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.

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.

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

BACKGROUND: Arctic 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. METHODS: In 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. RESULTS: Mean 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 mumol/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. CONCLUSION: Important 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.

Concurrent validity of the International Physical Activity Questionnaire (IPAQ) in an liyiyiu Aschii (Cree) community.

BACKGROUND: Culturally acceptable and validated instruments for assessing physical activity among Indigenous Peoples are lacking. Given the current trends in obesity, health behaviour surveillance tools are needed to evaluate trends and to determine the effectiveness of health promotion efforts aimed at curbing the obesity epidemic. OBJECTIVE: To evaluate whether the International Physical Activity Questionnaire (IPAQ) scores correlate with anthropometric indices in an liyiyiu Aschii community (Cree Territory of northern Quebec, Canada). METHODS: A cross-sectional study was carried out in a Cree community as part of a larger research effort entitled, "Nituuchischaayihitaau Aschii: A Multi-Community Environment-and-Health Longitudinal Study in liyiyiu Aschii". Randomly selected adult participants (n = 161) underwent an anthropometric assessment and answered the IPAQ which was administered by bilingual research assistants. Concurrent validity of the IPAQ was evaluated by the extent to which the physical activity scores were related to anthropometric measures. RESULTS: Significant inverse correlations were observed between the IPAQ Total MET score and % body fat (r = -.19, p < or = 0.01) and the IPAQ Vigorous MET score and % body fat (r = -.26, p < or = 0.001), but not for waist circumference or BMI. Walkers (6-7 days/wk for > or = 60 minutes/day), however, had a waist circumference that was, on average, 5 cm smaller than non-walkers in age- and sex-adjusted linear regression analyses (beta = -4.97; SE = 2.5; p < or = 0.05). DISCUSSION: The results indicate that the IPAQ holds promise as a culturally adaptable questionnaire for the liyiyiuch. However, modifications will help improve its acceptability for community members.

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.

Plasma concentrations of selected organobromine compounds and polychlorinated biphenyls in postmenopausal women of Québec, 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 (summation operatorPBDEs) increased, the relative contribution of PBDE-47 to the summation operatorPBDEs 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.

Biomarker measurements in a coastal fish-eating population environmentally exposed to organochlorines.

The Lower North Shore region of the St. Lawrence River is home to a fish-eating population that displays an unusually high body burden of several organochlorines, including polychlorinated biphenyls (PCBs) and dioxin-like compounds (DLCs). We measured biomarkers indicative of liver enzyme induction and investigated the relationship with organochlorine body burden in adult volunteers from this population. We determined plasma concentrations of PCBs and chlorinated pesticides by high-resolution gas chromatography (HRGC) with electron capture detection. DLC concentrations were measured by the dioxin-receptor chemically activated luciferase expression (DR-CALUX) assay and in a subset of participants, by HRGC/high-resolution mass spectrometry. We measured cotinine, d-glucaric acid, and porphyrins in morning urine samples and determined liver CYP1A2 activity in vivo using the caffeine breath test. Neither DLC concentrations as measured by the DR-CALUX nor PCB-153 concentrations, the latter representing total PCB exposure, were correlated with biomarkers of effects. Smoking (morning urinary cotinine concentration) was positively related to CYP1A2 activity as measured by the caffeine breath test (p < 0.01). Liver CYP1A2 activity was in turn negatively correlated with PCB-105:PCB-153 and PCB-118:PCB-153 congener ratios (p < 0.05). Hence, despite the relatively high body burden of PCBs and DLCs in this population, only smoking had a significant correlation with biomarkers of hepatic enzyme induction. Our data are consistent with smoking-induced liver CYP1A2 activity altering heme metabolism and increasing the biotransformation of mono-ortho PCB congeners.

Environmental exposure to polychlorinated biphenyls and placental CYP1A1 activity in Inuit women from northern Québec.

Some polychlorinated biphenyl (PCB) congeners are CYP1A1 inducers, and induction of this enzyme in the placenta has been linked to adverse effects on fetal development. The objective of this study was to determine if the body burden of PCBs is related to placental CYP1A1 activity in Inuit women from Nunavik (northern Québec), a population highly exposed to organochlorines. Placenta and cord blood samples were obtained from 35 Inuit women and 30 women from a southern Québec community exposed to background levels of organochlorines. We measured PCB concentrations in all cord plasma samples and in a subset of placenta samples from the Nunavik group and assessed CYP1A1 activity (ethoxyresorufin-O-deethylase; EROD) in placental microsomes from all participants. Concentrations of PCBs in cord plasma were strongly correlated to those in placenta (Pearson's r) = 0.77-0.97, p < 0.001) and were on average 4-fold higher in Inuit women than in southern Québec women [for PCB 153, the geometric means (geometric SDs) were 83.3 (1.9) ng/g lipid vs. 16.9 (1.6) ng/g lipid, respectively]. Despite this difference in PCB body burden, both study groups had similar EROD activities when data were stratified according to tobacco smoking. Although simple correlation analysis first showed that placental EROD activity was correlated with PCB 153 plasma concentration in the Nunavik group, a multivariate analysis failed to demonstrate a significant contribution of PCBs to EROD activity when tobacco smoking was included in the analysis. We conclude that dietary exposure to PCBs in Inuit women from Nunavik does not significantly influence EROD activity in the placenta, implicating tobacco smoking as the major modulating factor.

