The association between environmental exposures to chlordanes, adiposity and diabetes-related features: a systematic review and meta-analysis.

Chlordane compounds (CHLs) are components of technical chlordane listed in the Stockholm convention on persistent organic pollutants identified as endocrine disrupting chemicals (EDCs) and may interfere with hormone biosynthesis, metabolism or action resulting in an unbalanced hormonal function. There is increasing scientific evidence showing EDCs as risk factors in the pathogenesis and development of obesity and obesity-related metabolic syndromes such as type 2 diabetes, but there is no systematized information on the effect of CHLs in humans. Our aim is to identify the epidemiological data on the association between CHLs with adiposity and diabetes using a systematic approach to identify the available data and summarizing the results through meta-analysis. We searched PubMed and Web of Science from inception up to 15 February 2021, to retrieve original data on the association between chlordanes, and adiposity or diabetes. For adiposity, regression coefficients and Pearson or Spearman correlation coefficients were extracted and converted into standardized regression coefficients. Data were combined using fixed effects meta-analyses to compute summary regression coefficients and corresponding 95% confidence intervals (95% CI). For the association between chlordanes and diabetes, Odds ratios (ORs) were extracted and the DerSimonian and Laird method was used to compute summary estimates and respective 95% CI. For both, adjusted estimates were preferred, whenever available. Among 31 eligible studies, mostly using a cross-sectional approach, the meta-analysis for adiposity was possible only for oxychlordane and transchlordane, none of them were significantly associated with adiposity [(ß = 0.04, 95% CI 0.00; 0.07, I2 = 89.7%)] and (ß = 0.02, 95% CI - 0.01; 0.06), respectively. For diabetes, the estimates were positive for all compounds but statistically significant for oxychlordane [OR = 1.96 (95% CI 1.19; 3.23)]; for trans-nonachlor [OR = 2.43 (95% CI 1.64; 3.62)] and for heptachlor epoxide [OR = 1.88 (95% CI 1.42; 2.49)]. Our results support that among adults, the odds of having diabetes significantly increase with increasing levels of chlordanes. The data did not allow to reach a clear conclusion regarding the association with adiposity.

Alterations in macrophage phagocytosis and inflammatory tone following exposure to the organochlorine compounds oxychlordane and trans-nonachlor.

The role of macrophages in the innate immune response cannot be underscored however recent studies have demonstrated that both resident and recruited macrophages have critical roles in the pathogenesis of metabolic dysfunction. Given the recent data implicating exposure to persistent organic pollutants (POPs) in the pathogenesis of metabolic diseases, the current study was designed to examine the effects of the highly implicated organochlorine (OC) compounds oxychlordane and trans-nonachlor on overall macrophage function. Murine J774A.1 macrophages were exposed to trans-nonachlor or oxychlordane (0 - 20 µM) for 24 hours then phagocytosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, caspase activities, pro-inflammatory cytokine production, and macrophage plasticity were assessed. Overall, exposure to oxychlordane significantly decreased macrophage phagocytosis while both OC compounds significantly increased ROS generation. Exposure to trans-nonachlor significantly increased secretion of tumor necrosis factor alpha (TNFα) and interleukin-6 whereas oxychlordane had a biphasic effect on TNFα secretion. However, both oxychlordane and trans-nonachlor decreased basal expression of the M1 pro-inflammatory marker cyclooxygenase 2. Taken together, these data indicate that exposure to these two OC compounds have both compound and concentration dependent effects on macrophage function which may alter both the innate immune response and impact metabolic function of key organs involved in metabolic diseases.

Association of serum levels of p,p'- Dichlorodiphenyldichloroethylene (DDE) with type 2 diabetes in African American and Caucasian adult men from agricultural (Delta) and non-agricultural (non-Delta) regions of Mississippi.

