Satarug et al. cadmium in oysters and showed the effects of consuming oysters on cadmium body burden and serum elemental composition (selenium, zinc, copper). Copes et al. (2008) considered the potential confounding effects of age and cigarette smoking and restricted their study to nonsmokers (33 men, 28 women) between 33 and 64 years of age (mean age, 47.3 years). They estimated that the cadmium intake from oysters was 174 µg/week (24.8 µg/day). Significant increases in blood and urinary cad- mium levels were found to be associated with the duration of oyster farming of at least 12 years during which time the on average con- sumption rate was 18 oysters/week (87 g/week). For the study participants, the average (range) blood cadmium was 0.83 (0.34–2.27) µg/L, and the average urinary cadmium (range) was 0.76 (0.16–4.04) µg/g creatinine. The mean urinary cadmium 0.76 µg/g creatinine was 2.5-fold greater than that of U.S. female non- smokers, mean age 55 years, as defined in the study by McElroy et al. (2007). Cadmium in a shellfish diet was shown to be bioavailable in the study by Vahter et al. (1996) who found cadmium intake to be 11 µg/day for women in the mixed-diet group and 28 µg/day for those in the high-shellfish diet group. No differences in blood or urine cadmium levels were observed between the two groups. However, an increase in blood cadmium of 63% and an increase in urinary cadmium of 24% were found among those consuming the high-shellfish diet who had plasma ferritin levels < 20 µg/L when com- pared with those who consumed mixed diets and had the same low body iron stores. Thus, these studies strongly suggest that cadmium in oysters and shellfish is bioavailable and that long-term oyster consumption does result in a higher body burden of cadmium. Table 2. Exposure levels associated with diabetes and hypertension. Study population, age, reference United States, n = 8,722, ≥ 40 years of age; Schwartz et al. 2003 China, n = 229, 44–87 years of age with type 2 diabetes, mean diabetic duration 8.6 years; Chen et al. 2006 Pakistan, n = 238 men, 31–60 years of age with type 2 diabetes, diabetic duration 16 years, 196 controls; Afridi et al. 2008 Torres Strait, Australia, n = 182; Haswell-Elkins et al. 2008 Korea, n = 1,902; Eum et al. 2008 United States, n = 10,991 ≥ 20 years of age; Tellez-Plaza et al. 2008 OR, odds ratio. Exposure/outcomes OR for abnormal fasting glucose was 1.48, 2.05, comparing urinary cadmium < 1 versus 1.00–1.99 versus ≥ 2 µg/g creatinine, respectively. OR for diabetes was 1.24, 1.45, comparing urinary cadmium < 1 versus 1.00–1.99 versus ≥ 2 µg/g creatinine, respectively. OR for tubular impairment was 3.34, comparing urinary cadmium < 1 versus ≥ 1 µg/g creatinine; it was increased to 5.56, comparing those with low versus high levels of circulating metallothionein antibody. Subjects with diabetes had higher levels of cadmium in hair, blood, and urine than did controls. Mean blood (urinary) cadmium was 4.2 (3.2) µg/L among nonsmoker controls and 5.7 (4.6) µg/L among nonsmoker cases. A dose response between urinary cadmium and glomerular impairment was observed among subjects with type 2 diabetes after adjusting for confounders. OR for hypertension was 1.51, comparing blood cadmium in the lowest versus the highest tertile. Mean difference in systolic blood pressure between blood cadmium in the 90th versus 10th percentile was 1.36 mmHg (95% CI, –0.28 to 3.00), whereas the mean difference in diastolic blood pressure was 1.68 mmHg (95% CI, 0.57 to 2.78). Table 3. Exposure levels associated with effects on newly identified targets. Exposure/outcomes OR for PAD of 1.07, 1.30, and 2.82, when comparing blood cadmium quartiles 2, 3, and 4 versus the lowest (p for trend = 0.01). OR for PAD of 3.05, when comparing urinary cadmium of the 75th versus the 25th percentile. Increased body burden associated with lower aortic pulse wave velocity, lower pulse pressure, and higher