The gender differences in health effects of environmental cadmium exposure and potential mechanisms

On a viewpoint of gender differences in Cd body burden and its health effects, we reviewed the population-based research including our own which conducted in Japan, Thailand, Australia, Poland, Belgium and Sweden to assess health effects of human exposure to environmental cadmium and their potential mechanisms. As a result, six risk factors in Cd health effects in women have been identified; (1) more serious type of renal tubular dysfunction, (2) difference in calcium metabolism and its regulatory hormones, (3) kidney sensitivity; difference in P450 phenotype, (4) pregnancy, (5) body iron store status, and (6) genetic factors. Further studies of Cd toxicity targeted to women would now appear necessary.     

Influence of Drinking and/or Cooking with Jinzu River Water on the Development of Itai-Itai Disease

This study was undertaken to estimate the amount of cadmium (Cd) exposure needed for the development of Itai-itai disease and the influence of using Jinzu River water for drinking and/or cooking on its development. The subjects comprised 38 Itai-itai disease patients admitted both for questionnaire survey and medical testing. The period when the patients started to perceive leg/back pain was defined as ‘mild disease onset’ and that when they experienced the most severe manifestations such as ambulatory disturbance as ‘severe disease onset’. In a comparison of non-users/users of river water, mean age and lifetime Cd intake (LCd) estimated from the daily consumption of rice and other foods at the onset of mild or severe disease showed smaller values in the users than non-users. LCd in non-users/users of river water for drinking and/or cooking were estimated as 3.46–3.60 g/2.58–2.63 g at mild disease onset and 4.24–4.44 g/3.50–3.54 g at severe disease onset. A portion of the differences in LCd in non-users/users is attributable to the influence of Cd consumption from the use of river water, although it was suggested that LCd estimated from eating Cd-polluted rice exerted a greater influence on the development of Itai-itai disease than drinking and/or cooking with Cd-polluted river water.     

Influence of Consumption of Cadmium-Polluted Rice or Jinzu River Water on Occurrence of Renal Tubular Dysfunction and/or Itai-itai Disease

The aim of this study was to clarify whether consumption of cadmium (Cd)-polluted rice or Jinzu River water exerted any influence on the occurrence of renal tubular dysfunction and/or Itai-itai disease. From the participants of health examinations conducted in 1967 and 1968, 3,078 subjects who had resided for >30 years in the present hamlet and were aged >50 years were selected as the target population and were divided according to their residence in 55 hamlets. In a multiple regression analysis, the regression coefficients between rice-Cd concentration and prevalence of abnormal urinary findings (proteinuria, glucosuria, or proteinuria with glucosuria) or patients with Itai-itai disease were statistically significant between both sexes. The correlation between the prevalence of users of Jinzu River water and the occurrence of glucosuria in men as well as abnormal urinary findings in women was not statistically significant. We surmise that eating Cd-polluted rice and drinking and/or cooking with Jinzu River water influenced the occurrence of Itai-itai disease. The occurrence of renal tubular dysfunction is likely to have also been influenced by both factors, with eating Cd-polluted rice having a greater impact on the occurrence of renal tubular dysfunction as compared to drinking and/or cooking with Jinzu River water.     

Impact of perinatal dioxin exposure on infant growth: a cross-sectional and longitudinal studies in dioxin-contaminated areas in Vietnam

Dioxin exposure levels remain elevated in residents living around former US Air Force bases in Vietnam, indicating potential adverse impacts on infant growth. In this study, 210 mother-infant pairs in dioxin-contaminated areas in Vietnam were recruited at the infants' birth and followed up for 4 months. Perinatal dioxin exposure levels were estimated by measurement of polychlorinated dibenzo-p-dioxins/furans toxic equivalent (PCDDs/Fs-TEQ) in breast milk. The infants' size was measured at birth and 1 and 4 months after birth, and neurodevelopment was evaluated using the Bayley Scales III at 4 months of age. Among 4 dioxin groups (<25, 25-50, 50-75, ≥75 percentile of PCDDs/Fs-TEQ), cross-sectional comparisons of body size and neurodevelopment scales and comparisons of longitudinally assessed body size were performed respectively. At birth, head circumference of girls in the ≥75 percentile group was significantly larger than those in the <25 and 50-75 percentile groups. At 4 months of age, the weight and body mass index (BMI) of boys in the ≥75 percentile group were significantly lower than those in the other groups. Increase in weight was significantly lower in the ≥75 percentile group in both sexes from birth to 1 month but only in boys at 1-4 months of age. Estimated marginal mean values in a mixed model of weight and BMI during the first 4 months of life were significantly lower in the ≥75 percentile group in boys. In girls, marginal mean values for head circumference were increased with increase in dioxin levels. Only in boys, cognitive, language, and fine motor scores in the ≥75 percentile group were significantly lower than those in the other groups. These results suggested a considerable impact of perinatal dioxin exposure on infant growth, particularly in boys exposed to dioxins at high level of PCDDs/Fs-TEQ.     