Epidemiological associations were reported in several studies between persistent organochlorine organic pollutants and type 2 diabetes mellitus (T2D). Mississippi is a highly agricultural state in the USA, particularly the Delta region, with previous high usage of organochlorine (OC) insecticides such as p,p'- dichlorodiphenyltrichloroethane (DDT). In addition, there is a high proportion of African Americans who display elevated prevalence of T2D. Therefore, this State provides an important dataset for further investigating any relationship between OC compounds and metabolic diseases. The aim of this study was to assess whether soil and serum levels of OC compounds, such as p,p'- dichlorodiphenyldichloroethylene (DDE), arising from the heavy historical use of legacy OC insecticides, might serve as an environmental public health indicator for T2D occurrence. Soil samples from 60 Delta and 60 non-Delta sites randomly selected were analyzed for the presence of OC compounds. A retrospective cohort study of adult men (150 from each region) was recruited to provide a blood sample for OC compound quantitation and select demographic and clinical information including T2D. Using multivariable logistic regression, an association was found between increasing serum DDE levels and T2D occurrence in non-Delta participants (those subjects with lower serum DDE levels), as opposed to Delta participants (individuals with higher serum DDE levels). Thus, while there was a relationship between serum DDE levels and T2D in those with lower burdens of DDE, the lack of association in those with higher levels of DDE indicates a complex non-monotonic correlation between serum DDE levels and T2D occurrence complicating the goal of finding a public health marker for T2D. Abbreviations: BMI, body mass index; CVD, cardiovascular disease; CDC, Center for Disease Control, United States of America; DDE, p,p'- dichlorodiphenyldichloroethylene; DDT, p,p'- dichlorodiphenyltrichloroethane; GC/MS, gas chromatography/mass spectrometry; GIS, geographic information system; GPS, global positioning system; HDL, high-density lipoprotein; HTN, hypertension; IDW, inverse distance weighting; IRB, Institutional Review Board; LDL, low-density lipoprotein; LOQ, limit of quantitation; NHANES, National Health and Nutrition Examination Surveys; POPs, persistent organic pollutants; OC, organochlorine; PCB, polychlorinated biphenyl; SIM, single-ion monitoring; T2D, type 2 diabetes mellitus; USA, United States of America.

Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer: A case-control study nested within two prospective cohorts.

Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p'-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p'-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.

Organochlorine Levels in Plasma and Risk of Multiple Myeloma.

OBJECTIVE: The aim of this study was to estimate the association between organochlorine pesticides and polychlorinated biphenyls (PCBs) and multiple myeloma (MM). METHODS: The risk of MM from organochlorine compounds was examined in a population-based case-control study in British Columbia, Canada. Congeners of PCBs and pesticides or pesticide metabolites were measured in plasma of 325 cases and 327 controls. RESULTS: Most organochlorine analytes showed a significant association with MM. The strongest association (highest vs lowest quartile) was oxychlordane (odds ratio = 7.44; 95% confidence interval = 4.19 to 13.21). No heterogeneity was detected between organochlorines levels and MM subtypes. Only oxychlordane and ß-hexachlorocyclohexane (ß-HCCH) were identified as significant independent predictors of MM. CONCLUSION: Our study provides evidence that organochlorines contribute to the risk of MM.

Alterations in cellular lipid metabolism produce neutral lipid accumulation following exposure to the organochlorine compound trans-nonachlor in rat primary hepatocytes.

Recent epidemiological studies have revealed significant positive associations between exposure to organochlorine (OC) pesticides and occurrence of the metabolic syndrome and there are a growing number of animal-based studies to support causality. However, the cellular mechanisms linking OC compound exposure and metabolic dysfunction remain elusive. Therefore, the present study was designed to determine if direct exposure to three highly implicated OC compounds promoted hepatic steatosis, the hepatic ramification of the metabolic syndrome. First, the steatotic effect of p,p'-dichlorodiphenyldichloroethylene (DDE), oxychlordane, and trans-nonachlor was determined in freshly isolated rat primary hepatocytes. Exposure to trans-nonachlor significantly increased neutral lipid accumulation as opposed to DDE and oxychlordane. To determine possible mechanisms governing increased fatty acid availability, the effects of trans-nonachlor exposure on fatty acid uptake, de novo lipogenesis, triglyceride secretion, and fatty acid oxidation were explored. Trans-nonachlor did not significantly alter fatty acid uptake. However, insulin-stimulated de novo lipogenesis as well as basal expression of fatty acid synthase, a major regulator of lipogenesis were significantly increased following trans-nonachlor exposure. Interestingly, there was a significant decrease in fatty acid oxidation following trans-nonachlor exposure. This decrease in fatty acid oxidation was accompanied by a slight, but significant increase in oleic acid-induced cellular triglyceride secretion. Therefore, taken together, the present data indicate direct exposure to trans-nonachlor has a more potent pro-steatotic effect than exposure to DDE or oxychlordane. This pro-steatotic effect of trans-nonachlor appears to be predominately mediated via increased de novo lipogenesis and decreased fatty acid oxidation.

