Variations in thyroid hormone levels in endangered St. Lawrence Estuary belugas: Potential linkage with stress and organohalogen contaminant exposure.

The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the non-recovery of this endangered and declining population. In the last decade, an increasing number of parturition-associated complications and calf mortality has been reported in this population. It was suggested that elevated exposure to organohalogens (e.g., the halogenated flame retardants polybrominated diphenyl ethers [PBDEs]) and stress could play a role in this phenomenon by perturbing thyroid hormones. The objective of this study was to investigate the impact of concentrations of organohalogen contaminants and stress (cortisol levels) on thyroid hormone variations in adult male and female SLE belugas. Because plasma could not be collected in SLE belugas for ethical reasons, skin biopsy (n = 40) was used as a less-invasive alternative matrix to determine organohalogens (PBDEs and other halogenated flame retardants, polychlorinated biphenyls, and organochlorine pesticides), cortisol, and thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and their metabolites reverse T3 and 3,5-diiodothyronine [3,5-T2]). Cortisol and thyroid hormones were analyzed by ultra-performance liquid chromatography-multiple reactions monitoring mass spectrometry (UPLC-MRM/MS). This method was compared using skin and plasma samples obtained from Arctic belugas. Comparisons of linear models showed that cortisol was a weak predictor for T4, rT3 and 3,5-T2. Specifically, there was a weak significant negative association between T4 and cortisol levels. Moreover, in male SLE belugas, a weak significant positive association was found between T3 and Σ34PBDE concentrations in skin. Our findings suggest that stress (i.e., elevated skin cortisol levels) along with organohalogen exposure (mainly PBDEs) may be associated with thyroid hormone level perturbations in skin of cetaceans.

Drivers of maternal accumulation of organohalogen pollutants in Arctic areas (Chukotka, Russia) and 4,4'-DDT effects on the newborns.

BACKGROUND: One of the most worrying consequence of the production and use of persistent organohalogen pollutants (POPs) is the high accumulation in Arctic populations because of long-range transport. Study of the effects in these populations may illustrate human impacts that are difficult to assess in other locations with lower exposure to these compounds and more diverse pollutant influences. OBJECTIVE: We aimed to identify the main maternal characteristics influencing on the accumulation of these compounds and the effects on the newborns in a highly exposed Arctic population (Chukotka, Russia). METHODS: Organochlorine and organobromine compounds were analysed in maternal venous serum (n = 250). The study included data on residence, educational level, age, parity and body mass index (BMI) from self-reported questionnaires and measured anthropometric characteristics of newborns. RESULTS: Concentrations of ß-hexachlorocyclohexanes, hexachlorobenzene, 4,4'-DDT and polychlorobiphenyls were high when compared with those generally found in adult populations later than year 2000. The polybromodiphenyl ethers were negligible. These POP concentrations were higher than in Alaska and Arctic Norway and similar to those in Canada. The Chukotka mothers living in inland areas showed significant lower concentrations than those living in the coast (p < 0.001) except for 4,4'-DDT. The population from the Chukotsky District, a specific coastal area, showed the highest concentrations. Residence was therefore a main concentration determinant (p < 0.001) followed by maternal age, and in some cases parity and BMI (p < 0.05). 4,4'-DDT showed an association with the anthropometric characteristics of the newborns (p < 0.05). Mothers with higher 4,4'-DDT concentrations had longer gestational ages and gave birth to infants with higher weight and length. CONCLUSIONS: The maternal accumulation patterns of POPs were mainly related with residence. Most of these compounds were found in higher concentration in women living at coastal areas except 4,4'-DDE and 4,4'-DDT which were of inland origin. This last pesticide was the pollutant showing positive associations with gestational age and newborn's weight and length. To the best of our knowledge, this is the first study reporting statistically significant associations between maternal 4,4'-DDT exposure and anthropometric characteristics of the newborns.

First in vivo evaluation of a potential SPECT brain radiotracer for the gonadotropin releasing hormone receptor.

