64) from all schools had higher total (sum of 33 congeners) serum PCB concentrations than age-comparable NHANES reference values. Comparing the teachers to the referent population of men from the Greater Boston area (all under age 51), no difference in total serum PCB levels was observed between the referents and teachers up to 50 years age. However, the teachers had significantly elevated serum concentrations of lighter congeners (PCB 6-74). This difference was confirmed by comparing the congener-specific ratios between groups, and principal component analysis showed that the relative contribution of lighter congeners differed between the teachers and the referents. CONCLUSIONS: These findings suggest that the teachers in the PCB-containing buildings had higher serum levels of lighter PCB congeners (PCB 6-74) than the referent populations. Examination of the patterns, as well as concentrations of individual PCB congeners in serum is essential to investigating the contributions from potential environmental sources of PCB exposure.

Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009.

BACKGROUND: The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity. METHODS: Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry. RESULTS: The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the sum of PCBs decreased for six of eight women. During this nine year period, larger decreases in serum TEQs and PCBs were found in women with greater increases in body mass index. CONCLUSIONS: This study provides suggestive evidence that average serum concentrations of dioxins, furans, and PCBs are decreasing over time among residents of this town.

Prenatal organochlorine exposure and behaviors associated with attention deficit hyperactivity disorder in school-aged children.

Organochlorines are environmentally persistent contaminants that readily cross the placenta, posing a potential risk to the developing fetus. Evidence for neurodevelopmental effects at low levels of these compounds is growing, though few studies have focused on behavioral outcomes. The authors investigated the association between prenatal polychlorinated biphenyl (PCB) and p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) levels and behaviors associated with attention deficit hyperactivity disorder (ADHD), measured with the Conners' Rating Scale for Teachers (CRS-T), in a cohort of 607 children aged 7-11 years (median age, 8.2 years) born in 1993-1998 to mothers residing near a PCB-contaminated harbor in New Bedford, Massachusetts. The median umbilical cord serum level of the sum of 4 prevalent PCB congeners (118, 138, 153, and 180) was 0.19 ng/g serum (range, 0.01-4.41 ng/g serum). The authors found higher risk for ADHD-like behaviors assessed with the CRS-T at higher levels of PCBs and p,p'-DDE. For example, the authors found higher risk of atypical behavior on the Conners' ADHD Index for the highest quartile of the sum of 4 PCB congeners versus the lowest quartile (risk ratio = 1.76, 95% confidence interval: 1.06, 2.92) and a similar relation for p,p'-DDE. These results support an association between low-level prenatal organochlorine exposure and ADHD-like behaviors in childhood.

Plasma organochlorine levels and risk of non-Hodgkin lymphoma in a cohort of men.

BACKGROUND: Environmental exposure to polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) has been associated with the risk of non-Hodgkin lymphoma. METHODS: We conducted a case-control study nested within the Physicians' Health Study, a prospective cohort established in 1982. We measured concentrations of PCBs and p,p'-DDE in baseline blood samples from 205 men later diagnosed with non-Hodgkin lymphoma and 409 age- and race-matched controls. Lipid-adjusted organochlorine concentrations were categorized into quintiles based on the distribution among controls. We used conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for each quintile relative to the lowest quintile. We also evaluated these associations for major histologic subtypes of non-Hodgkin lymphoma. RESULTS: The risk of non-Hodgkin lymphoma was positively associated with the sum of 51 PCB congeners assayed (SigmaPCB); the group of immunotoxic congeners; the individual congeners 118, 138, 153, and 180; and the sum of these 4 congeners. The simple OR for the highest quintile of lipid-adjusted SigmaPCB versus the lowest was 1.9 (95% CI = 1.1-3.2; test for trend, P = 0.001), with similar trends for individual congeners and groups defined as above. Adjustment for height, body mass index, alcohol intake, smoking, and fish intake did not substantially change the effect estimates. No association was observed for p,p'-DDE. There was no evidence of statistical heterogeneity in effects by histologic subtype of lymphoma; however, this analysis was underpowered. CONCLUSIONS: These results support the hypothesis of a positive association between PCB exposure and development of NHL in men.

Serum and follicular fluid organochlorine concentrations among women undergoing assisted reproduction technologies.

