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High levels of cadmium (Cd) in paddy soil and rice, and a concurrent increase in urinary Cd of inhabitants in the Mae Sot District, Tak Province, Thailand first emerged in 2003. Risk factors such as occupation, sources of staple food and drinking water as well as biomarkers of adverse renal effects of the increased body burden of Cd were investigated in 795 residents, 30 years or older, whose urinary Cd levels were between 0.02 and 106mug/g creatinine. Farmers who consumed their own rice and residents who sourced drinking water from wells and/or the river demonstrated increased urinary Cd. Age-adjusted mean urinary cadmium for male and female subjects who consumed well water was 5.7mug/g vs. 6.1mug/g creatinine while the corresponding value for male and female subjects who did not consume well water was 3.7mug/g vs. 4.8mug/g creatinine, respectively. Increased urinary levels of beta(2)-microglobulin and N-acetyl-beta-d-glucosaminidase were observed with the increase in urinary Cd, indicating tubular dysfunction and renal damage associated with increase in Cd body burden. Consumption of well water and rice grown in the contaminated area increase the body burden of Cd. Cessation of exposure is essential to prevent and possibly recover from Cd toxicity, especially among the residents whose kidney damage and malfunction may be reversible.

Targeting persons requiring observation in the Cd-polluted Kakehashi River basin a serial observation study was conducted. Namely we followed the serial changes in 50 subjects who ingested household rice for 10 years after replacement of Cd-polluted soil in rice paddies. The serial changes in urinary substance levels in individuals were determined adjusting for the potential effect of age using a general linear mixed model. Cd excretions decreased with increasing number of years elapsed, with the partial regression coefficients of the number of years elapsed statistically significant in the women. The ratio of the Cd excretion theoretical values at the completion of soil replacement and 10 years later was 0.60 and the reduction rate was calculated as 5.0% per year in women. However, it was surmised that in practice a decrease to the level of inhabitants of non-polluted districts would not be achievable. The indices of renal tubular injury (2-microglobulin, retinol binding protein (RBP), total protein, amino-N and glucose) with the exception of amino-N in men showed increased excretion in both sexes with increasing number of years elapsed with statistically significant differences in RBP and total protein in both sexes and glucose in men. In this study using a general linear mixed model, which is an appropriate statistical method to perform a follow-up study, Cd concentrations in rice and urine were found to decrease after Cd exposure was reduced, but the degree of renal tubular injury was not found to improve, leading to the conclusion that the renal tubular injury induced by environmental Cd exposure is irreversible. © 2007 Elsevier Ireland Ltd. All rights reserved.

The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy on fetal brain growth and neurobehavioral development in early developmental stages were investigated using rat offspring. TCDD in corn-oil (0.1microg/kg) was orally administrated to the dams from the 9th to 19th gestational day. When TCDD effects on the fetal brain weight were analyzed on the 19th gestational day, weight ratio of the brain to the whole body, and that of the forebrain without the cerebral cortex to the whole brain were larger in the exposed group than those of the control group, suggesting premature fetal brain development. TCDD effects on motor functions were investigated using newborns in an inclined plane task. Motor development assessed by righting response on an inclination was delayed in the exposed offspring in the 8th-12th postnatal day, especially in male. Also, TCDD effects on active avoidance behavior in a shuttle box were investigated using the offspring after weaning. Latency in the active avoidance learning was longer, and locomotor activity was reduced in the exposed male offspring in the 41st-44th postnatal day. The results demonstrated that maternal TCDD exposure delayed fetal brain growth and neurodevelopment of the offspring in early stage, especially in male rats.

This study was undertaken to estimate the amount of cadmium (Cd) exposure needed for the development of Itai-itai disease. The investigated subjects comprised 82 Itai-itai disease patients and 11 persons requiring observation who were admitted in 1977 and 1978 for medical testing. With the period when the Itai-itai disease patients started to perceive leg/back pain defined as the 'mild disease onset', and the period when they experienced the most severe manifestations such as ambulatory disturbance and bone fractures defined as 'severe disease onset'. Relative cumulative person number distribution according to life time cadmium intake (LCD) at mild disease onset, severe disease onset, and time of death was depicted as an sigmoid curve and the establishment of probit regression lines was demonstrated between them. LCD at the time when mild disease onset and severe disease onset were recognized in half of the Itai-itai disease patients was 3.1 and 3.8 g, respectively. Furthermore, LCD at the time when mild disease onset and severe disease onset were recognized in 5% of the Itai-itai disease patients was calculated to be 2.6 and 3.3 g, respectively. The present results clarify that Itai-itai disease, the most severe stage of chronic Cd poisoning, occurs at levels of Cd consumption amounting to approximately three-fold of those currently seen in Japan.

The aim of the present study was to clarify the relationship between urinary cadmium concentration (U-Cd) and total cadmium intake (T-Cd) based on individual data of Cd in urine. Morning urine specimens were collected from 198 persons (100 men with average age of 45.8 years and 98 women with average age of 50.7 years) living in the Kakehashi River basin in Ishikawa Prefecture, Japan. The method used to calculate T-Cd basically mirrored that used in our previous study. Correlation coefficients between U-Cd and T-Cd of 0.879 and 0.835 were obtained in men and women, respectively, with both values statistically significant. Therefore, T-Cd is confirmed to be a useful indicator for external Cd exposure even on the basis of individual data of U-Cd.