femoral distensibility. OR for female myocardial infarction was 1.8, comparing urinary cadmium ≥ 0.88 versus < 0.43 µg/g creatinine. Increased body burden was associated with reduced lung function among smokers. A 3-fold increase in urinary cadmium associated with 54% higher prevalence odds for periodontal disease. Higher urinary cadmium associated with AMD in smokers. Intake of supplement was associated with lowered breast milk cadmium only in nonsmokers. Manganese, iron, and calcium in breast milk correlated with cadmium content. Oilseeds. Sunflower seeds, peanuts, flaxseed, and linseed accumulate cadmium from the soil in a manner similar to that of tobacco. Cadmium levels in sunflower ker- nels range from 0.2 to 2.5 mg/kg. Reeves and Vanderpool (1997) conducted a study on 75 male and female nonsmokers who were 30–70 years of age. Using a self-reported food- frequency survey, those subjects who reported consuming > 28 g of sunflower kernels per week were considered high consumers. An analysis of a duplicate diet among controls showed that on average cadmium intake was 36 µg/day, but intake was not determined for any of the high consumers. Blood and urinary cadmium levels were used as indicators of cad- mium body burden. The expected increased cadmium body burden could not be demon- strated, probably because of the limited num- ber of subjects and the short time frame of the study. However, evidence for kidney effects, reflected by urinary β2-MG and N-acetyl-β- d-glucosaminidase (NAG) levels, was found among high consumers of sunflower seeds. These data may indicate that cadmium in sunflower kernels possess a high nephrotoxic potential. Alternatively, they may indicate increased sensitivity to cadmium renal toxicity in the high sunflower-kernel consumers. Offal. High cadmium levels (7–76 mg/kg wet weight) were found in the offal of dugongs and turtles that constituted the diet in the Torres Strait (Australia). Haswell-Elkins et al. (2007a) examined cadmium body burden in relation to offal consumption among residents in two communities with varying dugong and turtle catch statistics. Of the 182 subjects, 12% had urinary cadmium > 2 µg/g creati- nine, and the group mean urinary cadmium was 0.83 µg/g creatinine. Age accounted for 46% of total variation in urinary cadmium levels, and sex (female) and current smok- ers accounted for 7% and 4.7% of variation, respectively. In a second study, Haswell-Elkins et al. (2007b) found high cadmium body bur- den associated with higher consumption of turtle liver and kidney and with locally gath- ered clams, peanuts, and coconuts. The sum of these foods, heavy smoking, age, and waist circumference accounted for 40% of variation in cadmium body burden (p < 0.05). Thus, this study showed that local offal consumption is linked with high cadmium body burden. Cadmium levels are higher in liver and kidney than in muscle and older animals (Prankel et al. 2005). Average cadmium in the liver and kidney of wild moose was 2.11 and 20.2 µg/g wet weight, respectively (Arnold et al. 2006). Notably, chronic, low-dose expo- sure situations produce 10- to 20-fold higher cadmium in kidney than liver. It is worth not- ing that no difference was observed in bioavail- ability of ionic cadmium versus protein bound cadmium. In the human gastrointestinal tract, ovlume 118 | number 2 | February 2010 • Environmental Health Perspectives Targets/study population, reference Blood vessels: United States, n = 2,125, Navas-Acien et al. 2004; n = 790, Navas-Acien et al. 2005 Blood vessels: Belgium, n = 557; Schutte et al. 2008a Heart: United States, n = 4,912; Everett and Frithsen 2008 Lung: United States, n = 96; Lampe et al. 2008 Periodontal tissues: United States, n = 11,412; Arora et al. 2009 Eye: United States, n = 53 cases, 53 controls; Erie et al. 2007 Mammary gland: Austria, n = 124; Gundacker et al. 2007 Mammary gland: Bangladesh, n = 123; Kippler et al. 2008 OR, odds ratio. 184