Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction in men - A population-based prospective cohort study.

BACKGROUND: Major food contaminants such as polychlorinated biphenyls (PCBs) are proposed to play a role in the etiology of cardiovascular disease (CVD), but to date the impact of PCBs on cardiovascular health need to be explored. METHODS AND RESULTS: We assessed the association between validated food frequency questionnaire-based estimates of dietary PCB exposure and risk of myocardial infarction, ascertained through register-linkage, among 36,759 men from the population-based Swedish Cohort of Men, free of cardiovascular disease, diabetes and cancer at baseline (1997). Relative risks were adjusted for known cardiovascular risk factors, long-chain omega-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) and methyl mercury exposure. During 12years of follow-up (433,243 person-years), we ascertained 3005 incident cases of myocardial infarction (654 fatal). Compared with the lowest quintile of dietary PCB exposure (median 113ng/day), men in the highest quintile (median 436ng/day) had multivariable-adjusted relative risks of 1.74 (95% confidence interval [CI], 1.30-2.33; p-trend<0.001) for total and 1.97 (95% CI 1.42-2.75; p-trend<0.001) for non-fatal myocardial infarction. In mutually adjusted models, dietary PCB exposure was associated with an increased risk of myocardial infarction, while the intake of long-chain omega-3 fish fatty acids was associated with a decreased risk. We also observed an effect modification by adiposity on the association between of dietary PCB exposure and myocardial infarction, with higher risk among lean men (p value for interaction =0.03). CONCLUSIONS: Exposure to PCBs via diet was associated with increased risk of myocardial infarction in men.

Dietary exposure to polychlorinated biphenyls and risk of myocardial infarction - a population-based prospective cohort study.

BACKGROUND: Fish consumption may promote cardiovascular health. The role of major food contaminants, such as polychlorinated biphenyls (PCBs) common in fatty fish, is unclear. We assessed the association between dietary PCB exposure and risk of myocardial infarction taking into account the intake of long-chain omega-3 fish fatty acids. METHODS: In the prospective population-based Swedish Mammography Cohort, 33,446 middle-aged and elderly women, free from cardiovascular disease, cancer and diabetes at baseline (1997) were followed-up for 12 years. Validated estimates of dietary PCB exposure and intake of fish fatty acids (eicosapentaenoic acid and docosahexaenoic acid; EPA-DHA) were obtained via a food frequency questionnaire at baseline. RESULTS: During follow-up 1386 incident cases of myocardial infarction were ascertained through register-linkage. Women in the highest quartile of dietary PCB exposure (median 286 ng/day) had a multivariable-adjusted RR of myocardial infarction of 1.21 (95% confidence interval [CI], 1.01-1.45) compared to the lowest quartile (median 101 ng/day) before, and 1.58 (95% CI, 1.10-2.25) after adjusting for EPA-DHA. Stratification by low and high EPA-DHA intake, resulted in RRs 2.20 (95% CI, 1.18-4.12) and 1.73 (95% CI, 0.81-3.69), respectively comparing highest PCB tertile with lowest. The intake of dietary EPA-DHA was inversely associated with risk of myocardial infarction after but not before adjusting for dietary PCB. CONCLUSION: Exposure to PCBs was associated with increased risk of myocardial infarction, while some beneficial effect was associated with increasing EPA and DHA intake. To increase the net benefits of fish consumption, PCB contamination should be reduced to a minimum.

Cadmium in diet and risk of cardiovascular disease in women.

