Jinzu River Basin Research Articles

Cadmium exposure aggravates mortality more in women than in men

This study aimed to examine whether the mortality associated with exposure to cadmium (Cd) differs between the sexes. Target subjects were 14,604 (6944 men, 7660 women) from a list of all residents in the Jinzu River basin in 1967 and 1968. Trend of proportion of the population aged 70 years and older was significantly higher in women in the following decreasing order: non-Jinzu River basin, a region receiving a mixed water supply, and the Jinzu River basin. Sex ratios (proportions of population of men to that of women) in those aged 70 years and older became significantly higher in the same order. This tendency was compatible with the geographical distribution of the prevalence of abnormal urinary findings and Cd concentration in rice which was grown and consumed in the area. This study revealed that Cd exposure aggravates mortality more in women than in men.

Renal Effects of Environmental Exposure to Cadmium in Middle-Aged Population of Jinzu River Basin in Toyama, Japan: 2000-2002 Study

In 2000-2002, the effects of environmental cadmium (Cd) exposure on renal tubular function were investigated in men and women born between January 1, 1946 and December 31, 1955, and living in the Cd-polluted Jinzu River basin in Toyama. It is assumed that these generations had been exposed to Cd mainly through the consumption of rice and vegetables grown locally, in contrast to older generations who had been exposed not only through the consumption of rice but also by drinking river water polluted with Cd discharged from a mine. Morning urine specimens, self-administered questionnaires and polished rice samples consumed daily were collected from 110 men and 121 women living in the polluted area and from 48 men and 45 women living in the reference area. Urinary Cd excretion level, an indicator of Cd accumulation in the kidneys, significantly increased with increased duration (years) of residence in the Cd-polluted area in both men and women. There was no case of urinary beta2-microglobulin (beta2-MG) level exceeding 1,000 microg/g Cr in either sex, in contrast to the high prevalence of beta2-MGuria observed in older generations. However, urinary beta2-MG and alpha1-MG levels were slightly but significantly increased with increased duration (years) of residence in the Cd-polluted area in women. The results indicate that men and women born between 1946 and 1955 and living in the Cd-polluted Jinzu River basin had Cd accumulation in the kidneys and a slight increase in urinary low-molecular weight protein level due to this accumulation.

Low-level cadmium exposure in Toyama City and its surroundings in Toyama prefecture, Japan, with references to possible contribution of shellfish intake to increase urinary cadmium levels

Objectives This study was initiated to examine if exposure to cadmium (Cd) was high also outside of the previously identified Itai-itai disease endemic region in the Jinzu River basin in Toyama prefecture in Japan. Methods Morning spot urine samples were collected in June–August 2004 from 651 adult women (including 535 never-smokers) in various regions in Toyama prefecture, and subjected to urinalyses for cadmium (Cd), α 1-microglobulin (α 1-MG), β 2-microglobulin (β 2-MG), N-acetyl-β- d-glucosaminidase (NAG), specific gravity (SG or sg) and creatinine (CR or cr). Three months later, the second urine samples were collected from those with elevated Cd in urine (e.g., ≧ 4 μg/g cr), together with answers to questionnaires on shellfish consumption. Results The geometric mean (GM) Cd, α 1-MG, β 2-MG and NAG (after correction for CR) for the total participants were 2.0 μg/g cr, 2.4 mg/g cr, 104 μg/g cr and 2.8 units/g cr, respectively; further analysis with never-smoking cases only did not induce significant changes in these parameters. Analyses of the second urine samples from the high Cd subjects showed that there was substantial decrease (to about a half) in Cd in the 3-month period, and that the decrease was accompanied by reduction in α 1-MG and NAG (β 2-MG did not show elevation even in the first samples). The urinalysis results in combination with the results of the questionnaire survey suggest that the high urinary Cd was temporary and might be induced by intake of shellfish that is edible whole. Conclusions The overall findings appear to suggest that Cd exposure in Toyama populations (outside of the Itai-itai disease endemic region) was at the levels commonly observed on the coast of the Sea of Japan, and that the Cd level in urine might be modified by the intake of some types of seafood. Further studies are necessary to elucidate the relation of urinary Cd with seafood intake.

