BackgroundThe 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individual's metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium.MethodsHigh-resolution 1H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress.ResultsSix urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction.ConclusionsThis study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research.

BackgroundExposure to heavy metals may cause kidney damage. The population living near the Avonmouth zinc smelter has been exposed to cadmium and other heavy metals for many decades.ObjectivesWe aimed to assess Cd body burden and early signs of kidney damage in the Avonmouth population.MethodsWe used dispersion modeling to assess exposure to Cd. We analyzed urine samples from the local population (n = 180) for Cd (U-Cd) to assess dose (body burden) and for three biomarkers of early kidney damage [N-acetyl-β-d-glucosaminidase (U-NAG), retinol-binding protein, and α-1-microglobulin]. We collected information on occupation, intake of homegrown vegetables, smoking, and medical history by questionnaire.ResultsMedian U-Cd concentrations were 0.22 nmol/mmol creatinine (nonsmoking 0.18/smoking 0.40) and 0.34 nmol/mmol creatinine (nonsmoking 0.31/smoking 0.46) in non-occupationally exposed men and women, respectively. There was a significant dose–response relationship between U-Cd and the prevalence of early renal damage—defined as U-NAG > 0.22 IU/mmol—with odds ratios of 2.64 [95% confidence interval (95% CI), 0.70–9.97] and 3.64 (95% CI, 0.98–13.5) for U-Cd levels of 0.3 to < 0.5 and levels ≥ 0.5 nmol/mmol creatinine, respectively (p for trend = 0.045).ConclusionU-Cd concentrations were close to levels where kidney and bone effects have been found in other populations. The dose–response relationship between U-Cd levels and prevalence of U-NAG above the reference value support the need for measures to reduce environmental Cd exposure.

[Figure]), and medication use for hypercholesterolemia was more than 10 times greater (25.9% vs 1.5%; PϽ.001). Baby boomers were also more likely to have diabetes (15.5% vs 12.0%; P = .003 [Figure]) and take medication for diabetes (11.3% vs 6.2%; P Ͻ .001). The slight trend toward higher prevalence of cancer in baby boomers vs the previous generation was not significant (10.6% vs 9.5%; P = .25). The frequency of emphysema decreased in the baby boomer generation (2.3%) relative to the previous generation (3.5%) (P = .03). Baby boomers were also less likely to have had a myocardial infarction (3.6%) compared with the previous generation (5.3%) (P=.004). A logistic regression was conducted to control for changes in demographic characteristics (age, sex, race, and socioeconomic status) of the population between 1988-1994 and 2007-2010. The results indicated, after adjustment, that baby boomers remained more likely than the previous generation to have diabetes (odds ratio [OR], 1.46; 95% CI, 1.16-1.83); hypertension (OR, 1.38; 95% CI, 1.14-1.67); and hypercholesterolemia (OR, 5.94; 95% CI, 4.94-7.14). Comment. Despite their longer life expectancy over previous generations, US baby boomers have higher rates of chronic disease, more disability, and lower self-rated health than members of the previous generation at the same age. On a positive note, baby boomers are less likely to smoke cigarettes and experience lower rates of emphysema and myocardial infarction than the previous generation. The findings from the present study documenting poorer health status and increased rates of obesity, hypertension, diabetes, and hypercholesterolemia support an increased likelihood for continued rising health care costs and a need for increased numbers of health professionals as baby boomers age. 5,6 Given the link between positive healthy lifestyles and subsequent health in this age group, 7 the present study demonstrates a clear need for policies that expand efforts at prevention and healthy lifestyle promotion in the baby boomer generation.

Cadmium is an osteotoxic metal present in food. It causes multiple fractures in those highly exposed and is associated with reduced bone mineral density at considerably lower exposures. Little is known about fracture rates following low-level cadmium exposure. We assessed the associations between dietary cadmium exposure and fracture incidence. Within a population-based prospective cohort of 22,173 Swedish men, we estimated individual dietary cadmium exposure using food frequency questionnaire data and levels of cadmium in food. The average intake was 19 mg/day. Hazard ratios (HRs) for any fracture and hip fracture were estimated using Cox's regression. During 10 years of follow-up, we ascertained 2183 cases of any fracture and 374 hip fractures by computerized linkage of the cohort to registry data. Multivariable-adjusted dietary cadmium intake was associated with a statistically significant 19% [HR ¼ 1.19, 95% confidence interval (CI) 1.06-1.34] higher rate of any fracture comparing highest tertile with lowest ( p .01 for trend). Moreover, men in the highest tertile of dietary cadmium and lowest tertile of fruit and vegetable consumption had a 41% higher rate of any fracture compared with contrasting tertiles. Hip fracture rates also were higher in the highest tertile of cadmium intake but only statistically significant among never smokers (HR ¼ 1.70, 95% CI 1.04-2.77). Our results indicate that dietary cadmium exposure at general population levels is associated with an increased rate of fractures among men. This association was independent of smoking and was most pronounced among men with low fruit and vegetable consumption. ß