OBJECTIVES: In vivo evaluations of a gonadotropin releasing hormone-receptor single photon emission computed tomography radiotracer for non-invasive detection of gonadotropin releasing homone-receptors in brain. RESULTS: We have used a simple, robust and high-yielding procedure to radiolabel an alpha-halogenated bioactive compound with high radiochemical yield. Literature findings showed similar alpha-halogenated compounds suitable for in vivo evaluations. The compound was found to possess nano molar affinity for the gonadotropin releasing hormone-receptor in a competition dependent inhibition study. Furthermore, liquid chromatography-mass spectrometry analysis in saline, human and rat serum resulted in 46%, 52% and 44% stability after incubation for 1 h respectively. In addition, rat brain single photon emission computed tomography and biodistribution studies gave further insight into the nature of the compound as a radiotracer.

Hundreds of Unrecognized Halogenated Contaminants Discovered in Polar Bear Serum.

Exposure of polar bears (Ursus maritimus) to persistent organic pollutants was discovered in the 1970s, but recent evidence suggests the presence of unknown toxic chemicals in their blood. Protein and phospholipid depleted serum was stirred with polyethersulfone capillaries to extract a broad range of analytes, and nontarget mass spectrometry with "fragmentation flagging" was used for detection. Hundreds of analytes were discovered belonging to 13 classes, including novel polychlorinated biphenyl (PCB) metabolites and many fluorinated or chlorinated substances not previously detected. All analytes were detected in the oldest (mid-1980s) archived polar bear serum from Hudson Bay and Beaufort Sea, and all fluorinated classes showed increasing trends. A mouse experiment confirmed the novel PCB metabolites, suggesting that these could be widespread in mammals. Historical exposure and toxic risk has been underestimated, and these halogenated contaminants pose uncertain risks to this threatened species.

Prenatal exposure to persistent organic pollutants and methylation of LINE-1 and imprinted genes in placenta: A CHECK cohort study.

Prenatal exposure to persistent organic pollutants (POPs) has been linked to numerous adverse birth outcomes among newborn infants in many epidemiological studies. Although epigenetic modifications have been suggested as possible explanations for those associations, studies have rarely reported a relationship between POP exposure during pregnancy and DNA methylation in the placenta. In the present study, we investigated the association between prenatal exposure to several POPs, including organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs), and methylation levels of long interspersed element 1 (LINE-1), as well as imprinted genes in placental DNAs among Korean mother-child pairs (N = 109). We assessed the association of DNA methylation not only with each target POP (single-POP models) but also with multiple POPs applying principal component analysis (multiple-POP models). Potential associations between placental DNA methylation and birth outcomes of newborn infants were also estimated. In single-POP models, significant associations were detected between OCP measurements and placental DNA methylation. Elevated concentrations of ß-hexachlorhexane (ß-HCH) in maternal serum collected during delivery were significantly associated with a decrease in methylation of LINE-1 in the placenta. Higher levels of p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) in maternal serum were associated with hypermethylation of insulin-like growth factor 2 (IGF2). In multiple-POP models, a significant and positive association between DDTs and IGF2 methylation was also observed. Placental LINE-1 methylation was inversely associated with birth length. Our observations indicate that prenatal exposure to several POPs including DDTs is associated with the changes in methylation of genes, including major imprinted genes in the placenta. The consequences of these epigenetic alterations in placenta during development deserve further investigation.

Influence of maternal and sociodemographic characteristics on the accumulation of organohalogen compounds in Argentinian women. The EMASAR study.