Serum concentrations of organochlorine compounds and predictors of exposure in children living in agricultural communities from South-Eastern Spain.

BACKGROUND: Information on exposure levels to organochlorine compounds (OCs) in child population is limited, despite their greater vulnerability to the adverse health effects of these chemicals. OBJECTIVE: To determine serum concentrations of 10 OCs (including organochlorine pesticides and polychlorinated biphenyls -PCBs-) in children living in agricultural communities from Almería (South-Eastern Spain), and to identify the main predictors of exposure related to socio-economic characteristics, diet and lifestyle. METHODS: A cross-sectional study was conducted on 133 children aged 6-11 years selected from public schools of the study area. OCs compounds were determined in serum samples by GC/ECD. Anthropometric measures were obtained during sample collection. Information on sociodemographic characteristics, parental occupation, residential history, lifestyle and frequency of food consumption, among other relevant factors, was obtained by questionnaires administered to the mothers. RESULTS: Geometric means of serum concentrations (ng/ml) were 0.11 for ß-hexachloro-cyclohexane (ß-HCH), 0.09 for endosulfan, 0.20 for endosulfan-ether, 0.51 for hexachorobenzene (HCB), 0.08 for mirex, 0.06 for oxychlordane, 0.36 for p,p'-DDE, 0.20 for PCB 138, 0.36 for PCB 153, and 0.45 for PCB 180. Percentage of samples above the limit of detection (0.05 ppb) ranged from 32 (ß-HCH) to 100 (HCB). A high variability in OC levels depending on the compound was observed between our results and others found in similar studies carried out in children. Variables related to fish consumption were found to be the major dietary determinant of PCB 138, p,p´-DDE, endosulfan-α, ß-HCH, mirex and oxychlordane levels. CONCLUSIONS: Children participating in this study showed detectable levels of many OC, despite these compounds are no longer used. Their presence in children serum can be explained by their high lipophilicity and environmental persistence, leading to contamination of fatty food. In this line, fish consumption seemed to be the most relevant determinant of OC levels found in our study.

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

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

The fate of technical-grade chlordane in mice fed a high-fat diet and its roles as a candidate obesogen.

Epidemiological studies indicate that exposure to persistent organic pollutants is positively associated with the prevalence of obesity. To delineate the potential role of technical-grade chlordane in obesity development, chlordane metabolism and chlordane-induced metabolic changes were investigated in mice fed high-fat diet (HFD) over a 6-week period. Gas chromatography-electron capture detector analysis showed that HFD induced more accumulation of technical chlordane in the liver, muscle and adipose tissue. The enantioselectivities of oxychlordane in selected tissues were also influenced by HFD. 1H NMR-based liver metabolome indicated that technical chlordane can enhance the metabolic alterations induced by HFD. Compared with the low-fat diet (LFD) group, no differences were observed in the LFD + chlordane group. However, as many as 16 metabolites were significantly different between the HFD group and HFD + chlordane group. Moreover, compared to the LFD + chlordane group, the abundances of 24 metabolites significantly increased or decreased in the HFD + chlordane group. Twenty metabolites were altered in the HFD group compared to the LFD group. Tryptophan profiling suggested that both chlordane and HFD can disturb tryptophan catabolism. These interactions between technical chlordane and HFD suggest that technical chlordane is a candidate obesogen.

