Serum dioxin levels and sperm DNA methylation age: Findings in Vietnam war veterans exposed to Agent Orange.

Exposure to dioxin, a known endocrine disruptor and carcinogen, is associated with poor reproductive outcomes. Yet, few studies have explored the role of DNA methylation in these relationships. Utilizing a publicly available dataset from 37 male Air Force Health Study participants exposed to dioxin-contaminated Agent Orange during the Vietnam war, we cross-sectionally examined the relationship of serum dioxin levels with a novel DNA methylation-based measure of sperm age (DNAm-agesperm). DNAm-agesperm was calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. We estimated associations of dioxin levels with DNAm-agesperm using linear regression models adjusted for chronological age, body mass index, and smoking status. Chronological age was highly correlated with DNAmagesperm (r = 0.80). In fully-adjusted linear models, a one percent increase in serum dioxin levels was significantly associated with a 0.0126-year (i.e. 4.6-day) increase in DNAm-agesperm (95%CI: 0.003, 0.022, p = 0.01). Further analyses demonstrated significant negative associations of dioxin levels (ß = -0.0005, 95%CI: -0.0010, 0.00004, P = 0.03) and DNAm-agesperm (ß = -0.02, 95%CI: -0.04, -0.001, P = 0.03) with methylation levels of FOXK2 - a gene previously reported to be hypomethylated in infertile men. In sum, we demonstrate associations of dioxin with increased methylation aging of sperm. DNAm-agesperm may provide utility for understanding how dioxin levels impact sperm health and potentially male reproductive capacity in human population studies. Moreover, our pilot study contributes further evidence that some environmental toxicants are associated with methylation aging. Additional studies are necessary to confirm these findings, and better characterize dioxin and sperm methylation relationships with male reproductive health.

Undernutrition combined with dietary mineral oil hastens depuration of stored dioxin and polychlorinated biphenyls in ewes. 1. Kinetics in blood, adipose tissue and faeces.

Food safety crises involving persistent organic pollutants [POPs, e.g. dioxins, polychlorinated biphenyls (PCBs), organochlorine pesticides] lead to systematic slaughter of livestock to prevent their entry into the food chain. Therefore, there is a need to develop strategies to depurate livestock moderately contaminated with POPs in order to reduce such economic and social damages. This study aimed to test a POPs depuration strategy based on undernutrition (37% of energy requirements) combined with mineral oil (10% in total dry matter intake) in nine non-lactating ewes contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and PCBs 126 and 153. In order to better understand the underlying mechanisms of the depuration process, POPs kinetics and body lipids dynamics were followed concomitantly over 57-day of depuration in POPs storage (adipose tissue, AT), central distribution (blood) and excretion (faeces) compartments. Faecal POPs concentrations in underfed and mineral oil supplemented ewes increased by 2.0 to 2.6-fold, but not proportionally to lipids concentration which increased by 6-fold, compared to the control ewes. Nonetheless, after 57 days of depuration in undernutrition and mineral oil supplementation, AT POPs concentrations were 1.5 to 1.6-fold higher while serum concentrations remained unchanged compared to the control ewes. This was concomitant with a decrease by 2.7-fold of the AT estimated lipids weight along the depuration period. This reduction of the volume of the storage compartment combined with the increase of POPs faecal excretion in underfed and mineral oil supplemented ewes led to a reduction by 1.5-fold of the PCB 126 AT burden, while no changes were observed for TCDD and PCB 153 burdens (vs. no change for PCB 126 and increases for TCDD and PCB 153 AT burdens in control ewes). The original approach of this study combining the fine description at once of POPs kinetic and of body lipids dynamic improved our understanding of POPs fate in the ruminant.

Dioxin-like compounds in paired maternal serum and breast milk under long sampling intervals.