The occurrence of organohalogen compounds in venous serum from post-partum mothers from two Argentinian cities, Salta and Ushuaia, has been investigated (n = 698). 4,4'-DDE was the most abundant compound in these cities, with geometric means of 33 and 67ng/g lipid weight, respectively. City of residence, age and parity were the main determinants of the accumulation of these compounds. Hexachlorobenzene (HCB) was the second most abundant pollutant in Ushuaia, 8.7ng/g lipid, and ß-hexachlorocyclohexane (ß-HCH) in Salta, 7.8ng/g lipid. Decabromodiphenyl ether was higher in Ushuaia than Salta, 8.2 and 4.1ng/g lipid, respectively. The predominance of ß-HCH, 4,4'-DDE and 4,4'-DDT in Salta was related with higher use of pesticides for agricultural applications. The observed higher concentrations of 4,4'-DDE and 4,4'-DDT in the mothers from rural+semi-urban sites than in urban areas were consistent with this agricultural origin. In addition, the most volatile organochlorine compounds included in this study, HCB and α-HCH, were mainly found in Ushuaia. The concentrations of the studied organohalogen pollutants in Argentina were lower than those found in other similar studies which is consistent with the location of these cities in the southern hemisphere. Age, mainly for 4,4'-DDE and polychlorobiphenyl (PCB) congeners 138, 153 and 180, and parity, mainly for HCB, ß-HCH, 4,4'-DDT and PCB congener 118, were the second main determinants of the concentrations of these compounds. Gestational weight gain also influenced on the maternal levels of HCB, ß-HCH, 4,4'-DDT and PCB congeners 118, 138 and 153. Higher weight accumulation during pregnancy involved dilution of these persistent pollutants. Body mass index (BMI) was a statistically significant determinant for 4,4'-DDT, α-HCH and PCB congeners 153 and 180. The observed direct correspondence between higher BMI and 4,4'-DDT concentrations was in agreement with the above reported inputs related with agricultural applications. The reverse correspondence of BMI with α-HCH and the PCB congeners indicated higher dilution at higher weight increase.

Potentiation of ecological factors on the disruption of thyroid hormones by organo-halogenated contaminants in female polar bears (Ursus maritimus) from the Barents Sea.

As apex predators, polar bears (Ursus maritimus) are among the most heavily polluted organisms in the Arctic. In addition to this anthropogenic stressor, climate warming has been shown to negatively affect their body condition, reproductive output and survival. Among potential underlying physiological mechanisms, thyroid hormones (THs), which control thermoregulation, metabolism and reproduction, can be affected by a variety of both natural and anthropogenic factors. While THs have been extensively used as proxies for pollution exposure in mammals, including polar bears, there is a lack of knowledge of their natural variations. In this context, we examined seasonal variations in body condition and circulating TH concentrations in free-ranging female polar bears. Females with variable reproductive status (i.e., solitary, with cubs of the year or with yearlings) were sampled from locations with contrasted sea ice conditions. Furthermore, we studied THs in relation to levels of organo-halogenated contaminants. As predicted, solitary females were in better condition than females caring for offspring, especially in spring. In addition, TH levels were lower in autumn compared to spring, although this seasonal effect was mainly observed in solitary females. Finally, the negative relationships between organochlorine and perfluoroalkyl substances and some THs suggest a possible alteration of homeostasis of THs. Since the latter relationships were only observed during spring, we emphasize the importance of considering the ecological factors when using THs as proxies for pollution exposure. Yet, the combined effects of natural and anthropogenic stressors on THs might impair the ability of polar bears to adapt to ongoing climate changes.

Organohalogenated contaminants in plasma and eggs of rockhopper penguins: Does vitellogenin affect maternal transfer?

Although many studies have investigated organohalogenated contaminants (OHCs) in yolk, little is known about the mechanisms and timing of transfer of OHCs from the female to the egg. Vitellogenin, a yolk precursor, has been suggested to play a role in this transport. We here report for the first time the temporal changes in OHC and an index of vitellogenin concentrations in female plasma from the pre-laying period to clutch completion in free-living birds: the southern rockhopper penguin (Eudyptes chrysocome chrysocome) breeding in the Falkland/Malvinas Islands. In addition, OHC concentrations in the corresponding clutches were analysed. OHC concentrations in female plasma and in the yolk of both the first (A-) and the second (B-)eggs followed a similar pattern, with hexachlorobenzene (HCB) > Σpolychlorinated biphenyls (PCBs) > Σdichlorodiphenyltrichloroethanes (DDTs) > Σmethoxylated polybrominated diphenyl ethers (MeO-PBDEs) > Σchlordanes (CHLs) > Σpolybrominated diphenyl ethers (PBDEs) ≈ Σhexachlorocyclohexanes (HCHs). The higher concentrations of MeO-PBDEs compared to PBDEs indicate a diet containing naturally-produced MeO-PBDEs. All OHC compounds except for PBDEs increased from the pre-laying period to A-egg laying and subsequently declined from A-egg laying to B-egg laying, and female plasma vitellogenin showed the same pattern. For ΣPCBs and ΣMeO-PBDEs, we found positive correlations between female plasma during A-egg laying and both eggs, and for HCB between female plasma and A-eggs only. During pre-laying, only ΣMeO-PBDEs correlated between both eggs and female plasma, and no correlations between OHC concentrations in eggs and female plasma were found during B-egg laying, highlighting that maternal transfer of OHCs is time- and compound-specific. Finally, female vitellogenin concentrations did not significantly correlate with any OHC compounds in either female plasma or eggs, and our results therefore did not confirm the suggested role of vitellogenin in the maternal transfer of OHC molecules into their eggs.