BACKGROUND: The toxic metal cadmium is suggested to increase the risk of cardiovascular disease, but only one incidence study has explored this association. We evaluated the association between quartiles of food frequency questionnaire-based estimates of cadmium exposure from food (the predominant source of exposure to the metal) and incident cardiovascular disease and its subtypes. METHODS: From the population-based Swedish Mammography cohort, 33,333 women were followed prospectively from baseline (1997) through 2010. We estimated relative risks (RRs) with 95% confidence intervals (CIs) using Cox proportional hazard models. RESULTS: During 12 years of follow-up, we identified 3155 incident cases of total cardiovascular disease (1322 cases of myocardial infarction and 1833 cases of total stroke [1485 ischemic and 208 hemorrhagic stroke]). Dietary cadmium exposure was not associated with risk of total cardiovascular disease, myocardial infarction, or total stroke or its subtypes. For total cardiovascular disease, the multivariable-adjusted RR comparing the highest quartile of cadmium exposure with the lowest was 0.96 (95% CI = 0.85-1.09). The corresponding RRs were 1.07 (0.88-1.29) for myocardial infarction, 0.90 (0.76-1.05) for total stroke, 0.89 (0.74-1.06) for ischemic stroke, and 1.11 (0.68-1.80) for hemorrhagic stroke. CONCLUSIONS: Our study lends no support to an overall association between low-level exposure to cadmium via food and incident cardiovascular disease.

Establishment of the cumulative margin of exposure for a group of polychlorinated biphenyl (PCB) congeners using an improved approach that accounts for both variability and uncertainty.

In this study, the cumulative margin of exposure (MOE) was estimated for a group of polychlorinated biphenyls (PCBs) based on reduction of hepatic retinoids as a mode-of-action relevant toxicological endpoint. The MOE was defined as the ratio between a reference dose, derived using the benchmark dose (BMD) approach, and the estimated human dietary PCB exposure. A distribution for the cumulative MOE was established, taking into account inter- and intra-individual variability as well as uncertainty in data measurements. The cumulative MOE reflected mainly the MOE for PCB 126; other PCB congeners had little contribution to the cumulative exposure and MOE. The median of the 0.1st percentile for the cumulative MOE was about 20 for women; depending on the percentile, cumulative MOE was 2-4 times higher for men compared to women. Furthermore, a relative potency factor (RPF) based approach was compared to an RPF-free approach for estimating the cumulative MOE. The RPF-free approach more completely accounts for variability and uncertainty but is more data intensive than the RPF-based approach, which can be more easily implemented in practice and allows for a use of historical data on RPFs. Consideration of the discussed approaches may contribute to improving cumulative health risk assessments.

Validation of questionnaire-based long-term dietary exposure to polychlorinated biphenyls using biomarkers.

SCOPE: The health consequences of lifelong low-level exposure to polychlorinated biphenyls (PCBs) via food are largely unknown, mainly due to the lack of large population-based prospective studies addressing this issue. We validated long-term food frequency questionnaire (FFQ)-based dietary PCB exposure against concentrations of six PCB congeners in serum. METHODS AND RESULTS: Dietary PCB exposure was estimated in the Swedish Mammography Cohort by constructing a recipe-based database of CB-153, an indicator for total PCBs in food. The Spearman rank correlation (adjusted for within-person variability) was assessed between concurrent (2004-2006), past (1997), and long-term (mean of 1997 and 2004-2006) FFQ-based dietary PCB exposure, respectively, and the following serum PCB congeners, CB-118, CB-138, CB-153, CB-156, CB-170, and CB-180, in women (56-85 years of age, n = 201). The correlation between FFQ-based dietary PCB exposure and serum CB-153 was 0.41 (p < 0.001) for the concurrent (median 1.6 ng/kg body weight) and 0.34 (p < 0.05) for the past (median 2.6 ng/kg body weight) exposure assessment. Long-term validity of FFQ-based PCB estimates and the six serum PCB congeners ranged from 0.30 to 0.58 (p < 0.05). CONCLUSION: FFQ-based PCB exposure estimates show acceptable validity in relation to PCB concentrations in serum, justifying their use in large-scale epidemiological studies.

Occurrence and levels of organochlorine compounds in human breast milk in Bangladesh.

