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Background: Childhood exposure to organochlorines has been associated with alterations in somatic growth. We evaluated the associations of peri-pubertal serum levels of dioxin-like compounds (DLCs) and nondioxin-like polychlorinated biphenyls (NDL-PCBs), with adolescent growth, body composition, and near adult height (NAH) in a longitudinal cohort study of Russian boys., Methods: 473 8-9 year-old boys had serum DLCs and associated toxic equivalents (TEQs) and NDL-PCBs concentrations measured. Physical examinations were performed at enrollment between 2003 and 2005, and annually over 11 years to 2016; annual bio-electric impedance analysis (BIA) of body composition began in 2006. We used mixed effects models to evaluate associations of quartiles of serum chemical concentrations with longitudinal measurements through age 19 of body mass index (BMI-Z) and height (HT-Z) z-scores, annual height velocity (HV), and BIA-derived height-adjusted fat (FMi) and fat-free mass (FFMi) indexes. Potential modification by age of the associations of chemical exposures with growth was evaluated. NAH (defined as HV < 1 cm/year) and age at NAH attainment were estimated using parametric survival models accounting for right censoring., Results: The medians of serum ∑TEQs, ∑DLCs, and ∑NDL-PCBs were 21.1 pg TEQ/g lipid, 362 pg/g lipid, and 250 ng/g lipid, respectively. In multivariable models, higher serum concentrations of peri-pubertal ∑TEQs, ∑DLCs, and ∑NDL-PCBs were associated with significantly lower BMI-Z, FMi, and FFMi over 11 years of follow-up. The differences in FFMi for boys with higher versus lower ΣTEQs and ΣNDL-PCBs increased with age. In multivariable models, higher ∑NDL-PCBs were associated with lower HT-Z, with attenuation of the association with age (interaction p < 0.001). The highest versus the lowest quartiles of ∑NDL-PCBs were not associated with differences in NAH, but were associated with an average of 6 months later attainment of NAH., Conclusions: Our findings suggest that dioxin and NDL-PCB exposures during childhood are associated with alterations in body composition and subsequent somatic growth., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

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.

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.

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.

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.

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.

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.

Chapayevsk has a 30-year history of producing organochlorines, leading to environmental dioxin pollution. As much as 3 kg of these substances are annually formed at the plant. The concentrations of dioxins in the ambient air were found to be 0.001 to 1.13 pg/m3, in 1-TEF dioxin equivalent or 0.00001-1.76 pg/m3, as calculated by using WHO-TEF for dioxin-like compounds, those in the urban drinking water were 0.1 to 20.83 pg/liter, in the soil near the plant, 141 ng TEQ/kg, by decreasing to 37 ng/kg in the downtown (2-7 km from the plant) and 4 ng/kg at a distance of 7-10 km from the plant, their levels in the vegetables and fruits were 0.002 to 10.6 pg/kg. The direct indicator of dioxin exposure is its detection in human breast milk and blood. Examination of the content of dioxins in the breast milk of Chapayevsk women versus those living in other towns and cities of Russia has shown considerably higher levels of dioxins, such as 2,3,7,8-TCDD, 1,2,3,7,8-PCDD, 1,2,3,4,7,8-GCDD, and octa-dioxins. The mean content of dioxins in the breast milk (7 pooled samples from 40 individual trials) was 43.3 pgTEQ/fat. It is significantly higher than that detected in the populations of other Russian territories and other countries. The mean blood concentrations of dioxins in peoples living near the plant was 75.2 pgTEQ/fat, those were lower (24.5 pgTEQ/fat) in those living at 5-7 km of the plant.

Forty five women from Chapaevsk town (three groups of 14-16 persons aged 20-40 yr) with different exposures to dioxins and different dioxin levels in blood were tested by four standard psychological questionnaires to detect emotional stress. Results of psychological testing were compared with individual dioxin blood contents and chromosome aberration level in blood cells. Results of the investigation were the next: (1) three groups tested differed significantly (P < or = 0.05) in emotional stress level, thus that highest level of stress was detected within the group with the highest dioxin blood contents (group "Workers"); (2) high level of correlation between emotional stress and individual dioxins blood contents (up P < or = 0.001) as well as between emotional stress and individual chromosome aberration level (up P < or = 0.05) was revealed. These results are discussed from the position of desadaptation induced by dioxins, which led to chromosome aberration induction.