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.

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 organochlorine pesticide concentrations and age of pubertal onset among Russian boys.

BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV)>3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with physician-assessed pubertal onset. RESULTS: In adjusted models, boys with higher HCB concentrations had later mean ages of TV>3 mL and P2+ (but not G2+). Mean age at attaining TV>3 mL was delayed 3.6 (95% CI: -2.6, 9.7), 7.9 (95% CI: 1.7, 14.0), and 4.7 months (95% CI: -1.4, 10.9) for HCB Q2, Q3, and Q4, respectively, compared to Q1 (trend p: 0.06). Boys with higher HCB concentrations reached P2+ 0.1 months earlier (95% CI: -5.8, 5.6) for Q2, 4.7 months later (95% CI: -1.0, 10.3) for Q3 and 4.6 months later (95% CI: -1.1, 10.3) for Q4 compared to Q1 (trend p: 0.04). There were no associations of serum ß-HCH and p,p'-DDE concentrations with age of pubertal onset. CONCLUSION: Higher prepubertal serum HCB concentrations were associated with later age of gonadarche and pubarche.

Prenatal organochlorine and methylmercury exposure and memory and learning in school-age children in communities near the New Bedford Harbor Superfund site, Massachusetts.

BACKGROUND: Polychlorinated biphenyls (PCBs), organochlorine pesticides, and methylmercury (MeHg) are environmentally persistent with adverse effects on neurodevelopment. However, especially among populations with commonly experienced low levels of exposure, research on neurodevelopmental effects of these toxicants has produced conflicting results. OBJECTIVES: We assessed the association of low-level prenatal exposure to these contaminants with memory and learning. METHODS: We studied 393 children, born between 1993 and 1998 to mothers residing near a PCB-contaminated harbor in New Bedford, Massachusetts. Cord serum PCB, DDE (dichlorodiphenyldichloroethylene), and maternal peripartum hair mercury (Hg) levels were measured to estimate prenatal exposure. Memory and learning were assessed at 8 years of age (range, 7-11 years) using the Wide Range Assessment of Memory and Learning (WRAML), age-standardized to a mean ± SD of 100 ± 15. Associations with each WRAML index-Visual Memory, Verbal Memory, and Learning-were examined with multivariable linear regression, controlling for potential confounders. RESULTS: Although cord serum PCB levels were low (sum of four PCBs: mean, 0.3 ng/g serum; range, 0.01-4.4), hair Hg levels were typical of the U.S. fish-eating population (mean, 0.6 µg/g; range, 0.3-5.1). In multivariable models, each microgram per gram increase in hair Hg was associated with, on average, decrements of -2.8 on Visual Memory (95% CI: -5.0, -0.6, p = 0.01), -2.2 on Learning (95% CI: -4.6, 0.2, p = 0.08), and -1.7 on Verbal Memory (95% CI: -3.9, 0.6, p = 0.14). There were no significant adverse associations of PCBs or DDE with WRAML indices. CONCLUSIONS: These results support an adverse relationship between low-level prenatal MeHg exposure and childhood memory and learning, particularly visual memory.

Predictors of serum chlorinated pesticide concentrations among prepubertal Russian boys.

BACKGROUND: Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals. OBJECTIVES: Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)-among boys in Chapaevsk, Russia. METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and ß-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, ß-HCH, and p,p´-DDE concentrations. RESULTS: Among 355 boys with OCP measurements, median serum HCB, ß-HCH, and p,p´-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and ß-HCH concentrations, respectively, than boys who lived ≥ 5 km away. Living > 3 years in Chapaevsk predicted higher ß-HCH concentrations, and having parents who lacked a high school education predicted higher p,p´-DDE concentrations. CONCLUSIONS: Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.

Pulmonary delivery of d-methionine is associated with an increase in ALCAR and glutathione in cochlear fluids.