Relationships between concentrations of selected organohalogen contaminants and thyroid hormones and vitamins A, E and D in Faroese pilot whales.

Pilot whales (Globicephala melas) from the Faroe Islands, North-East Atlantic, have high body concentrations of organohalogenated compounds (OHCs), such as polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and brominated flame retardants (BFRs). The aim of the present study was to examine if and to what extent blood plasma and liver concentrations of several groups of these OHCs are related to concentrations of relevant nutritional and hormonal biomarkers in pilot whales. Thyroid hormones (THs: total and free thyroxine and total and free triiodothyronine) and vitamin A (retinol), D (25-hydroxyvitamin D3) and E (α-tocopherol) were analysed in plasma (n=27) and vitamin A (total vitamin A, retinol and retinyl palmitate) and E (α- and γ-tocopherol) were analysed in liver (n=37) of Faroe Island pilot whales. Correlative relationships between the biomarkers and OHC concentrations previously analysed in the same tissues in these individuals were studied. The TH concentrations in plasma were significantly higher in juveniles than in adults. Vitamin D concentrations in plasma and α- and γ-tocopherol in liver were higher in adults than in juveniles. Multivariate statistical modelling showed that the age and sex influenced the relationship between biomarkers and OHCs. Some significant positive relationships were found between OHCs and thyroid hormone concentrations in the youngest juveniles (p<0.05). In plasma of juvenile whales α-tocopherol was also positively correlated with all the OHCs (p<0.05). Only few significant correlations were found between single OHCs and retinol and vitamin D in plasma within the age groups. There were significant negative relationships between hepatic PBDE concentrations and retinol (BDE-47) and γ-tocopherol (BDE-49, -47, -100, -99, -153) in liver. The relationships between OHCs and THs or vitamins suggest that in pilot whales OHCs seem to have minor effects on TH and vitamin concentrations.

Persistent organic pollutants in blood samples of Southern Giant Petrels (Macronectes giganteus) from the South Shetland Islands, Antarctica.

Seabirds play an important role as top consumers in the food web and can be used as biomonitors of exposure to pollutants. Contamination studies involving non-destructive sampling methods are of considerable importance, allowing better evaluation of the levels of pollutants and their toxic effects. In the present study, organohalogen contaminants were analyzed in 113 blood samples from Southern Giant Petrel (Macronectes giganteus) adults and chicks collected in the austral summer of 2011/2012 and 2012/2013 from colonies on Elephant and Livingston Islands, South Shetland, Antarctica. Polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), pentachlorobenzene (PeCB), mirex, dichlorodiphenyltrichloroetane and derivatives (DDTs) and chlordanes were detected in all birds, whereas polybrominated diphenyl ethers (PBDEs) were not detected in any blood samples. No significant differences were found in organochlorine levels between sampling events. Adults exhibited significantly higher levels than chicks, except for PeCB. PCBs, HCB, mirex and DDTs were statistically similar in males and females from Elephant Island. Females on Livingston Island exhibited higher HCB values than males, but no sex differences were found regarding other organochlorines. The similarity in organochlorine levels between sexes in birds with very marked sexual segregation in feeding habits during the breeding season may indicate that significant amounts of contaminants are acquired during migration to lower latitudes, when the diets of males and females are similar. Birds sampled on Livingston Island exhibited significantly lower levels of PCBs, HCB, DDTs, mirex and chlordanes in comparison to those on Elephant Island, which could be the result of distinct foraging patterns between the two colonies. Organochlorine levels were similar between years in birds captured in two consecutive breeding seasons. Blood samples from Southern Giant Petrels adults and chicks proved to be useful for the comparison of intraspecific contamination levels and appear to be adequate for the long-term assessment of organohalogen contaminants in antarctic top predators. Organochlorine contaminants in blood samples of Southern Giant Petrels reflected intra-specific differences and suggested distinct foraging patterns between colonies.