DNA adduction by polychlorinated biphenyls: adducts derived from hepatic microsomal activation and from synthetic metabolites.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants and complete carcinogens in rodents. Metabolism of lower chlorinated congeners with rat liver microsomes was investigated in earlier studies and DNA adduction was also reported. The current study was designed to compare DNA adducts formed after bioactivation of PCBs with rat, mouse and human hepatic microsomes, and to investigate the role of quinoid PCB metabolites in DNA adduct formation. Eight congeners ranging from mono- to hexachlorinated biphenyls were tested. Metabolites obtained through microsomal bioactivation as well as synthetic quinoid metabolites of 4-monochlorobiphenyl (4-CB) were incubated with calf-thymus DNA (CT-DNA), and the resulting adducts were analyzed by the 32P-post-labelling method. DNA adducts were formed with mono- di- and tri-chlorinated congeners, but not with higher chlorinated congeners. Similar adduct patterns were observed for 2-monochlorobiphenyl (2-CB) activated with hepatic microsomes from rat, mouse and human, while 4-CB, 3,4-dichlorobiphenyl (3,4-CB) and 3,4,5-trichlorobiphenyl (3,4,5-CB) showed similar patterns for two out of the three microsomal systems tested. 4,4' -trichlorobiphenyl (4,4' -CB) showed different adduct patterns in all microsomal systems. Higher adduct levels were obtained with the rodent microsomes compared with human microsomes and were related to higher cytochrome P450 activity. When adducts derived from microsomal activation of 4-CB were compared by co-chromatography with those derived from the incubation of DNA with synthetic 2-(4' -chlorophenyl)-1,4-benzoquinone (4-BQ), one adduct co-migrated in three different chromatography systems. This study demonstrates that rodents as well as human hepatic enzymes metabolize lower chlorinated biphenyl congeners to reactive intermediates that form DNA adducts in vitro and shows that the para-quinone metabolites of PCBs are, in part, involved in direct DNA adduction.

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.

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 (fT(4)), total triiodothyronine (tT(3)), 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 tT(3) concentrations and levels of 14 PCBs, 7 hydroxylated PCBs (HO-PCBs), all methylsulfonyl metabolites of PCBs (MeSO(2)-PCBs), and 2 OCPs. Moreover, we found negative associations between fT(4) 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, tT(3,) and TBG and positively with fT(4) concentrations. CONCLUSION: Exposure to several PHCs was associated with modifications of the thyroid parameters in adult Inuit, mainly by reducing tT(3) 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.

Determinants of plasma concentrations of perfluorooctanesulfonate and brominated organic compounds in Nunavik Inuit adults (Canada).

Perfluorooctanesulfonate (PFOS) and brominated organic compounds (BOCs) have been found in biota and humans worldwide with levels of BOCs being the highest in North America. PFOS and BOC exposure of remote populations that consume species of a marine food web for their subsistence has seldom been investigated. In 2004, we determined the concentrations of these contaminants in 883 Nunavik Inuit adults from the Canadian Arctic and investigated the demographic and dietary factors associated with them. Demographic and dietary information were collected by questionnaires. Multiple linear regressions were conducted to investigate predictors of exposure to those contaminants. Polychlorinated biphenyl (PCB) congener 153 concentrations are presented for comparative purposes. PFOS and PCB 153 were detected in all samples, with plasma concentrations several times higher than BOCs. The consumption of fish and marine mammals appears to be an important contributor to PFOS exposure among Nunavik Inuit. While PBDE 153 also appears as a persistent PBDE congener, exposure to PBDE 47 seems to be more recent in this population. Adoption of a westernized lifestyle seems to be related to an increased exposure to PBDE 47, but specific sources remain to be elucidated. In conclusion, we found that the remote geographical location and traditional lifestyle of the Nunavik Inuit population do not protect them against exposure to emerging POPs, particularly PFOS.

In utero and lactational exposure to an environmentally relevant organochlorine mixture disrupts reproductive development and function in male rats.

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.