In animals, hearing loss resulting from cochlear mechanosensory cell damage can be mitigated by antioxidants such as d-methionine (d-met) and acetyl-l-carnitine (ALCAR). The systemic routes of administration of these compounds, that must of necessity transit trough the cochlear fluids, may affect the antioxidant levels in the cochlea and the resulting oto-protective effect. In this study, we analyzed the pharmacokinetics of [(14)C]d-met in the cochlea and four other tissues after intratracheal (IT), intranasal (IN), and oral by gavage (OG) administration and compared it to intravenous administration (IV). We then analyzed the effect of these four routes on the antioxidant content of the cochlear fluids after d-met or ALCAR administration, by liquid chromatography/mass spectrometry. Our results showed that the concentration of methionine and ALCAR in cochlear fluids significantly increased after their respective systemic administration. Interestingly, d-met administration also contributed to an increase of ALCAR. Our results also showed that the delivery routes differently affected the bioavailability of administered [(14)C]d-met as well as the concentrations of methionine, ALCAR and the ratio of oxidized to reduced glutathione. Overall, pulmonary delivery via IT administration achieved high concentrations of methionine, ALCAR, and oxidative-related metabolites in cochlear fluids, in some cases surpassing IV administration, while IN route appeared to be the least efficacious. To our knowledge, this is the first report of the direct measurements of antioxidant levels in cochlear fluids after their systemic administration. This report also demonstrates the validity of the pulmonary administration of antioxidants and highlights the different contributions of d-met and ALCAR allowing to further investigate their impact on oxidative stress in the cochlear microenvironment.

Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys.

BACKGROUND: Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins. OBJECTIVES: We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset. METHODS: In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations. RESULTS: After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-α (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations. CONCLUSIONS: Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-α genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.

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.

Serum concentrations of p, p'-DDE, HCB, PCBs and reproductive hormones among men of reproductive age.

Exposure to polychlorinated biphenyls (PCBs) has been associated with changes in reproductive hormone levels, however most groups studied have been highly exposed. We investigated the association of PCBs, hexachlorobenzene (HCB) and p, p'-DDE with serum sex hormones in 341 adult men from a US infertility clinic with exposure levels consistent with those observed in the general population. In crude regression models we observed several negative associations of PCBs and HCB with steroid hormone-binding globulin (SHBG) and total and free testosterone. After adjustment for lipids, age and BMI, nearly all significant associations were attenuated. A negative relationship remained between PCB 118 and SHBG (p<0.01), and relationships of dioxin-like PCBs with SHBG and total testosterone, and between PCB 118 and total testosterone, were suggestive. These results suggest a minimal relationship between PCB exposures at low background levels similar to those observed in the general population of the US and circulating reproductive hormones.

Serum and follicular fluid concentrations of polybrominated diphenyl ethers and in-vitro fertilization outcome.

There is evidence of endocrine disruption and reproductive effects in animals following exposure to certain PBDEs, but human studies are limited. The goal of this study was to investigate the use of serum and follicular fluid as biomarkers of exposure to PBDEs and to explore whether a relationship between PBDE exposure and early pregnancy loss exists. We measured 8 PBDE congeners in archived serum and ovarian follicular fluid samples from 65 women undergoing in-vitro fertilization (IVF). Logistic regression models were used to predict the odds of failed embryo implantation associated with higher levels of PBDEs among the women in the study. There were moderate Kendall's Tau-beta correlations between serum and follicular fluid concentrations of BDE 28, 47, 100 and 154 (T(ß)=0.29-0.38, all p-values<0.005), but BDE 99 and 153 were not correlated between the two matrices (T(ß)<0.2, p-values>0.05). Women with detectable concentrations of BDE 153 (39% had detectable levels) in follicular fluid had elevated odds of failed implantation compared with women who had non-detectable concentrations (adjusted OR=10.0; 95%CI: 1.9 to 52; p=0.006; adjusted by age and body mass index). These findings suggest that exposure to BDE 153 may be associated with failed embryo implantation. Due to our observation of only moderate correlations between matrices, serum PBDE concentrations may not be a good indicator of follicular fluid concentrations when studying early pregnancy endpoints in women undergoing IVF.