Serum and breast milk are both important biological samples to evaluate body burden of dioxin-like compounds which include polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs). We collected maternal serum at early pregnancy, and breast milk at 3-8 weeks after delivery from 55 mothers living in Beijing, China, and measured 29 dioxin-like compounds in these samples. The sampling intervals in this study were extended up to 10 months to analyze differences of contents between serum and breast milk under long sampling intervals. The results showed that mean TEq level of PCDD/Fs in serum (9.8 pg TEq g-1 lipid) was 1.7 times higher than that in milk (4.5 pg TEq g-1 lipid), while the TEq concentrations of dl-PCBs in serum (1.2 pg TEq g-1 lipid) was significantly lower than that in milk (2.0 pg TEq g-1 lipid). There were only two congeners, OCDD (r = 0.32) and PCB105 (r = 0.33), the correlations of which between serum and milk were significant. The differences in distributions of congeners in serum and milk might be influenced by number of chlorine substituents and structures of congeners. In addition, maternal age and BMI were positively and negatively correlated with mass concentrations of dioxin-like compounds in milk and serum respectively. These results suggest that, compared with serum, it is limited to use breast milk to assess long-term exposure for the wider population.

Associations of peri-pubertal serum dioxins and polychlorinated biphenyls with growth and body composition among Russian boys in a longitudinal cohort.

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.

Analysis of Postdeployment Serum Samples Identifies Potential Biomarkers of Exposure to Burn Pits and Other Environmental Hazards.

OBJECTIVE: The potential health risks of deployment to sites with open burn pits remain poorly understood, in part, because personal exposure monitoring was not performed. Here, we investigated whether postdeployment serum samples contain biomarkers associated with exposure to burn pits. METHODS: A total of 237 biomarkers were measured in 800 serum samples from deployed and never-deployed subjects. We used a regression model and a supervised vector machine to identify serum biomarkers with significant associations with exposures and deployment. RESULTS: We identified 101 serum biomarkers associated with polycyclic aromatic hydrocarbons, dioxins or furans, and 54 biomarkers associated with deployment. Twenty-six of these biomarkers were shared in common by the exposure and deployment groups. CONCLUSIONS: We identify a potential signature of exposure to open burn pits, and provide a framework for using postexposure sera to identify exposures when contemporaneous monitoring was inadequate.

Serum dioxin and DNA methylation in the sperm of operation ranch hand veterans exposed to Agent Orange.

BACKGROUND: Exposure to the herbicide Agent Orange during the Vietnam War was widespread and is associated with numerous adverse health outcomes. A continuing concern of veterans is the possibility that exposure to the dioxin-containing herbicide might induce adverse reproductive outcomes. We sought to assess whether exposure to Agent Orange in Vietnam was associated with changes in DNA methylation in sperm in a subset of Vietnam veterans who participated in the Air Force Health Study (AFHS). METHODS: We studied 37 members of the AFHS chosen to have no, low, medium or high exposure to Agent Orange, based upon serum dioxin levels obtained during a series of examinations. DNA from stored semen was extracted and DNA methylation assessed on the Illumina 450 K platform. RESULTS: Initial epigenome-wide analysis returned no loci that survived control for false discovery. However, the TEAD3 gene had four different CpG sites that showed loss of DNA methylation associated with dioxin exposure. Analysis assessing regional DNA methylation changes revealed 36 gene regions, including the region of the imprinted gene H19 to have altered DNA methylation associated with high exposure compared to the low exposure group. Additional comparison of our data with sperm DNA methylation data from Russian boys exposed to dioxin found an additional 5 loci that were altered in both studies and exhibited a consistent direction of association. CONCLUSIONS: Studying a small number of sperm samples from veterans enrolled in the AFHS, we did not find evidence of significant epigenome-wide alterations associated with exposure to Agent Orange. However, additional analysis showed that the H19 gene region is altered in the sperm of Agent Orange-exposed Ranch Hand veterans. Our study also replicated several findings of a prior study of dioxin-exposed Russian boys. These results provide additional candidate loci for further investigation and may have implications for the reproductive health of dioxin-exposed individuals.

Biomonitoring of mercury and persistent organic pollutants in Michigan urban anglers and association with fish consumption.