Exposure to oxychlordane is associated with shorter telomeres in arctic breeding kittiwakes.

Telomeres are DNA-protein complexes located at the end of chromosomes, which play an important role in maintaining the genomic integrity. Telomeres shorten at each cell division and previous studies have shown that telomere length is related to health and lifespan and can be affected by a wide range of environmental factors. Among them, some persistent organic pollutants (POPs) have the potential to damage DNA. However, the effect of POPs on telomeres is poorly known for wildlife. Here, we investigated the relationships between some legacy POPs (organochlorine pesticides and polychlorobiphenyls) and telomere length in breeding adult black-legged kittiwakes (Rissa tridactyla), an arctic seabird species. Our results show that among legacy POPs, only blood concentration of oxychlordane, the major metabolite of chlordane mixture, is associated with shorter telomere length in females but not in males. This suggests that female kittiwakes could be more sensitive to oxychlordane, potentially explaining the previously reported lower survival rate in most oxychlordane-contaminated kittiwakes from the same population. This study is the first to report a significant and negative relationship between POPs and telomere length in a free-living bird and highlights sex-related susceptibility to banned pesticides.

Organochlorine pesticides and prostate cancer, Is there an association? A meta-analysis of epidemiological evidence.

PURPOSE: The results of epidemiological studies about exposure to organochlorine pesticides (OCPs) and risk of prostate cancer (PC) are inconclusive. We conducted a meta-analysis to evaluate the association between exposure to specific OCPs and PC. METHODS: We searched PubMed, Scopus, and Web of science databases for case-control and cohort studies published till March 2015 that provided data about exposure to OCPs and PC. We also contacted authors and hand-searched references of the included articles. We calculated pooled estimates using random effects model and explored heterogeneity between studies. RESULTS: We systematically reviewed 15 articles and based our meta-analysis on 10 articles covering nine case-control studies and a large prospective cohort study. Pooled estimates of PC for highest versus lowest exposed category to p,p'-DDE was 1.02 (0.69-1.35), I (2) = 12.7 %, p = 0.333, trans-nonachlor, 0.88 (0.45-1.31), I (2) = 0.00 %, p = 0.892, oxychlordane, 0.91 (0.46-1.35), hexachlorobenzene, 0.88 (0.18-1.57), I (2) = 36.0 %, p = 0.210 from combining results of studies that applied serum OCPs measurements among the general population. For DDT, stratifying studies by exposed population revealed homogeneity, pooled estimate for serum level measurement for the highest exposed versus the lowest exposed of the general population was 0.81 (0.95-1.26), I (2) = 0.00 %, p = 0.400, and for occupational exposure 1.30 (0.94-1.67), I (2) = 13.4 %, p = 0.315. A positive but also insignificant association was obtained for pooling results for high exposure to lindane among farmers and pesticide applicators, 1.56 (0.82-2.29), I (2) = 41.7 %, p = 0.180. CONCLUSIONS: The existing epidemiological data do not support the hypothesis that exposure to specific OCPs is associated with an increased incidence of PC in the general population.

Greater cognitive decline with aging among elders with high serum concentrations of organochlorine pesticides.

Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), ß-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. "Lower cognitive function" was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of ß-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in prospective studies.

Association between Several Persistent Organic Pollutants in Serum and Adipokine Levels in Breast Milk among Lactating Women of Korea.