BACKGROUND: Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) and organochlorine pesticides, is widespread among the general population. There is evidence of adverse effects on reproduction and early pregnancy in relation to organochlorine exposure but human studies remain limited. The increased use of assisted reproductive technologies (ART) presents unique opportunities for the assessment of environmental influences on early pregnancy outcomes not otherwise observable in humans, but studies need to be designed to maximize the efficiency of the exposure data collected while minimizing exposure measurement error. METHODS: The present study was conducted to assess the correlation between concentrations of organochlorines in serum and follicular fluid samples collected from a subset of women undergoing ART in a large study that took place between 1994 and 2003, as well as the temporal reliability of serum organochlorine concentrations among women undergoing multiple ART cycles in the study. PCB congeners (118, 138, 153, and 180), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), the DDT metabolite p,p'-DDE, hexachlorobenzene (HCB), oxychlordane, trans-nonachlor and mirex were measured in 72 follicular fluid samples and 265 serum samples collected from 110 women. RESULTS: Organochlorine concentrations in paired serum and follicular fluid samples were correlated, with Pearson and Spearman coefficients ranging from 0.60 to 0.92. Serum organochlorine concentrations were two- to three-fold greater than in follicular fluid, and a significant inverse trend was observed in the distribution of follicular fluid:serum ratios with increasing molecular weight of the compound (p-value for trend < 0.0001). Serum organochlorine concentrations were highly reliable over the course of several months, with intraclass correlation coefficients ranging from 0.86 to 0.98. Finally, there was evidence for a declining trend in organochlorine concentrations between samples collected between years 1994-1998 and those collected in 1999-2003. CONCLUSION: Our results support the use of a single serum sample to adequately represent a more biologically relevant dose (concentrations in follicular fluid), as well as exposure levels over time, in epidemiological studies of ART outcomes in relation to organochlorine exposure.

Prenatal organochlorine exposure and measures of behavior in infancy using the Neonatal Behavioral Assessment Scale (NBAS).

BACKGROUND: Previous literature suggests an association between organochlorines and behavioral measures in childhood, including inattention. OBJECTIVE: This study was designed to assess whether prenatal organochlorine exposure is associated with measures of attention in early infancy. METHODS: We investigated an association between cord serum polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyl dichloroethene (DDE) levels and measures of attention from the Neonatal Behavioral Assessment Scale (NBAS) in a cohort of 788 infants born 1993-1998 to mothers residing near a PCB-contaminated harbor and Superfund site in New Bedford, Massachusetts. RESULTS: Medians (ranges) for the sum of four prevalent PCB congeners and DDE levels were 0.19 (0.01-4.41) and 0.30 (0-10.29) ng/g serum, respectively. For the 542 subjects with an NBAS exam at 2 weeks, we observed consistent inverse associations between cord serum PCB and DDE levels and NBAS measures of alertness, quality of alert responsiveness, cost of attention, and other potential attention-associated measures including self-quieting and motor maturity. For example, the decrement in quality of alert responsiveness score was -0.51 (95% confidence interval, -0.99 to -0.03) for the highest quartile of exposure to the sum of four prevalent PCB congeners compared with the lowest quartile. We found little evidence for an association with infant orientation, habituation, and regulation of state, assessed as summary cluster measures. CONCLUSIONS: Our findings provide evidence for an association between low-level prenatal PCB and DDE exposures and poor attention in early infancy. Further analyses will focus on whether organochlorine-associated decrements in attention and attention-related skills in infancy persist in later childhood.

Serum PCB levels and congener profiles among US construction workers.

BACKGROUND: The presence of PCB in caulking (sealant) material found in masonry buildings has been well-documented in several countries. A recent investigation of 24 buildings in the greater Boston area found that 8 buildings had high PCB levels in caulking materials used around window frames and in joints between masonry blocks. Workers removing caulking material have been shown to have elevated serum PCB levels. METHODS: This project compared serum PCB levels among male workers who installed and/or removed PCB-containing caulking material from buildings in the greater Boston area with reference serum PCB levels from 358 men from the same area. Serum PCB levels were measured in the same laboratory by liquid-liquid extraction, column chromatography clean-up and dual capillary column GC/microECD analysis. RESULTS: When the congener profiles were compared between the reference population and the construction workers, the serum levels of the more volatile, lighter PCBs (di-, tri-and tetrachloro, sum of IUPAC# 6-74) were substantially higher among the construction workers. One of the youngest workers had the lowest total serum PCB levels (sum of 57 congeners) of all 6 workers, but the contribution of more volatile (less chlorinated) PCB congeners (#16, 26,28,33,74,66, and 60) was markedly higher than in other 5 workers and reference men. Only this worker was working on a job that involved removing PCB caulking at the time of the blood sampling. CONCLUSION: While the results of this pilot study are based upon small numbers (6 construction workers who handled PCB caulking), the serum PCB levels among the construction workers exceed the referents. Comparison of the congener profiles suggests that there are substantial differences between the construction workers and the general population samples. These differences, and the similarities of profiles among the construction workers strongly suggest that occupational contact with caulking material can be a major source of PCB exposure for construction workers.