BackgroundBone toxicity has been linked to organochlorine exposure following a few notable poisoning incidents, but epidemiologic studies in populations with environmental organochlorine exposure have yielded inconsistent results.ObjectivesThe aim of this study was to investigate whether organochlorine exposure was associated with bone mineral density (BMD) in a population 60–81 years of age (154 males, 167 females) living near the Baltic coast, close to a river contaminated by polychlorinated biphenyls (PCBs).MethodsWe measured forearm BMD in participants using dual energy X-ray absorptiometry; and we assessed low BMD using age- and sex-standardized Z-scores. We analyzed blood samples for five dioxin-like PCBs, the three most abundant non-dioxin-like PCBs, and p,p′-dichloro-phenyldichloroethylene (p,p′-DDE).ResultsIn males, dioxin-like chlorobiphenyl (CB)-118 was negatively associated with BMD; the odds ratio for low BMD (Z-score less than −1) was 1.06 (95% confidence interval, 1.01–1.12) per 10 pg/mL CB-118. The sum of the three most abundant non-dioxin-like PCBs was positively associated with BMD, but not with a decreased risk of low BMD. In females, CB-118 was positively associated with BMD, but this congener did not influence the risk of low BMD in women.ConclusionsEnvironmental organochlorine exposures experienced by this population sample since the 1930s in Sweden may have been sufficient to result in sex-specific changes in BMD.

With the expansion of urban agriculture in many North American cities, there is a current need to evaluate the soil and urban environment to assess potential risks of metal contamination in urban grown food. In this study, a university farm, a community garden, and a brownfield located in Vancouver, BC were characterized with respect to soil metal concentrations, atmospheric deposition of metals, and bioaccumulation of metals in Poa pratensis. Wet and dry deposition were collected over five months. Aqua regia and HCl extractions were used to evaluate total and labile metal fractions of Zn, Pb, Ni, Mn, and Cu. Highest soil metal concentrations, atmospheric deposition flux, and bioaccumulation in Poa were found at the community garden, followed by the brownfield site, and the University of British Columbia Farm. Concentrations of Ni and Mn seem to be associated with soil parent material, while Zn, Pb, and Cu were indicators of industrial activity. Concentrations of metals in atmospheric deposition were not an immediate concern but their potential accumulation in the soil requires attention. The framework developed by the case study identified three factors meaningful for assessing metal contamination on an urban agriculture site: site history, atmospheric deposition trends, and parent material.

Cadmium exposure is associated with increased urinary calcium excretion. Hypercalciuria is recognised as a major risk factor for kidney stone formation. Increased prevalence of kidney stones among those occupationally exposed to cadmium has previously been suggested. Food is the main source of cadmium exposure in the general population with tobacco representing an important additional source among smokers. We aimed to assess the association between dietary cadmium exposure and kidney stone incidence in two large population-based, prospective cohorts of men (Cohort of Swedish Men; COSM) and women (The Swedish Mammography Cohort; SMC). Those with a history of kidney stones were excluded. At baseline 1997, men (45-79yrs) and women (48 to 83yrs), completed a self-administered questionnaire on diet and lifestyle. During 12years of follow-up, we ascertained 707 cases of kidney stones in men and 290 in women through linkage of the cohorts to the national inpatient and outpatient registers. Individual dietary cadmium exposure was estimated using dietary data and concentrations of cadmium in food. Hazard ratios (HR) were calculated using the Cox proportional hazards regression models with adjustment for other risk factors. Estimated dietary cadmium exposure was not associated with increased kidney stone incidence among men HR 0.97 (95% confidence interval (CI): 0.77-1.23) or women HR 0.99 (95% CI: 0.89-1.43), comparing the highest tertile with the lowest. In conclusion, our results do not support a strong association between dietary cadmium and kidney stone risk at the exposure levels seen in the general population.

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