Exposure to several persistent organic pollutants (POPs) has been linked to alteration of lipid metabolism. Adipokines, such as leptin and adiponectin, are hormones that play roles in lipid metabolism, and have been suggested as markers of health effects that may lead to obesity. To date, only serum adipokines have been associated with POPs exposure. In the present study, for the first time, the associations between leptin and adiponectin in breast milk, and several POPs in serum were investigated among 82 lactating Korean women between 25 and 46 years of age. Breast milk adipokines are important because adipokine intake of infant through breastfeeding may influence the growth of infants. The median concentrations of leptin and adiponectin in skimmed milk of the Korean lactating women were 17.9 ng/L and 16.5 µg/L, respectively. Leptin concentrations in breast milk were negatively associated with ∑hexachlorohexane (HCH), oxychlordane, ∑chlordane, or 2,2',4,4',5,5'-hexachlorobiphenyl (CB 153) levels in maternal serum. Linear relationships between adiponectin and POPs concentrations were not observed, however, nonmonotonic relationship which showed generally positive associations was suggested for p,p'-dichlorodiphenyltrichloroethane (DDT) and ∑chlordane in quartile analysis. Our observations show that POPs at the current level of exposure may be associated with the alteration of lipid metabolism among lactating women. Implication of adipokine transfer to breastfed infants is of concern and deserves further investigation.

Survival rate and breeding outputs in a high Arctic seabird exposed to legacy persistent organic pollutants and mercury.

Chronic exposure to pollutants may represent a threat for wildlife. We tested whether adult survival rate, breeding probability and breeding success the year of sampling and the following year were affected by blood levels of mercury or persistent organic pollutants in Svalbard black-legged kittiwake Rissa tridactyla, by using capture-mark-recapture models over a five-year period. Survival rate was negatively linked to HCB levels in females, to chlordane mixture and oxychlordane, tended to decrease with increasing PCBs or DDE levels, but was unrelated to mercury. Breeding probability decreased with increasing mercury levels during the sampling year and with increasing CHL or HCB levels during the following year, especially in males observed as breeders. Surprisingly, the probability of raising two chicks increased with increasing HCB levels. Although levels of these legacy pollutants are expected to decline, they represent a potential threat for adult survival rate and breeding probability, possibly affecting kittiwake population dynamics.

Enantiomer-selective and quantitative trace analysis of selected persistent organic pollutants (POP) in traditional food from western Greenland.

Enantiomeric fractions (EF) are today considered a powerful tool to elucidate selective uptake processes of chiral contaminants in biota. In this study, concentration levels and EF were determined by gas chromatograph-mass spectrometer (GC/MS) for α-hexachlorocyclohexane (α-HCH) and trans-, cis-, and oxychlordane in selected Greenlandic traditional food items, collected at the local market in Nuuk in 2010. The food items selected were raw and smoked fish (salmon and halibut, n = 6), whale meat (n = 8), seal meat (n = 2) and narwhal mattak (skin and blubber, n = 6). The EF were nonracemic (≠0.5) for all samples except for α-HCH in narwhal, trans-chlordane in whale and smoked salmon, and cis- and oxychlordane in seal. The EF for α-HCH were significant for all fish samples, but not for mammalian samples. Data indicate that different uptake and/or transformation mechanisms may be responsible for nonracemic distributions of chiral pesticides in mammals and fish species analyzed. There were no general enantiomer-selective transformation/accumulation trends found for chlordanes. Data indicate that enantiomer-specific properties are an important prerequisite for interaction of chiral contaminant with internal metabolic processes. However, marked differences within these groups were identified. The EF in ringed seals were racemic for most of the analyzed pesticides (i.e., chlordanes). However, narwhal were characterized by nonracemic EF for all chiral pesticides analyzed. Median levels of α-HCH ranged from 2 to 24 ng/g lw and from 15.1 to 626.6 ng/g lw for trans-nonachlor, with lowest levels observed in smoked salmon and highest levels in narwhal mattak. This study confirmed that concentration levels of analyzed pesticides in the investigated food items were below the tolerable daily intake (TDI) threshold.

A pilot study for foetal exposure to multiple persistent organic pollutants and the development of infant atopic dermatitis in modern Japanese society.