Neuropsychological measures of attention and impulse control among 8-year-old children exposed prenatally to organochlorines.

BACKGROUND: We previously reported associations between organochlorines and behaviors related to attention deficit hyperactivity disorder among boys and girls at 8 years of age using a teacher's rating scale for a birth cohort in New Bedford, Massachusetts (USA). OBJECTIVES: Our goal was to corroborate these findings using neuropsychological measures of inattentive and impulsive behaviors. METHODS: We investigated the association between cord serum polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) and attention and impulse control using a Continuous Performance Test (CPT) and components of the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III). Participants came from a prospective cohort of children born during 1993-1998 to mothers residing near a PCB-contaminated harbor in New Bedford. Median (range) cord serum levels for the sum of four prevalent PCBs [congeners 118, 138, 153, and 180 (ΣPCB4)] and p,p'-DDE were 0.19 (0.01-2.59) and 0.31 (0-14.93) ng/g serum, respectively. RESULTS: We detected associations between PCBs and neuropsychological deficits for 578 and 584 children with CPT and WISC-III measures, respectively, but only among boys. For example, boys with higher exposure to ΣPCB4 had a higher rate of CPT errors of omission [rate ratio for the exposure interquartile range (IQR) = 1.12; 95% confidence interval (CI): 0.98, 1.27] and slower WISC-III Processing Speed (change in score for the IQR = -2.0; 95% CI: -3.5, -0.4). Weaker associations were found for p,p'-DDE. For girls, associations were in the opposite direction for the CPT and null for the WISC-III. CONCLUSIONS: These results support an association between organochlorines (mainly PCBs) and neuropsychological measures of attention among boys only. Sex-specific effects should be considered in studies of organochlorines and neurodevelopment.

Serum concentrations of organochlorine pesticides and growth among Russian boys.

BACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders. RESULTS: Among the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ßHCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, ßHCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile. CONCLUSIONS: Serum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.

Environmental exposure to polychlorinated biphenyls and p,p'-DDE and sperm sex-chromosome disomy.

BACKGROUND: Chromosomal abnormalities contribute substantially to reproductive problems, but the role of environmental risk factors has received little attention. OBJECTIVES: We evaluated the association of polychlorinated biphenyl (PCB) and dichlorodiphenyldichloroethylene (p,p'-DDE) exposures with sperm sex-chromosome disomy. METHODS: We conducted a cross-sectional study of 192 men from subfertile couples. We used multiprobe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 to determine XX, YY, XY, and total sex-chromosome disomy in sperm nuclei. Serum was analyzed for concentrations of 57 PCB congeners and p,p'-DDE. Poisson regression models were used to calculate incidence rate ratios (IRRs) for disomy by exposure quartiles, controlling for demographic characteristics and semen parameters. RESULTS: The median percent disomy was 0.3 for XX and YY, 0.9 for XY, and 1.6 for total sex-chromosome disomy. We observed a significant trend of increasing IRRs for increasing quartiles of p,p'-DDE in XX, XY, and total sex-chromosome disomy, and a significant trend of increasing IRRs for increasing quartiles of PCBs for XY and total sex-chromosome disomy; however, there was a significant inverse association for XX disomy. CONCLUSIONS: Our findings suggest that exposure to p,p'-DDE may be associated with increased rates of XX, XY, and total sex-chromosome disomy, whereas exposure to PCBs may be associated with increased rates of YY, XY, and total sex-chromosome disomy. In addition, we observed an inverse association between increased exposure to PCBs and XX disomy. Further work is needed to confirm these findings.

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.

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.

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.

Dioxin exposure and age of pubertal onset among Russian boys.

BACKGROUND: Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. OBJECTIVES: We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment. RESULTS: The median (range) total serum TEQ concentration was 21 (4-175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49-0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses. CONCLUSIONS: Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation.

Serum concentrations of polychlorinated biphenyls in relation to in vitro fertilization outcomes.