The 32-mile Detroit River and surrounding tributaries have been designated as a Great Lakes Area of Concern due to pollution from decades of municipal and industrial discharges, sewer overflows and urban development. Key pollutants in fish samples from the Detroit River include mercury, polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dioxins and furans. A biomonitoring study was conducted to assess exposures to these persistent toxic substances in Detroit urban shoreline anglers who may be at high exposure risk due to consumption of locally caught fish. Using a modified venue-based sampling approach, 287 adult shoreline anglers along the Detroit River were recruited and participated in the program. Study participants provided blood and urine specimens and completed a questionnaire following informed consent. We examined percentile estimates for total blood mercury, PCBs, DDE, and dioxin-like total toxic equivalency (TEQ) concentrations among study participants. Multiple linear regression was used to identify important predictors of contaminant concentrations. Participants consumed a median of 64 Detroit River caught fish meals in the past year. The Detroit urban anglers' median total blood mercury concentrations was 3.2 times higher than that for the general adult U.S. population. PCB concentrations among the Detroit anglers aged 18-39 years were higher than the U.S. population of the same race/ethnicity. Elevated levels of DDE and total TEQ concentrations were not observed in the cohort. Eating more locally caught fish was associated with higher total blood mercury and serum PCB concentrations. The biomonitoring data served to inform public health officials and help guide environmental public health actions to reduce harmful exposures.

Are the civilization diseases the result of organohalogen environmental pollution?

The notion of 'civilization diseases' is used to describe certain ailments whose aetiology is difficult to explain based on the knowledge about the functioning of the body and its metabolism. Only studies at the cellular level, on biochemical changes shed light on the causes of some diseases described as civilization diseases (cancers, cardiovascular and respiratory diseases, obesity, psychomotor disorders in children and an increase in the frequency of malformations). The factors whose incontestable influence on the increase in the frequency of occurrence of various 'civilization diseases' has been proved are persistent organic pollutants, among others belonging to the group of organohalogen compounds. Among organohalogen pollutants one needs to distinguish organochlorine compounds, which have been used as pesticides, and pollution emitted by various industries such as dioxins and furans, polychlorinated biphenyls, and polybrominated organic compounds used as flame retardants and perfluoroalkylated substances, which are characterized by high chemical and thermal stability as well as high surface activity due to which they may be widely used as oleophobic and hydrophobic factors.

[The study of exposure levels of dioxin-like compounds in cord blood of newborns in an e-waste dismantling area in Guangdong Province].

Objective: To study the pollution status of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in cord blood of newborns in an e-waste dismantling area of Guangdong Province. Methods: We recruited 20 eligible mothers and newborns who could meet the inclusion criteria in local hospitals of Guiyu in 2007. The inclusion criteria included directly engaged in dismantling e-waste during pregnancy and within 1 year before pregnancy; living in the e-waste dismantling workshops or the distance between living place and the e-waste dismantling areas was ≤200 m; the father of newborn was directly engaged in electronic waste dismantling for more than 1 year; the frequency of visiting the e-waste dismantling workshop during pregnancy was ≥3 times in a week. Questionnaires and physical examinations were performed on maternal and neonatal, and cord blood was collected from newborns to detect PCDD/Fs, PCB and PBDE. The concentration level of organic pollutants was corrected by the blood lipid content, and the total toxicity equivalent was calculated. The correlation between three compounds was analyzed by Spearman correlation. Results: The mothers of the 20 newborns were (23.45±3.27) years old and lived for more than 5 years. The number of one parent engaged in e-waste dismantling, the mother or father smoking, and parent engaged in e-waste dismantling work were 3, 13, 15 and 19, respectively. The weight of newborns ranged from 2.5 to 3.6 kilogram and the Apgar score was 10 points. No adverse birth outcomes such as preterm birth, malformation or stillbirth were found. The median (maximum, minimum) concentration of PCBs, PCDD/Fs and PBDEs in cord blood were 263.22 (328.29, 244.19), 38.42 (147.49, 12.68), 39.33 (265.11, 14.81) pg/g lipid, respectively. The median (maximum, minimum) of toxic equivalence concentrations of PCDD/Fs and PCB were 3.94 (9.24, 2.69) and 15.95 (26.64, 9.28) pg TEQ/g lipid. PBDE, the proportion of PBDE, PCB and PCDD/Fs in cord blood was 50.41%, 49.25% and 0.34%, respectively. PCBs and PBDEs were positively correlated (r=0.733, P=0.039). Conclusion: The high concentrations of PCDD/Fs, PCB, and PBDE were detected in the e-waste dismantling area. It is recommended that the risk of such substances on the health of local people should be assessed in a timely manner.