Occurrence of chlorinated and brominated dioxins/furans, PCBs, and brominated flame retardants in blood of German adults.

Persistent organic pollutants are widespread in the environment, and are associated with a particular health and ecological concern. The human body burden of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs), polybrominated dibenzo-p-dioxins and dibenzofurans (PBDDs/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenylether (PBDEs), and hexabromocyclododecanes (HBCDs) was determined. Blood samples were collected in Germany, originating from 42 randomly selected subjects between 20 and 68 years old. The median (95th percentile) concentrations, expressed as WHO2005-TEQ for PCDD/PCDFs and dioxin-like PCBs, were 6.2 (19.1) pg/g l.w. and 4.1 (8.8) pg/g l.w., respectively. PBDDs/Fs were found with a median of 2.8 pgTEQ/g l.w. and a 95th percentile of 8.7 pgTEQ/g l.w. (using similar interim TEF values as for PCDDs/Fs) On a median basis, the contribution of PCDD/Fs, dioxin-like PCBs, and PBDDs/Fs to total TEQ were 47%, 31%, and 21%, respectively. The sum of the 6 non-dioxin-like PCBs exhibited a median of 267ng/g l.w. and a 95th percentile of 834ng/g l.w. The median value for the sum of six tetra- to hepta-PBDE congeners was 1.7ng/g l.w. (95th percentile: 4.9ng/g l.w.). BDE 209 was the most abundant congener with a median of 1.8ng/g l.w. HBCDs were only found in some samples, and concentrations ranged between the limit of detection (5ng/g l.w.) and the limit of quantification (16ng/g l.w.). Results for PBDEs and HBCDs are comparable to other European studies. Our study demonstrated that the body burden of PCDD/Fs and PCBs declined continously since the last three decades, but exposure may exceed precautionary guideline levels.

Menstrual cycle perturbation by organohalogens and elements in the Cree of James Bay, Canada.

Persistent organohalogens (POHs) and metals have been linked to alterations in menstrual cycle function and fertility in humans. The Cree First Nations people living near James Bay in Ontario and Quebec, Canada, have elevated levels of POHs, mercury and lead compared to other Canadians. The present study examines the interrelationships between selected POHs and elements on menstrual cycle function in these Cree women. Menstrual cycle characteristics were derived from structured daily diaries and endocrine measurements from daily urine samples collected during one cycle for 42 women age 19-42. We measured 31 POHs in blood plasma and 18 elements in whole blood, for 31 of the participants. POHs and elements detected in ≥ 70% of the participants were transformed by principal component (PC) analysis to reduce the contaminant exposure data to fewer, uncorrelated PCA variables. Multiple regression analysis revealed that, after adjusting for confounders, PC-3 values showed significant negative association with cycle length, after adjusting for confounders (p = 0.002). PC-3 accounted for 9.2% of the variance and shows positive loadings for cadmium, selenium, and PBDE congeners 47 and 153, and a negative loading for copper. Sensitivity analysis of the model to quantify likely effect sizes showed a range of menstrual cycle length from 25.3 to 28.3 days using the lower and upper 95% confidence limits of mean measured contaminant concentrations to predict cycle length. Our observations support the hypothesis that the menstrual cycle function of these women may be altered by exposure to POHs and elements from their environment.