Increasing evidence supports that harmful chemicals accumulating in the human body may pose a significant threat to infant health through foetal exposure. Persistent organic pollutants (POPs) are thought to enhance the risk for later development of allergic disease like atopic dermatitis (AD). However, few studies have evaluated the effect of foetal exposure to various POPs on the development of AD in early infancy. Here, we describe the impact of foetal exposure to a number of POPs on the occurrence of AD in 7-month-old infants. The participants were 81 infants with or without AD who participated in a birth cohort study, where the concentrations of 15 polychlorinated biphenyl (PCBs) congeners, dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethylene (p,p'-DDE), ß-hexachlorocyclohexane (ß-HCH), hexachlorobenzene (HCB), cis-nonachlor, trans-nonachlor, mirex, oxychlordane, and 27 polybrominated diphenyl ether (PBDEs) congeners were measured in the umbilical cord tissues collected immediately after birth. At 7 months, 27 of the 81 infants (33.8%) were diagnosed with AD. Of all POPs examined, total concentrations of 27 PBDE congeners were associated with a significantly decreased incidence of AD. Notably, the concentration of 27 PBDEs was significantly lower in AD infants than in non-AD infants (P<0.01), and the risk of AD development decreased with increasing PBDE levels. These results suggest that foetal exposure to PBDEs is a possible contributing factor to reducing AD in early infancy.

Toxicokinetics of dioxins and other organochlorine compounds in Japanese people: association with hepatic CYP1A2 expression levels.

Concentrations of persistent organochlorine compounds (OCs) including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in the liver and adipose tissue of Japanese cadavers were measured, and their toxicokinetics were examined in association with hepatic cytochrome P450 (CYP) 1A protein expression levels. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were 66±74 and 65±57 pg/g lipid weight (mean±S.D.) in the liver and adipose tissue, respectively. Total PCBs (sum of 62 congeners targeted), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) and ß-hexachlorocyclohexane (ß-HCH) were detected at concentrations over 1 µg/g lipid in both tissues of some specimens. For most of the dioxin-like congeners, total PCBs, p,p'-DDE, oxychlordane, α- and ß-HCH, hexachlorobenzene (HCB), and tris(4-chlorophenyl)methane (TCPMe), age-dependent increases in concentrations were found in the adipose tissue of males. No such age-dependent trend was observed in the liver, suggesting that there are different mechanisms underlying the hepatic concentrations of OCs. Immunoblot analyses indicated detectable expression of hepatic CYP1A2 protein, whereas no CYP1A1 protein was detected. The CYP1A2 expression levels were positively correlated with concentrations (on wet weight basis) of 2,3,4,7,8-P5CDF, the dominant TEQ-contributed congeners in the liver, indicating the induction of this CYP. Hepatic CYP1A2 protein levels were strongly correlated with the liver to adipose concentration (L/A) ratios of PCDD/F congeners with more than 5 chlorine atoms. Together with higher concentrations of the congeners in the liver than in the adipose tissue, the observation on L/A ratios of highly chlorinated PCDD/Fs suggests that induced hepatic CYP1A2 protein is involved in their sequestration in this human population, as observed in model animals (rodents). Nonetheless, the magnitude of hepatic sequestration (L/A ratio) of PCDD/Fs in this human population was lower than in other mammals and birds, reported previously. This study emphasizes the fact that toxicokinetics of some OCs can be affected at least partly by CYP1A2 protein levels in humans. For the extrapolation of their toxicokinetics from model animals to humans, knowledge on the induction and sequestration potencies of CYP1A is necessary.

Three decades (1983-2010) of contaminant trends in East Greenland polar bears (Ursus maritimus). Part 1: legacy organochlorine contaminants.

Legacy organochlorine contaminants were determined in adipose tissues from 294 polar bears (Ursus maritimus) sampled in East Greenland in 23 of the 28years between 1983 and 2010. Of 19 major legacy contaminants and congeners (ΣPCB, 4 PCB congeners (CB153, 180, 170/190), ΣDDT, p,p'-DDE, p,p' -DDD and p,p'-DDT, α- and ß-hexachlorocyclohexane (HCH), HCB, octachlorostyrene, dieldrin, oxychlordane, cis- and trans-chlordane, cis- and trans-nonachlor, heptachlor epoxide and BB-153), 18 showed statistically significant average yearly declines of -4.4% (range: -2.0 to -10.8%/year) among subadult polar bears (i.e. females<5years, males<6years). For example, the ∑PCB concentrations declined 2.7 fold from 22730ng/g lw (95% C.I.: 12470-32990ng/g lw) in 1983-1986 to 8473ng/g lw (95% C.I.: 6369-9776ng/g lw) in 2006-2010. Similar but fewer statistically significant trends were found for adult females and adult males likely due to smaller sample size and years. Despite declines as a result of international regulations, relatively high levels of these historic pollutants persist in East Greenland polar bear tissues.