Does living near a Superfund site contribute to higher polychlorinated biphenyl (PCB) exposure?

We assessed determinants of cord serum polychlorinated biphenyl (PCB) levels among 720 infants born between 1993 and 1998 to mothers living near a PCB-contaminated Superfund site in Massachusetts, measuring the sum of 51 PCB congeners (capital sigmaPCB) and ascertaining maternal address, diet, sociodemographics, and exposure risk factors. Addresses were geocoded to obtain distance to the Superfund site and neighborhood characteristics. We modeled log10(capital sigmaPCB) as a function of potential individual and neighborhood risk factors, mapping model residuals to assess spatial correlates of PCB exposure. Similar analyses were performed for light (mono-tetra) and heavy (penta-deca) PCBs to assess potential differences in exposure pathways as a function of relative volatility. PCB-118 (relatively prevalent in site sediments and cord serum) was assessed separately. The geometric mean of capital sigmaPCB levels was 0.40 (range, 0.068-18.14) ng/g serum. Maternal age and birthplace were the strongest predictors of capital sigmaPCB levels. Maternal consumption of organ meat and local dairy products was associated with higher and smoking and previous lactation with lower capital sigmaPCB levels. Infants born later in the study had lower capital sigmaPCB levels, likely due to temporal declines in exposure and site remediation in 1994-1995. No association was found between capital sigmaPCB levels and residential distance from the Superfund site. Similar results were found with light and heavy PCBs and PCB-118. Previously reported demographic (age) and other (lactation, smoking, diet) correlates of PCB exposure, as well as local factors (consumption of local dairy products and Superfund site dredging) but not residential proximity to the site, were important determinants of cord serum PCB levels in the study community.

Body mass index and serum 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane in nulliparous Chinese women.

BACKGROUND: Basic health indicators, such as body mass index (BMI), have been associated with serum 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane/1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT/DDE) levels; however, both positive and inverse associations of BMI with serum DDT/DDE have been reported. Given the association of BMI with a number of outcomes, it may confound studies of DDT/DDE-associated health effects. We investigated the relationship of BMI with serum DDT/DDE accounting for other determinants of exposure among women with relatively recent environmental exposures to DDT. METHODS: Serum DDT/DDE was analyzed in 466 nonsmoking, nulliparous women recruited from Anhui province in China between 1996 and 1998 as part of a reproductive health study of textile workers. The women in the sample were born between 1963 and 1977, 8 to 21 years before China's 1984 DDT ban. We used multivariate linear regression to investigate associations of BMI, age, and birth year with serum DDT/DDE. RESULTS: Mean (SD) serum total DDT concentration was 32 ng/g (17.8 ng/g). Birth year showed an inverse relationship with serum DDT independent of age. Despite limited variability in BMI, there was a consistent inverse relationship between BMI and serum DDT. Specifically, each kg/m(2) increase in BMI was associated with a -1.34 ng/g (95% confidence interval, -2.12 to -0.56 ng/g) decrease in serum total DDT. CONCLUSIONS: There were high total DDT levels in this sample of nulliparous Chinese women relative to Western populations, birth year was more strongly associated with serum DDT than age, and BMI was inversely related to serum DDT in this study.

Evidence of interaction between polychlorinated biphenyls and phthalates in relation to human sperm motility.

Previously, we reported evidence of inverse associations between exposure to some polychlorinated biphenyls (PCBs) and some phthalate monoesters in relation to semen parameters, specifically sperm motility. Because humans are exposed to both phthalates and PCBs and because experimental studies suggest that PCBs may interact with glucuronidative enzymes that are responsible for phthalate metabolism, we explored the potential interaction between phthalates and PCBs in relation to human semen quality. We studied 303 men who were partners in subfertile couples seeking infertility diagnosis from the andrology laboratory at Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values, and phthalate and PCB levels were dichotomized at their respective medians. After adjusting for age and abstinence time, for below reference sperm motility there was a greater than additive interaction between monobenzyl phthalate and PCB-153 [relative excess risk due to interaction (RERI) = 1.40; 95% confidence interval (CI), 0.41-3.22], sum of PCBs (RERI = 1.24; 95% CI, 0.15-2.94), and cytochrome P450 (CYP450)-inducing PCBs (RERI = 1.30; 95% CI, 0.21-3.06). For below-reference sperm motility, there was also a greater than additive interaction between monobutyl phthalate (MBP) and PCB-153 (RERI = 1.42; 95% CI, 0.09-3.76) and CYP450-inducing PCBs (RERI = 1.87; 95% CI, 0.56-4.52) and a suggestive interaction between MBP and sum of PCBs (RERI = 1.35; 95% CI, -0.11 to 3.48). In conclusion, because there are important risk assessment and public health implications of interactions between these two ubiquitous classes of compounds, further studies need to be conducted to confirm these results and identify potential mechanisms of interactions.