BACKGROUND: Human exposure to polychlorinated biphenyls (PCBs) remains widespread. PCBs have been associated with adverse reproductive health outcomes including reduced fecundability and increased risk of pregnancy loss, although the human data remain largely inconclusive. OBJECTIVE: Our goal was to explore the relationship between serum PCB concentrations and early pregnancy loss among a large cohort of women undergoing in vitro fertilization (IVF) between 1994 and 2003. METHODS: Concentrations of 57 PCB congeners were measured in serum samples collected during 827 IVF/intracytoplasmic sperm injection cycles from 765 women. Joint statistical models that accommodate multiple outcomes and multiple cycles per woman were used to assess the relationship between serum PCB quartiles and implantation failure, chemical pregnancies (human chorionic gonadotropin level > 5.0 mIU/mL) that did not result in clinical pregnancy, or spontaneous abortion, while also adjusting for confounders. RESULTS: PCB-153 was the congener present in the highest concentration (median, 46.2 ng/g lipid). Increasing quartiles of PCB-153 and the sum of all measured PCB congeners (ΣPCBs) were associated with significantly elevated dose-dependent odds of failed implantation. Adjusted odds ratios (95% confidence interval) for highest versus lowest quartile were 2.0 (1.2-3.4) for PCB-153 and 1.7 (1.0-2.9) for ΣPCBs. There were suggestive trends for increased odds of implantation failure for PCB-118 and cytochrome P450-inducing congeners (p-values for trend = 0.06). No statistically significant associations between PCBs and chemical pregnancy or spontaneous abortion were found. CONCLUSIONS: Serum PCB concentrations at levels similar to the U.S. general population were associated with failed implantation among women undergoing IVF. These findings may help explain previous reports of reduced fecundability among women exposed to PCBs.

Serum dioxins and polychlorinated biphenyls are associated with growth among Russian boys.

OBJECTIVE: We evaluated the associations of serum dioxins and polychlorinated biphenyls (PCBs) with longitudinally assessed growth measurements among peripubertal Russian boys. METHODS: A total of 499 boys from Chapaevsk, Russia, aged 8 to 9 years were enrolled in the study from 2003 to 2005 and were followed prospectively for 3 years. Blood samples were collected and physical examinations were conducted at entry and repeated at annual study visits. Multivariate mixed-effects regression models for repeated measures were used to examine the associations of serum dioxins and PCBs with longitudinal measurements of BMI, height, and height velocity. RESULTS: Serum dioxin (total 2005 toxic equivalency [TEQ] median: 21.1 pg/g lipid) and PCBs (median sum of PCBs: 250 ng/g lipid) were measured in 468 boys. At study entry and during 3 years of follow-up, >50% of the boys had age-adjusted BMI and height z scores within 1 SD of World Health Organization-standardized mean values for age. Boys in the highest exposure quintile of the sum of dioxin and PCB concentrations and total TEQs had a significant decrease in mean BMI z scores of 0.67 for dioxins and TEQs and 1.04 for PCBs, compared with boys in the lowest exposure quintile. Comparison of the highest versus the lowest quintile revealed that higher serum PCB concentrations were associated with significantly lower height z scores (mean z-score decrease: 0.41) and height velocity (mean decrease: 0.19 cm/year) after 3 years of follow-up. CONCLUSIONS: Our findings suggest that exposures to dioxins and PCBs are associated with reduced growth during the peripubertal period and may compromise adult body mass, stature, and health.

Predictors of serum dioxin, furan, and PCB concentrations among women from Chapaevsk, Russia.

Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total TEQs were 260 ng/g lipid and 25 pg TEQ/g lipid, respectively. In multivariate analyses, both total PCB concentrations and total TEQs increased significantly with age, residential proximity to a local chemical plant, duration of local farming, and consumption of local beef. Both decreased with longer breastfeeding, recent increases in body mass index, and later blood draw date. These demographic and lifestyle predictors showed generally similar associations with the various measures of serum dioxins, furans, and PCBs.