Monitoring dioxins and furans in plasma of individuals living near a hazardous waste incinerator: Temporal trend after 20 years.

The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were analyzed in 40 plasma samples of individuals living in zones under potential influence of the emissions of a hazardous waste incinerator (HWI) (Tarragona County, Catalonia, Spain). Samples corresponded to subjects of different gender, age and specific areas of residence. The levels of PCDD/Fs were compared to those obtained in a baseline study (1998), as well as in previous surveys (2002, 2007 and 2012). The current mean concentration of PCDD/Fs in plasma was 6.79 pg I-TEQ/g lipid, which was significantly lower than the baseline concentration (27.0 pg I-TEQ/g lipid). A significant decrease was also observed in comparison to the results obtained in 2002 and 2007 (15.7 and 9.4 pg I-TEQ/g, respectively), while the current PCDD/F levels were similar to those obtained in 2012 (6.18 pg I-TEQ/g lipid). This important reduction in plasma PCDD/F levels is in accordance with the decreasing trend in the daily dietary intake of PCDD/Fs, which diminished from 210.1 pg I-TEQ (baseline) to 8.54 pg WHO-TEQ (current). OCDD was the predominant congener in plasma, while 2,3,7,8-TeCDD and 1,2,3,4,7,8,9-HpCDF showed the lowest levels. Based on the above results, as well as other recent data on the levels of PCDD/Fs in human milk, we conclude that the presence of the HWI does not mean additional and significant risks -as regards to PCDD/F exposure-for the population living in the neighborhood of the facility.

[Investigation of the Effects of Exposure to Chemical Substances on Child Health].

There is mounting concern about the effects of early-life exposure to chemical substances on children's health and development. We summarize the past and ongoing birth cohort studies carried out worldwide on the association between environmental exposure and children's health. Our PubMed search with the keywords 'birth cohort' revealed that the number of articles jumped from 200-300 in the 1980s to over 1,000 in the 1990s. Many of these articles reported elevated risks to children's health posed by chemical exposure owing their vulnerability. At the same time, policies implemented to reduce exposure to lead and dioxins were successful in the past few decades. Research also demonstrated that intervention to reduce exposure to certain chemicals whose exposure routes were well documented was also successful. We summarize the effects of early-life exposure to chemical substances on children's health and development. Our findings will hopefully help safeguard the environment in which future generations grow and live.

Age-dependent human elimination half-lives of dioxin-like polychlorinated biphenyls derived from biomonitoring data in the general population.

Constant elimination half-life is usually used in first-order one-compartment pharmacokinetic models to assess human exposure to dioxin-like polychlorinated biphenyls (PCBs). However, hepatic clearance rates are usually lower for elders than for young people. In this study, levels of 12 dioxin-like PCBs were determined in blood samples collected in 2012 from 305 individuals from the general population. We estimated the historical daily intake of dioxin-like PCBs for individuals with a validated annual exponential decay function. Based on the blood levels and historical daily intake levels, and using the maximum likelihood estimation by running the first-order one-compartment pharmacokinetic model, elimination rates were optimized as exponential functions of age for PCB118, PCB157, PCB189 and PCB126; linear functions of age for PCB114, PCB123, PCB167 and PCB169; and constant functions of age for PCB105 and PCB156. With the exception of PCB105 and PCB156, half-lives generally increased with age for individuals from 24 to 50 years old: from 0.805 to 1.95 years for PCB189, 2.08-4.54 years for PCB157, 3.32-5.58 years for PCB126, 3.52-6.81 years for PCB123, 5.24-12.29 years for PCB169, 6.60-14.40 years for PCB114, 7.50-14.01 years for PCB118, and 9.97-21.97 years for PCB167. The half-lives of PCB105 (5.79 years) and PCB156 (15.1 years) were independent of age. Our research for the first time clarified the effects of age on the elimination rate of dioxin-like PCBs in individuals from the general population, thus reducing uncertainty in future health risk assessments.

Recent decreasing trends of exposure to PCDDs/PCDFs/dioxin-like PCBs in general populations, and associations with diabetes, metabolic syndrome, and gout/hyperuricemia.