Organohalogenated contaminants in type 2 diabetic serum from Jeddah, Saudi Arabia.

Most of the organohalogenated contaminants (OHCs) have high environmental stability and are lipophilic in nature, thus bioaccumulate through the various routes e.g., inhalation, dermal contact and food intake. Human exposure to these OHCs can induce adverse health effects. Studies on the occurrence of OHCs in human samples from Saudi Arabia are scarce. Therefore, this study aimed at providing preliminary insight on the occurrence of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated biphenyl ethers (PBDEs) in diabetic and non-diabetic donors from KSA. Serum samples were collected from type 2 diabetic patients (n = 40) and control donors (n = 20) to study the impact of OHCs on their health. For the first time we studied the difference of Æ©OHCs in type 2 diabetic and control participants. The order of obtained results was Æ©OCPs (35-650 ng/g lw)> Æ©PCBs (15-90 ng/g lw)> Æ©PBDEs (1.5-68 ng/g lw). The major contributors were p,p'-DDE (median 44 ng/g lw), PCB 153 (2.3 ng/g lw), PCB 138 (2.1 ng/g lw), BDE 153 (1.2 ng/g lw) and BDE 47 (0.85 ng/g lw). Exposure to different OHCs between male and female donors was not significantly different (p > 0.05). However, Æ©PCBs and Æ©OHCs were significantly higher (p < 0.05) in diabetic donors than those of control group. We computed significantly positive correlations (p < 0.05) among different OHCs and between OHCs and age factor. The current study highlights the presence of different OHCs in humans from Jeddah, KSA. This is a preliminary study based on small sample size but our results suggested that detailed studies are required to understand the sources of these pollutants and their impact on human health.

Residue profiles of organohalogen compounds in human serum from e-waste recycling sites in North Vietnam: Association with thyroid hormone levels.

This study demonstrated the contamination levels of polychlorinated biphenyls (PCBs), hydroxylated PCBs (OH-PCBs), polybrominated diphenyl ethers (PBDEs), methoxylated PBDEs (MeO-PBDEs), hydroxylated PBDEs (OH-PBDEs), and bromophenols (BPhs), and their relationships with thyroid hormones (THs), in the serum of human donors from an e-waste recycling site and a rural site in Hung Yen province, Vietnam. Occupationally related exposure was indicated by significantly higher residue levels of PCBs, OH-PCBs, PBDEs, and BPhs in the serum of donors from the e-waste recycling site (median: 420, 160, 290, and 300pgg(-1) wet wt, respectively) than those in the serum of donors from the rural site (median: 290, 82, 230, and 200pgg(-)(1) wet wt, respectively). On the other hand, levels of OH-/MeO-PBDEs were significantly higher in serum of donors from the reference site (median: 160 and 20pgg(-1) wet wt, respectively) than in those from the e-waste recycling site (median: 43 and 0.52pgg(-1) wet wt, respectively). In addition, we implemented stepwise generalized linear models to assess the association between the levels of TH and PCBs, PBDEs, and their related compounds. In females, we found positive associations of PCBs and OH-PCB concentrations with total thyroxine, free thyroxine, total triiodothyronine, and free triiodothyronine, and a negative association with thyroid-stimulating hormone concentrations.

Preconception maternal and paternal exposure to persistent organic pollutants and birth size: the LIFE study.