Circulating metals and persistent organic pollutant concentrations in Canadian and non-Canadian born primiparous women from five Canadian centres: results of a pilot biomonitoring study.

The developing foetus is thought to be at increased risk from exposure to environmental contaminants; however, developmental exposure data is notably lacking for many contaminants. Moreover, potential regional differences or effect of place of birth on residue levels measured in pregnant women is also unknown. Therefore, as part of a multinational biomonitoring study, 125 primiparous pregnant Canadian women were recruited from five Canadian centres (Vancouver, Calgary, Hamilton, Ottawa, and Halifax). Metals in whole blood and persistent organic pollutants (POPs) in plasma were measured by inductively coupled plasma mass spectrometry (ICPMS) and gas chromatography-mass spectrometry (GCMS), respectively. Of the 125 women recruited to this study, complete data sets were available for 123 of which 103 were Canadian born. Data were analysed by analysis of covariance and linear mixed models using age and body mass index as covariates. The metals cadmium (Cd), cobalt (Co), lead (Pb), nickel (Ni), selenium (Se), and total mercury (Hg) were detected in more than 93% of the samples tested. ß-Hexachlorohexane (ß-HCH), oxychlordane, trans-nonachlor, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), polybrominated diphenyl ether (PBDE) congeners (PBDE-153, PBDE-47), polychlorinated biphenyl (PCB) congeners (PCB-138, -153, and -180), and the dioxin-like PCB congener PCB-118 were quantified in greater than 70% of the samples tested. Significant differences in the concentrations of Cd, Ni, PCB-153, and p,p'-DDE were found between the centres studied. Furthermore, foreign-born pregnant women had significantly higher concentrations of Cd, ß-HCH, PBDE-47, PCB-138, -153, -180, and p,p'-DDE compared to Canadian born pregnant women. Taken together, the data suggest that there are potential regional differences in contaminant body burden and place of birth may also contribute to differences in maternal residue concentrations.

Maternal pregnancy levels of trans-nonachlor and oxychlordane and prevalence of cryptorchidism and hypospadias in boys.

BACKGROUND: The etiologies of the male urogenital anomalies--cryptorchidism and hypospadias--are poorly understood. Given positive associations between chlordane isomers and testicular germ cell tumors, it is reasonable to assume that chlordanes might also be associated with other testicular dysgenesis syndrome disorders, namely cryptorchidism and hypospadias. OBJECTIVE: To examine whether exposure to in utero chlordane is related to cryptorchidism and hypospadias, we evaluated levels of chlordane derivatives, trans-nonachlor and oxychlordane, among pregnant women enrolled in the Collaborative Perinatal Project (CPP). METHODS: From 1959 to 1965, the CPP enrolled pregnant women at 12 U.S. medical centers. We analyzed serum trans-nonachlor and oxychlordane levels measured in third-trimester serum from the mothers of 217 sons with cryptorchidism, 197 sons with hypospadias, and 557 sons with neither condition. Adjusted odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression. RESULTS: The quartile-specific ORs for cryptorchidism or hypospadias show no notable associations with trans-nonachlor or oxychlordane. Further, there were no significant trends with increasing quartile of maternal trans-nonachlor or oxychlordane level in either cryptorchidism or hypospadias (p-trend all > 0.45). CONCLUSIONS: The results do not support an association between chlordane levels and cryptorchidism or hypospadias. It is unlikely that current chlordane exposure is related to the development of either anomaly, given that serum chlordane levels at the time of sample collection, the early 1960s, were considerably higher than levels at present.