The author reviewed recent reports about the blood levels and dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs)/furans (PCDFs)/dioxin-like polychlorinated biphenyls (DL-PCBs) to investigate the trends of dioxin exposure, and epidemiologic studies on the associations of blood levels of dioxins with metabolic diseases. In recent years, dietary intake of dioxins has been decreasing, and the means are equal to or less than 1.0 pg Toxic Equivalents (TEQ)/kg/day in the general populations of several countries. The blood levels of dioxins are also decreasing, probably because of reduced dietary intake. Many cross-sectional studies reported positive associations between blood levels of some isomers or TEQ-based concentrations of PCDDs/PCDFs/DL-PCBs and diabetes in general populations. Three cohort studies on populations with heavy exposure and two nested case-control studies on general populations have also been published, but the results are inconsistent. Three large-scale cross-sectional studies and two cohort studies reported an association between blood levels of some isomers or TEQ-based concentrations of PCDDs/PCDFs/DL-PCBs and metabolic syndrome. In addition, three cross-sectional studies reported significant positive associations with gout/hyperuricemia. Further prospective studies and experimental studies are needed to establish cause-effect relationships, and to clarify the biological mechanisms for the association between background exposure to dioxins and potential health effects. J. Med. Invest. 65:151-161, August, 2018.

Whole genome sequencing and mutation rate analysis of trios with paternal dioxin exposure.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) or dioxin, is commonly considered the most toxic man-made substance. Dioxin exposure impacts human health and diseases, birth defects and teratogenesis were frequently observed in children of persons who have been exposed to dioxin. However, the impact of dioxin on human mutation rate in trios has not yet been elucidated at the whole genome level. To identify and characterize the genetic alterations in the individuals exposed to dioxin, we performed whole genome sequencing (WGS) of nine Vietnamese trios whose fathers were exposed to dioxin. In total, 846 de novo point mutations, 26 de novo insertions and deletions, 4 de novo structural variations, and 1 de novo copy number variation were identified. The number of point mutations and dioxin concentrations were positively correlated (P-value < 0.05). Considering the substitution pattern, the number of A > T/T > A mutation and the dioxin concentration was positively correlated (P-value < 0.05). Our analysis also identified one possible disease-related mutation in LAMA5 in one trio. These findings suggested that dioxin exposure might affect father genomes of trios leading to de novo mutations in their children. Further analysis with larger sample sizes would be required to better clarify mutation rates and substitution patterns in trios caused by dioxin.

Sleep disorders among Yusho patients highly intoxicated with dioxin-related compounds: A 140-case series.

PURPOSE: Patients with Yusho, a condition caused by exposure to dioxins and dioxin-like compounds, have diverse mental and physical complaints. However, the relationship between dioxins and sleep disorders has not yet been examined. This cross-sectional study was designed to investigate problems associated with sleep among patients with Yusho. METHODS: A total of 140 participants (52.9% men, average age: 67.1 ±â€¯12.2 years) were examined using questionnaires and medical interviews by an expert on sleep medicine. Demographic and clinical characteristics, including blood concentrations of 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), which is the major cause of Yusho, were obtained from the results of recent surveys conducted by the Yusho Study Group. RESULTS: Moderate to severe symptoms of insomnia were present in 51.8% of the patients. The median Pittsburgh Sleep Quality Index global score (PSQI GS) was 8 (interquartile range: 5-11). The prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) was 30.7%; 24.3% of patients had severe RLS/WED (distressing symptoms with a frequency ≥ 1day per week). A higher blood concentration of 2,3,4,7,8-PeCDF (≥72.27 pg/g lipid) and severe RLS/WED were associated with higher odds of a PSQI GS ≥8, after adjusting for covariates (odds ratio [95% confidence interval]: 4.84 [1.10-21.25] and 4.15 [1.53-11.28], respectively). CONCLUSIONS: Symptoms of insomnia were frequent, and the prevalence of RLS/WED was high in patients with Yusho. In addition to the presence of RLS/WED, a higher blood concentration of 2,3,4,7,8-PeCDF was associated with lower subjective sleep quality.

Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women.