BACKGROUND: Persistent organic pollutants (POPs) are developmental toxicants, but the impact of both maternal and paternal exposures on offspring birth size is largely unexplored. OBJECTIVE: We examined associations between maternal and paternal serum concentrations of 63 POPs, comprising five major classes of pollutants, with birth size measures. METHODS: Parental serum concentrations of 9 organochlorine pesticides, 1 polybrominated biphenyl (PBB), 7 perfluoroalkyl chemicals (PFCs), 10 polybrominated diphenyl ethers (PBDEs), and 36 polychlorinated biphenyls (PCBs) were measured before conception for 234 couples. Differences in birth weight, length, head circumference, and ponderal index were estimated using multiple linear regression per 1-SD increase in natural log-transformed (ln-transformed) chemicals. Models were estimated separately for each parent and adjusted for maternal age, maternal prepregnancy body mass index (kilograms per meter squared) and other confounders, and all models included an interaction term between infant sex and each chemical. RESULTS: Among girls (n = 117), birth weight was significantly lower (range, 84-195 g) in association with a 1-SD increase in ln-transformed maternal serum concentrations of DDT, PBDE congeners 28 and 183, and paternal serum concentrations of PBDE-183 and PCB-167. Among boys (n = 113), maternal (PCBs 138, 153, 167, 170, 195, and 209 and perfluorooctane sulfonamide) and paternal (PCBs 172 and 195) serum concentrations of several POPs were statistically associated with lower birth weight (range, 98-170 g), whereas paternal concentrations of PBDEs (66, 99) were associated with higher birth weight. Differences in offspring head circumference, length, and ponderal index were also associated with parental exposures. CONCLUSIONS: Preconceptional maternal and paternal concentrations of several POPs were associated with statistically significant differences in birth size among offspring.

Association of persistent organic pollutants and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia: A systematic review.

BACKGROUND: Over half of the people with diabetes in the world live in Asia. Emerging scientific evidence suggests that diabetes is associated with environmental pollutants, exposures that are also abundant in Asia. OBJECTIVE: To systematically review the literature concerning the association of persistent organic pollutants (POPs) and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia. METHODS: PubMed and Embase were searched to identify studies published up to November 2014. A secondary reference review of all extracted articles and the National Toxicology Program Workshop on the association of POPs with diabetes was also conducted. A total of 19 articles met the inclusion criteria and were evaluated in this review. RESULTS: To date, the evidence relating POPs and non-persistent pesticides with diabetes in Asian populations is equivocal. Positive associations were reported between serum concentrations of polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and several organochlorine pesticides (DDT, DDE, oxychlordane, trans-nonachlor, hexachlorobenzene, hexachlorocyclohexane) with diabetes. PCDD/Fs were also associated with blood glucose and insulin resistance, but not beta-cell function. There were substantial limitations of the literature including: most studies were cross-sectional, few studies addressed selection bias and confounding, and most effect estimates had exceptionally wide confidence intervals. Few studies evaluated the effects of organophosphates. CONCLUSIONS: Well-conducted research is urgently needed on these pervasive exposures to inform policies to mitigate the diabetes epidemic in Asia.

Persistent organic pollutants measured in maternal serum and offspring neurodevelopmental outcomes--a prospective study with long-term follow-up.

Fetal exposure to persistent organic pollutants (POPs) has been linked to adverse neurodevelopment, but few studies have had follow-up beyond childhood. The purpose of this study was to examine the association of maternal serum concentrations of two perfluoroalkyl acids (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)), polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) with offspring behavioural and affective disorders and scholastic achievement in a prebirth cohort study with 20 years of follow up. Between 1988 and 1989 pregnant women (n=965) were recruited for the prebirth Danish Fetal Origins 1988 (DaFO88) Cohort in Aarhus, Denmark. Perfluoroalkyl acids, PCBs, p,p'-DDE, and HCB were quantified in serum from week 30 of gestation (n=876 for perfluoroalkyl acids/872 for PCBs, p,p'-DDE, HCB). Offspring were followed up through national registries until 2011. We evaluated associations between maternal serum concentrations of these POPs and offspring neurodevelopmental outcomes, defined as: first admission diagnosis or prescription of medication until age >20 for (1) ADHD; (2) depression; and (3) scholastic achievement defined as mean grade on a standardized written examination given in the 9th grade (final exams of compulsory school in Denmark). Maternal concentrations of organochlorine substances and perfluoroalkyl acids were higher than present day levels. During the follow-up period there were 27 (3.1%) cases of ADHD and 104 (11.9%) cases of depression; the mean scholastic achievement was 6.7 (SD 2.3). Overall we found no association for maternal levels of any of the measured pollutants with offspring behavioural and affective disorders or with scholastic achievement. Our analyses based on biomarkers from a cohort of over 800 pregnant women with long-term close to complete follow-up through national registries showed little evidence of a programming effect of PFOA, PFOS, PCBs, p,p'-DDE, and HCB in relation to clinically and functionally relevant offspring neurodevelopmental outcomes.

Effect of para halogen modification of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamides on metabolism and clearance.

The purpose of this study was to better understand why para-halogen modifications of S-3-(4-halophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl) propionamide selective androgen receptor modulators (SARMs) had the opposite of expected effects on total clearance, in which electron-withdrawing groups generally protect benzene ring from hydroxylation. We determined the plasma protein binding of this series of halogen substituted SARMs and characterized the qualitative effects of B-ring halogen substitution on in vivo metabolism. In vivo metabolism of S-9, S-10, and S-11 were determined in rats using LC-MS(n) analysis. Intrinsic clearance was measured by in vitro metabolism using rat liver microsomes. Rat plasma protein binding was measured by equilibrium dialysis and drug concentrations after dialysis were analyzed by LC-MS. The major metabolic pathways of the halogen-substituted SARMs examined were very similar and included three major phase I pathways; (1) hydrolysis of the amide bond, (2) B-ring hydroxylation, and (3) A-ring nitro reduction to an aromatic amine. In plasma protein binding studies, S-1 (F, fu = 0.78 ± 0.17 %) showed the greatest unbound fraction, followed by S-9 (Cl, fu = 0.10 ± 0.04 %), S-10 (Br, fu = 0.03 ± 0.01 %), and S-11 (I, fu = 0.008 ± 0.001 %). The CLint values of S-1, S-9, S-10, and S-11 were 2.4, 2.5, 2.8, and 4.6 µL/min/mg, respectively. These findings suggest that as lipophilicity increased the free fraction was reduced thus compensating for metabolic liability and resulting in the apparent discrepancy between CLint and CL total of halogen-substituted SARMs series.

Temporal trend and age-dependent serum concentration of phenolic organohalogen contaminants in Japanese men during 1989-2010.

The temporal trend in serum concentrations of phenolic organohalogen contaminants (POCs) were investigated in two age groups of men from Kyoto, Japan, from 1989 to 2010. These concentrations and trends were compared with neutral contaminants including polychlorinated biphenyls (PCBs) and pesticides. Serum concentrations of pentachlorophenol (PenCP) and 4-hydroxy-PCB187 were age-dependent and decreased to approximately one-half during the two decades, whereas no contamination trends were observed for 2,4,6-tribromophenol (TriBP), tetrabromobisphenol A (TBBPA) and 6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE47). 6-OH-BDE47 was found in all samples (up to 3000 pg/g wet weight), whereas TBBPA was detected in 17 of 60 serum samples (up to 950 pg/g wet weight). The concentrations of TriBP, TBBPA and 6-OH-BDE47 were not correlated to those of PenCP or 4-OH-PCB187 in either age group, suggesting the different kinetics on exposure routes and fate between these brominated and chlorinated POCs.

Comparative study of organohalogen contamination between two populations of Eastern Atlantic loggerhead sea turtles (Caretta caretta).

We evaluated the presence of 37 organohalogen contaminants in plasma samples from 162 juvenile and 197 adult loggerhead turtles (Caretta caretta) from the archipelagos of the Canary Islands and Cape Verde, respectively, and compared the contamination profiles found. We detected five organochlorine pesticides (OCP) and 16 polychlorinated biphenyls (PCBs). The concentrations of the two groups of contaminants were higher in turtles from the Canary Islands (OCPs, 1.04 vs. 0.37 ng/mL; PCBs, 1.92 vs. 0.08 ng/mL). We also observed a different profile of PCB contamination between the two populations. In addition, there was a negative correlation between body size and the total concentration of PCBs in the Canary Islands turtles, but not in turtles from Cape Verde. The present study presents the first data on the organochlorine contaminants (OCs) of live turtles from Canary Islands. In addition, we perform a comparison of the levels and profiles of OCs between these two different groups of loggerhead sea turtles from the Eastern Atlantic.