Tissue cadmium (Cd) concentrations of people living in a Cd polluted area, Japan

There are more than 50 cadmium (Cd) polluted areas in Japan. The severest general environmental Cd polluted area in Japan was the Jinzu River basin in Toyama Prefecture where Itai-itai disease had been endemic. The present study aimed to compare organ Cd concentrations of inhabitants who had been exposed to different levels of environmental Cd and to clarify the health effects of the environmental Cd exposure in Japan. Since 1960 we have measured tissue Cd concentrations of inhabitants with a history of living in a different Cd polluted areas. Study population living in Cd polluted areas were 36 (1 male, 35 females) patients with Itai-itai disease, 20 (7 males, 13 females) subjects suspected of having Itai-itai disease, 8 (2 males, 6 females) inhabitants in Cd polluted areas other than the Jinzu River basin. Subjects who had lived in Cd non-polluted area were 72 inhabitants. Cd concentrations in liver, pancreas and thyroid of those living in Cd polluted areas were as high as those of patients with Itai-itai disease, and their Cd concentrations in renal cortex were as low as those of patients with Itai-itai disease. The present study demonstrated that tissue Cd concentrations of some inhabitants in Cd polluted areas other than Jinzu River basin are equal to those of the patients with Itai-itai disease and that patients with Itai-itai disease were present even in these areas.     

Biological half-life of cadmium in the urine of inhabitants after cessation of cadmium exposure

We investigated the biological half-life of the urinary cadmium concentration (U-Cd) based on a 24-year follow-up study after cessation of cadmium exposure in a cadmium-polluted area. Spot urine samples were obtained from all inhabitants in this area in 1979, 1986, 1991, 1999 and 2003. Biological half-life was calculated in the inhabitants whose U-Cd was more than 5 μg?l^?1 (9 men and 12 women) or 5 μg?g^?1 creatinine (9 men and 19 women) using a one-compartment model. The estimated half-life and 95% confidence intervals were 13.6 years (9.0–28.2 years) and 13.9 years (9.6–25.6 years) for unadjusted U-Cd in men and women, respectively. For creatinine-adjusted U-Cd, they were 14.2 years (11.2–19.4 years) and 23.5 years (17.7–35.0 years) in men and women, respectively. The biological half-lives of U-Cd obtained in this study were identical with the values of total body burden determined by a different method.     

Changes in Renal Tubular and Glomerular Functions and Biological Acid–Base Balance after Soil Replacement in Cd-Polluted Rice Paddies Calculated with a General Linear Mixed Model

Using a general linear mixed model, we conducted a 10-year follow-up investigation of 29 persons requiring observation in the cadmium (Cd)-polluted Kakehashi River basin to determine serial changes in biological parameters after removal of Cd-polluted soil present in rice paddies. In particular, we investigated changes in urinary Cd, urinary total protein, biological acid-base balance based on arterial blood pH, carbon dioxide tension (Pa(CO2)), base excess (BE), serum chloride ion (SCl(-)), and renal glomerular function based on serum creatinine (SCr) and creatinine clearance (C(Cr)). In both sexes, urinary Cd concentrations decreased and total protein concentrations increased with increasing number of years elapsed, with the partial regression coefficients statistically significant in the women. Partial regression coefficients showed positive values for SCl(-), with statistical significance in both sexes. The value for Pa(CO2) was significantly negative in men. Given the serial changes in arterial blood pH, Pa(CO2), BE, SCl(-), it is suggested that the biological acid-base balance will progress to metabolic acidosis with hyperchloremia. Moreover, glomerular dysfunction as indicated by an increase in SCr and a decrease in C(Cr) will continue to progress even after soil replacement. Interventions such as soil replacement appear to be too late to prevent progressive renal failure in Cd-exposed populations.