Predictors of serum dioxin levels among adolescent boys in Chapaevsk, Russia: a cross-sectional pilot study.

BACKGROUND: Toxicological studies and limited human studies have demonstrated associations between exposure to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) and adverse developmental and reproductive health effects. Given that children may be particularly susceptible to reproductive and developmental effects of organochlorines, and the paucity of information available regarding childhood exposures to dioxins in particular, we undertook a pilot study to describe the distribution of, and identify potential predictors of exposure to, dioxin-like compounds and dioxins among adolescent boys in Chapaevsk, Russia. The pilot study was also designed to guide the development of a large prospective cohort study on the relationship of exposure to PCDDs, PCDFs, and PCBs with growth and pubertal development in peri-pubertal Chapaevsk boys. METHODS: 221 boys age 14 to 17 participated in the pilot study. Each of the boys, with his mother, was asked to complete a nurse-administered detailed questionnaire on medical history, diet, and lifestyle. The diet questions were used to measure the current and lifetime consumption of locally grown or raised foods. Blood samples from 30 of these boys were sent to the Centers for Disease Control and Prevention (CDC) for analysis of dioxins, furans and PCBs. RESULTS: The median (25th, 75th percentile) concentrations for total PCDDs, PCDFs and coplanar PCBs were 95.8 pg/g lipids (40.9, 144), 33.9 pg/g lipids (20.4, 61.8), and 120 pg/g lipids (77.6, 157), respectively. For WHO-TEQs, the median (25th, 75th percentile) for total PCDDs, PCDFs, and coplanar PCBs were 0.29 (0.1, 9.14), 7.98 (5.27, 12.3), and 7.39 (4.51, 11.9), respectively. Although TCDD was largely non-detectable, two boys had high TCDD levels (17.9 and 21.7 pg/g lipid). Higher serum levels of sum of dioxin-like compounds and sum of dioxin TEQs were positively associated with increased age, consumption of fish, local meats other than chicken, PCB 118, and inversely with weeks of gestation. CONCLUSION: The total TEQs among Chapaevsk adolescents were higher than most values previously reported in non-occupationally exposed populations of comparable or even older ages. Dietary consumption of local foods, as well as age and weeks of gestation, predicted dioxin exposure in this population.

Measured Prenatal and Estimated Postnatal Levels of Polychlorinated Biphenyls (PCBs) and ADHD-Related Behaviors in 8-Year-Old Children.

BACKGROUND: Epidemiologic studies of postnatal PCB exposure and behavior have not reported consistent evidence of adverse associations, possibly because of challenges in exposure estimation. We previously developed a pharmacokinetic model to improve estimation of children's PCB exposure. OBJECTIVES: We aimed to assess whether estimated serum PCB levels in infancy are associated with attention deficit/hyperactivity disorder (ADHD)-related behaviors at 8 years of age among children whose cord serum PCB levels were previously shown to be associated with ADHD-related behaviors. METHODS: We used a pharmacokinetic model to estimate monthly serum polychlorinated biphenyl (PCB)-153 levels in 441 infants (ages 1-12 months) based on parameters such as breastfeeding and cord serum PCB-153 levels. Behavior was evaluated at age 8 using the Conners' Rating Scale for Teachers (CRS-T). Associations between PCB-153 levels and ADHD-related CRS-T indices were assessed using multivariable quantile regression at the 50th and 75th percentiles of CRS-T scores, where higher percentiles reflect more adverse behaviors. RESULTS: Cord serum PCB-153 levels (median, 38 ng/g lipids) were associated with ADHD-related behaviors, although statistical significance was observed with quantile regression models only at the 75th percentile. Associations with postnatal exposure estimates were attenuated. For example, hyperactive-impulsive behavior scores at age 8 years were 0.9 points (95% CI: 0.2, 2.5), 0.5 points (95% CI: 0.3, 2.3), and 0.3 points (95% CI: -0.2, 1.5) higher in association with interquartile range increases in serum PCB-153 at birth, 2 months, and 12 months of age, respectively. CONCLUSIONS: Associations between estimated postnatal PCB-153 exposures and ADHD-related behaviors at 8 years of age were weaker than associations with PCB-153 concentrations measured in cord serum at birth. CITATION: Verner MA, Hart JE, Sagiv SK, Bellinger DC, Altshul LM, Korrick SA. 2015. Measured prenatal and estimated postnatal levels of polychlorinated biphenyls (PCBs) and ADHD-related behaviors in 8-year-old children. Environ Health Perspect 123:888-894; http://dx.doi.org/10.1289/ehp.1408084.