BACKGROUND: Prospective cohort studies evaluating the temporal trends of background-level persistent organic pollutants (POPs) and their potential negative health effects in humans are needed. OBJECTIVE: The objectives of this study are to examine the five year longitudinal trend in chlorinated and brominated (Cl/Br) POP concentrations in a sample of elderly individuals and to investigate the relationship between gender, changes in body weight, plasma lipid levels and POP concentrations. METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, plasma samples were collected from the same individuals over a 5 year period. Originally 992 subjects (all aged 70) were sampled between 2001 and 2004 and 814 returning subjects (all aged 75) were sampled again from 2006 to 2009. Plasma concentrations of 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and one polybrominated diphenylether (BDE 47) were determined using high-throughput 96-well plate solid phase extraction and gas chromatography-high resolution mass spectrometry (GC-HRMS). RESULTS: During the 5-year follow-up, plasma concentrations of all POPs significantly decreased (p < 0.00001). Median reductions ranged from 4% (PCB105) to 45% (PCB 99), with most reductions being in the 30-40% range. For most POPs, a larger decline was seen in men than in women. The relationship between the weight change and change in POP concentrations was generally negative, but a positive relationship between lipid levels and POP concentrations when expressed as wet-weight was observed. In general, similar changes in POP concentrations and their relationships to body weight were observed regardless of using either wet-weight (pg/mL) or lipid-normalized (ng/g lipid) concentrations. CONCLUSION: In this longitudinal cohort study, gender and minor, but varying changes in body weight and lipid levels greatly influenced the individual-based changes in POP concentrations. In general, our findings suggest that men and women with larger decreases in body weight and greater increases in lipid levels have the slowest decline in body burden of POPs. Based on the results from this study, either wet-weight or lipid normalized concentrations can be used to determine the percent change in POP concentrations and their relationships to physiological changes and differences.

Sex-related differences in the associations between maternal dioxin-like compounds and reproductive and steroid hormones in cord blood: The Hokkaido study.

BACKGROUND: Prenatal exposure to dioxin-like compounds (DLCs) irreversibly affects fetal reproductive and steroid hormone synthesis. OBJECTIVE: This study aimed to assess the relationships between maternal DLCs and cord blood reproductive and steroid hormones. METHODS: Participants in this study were pregnant women who enrolled in the Sapporo Cohort of the Hokkaido Study between 2002 and 2005. We quantified 29 DLCs during the 2nd and 3rd trimesters in maternal blood. Additionally, we measured the concentrations of progesterone, estradiol (E2), testosterone (T), androstenedione, dehydroepiandrosterone (DHEA), cortisol, cortisone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, inhibin B, and insulin-like factor-3 (INSL3) in cord blood samples. RESULTS: Data from 183 mother-child pairs were analyzed. We observed sex-dependent associations of DLCs on T/E2 ratios, DHEA, cortisol, cortisone, adrenal androgen/glucocorticoid (AA/GC: sum of DHEA and androstenedione)/(sum of cortisol and cortisone) ratios and SHBG. An increase in maternal DLCs related to decreased T/E2 ratios and SHBG and inhibin B levels, and increased AA/GC ratios and FSH and DHEA levels in male cord blood samples. However, an increase in maternal mono-ortho polychlorinated biphenyls related to increased cortisol, cortisone, and SHBG levels, and decreased DHEA levels and AA/GC ratios in female cord blood samples. CONCLUSIONS: Prenatal exposure to DLCs alters steroidogenesis and suppresses the secretion of inhibin B in male cord blood. Relationships between maternal DLCs and cord blood hormones differ between boys and girls. Further studies are required to clarify whether the effects of in utero exposure to DLCs on adrenal hormones extend into infancy and puberty.

Environmental Exposure to Dioxins, Dibenzofurans, Bisphenol A, and Phthalates in Children with and without Autism Spectrum Disorder Living near the Gulf of Mexico.