In low-income countries, the use of some organochlorine pesticides is still common in order to increase food production. Monitoring the chemical exposure is an important step in risk-reducing strategies. This is the first study to report concentrations of organochlorines in breast milk of women from Bangladesh where farming is the main income source. Organochlorines such as p,p'-DDT, o,p'-DDT, p,p'-DDE, p,p'-DDD (i.e., ∑DDT), HCB, α-, ß- and γ-HCH, trans-chlordane, cis-chlordane, oxy-chlordane, trans-nonachlor, cis-nonachlor, mirex and polychlorinated biphenyls (CB 28, 52, 99, 101, 105, 114, 118, 123, 128, 138, 141, 149, 153, 156, 157, 163, 167, 170, 180, 183, 187, 189, 194) were analyzed in breast milk collected in 2002 from 72 first-time mothers (median age 20years) living in the rural area Matlab, Bangladesh. While the concentrations of PCBs and many of the pesticides were low, the concentrations of p,p'-DDT and its metabolite p,p'-DDE were high (median 349 and 1645ngg(-1)lipid, respectively) in comparison to other countries. The median value of ∑DDT was 2123ngg(-1)lipid. The estimated daily exposure to p,p'-DDT, p,p'-DDE and ∑DDTs was 10, 30 and 42µgkg(-1) body weight, respectively, in 3months old infants. The p,p'-DDE/p,p'-DDT ratio ranged from 1 to 23, where 58% of the mothers had a ratio below 5 indicating recent or ongoing DDT exposure. This study reports infant exposure and maternal body burden of organochlorines through breast milk. Although the findings give no reason to limit breast-feeding, it is essential to identify the main exposure sources and find means to decrease the exposure.

A probabilistic approach for estimating infant exposure to environmental pollutants in human breast milk.

Effective risk assessment and management are often hampered by a lack of reliable exposure data. The probabilistic exposure assessment approach takes into account individual variations in exposure, and thus, overly conservative estimates based on worst case scenarios can be avoided. The aim was to provide reliable information on the intake of non-dioxinlike (NDL) and dioxinlike PCBs, PCDDs and PCDFs in breastfed infants and their mothers during 2000-2006. Hence, a probabilistic model was developed to estimate the exposure and compare it with a deterministic exposure assessment approach. The estimated probabilistic mean intake in 1, 3 and 6 months old infants was 44, 31 and 17 pg total-TEQ/kg bw per day, and 418, 294 and 165 ng NDL-PCBs/kg bw per day, respectively. Intakes differed up to 41% between the upper-bound percentiles of the probabilistic approach and the deterministic worst case scenario approach, whereas no difference in mean values was observed between the two approaches. The median cumulative intake increased during 6 months of breastfeeding to 20 ng total-TEQ and 352 µg NDL-PCBs. There was a significant temporal decrease in infant exposure during 2000-2006 (30%). Less than 4% of the mothers had an intake exceeding the TDI of 2 pg TEQ/kg bw per day (median: 1.2 pg total-TEQ/kg bw). To conclude, by use of a probabilistic approach and biomonitoring data we were able to calculate reliable estimates of infant exposure to environmental pollutants and the daily intakes of the nursing mothers using the same data.

Exposure to dioxin-like pollutants via different food commodities in Swedish children and young adults.

The dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in terms of toxic equivalents (TEQs) was investigated in Swedish children and young adults. Exposure was estimated from concentration data of six groups of individual food commodities (meat, fish, dairy products, egg, edible fats and other foodstuff) combined with food intake data from a 7-day record book obtained from 670 individuals aged 1-24 years. The results showed that Swedish boys and girls, up to the age of ten, had a median TEQ intake that exceeded the tolerable daily intake (TDI) of 2 pg TEQ/kg body weight. Children exceeding the TDI varied from almost all individuals among the youngest children to about 20% among young men and women. Dairy and fish products were the main sources of exposure for the average child, accounting for 59% of the total TEQ intake. The individuals most highly exposed were, on the other hand, characterized by a high consumption of fish. Since children constitute a vulnerable group, results obtained from the present study show that it is essential to perform age specific dietary intake assessments of pollutants and more carefully consider sensitive and/or highly exposed groups in the population in the risk management processes.