A follow-up survey was conducted to investigate the relationship between total Cd intake and mortality in the Jinzu River basin for 6128 days among 757 inhabitants who ingested household rice. When the subjects were divided into two groups, standardized mortality ratios (SMRs) were 0.94 in men and 1.36 in women for theor = 2.0 g group and 0.68 in men and 0.29 in women for the2.0 g group (significant in the women). Cox's hazard ratios for men, women, and men+women for theor = 2.0 g group relative to those in the2.0 g group were 1.406, 3.955 and 1.950 (significant in the men+women). Using total Cd intake as a continuous variable, the hazard ratios were 1.045, 1.146 and 1.049 in men, women, and men+women (significant in the women), respectively. In the Jinzu River basin, increased total Cd intake appears to exert an adverse influence on life prognosis.

Female rats were exposed by intragastric administration with a cannula 1mg/kg/day or 10mg/kg/day CdCl2 for the 11 days from the 9th to 19th day of pregnancy, and the effects of Cd exposure on eight elements, Na, K, Ca, Mg, P, Fe, Zn, and Cu in fetal liver, kidney, brain, fetal membrane and placenta then examined. We found that: (1) although Cd was not detected in fetal kidney and brain, significant Cd accumulation was found in fetal liver, fetal membrane and placenta in the 10 mg/kg Cd group, (2) the Zn and Fe concentrations in fetal liver in the 10 mg/kg Cd group were significantly lower than those in the control group, but no difference was found in the placenta, (3) the Cu concentrations in the placenta, fetal membrane and liver in the 10 mg Cd groups were significantly lower than those in the control group, (4) Na/K ratio in the placenta and fetal kidney and the Ca concentration in the placenta in the 10 mg/kg Cd group were lower than those in the controls. These results suggest that Cd exposure inhibits Zn and Fe transportation from the placenta to fetus, as well as Cu, Ca, Na and K uptake and transportation across the placenta, possibly influencing fetal growth and metabolism.

A study to clarify the food composition and nutritional factors that contribute to the levels of blood and urinary cadmium (Cd) was conducted on 50 pregnant Japanese women with mean age of 29 years. The mean iron (Fe) intake of subjects was 9.2 mg, which is much lower than the recommended level of 20 mg for pregnant women. Cd in urine samples collected at 30–32 weeks of gestation were correlated (r=0.354), but urinary Cd was related to age more than blood Cd. Urinary Cd and blood Cd levels were inversely related to total energy ( r partial =−0.325, and −0.334 , respectively) and fat intake ( r partial =−0.419, and −0.379 , respectively), even after adjustment for age. Blood Cd was also correlated to protein and iron intake ( r partial =−0.299, and −0.353 , respectively). These results indicate that Cd exposure levels of pregnant women with low energy intake, especially less fat intake, were higher than those of women with more energy and fat intake. In particular, blood Cd may be affected by protein and iron intake in pregnant women with increased these nutrients demand.

To determine whether current environmental lead (Pb) levels are causing any progressive changes in urinary Pb levels, 24-h urine samples were collected from 277 subjects (159 men and 118 women) in 1985, 312 subjects (155 men and 157 women) in 1993, and 311 subjects (156 men and 155 women) in 1998. All of the subjects worked in the same factory. The urinary Pb concentration was analyzed by flameless atomic absorption spectrophotometry. The geometric means for men were 4.74, 2.67 and 1.31 mg:day; 3.17, 1.78 and 1.04 mg:g creatinine; and 3.18, 1.99 and 0.98 mg:l urine in 1985, 1993 and 1998, respectively. The values for women were 3.22, 2.14 and 0.97 mg:day; 3.35, 2.26 and 1.15 mg:g creatinine; and 2.49, 1.86 and 0.83 mg:l urine, respectively. These results demonstrated that Pb levels in 24-h urine decreased significantly in the 13-year period (PB0.01). © 2000 Elsevier Science Ireland Ltd. All rights reserved.

A 15 year follow-up study of 3119 inhabitants living in a cadmium polluted area was conducted to investigate the influence of environmental cadmium exposure on the mortality. The cumulative survival curves of the subjects with urinary cadmium concentrationor = 10 microg/g creatinine was lower than that of the subjects with10 microg/g creatinine in the men aged 50-59 and 60-69 years and in the women aged 60-69 and 70-79 years. In the men aged 50-69 years and the all aged women, the cumulative survival curves became lower in proportion to the increase of urinary cadmium concentration, when the subjects were divided into four groups according to the amount of urinary cadmium concentration (5, 5-9.9, 10.1-19.9,or = 20 microg/g creatinine). These results suggested a dose response relationship between cadmium exposure and mortality.

Samples of 24-h urine were collected from 278 subjects (159 males and 119 females) in 1985, and 321 subjects (161 males and 160 females) in 1993 in the same factory with no occupational exposure to lead (Pb) in Japan. The age range of the subjects was 20-59 years. The urinary Pb concentrations were analyzed by flameless atomic absorption spectrophotometry after wet digestion followed by solvent extraction. The Pb levels in 24-h urine were distributed log-normally with geometric means (geometric S.D.) of 4.74 (1.46) and 2.67 (1.98) micrograms/day for males; and 3.22 (1.42) and 2.14 (2.05) micrograms/day for females in 1985 and 1993, respectively. No age-related changes in Pb levels in 24-h urine in either sex from 20 to 59 years were apparent. Pb levels in 24-h urine were significantly higher in males than in females (P < 0.01). Analysis of male smokers together with age-matched non-smokers failed to show an elevation of Pb levels in 24-h urine as related to smoking habits. Comparison of the Pb levels in 24-h urine in 1985 and 1993 disclosed that the Pb levels in 24-h urine were significantly lower in 1993 than in 1985 in both sexes (P < 0.01).

Urinary human intestinal alkaline phosphatase (IAP), β 2 -microglobulin ( β 2 -MG) and N -acetyl- β - d -glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cdexposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between β 2 -MG and IAP or NAG. The β 2 -MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and β 2 -MG is considered to be more useful.