Environmental exposure to organic endocrine disrupting chemicals, including dioxins, dibenzofurans, bisphenol A (BPA), and phthalates has been associated with neurodevelopmental disorders, including autism spectrum disorder (ASD). We conducted a pilot monitoring study of 30 ASD cases and 10 typically developing (TD) controls ages 2-8 years from communities along the Gulf of Mexico near Alabama, which houses 14 Superfund sites, to assess the concentrations of dioxins and dibenzofurans in serum, and BPA and phthalate ester metabolites in urine. Based on General Linear Models, the lipid- or creatinine-adjusted geometric mean concentrations of the aforementioned chemicals did not differ between the ASD case and TD control groups (all p ≥ 0.27). We compared our findings to the adjusted means as reported by the National Health and Nutrition Examination Survey, survey years 2011-2012, and found that TD controls in our study had lower BPA (59%) and MEHHP (26%) concentrations, higher MBP (50%) concentration, and comparable (<20% difference) MEP, MBZP, MEOHP, and MCPP concentrations. We also conducted a preliminary investigation of dietary exposures and found that the consumption of certain types of fish may be associated with higher OCDD concentrations, and the consumption of soft drinks and juices may be associated with lower BPA and MEOHP concentrations, respectively.

Alterations in the programming of energy metabolism in adolescents with background exposure to dioxins, dl-PCBs and PBDEs.

OBJECTIVES: Dioxins and PCBs are highly toxic and persistent environmental pollutants that are measurable in humans worldwide. These persistent organic pollutants are associated with a higher incidence of diabetes mellitus. We hypothesise that perinatal (background) exposure to industrial pollutants like dioxins also influences body mass development and energy metabolism in later life. STUDY DESIGN: In The Netherlands, the perinatal exposure (prenatal exposure and postnatal lactational intake) to dioxins has been studied prospectively since 1987. Fasting glucose, insulin, HbA1c and leptin were analysed in 33 children of the original cohort of 60. BMI, glucose:insulin and BMI:leptin ratios were calculated. Prenatal exposure, lactational intake and current serum levels of dioxins (PCDD/F), dl-PCBs and PBDE concentrations were determined using (HR)GC-MS. RESULTS: Prenatal dioxin (PCDD/F) exposure was positively correlated to the glucose:insulin ratio (p = 0.024) and negatively correlated to the fasting insulin concentration (p = 0.017) in adolescence. Postnatal lactational PCDD/F intake was also negatively correlated to fasting insulin concentration (p = 0.028). Current serum levels of PCDD/Fs and total TEQ (dl-PCBs+PCDD/Fs) were positively correlated to the fasting serum glucose concentration (p = 0.015 and p = 0.037, respectively).No metabolic effects were seen in association with current serum levels of PBDEs. A positive correlation between the insulin and leptin concentrations (p = 0.034) was observed. No effects were found on leptin levels, BMI:leptin ratio, HbA1c levels or BMI. DISCUSSION/CONCLUSION: This study indicates that prenatal and lactational exposure influences glucose metabolism in adolescents, presumably through a negative effect on insulin secretion by pancreatic beta cells. Additionally, the very low recent background exposure to dioxins in puberty possibly has an effect on the glucose level.

Sex-specific differences in effect of prenatal exposure to dioxin-like compounds on neurodevelopment in Japanese children: Sapporo cohort study.

BACKGROUND: Consistent reports are not available on the effects of dioxin-like polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDD)/ polychlorinated dibenzofurans (PCDF) (dioxin-like compounds [DLCs]) on child neurodevelopment. Further, the effect of background-level exposure to individual DLC isomers is not known. OBJECTIVES: We carried out the Sapporo cohort study to evaluate the effect of prenatal exposure to each DLC isomer on child neurodevelopment at 6 and 18 months of age, and assessed sex-specific differences in these effects. METHODS: The levels of all and each individual DLC isomers were estimated in maternal peripheral blood. Neurodevelopment was evaluated using the Bayley Scales of Infant Development-2nd Edition for 6-month-old infants (n = 190) and 18-month-old children (n = 121). RESULTS: In male children, levels of 10 DLC isomers were significantly negatively associated with the Psychomotor Developmental Index (PDI) at 6 months of age after adjustment for potential confounding variables. However, at 18 months of age, these associations were absent. In female children, the level of only one DLC isomer was significantly negatively associated with PDI at 6 months of age. However, in contrast to the male children, the levels of six DLC isomers in 18-month-old female children were significantly positively associated with the Mental Developmental Index. CONCLUSIONS: These findings indicate that adverse neurodevelopmental effects of prenatal background-level exposure to DLCs may be stronger in male children.