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.

The relationship between levels of PCBs and pesticides in human hair and blood: preliminary result.

Human hair as a biologic measure of exposure to persistent organic pollutants (POPs) has some advantages over the more commonly used blood and adipose tissue samples. However, one of the primary limitations is the difficulty in distinguishing between exogenous and endogenous contamination. In addition, there are currently no standardized methods for hair sample collection, washing, and chemical analysis. There is also very limited information describing the correlation between levels of organic contaminants in hair and other body compartments. To explore levels of POPs in blood and hair, samples from 10 volunteers were collected and analyzed for select organochlorine pesticides and 57 individual polychlorinated biphenyl (PCB) congeners. We demonstrated that the method for analyzing organic contaminants in human hair was reliable and reproducible. Washing hair with shampoo decreased levels of PCBs, pesticides, and lipids by 25-33% on average and up to 62% for low-chlorinated congeners. The percentage of lipids and the levels of organochlorines in hair were higher than in serum. We found strong correlation (r = 0.8) between p,p -DDE (dichlorodiphenyldichloroethylene) levels in hair and blood and moderate correlations for the more persistent PCB congeners, but no correlations or weak correlations for other organochlorines. The present study provides preliminary evidence on the utility of hair analysis for POPs; however, further larger studies are recommended before hair analysis can be successfully applied in epidemiologic studies on POPs.

The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p'-DDE.

Scientific and public concern exists about potential reproductive health effects of persistent chlorinated organic chemicals, such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), and dichlorodiphenyldichloroethylene (DDE, the most stable daughter compound of DDT). To explore the hypothesis that environmental exposures to PCBs and DDE are associated with altered semen parameters, we conducted a cross-sectional study of 212 male partners of subfertile couples who presented to the Massachusetts General Hospital Andrology Laboratory. Semen parameters were analyzed as both a continuous measure and dichotomized based on World Health Organization reference values for sperm concentration (< 20 million/mL), motility (< 50% motile), and Kruger strict criteria for morphology (< 4% normal). The comparison group for the dichotomized analysis was men with all three semen parameters above the reference values. In serum, 57 PCB congeners and p,p -DDE were measured by congener-specific analysis using gas chromatography with electron capture detection. There were dose-response relationships among PCB-138 and sperm motility (odds ratio per tertile, adjusted for age, abstinence, and smoking, and p-value for trend were, respectively, 1.00, 1.68, 2.35, and p-value = 0.03) and morphology (1.00, 1.36, 2.53, p-value = 0.04). There was limited evidence of an inverse relationship between sum of PCBs, as well as those PCBs classified as cytochrome P450 enzyme inducers, with sperm motility and sperm morphology, as well as limited evidence of an inverse association between p,p -DDE and sperm motility. The lack of a consistent relationship among semen parameters and other individual PCB congeners and groupings of congeners may indicate a difference in spermatotoxicity between congeners.

Environmental organochlorines and semen quality: results of a pilot study.

There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

There is limited information on the prevalence of the potent mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in U.S. water supplies. We measured MX concentrations and mutagenic activity in tap water samples from 36 surface water systems throughout Massachusetts. We found MX levels much higher (up to 80 ng/L) than previously reported in the United States. We also evaluated the role of water treatment on mutagenic activity and disinfection by-product formation. After adjusting for other covariates, chloramination and filtration were the most important treatment options for reducing mutagenic activity and disinfection by-product formation. Multiple chlorine application (before and after filtration) was associated with increased mutagenicity. Chlorine dose, pH, and total organic carbon were also associated with mutagenicity, MX, and total trihalomethane (TTHM) concentration. Seasonal variation was evident for MX and mutagenic activity, with higher levels occurring in the spring compared to the fall. In contrast, TTHM concentrations were greater in the fall.

Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment.

Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Québec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies.