Daria Pereg

Environmental contaminants and human health in the Canadian Arctic.

The third Canadian Arctic Human Health Assessment conducted under the Canadian Northern Contaminants Program (NCP), in association with the circumpolar Arctic Monitoring and Assessment Programme (AMAP), addresses concerns about possible adverse health effects in individuals exposed to environmental contaminants through a diet containing country foods. The objectives here are to: 1) provide data on changes in human contaminant concentrations and exposure among Canadian Arctic peoples; 2) identify new contaminants of concern; 3) discuss possible health effects; 4) outline risk communication about contaminants in country food; and 5) identify knowledge gaps for future contaminant research and monitoring. The nutritional and cultural benefits of country foods are substantial; however, some dietary studies suggest declines in the amount of country foods being consumed. Significant declines were found for most contaminants in maternal blood over the last 10 years within all three Arctic regions studied. Inuit continue to have the highest levels of almost all persistent organic pollutants (POPs) and metals among the ethnic groups studied. A greater proportion of people in the East exceed Health Canadas guidelines for PCBs and mercury, although the proportion of mothers exceeding these guidelines has decreased since the previous assessment. Further monitoring and research are required to assess trends and health effects of emerging contaminants. Infant development studies have shown possible subtle effects of prenatal exposure to heavy metals and some POPs on immune system function and neurodevelopment. New data suggest important beneficial effects on brain development for Inuit infants from some country food nutrients. The most successful risk communication processes balance the risks and benefits of a diet of country food through input from a variety of regional experts and the community, to incorporate the many socio-cultural and economic factors to arrive at a risk management decision that will be the most beneficial in Arctic communities.

Thyroid Function and Plasma Concentrations of Polyhalogenated Compounds in Inuit Adults

Background Several ubiquitous polyhalogenated compounds (PHCs) have been shown to alter thyroid function in animal and in vitro studies. So far, epidemiologic studies have focused on the potential effect of a small number of them, namely, polychlorinated biphenyls (PCBs) and some organochlorines (OCs), without paying attention to other important PHCs. Objectives We investigated the relationship between exposure to several PHCs and thyroid hormone homeostasis in Inuit adults from Nunavik. Methods We measured thyroid parameters [thyroid-stimulating-hormone (TSH), free thyroxine (fT4), total triiodothyronine (tT3), and thyroxine-binding globulin (TBG)] and concentrations of 41 contaminants, including PCBs and their metabolites, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), perfluorooctanesulfonate (PFOS), and a measure of dioxin-like compounds, detected in plasma samples from Inuit adults (n = 623). Results We found negative associations between tT3 concentrations and levels of 14 PCBs, 7 hydroxylated PCBs (HO-PCBs), all methylsulfonyl metabolites of PCBs (MeSO2-PCBs), and 2 OCPs. Moreover, we found negative associations between fT4 levels and hexachlorobenzene Concentrations. TBG concentrations were inversely related to 8 PCBs, 5 HO-PCBs, and 3 OCPs. Exposure to BDE-47 was positively related to tT 3, whereas PFOS concentrations were negatively associated with TSH, tT3, and TBG and positively with fT4 concentrations. Conclusion Exposure to several PHCs was associated with modifications of the thyroid parameters in adult Inuit, mainly by reducing tT3 and TBG circulating concentrations. The effects of PFOS and BDE-47 on thyroid homeostasis require further investigation because other human populations display similar or higher concentrations of these chemicals.

Plasma Concentrations of Selected Organobromine Compounds and Polychlorinated Biphenyls in Postmenopausal Women of Quebec, Canada

Background Brominated flame retardants, especially polybrominated diphenyl ethers (PBDEs), have been widely used in North America, but little is known about the level of exposure of human populations to these compounds. Objectives We set out to assess the internal exposure of postmenopausal Canadian women to selected organobromine compounds and to investigate factors associated with this exposure. Methods We measured concentrations of four PBDEs, one polybrominated biphenyl, and for comparative purposes, 41 polychlorinated biphenyl (PCB) congeners in plasma samples from 110 healthy postmenopausal women who were recruited at a mammography clinic in 2003–2004. Results PBDE-47 was the major PBDE congener, with a mean (geometric) concentration of 8.1 ng/g lipids and extreme values reaching 1,780 ng/g. By comparison, the mean concentration of the major PCB congener (PCB-153) was 41.7 ng/g and the highest value was 177 ng/g. PBDEs 47, 99, and 100 were strongly intercorrelated, but weaker correlations were noted with PBDE-153. As the sum of PBDEs (∑PBDEs) increased, the relative contribution of PBDE-47 to the ∑PBDEs increased, whereas that of PBDE-153 decreased. PBDE-153 was the only brominated compound correlated to PCB-153. PBDE levels were not linked to any sociodemographic, anthropometric, reproductive, or lifestyle variables documented in the present study. Age and body mass index gain since the age of 18 years were significant predictors of PCB-153 plasma levels. Conclusion Our results suggest that exposure to PBDE-47 likely occurs through direct contact with the penta-PBDE formulation, whereas exposure to PBDE-153 may originate in part from the food chain.

Re-evaluation of blood mercury, lead and cadmium concentrations in the Inuit population of Nunavik (Québec): a cross-sectional study.

BackgroundArctic populations are exposed to mercury, lead and cadmium through their traditional diet. Studies have however shown that cadmium exposure is most often attributable to tobacco smoking. The aim of this study is to examine the trends in mercury, lead and cadmium exposure between 1992 and 2004 in the Inuit population of Nunavik (Northern Québec, Canada) using the data obtained from two broad scale health surveys, and to identify sources of exposure in 2004.MethodsIn 2004, 917 adults aged between 18 and 74 were recruited in the 14 communities of Nunavik to participate to a broad scale health survey. Blood samples were collected and analysed for metals by inductively coupled plasma mass spectrometry, and dietary and life-style characteristics were documented by questionnaires. Results were compared with data obtained in 1992, where 492 people were recruited for a similar survey in the same population.ResultsMean blood concentration of mercury was 51.2 nmol/L, which represent a 32% decrease (p < 0.001) between 1992 and 2004. Mercury blood concentrations were mainly explained by age (partial r2 = 0.20; p < 0.0001), and the most important source of exposure to mercury was marine mammal meat consumption (partial r2 = 0.04; p < 0.0001). In 2004, mean blood concentration of lead was 0.19 μmol/L and showed a 55% decrease since 1992. No strong associations were observed with any dietary source, and lead concentrations were mainly explained by age (partial r2 = 0.20.; p < 0.001). Blood cadmium concentrations showed a 22% decrease (p < 0.001) between 1992 and 2004. Once stratified according to tobacco use, means varied between 5.3 nmol/L in never-smokers and 40.4 nmol/L in smokers. Blood cadmium concentrations were mainly associated with tobacco smoking (partial r2 = 0.56; p < 0.0001), while consumption of caribou liver and kidney remain a minor source of cadmium exposure among never-smokers.ConclusionImportant decreases in mercury, lead and cadmium exposure were observed. Mercury decrease could be explained by dietary changes and the ban of lead cartridges use likely contributed to the decrease in lead exposure. Blood cadmium concentrations remain high and, underscoring the need for intensive tobacco smoking prevention campaigns in the Nunavik population.

Effects of perfluorooctanesulfonate exposure on plasma lipid levels in the Inuit population of Nunavik (Northern Quebec)

BACKGROUND Perfluorooctanesulfonate (PFOS) was used as a surfactant in various commercial products. In rodents, exposure to this compound induced various health effects, including hypolipidemia. In human populations, the potential toxicity of PFOS is not yet fully characterized, but indications of effects on lipids are reported. A recent study reported an increase in plasma cholesterol associated with exposure to perfluorinated compounds in humans exposed through drinking water, but similar effects were not reported in all exposed human populations. PFOS is widely distributed in the environment, including the arctic biota. The Inuit of Nunavik are exposed to environmental contaminants through the consumption of fish and game. This diet is also a source of omega3-polyunsaturated fatty acids (n-3 PUFAs) that are known to lower plasma triacylglycerols. OBJECTIVE This cross-sectional epidemiologic study aims at assessing the relationship between PFOS exposure and plasma lipids, while taking account of the concomitant hypolipidemic effect exerted by n-3 PUFAs. METHODS Plasma concentrations of PFOS and lipids were assessed in Nunavik Inuit adults (n=723) in the framework of a large-scale environmental health study. Associations of exposure levels to age, gender and selected wild food consumption associated with n-3 PUFAs intake, as well as the exposure on lipid levels were investigated by multivariate linear modeling. RESULTS In the Inuit population, PFOS exposure and n-3 PUFAs intake are related to traditional food consumption. Triacylglycerol and ratio of total cholesterol to high density lipoprotein cholesterol (HDL-C) levels were negatively associated with PFOS plasma levels, while HDL-C levels were positively associated, after adjustment for circulating levels of n-3 PUFAs and for the interaction between gender and PFOS plasma levels. Other plasma lipids, such as low density lipoprotein-cholesterol and non-HDL-C were not related to PFOS plasma concentrations. CONCLUSION The results of this study show a relationship between PFOS and plasma lipid levels in an environmentally exposed human population, and this effect appears distinct from that of n-3 PUFAs.

In Utero and Lactational Exposure to an Environmentally Relevant Organochlorine Mixture Disrupts Reproductive Development and Function in Male Rats

Abstract We hypothesized that in utero and lactational exposure of male rats to a mixture of more than 15 organochlorines, resembling that found in blubber from northern Quebec seals, alters reproductive development and function. Female rats were gavaged with either corn oil (controls) or the organochlorine mixture in increasing doses (low, medium, and high) for 5 wk before mating and through gestation. Developmental effects were monitored in the male offspring from Postnatal Day (PND) 2 until PND 90. The high-dose mixture reduced the number of pups per litter, percentage of live offspring, and pup weights (P < 0.05). Because only three rats from the high-dose treatment survived, data from this group beyond PND 2 were not included in the statistical analyses. As assessed by the time of preputial separation, puberty was delayed in the pups from treated dams (P < 0.05). Testes weights in the medium-dose group were greater than those in controls on PND 21 (P < 0.05). Ventral prostate weights were lower for the medium-dose group on PND 60 (P < 0.05). On PND 90, weights of the epididymis, ventral prostate, and seminal vesicle of the medium-dose rats were reduced compared to those of controls (P < 0.05). On PND 90, sperm motility parameters assessed by computer-assisted sperm analysis were altered in the low- and medium-dose groups (P < 0.05). Testicular and epididymal morphology was severely affected in rats exposed to the high dose of the mixture. Serum testosterone, LH, FSH, prolactin, and total thyroxine levels did not differ because of organochlorine treatment. Therefore, in utero and lactational exposure to an environmentally relevant organochlorine mixture adversely affects the reproductive system of male rats, perhaps via antiandrogenic effects during testis development, suggesting a possible reproductive health hazard for humans and other species.

Protective effects of selenium against DNA adduct formation in inuit environmentally exposed to PCBs.

Dietary habits that expose populations to potential toxicants as well as protective agents simultaneously are a realistic scenario where a meaningful assessment of the interactions and net benefit or damage can be made. A group of Inuit from Salluit, Northern Canada are exposed to high levels of PCBs and selenium, both present in the Inuit traditional foods such as blubber from sea mammals and fatty fish. Blood samples were collected from 83 Inuit, 22-70 years old. Blood selenium and PCB levels were determined previously and ranged from 227 to 2069µg/L and 1.7 to 143µg/L, respectively. DNA isolated from white blood cells were analyzed by modified (32)P-postlabeling adductomics technology that detects a multitude of highly polar to lipophilic adducts. The levels of 8-oxodG adducts ranged from 470 to 7400 adducts/10(9) nucleotides. Other as yet unidentified polar adducts showed a 30 to 800-fold inter-individual variability. Adduct levels were negatively associated with PCB and selenium levels. The subjects were classified into high and low ratio groups, with respect to selenium/PCB. In the high ratio group, the coefficient of selenium is significantly negatively correlated with 8-oxodG (r = -0.38, p = 0.014) and total adducts (r = -0.41, p = 0.009) while there was no correlation within the low selenium/PCB group. This study suggests that increasing selenium has mitigating effect in reducing DNA adducts and therefore, possible negative effects of PCB were not seen. A protective effect of selenium is highlighted.

Cigarette smoking during pregnancy: comparison of biomarkers for inclusion in epidemiological studies

Prenatal exposure to tobacco smoke represents an important confounding factor in epidemiological studies addressing developmental effects and requires careful controlling by the use of biomarkers. We compared the following biomarkers of exposure to tobacco smoke during pregnancy and related biological effects in 23 smokers and 17 non-smokers: placental concentrations of heavy metals (cadmium, chrome, lead and zinc), cotinine concentration in meconium, placental CYP1A1 activity (EROD) and bulky DNA adducts. Cadmium was detected in all samples and found in higher concentration in placentas of smokers compared with non-smokers (geometric mean ± GSD: 56.1 ± 1.8 vs 27.4 ± 1.6 μg kg -1 dry weight; p < 0.001). Cotinine was not detected in meconium samples from the non-smoker group, while samples from the smoker group contained a mean concentration of 114.1 ± 2.9 μg kg -1 . Correlation analysis of biomarkers among smokers revealed that daily cigarette consumption was strongly correlated to placental cadmium (Pearsons r = 0.83, p < 0.001) and to cotinine (r = 0.73, p < 0.001). EROD activity was also higher in smokers than in non-smokers (9.4 ± 3.4 vs 2.5 ± 1.8 pmol resorufin min -1 mg -1 protein; p < 0.001) and values were correlated to cotinine concentration in meconium (r = 0.80, p < 0.001) and placental cadmium level (r = 0.66, p < 0.001). The amount of bulky DNA adducts in placenta was highly variable and poorly associated with smoking status. Because of their high sensitivity and specificity to detect women who smoke during pregnancy, cotinine concentrations in meconium and placental EROD activity should be incorporated in epidemiological studies that investigate adverse developmental effects induced by in utero exposure to environmental contaminants.

Diabetes and Related Metabolic Conditions in an Aboriginal Cree Community of Quebec, Canada

OBJECTIVE We evaluated the prevalence of type 2 diabetes, obesity and metabolic syndrome according to International Diabetes Federation criteria in the First Nations Cree community of Mistissini, Quebec. METHODS A cross-sectional study of 172 adults was performed as part of a broader regional environmental study. RESULTS Type 2 diabetes, hyperinsulinemia and abdominal obesity were documented in 20%, 70% and 91% of participants, respectively. The prevalence of metabolic syndrome was 54%, with the main profile including abnormal plasma glucose levels (60%) associated with high triacylglycerol (40%). Women displayed the highest prevalence of abdominal obesity (99%). In both sexes, waist circumference was clearly associated with other metabolic parameters, such as blood glucose and lipid profile (p<0.0001). However, a significant proportion of the population (13%), especially women, showed high waist circumference with no metabolic disturbances. CONCLUSION Among the Cree population of Mistissini, the results suggest that the high prevalence of abdominal obesity occurs most frequently in women, and earlier in women than in men. Subsequent metabolic disturbances associated with metabolic syndrome develop with age, supporting the core role of abdominal obesity in the cascade of events leading to diabetes and cardiovascular disease.

DNA damage associated with PCBs in the whole blood cells of Inuit

Lower chlorinated PCBs can damage DNA directly or via free radical mechanisms. In order to assess the DNA-damaging potential of PCBs in humans, blood samples were collected from Inuit population from Salluit, Northern Canada. Their diet comprises blubber from sea mammals and fatty fish, which accumulate non-biodegradable PCBs at varying levels. The 103 samples thus collected were categorized into low-, medium- and high-PCB exposure groups. A comprehensive (32)P-postlabeling adductomics technology, which allows measure differences in DNA adduct profiles of polar and lipophilic adducts between control and exposure groups, was applied to these samples to assess the effect of PCB on DNA damage. The adduct patterns obtained were qualitatively similar to other human tissues studied previously. A range of highly polar to lipophilic subgroups of adducts were detected. The known oxidative lesion, 8-oxodG was predominant. While some individual adducts appear to accumulate with increasing PCB levels, a definitive association could not be made. A possible confounder effect of selenium is discussed.