Seasonal Variations in Plasma Concentrations of Sex Steroid Hormones and Vitellogenin in Wild Male Japanese Dace (Tribolodon hakonensis) Collected from Different Sites of the Jinzu River Basin

In order to clarify the seasonal variations of plasma sex steroid hormones and vitellogenin (VTG) concentrations in the wild male Japanese dace, Tribolodon hakonensis, we measured plasma levels of testosterone (T), 11-ketotestosterone (11-KT), estradiol-17 beta (E2) and VTG, as well as spermatogenetic stages and gonadosomatic index (GSI). Wild Japanese dace were collected from different sites of the Jinzu River basin (including the Takahara River and the Itachi River). The fish from Toyama Bay were also measured the spermatogenetic stages, GSI and VTG levels. The seasonal variations of the hormone levels were discussed in the relationship with various environmental factors. In landlocked fish of the Takahara River, the plasma concentrations of T and E2 reached the highest levels in May and June. In the fish collected from the Itachi River, plasma concentrations of T, 11-KT and E2 reached the highest levels during breeding season of April and May. Sexual maturation, evaluating from GSI and the spermatogenetic stages, proceeded earlier in the fish population at Toyama Bay, and afterward it was followed in the fish population at the Takahara River, in associated with a rise of environmental water temperature at fish captured sites. In the male dace, low but detectable levels of plasma E2 were measured and there were significantly positive correlations between E2 level and the levels of GSI, VTG or T. These results suggest that E2 might be a necessary sex steroid hormone related to gonad maturation, and that circulating E2 may induce VTG production in the wild male Japanese dace.

Micro-organic ion-associate phase extraction and solid extraction / HPLC determination of di(2-ethylhexyl) phthalate and its behavior in Jinzu River basin

Micro-organic ion-associate phase extraction and solid extraction / HPLC determination of di(2-ethylhexyl) phthalate and its behavior in Jinzu River basin

Environmental cadmium exposure, adverse effects and preventive measures in Japan

In Japan the most heavily cadmium (Cd)-polluted region is the Jinzu river basin, where Itai-itai disease is endemic and the Kakehashi river basin is the second most polluted region.. The village average Cd concentrations in rice were distributed in the range between 0.02 microg/g and 1.06 microg/g in the Jinzu river basin and 0.11 microg g and 0.67 microg g in the Kakehashi river basin. Severe renal damage has occurred widely in the Jinzu river basin. Even after Cd exposure had ceased, renal dysfunction became worse. Dose-response relationships between Cd exposure and health effects were clearly demonstrated in both regions. The allowable limits (according to the present authors' assessment) of Cd concentrations in rice were estimated to be 0.08 microg g to 0.13 microg g and approximately 2 g for total Cd intake. Renal dysfunction caused by exposure to Cd was associated with an increased mortality in both regions. The increased total Cd intake and high concentration of Cd in rice also exerts an adverse influence on life prognosis.

Relationship among prevalence of patients with Itai-itai disease, prevalence of abnormal urinary findings, and cadmium concentrations in rice of individual hamlets in the Jinzu River basin, Toyama prefecture of Japan

This study investigated the associations among prevalence of patients with Itai-itai disease, and prevalence of abnormal urinary findings and cadmium (Cd) concentrations in rice in individual hamlets of the Jinzu River basin. From the 13,183 participants of the 1967 and 1968 health examinations, we selected 3,094 subjects as the target population who had resided in the current hamlet for a total of 30 years or longer and aged ⩾ 50 years, and in the hamlet both the Cd concentration in rice and prevalence of patients with Itai-itai disease were known. When the inhabitants were divided into four groups according to the Cd concentration in rice or prevalence of abnormal urinary findings, significant relationships among three factors (Cd concentration in rice, prevalence of abnormal urinary findings and prevalence of patients with Itai-itai disease) were demonstrated clearly using the Cochran – Armitage test. Correlation coefficients among the three factors in 55 hamlets showed that the prevalence of the patients with Itai-itai disease increased according to increases in the mean Cd concentration in rice and increasing prevalence of urinary findings. This study demonstrated that Itai-itai disease is induced by exposure to environmental Cd and that renal dysfunction plays an important role in its development.

Tolerable lifetime cadmium intake calculated from the inhabitants living in the Jinzu River basin, Japan.

Tolerable lifetime cadmium intake calculated from the inhabitants living in the Jinzu River basin, Japan.

Reduction of erythrocyte catalase and superoxide dismutase activities in male inhabitants of a cadmium-polluted area in Jinzu river basin, Japan

Cadmium (Cd) is a toxic heavy metal which causes oxidative damage in organisms. In this study, we investigated the activities of the antioxidant enzymes erythrocyte catalase and copper/zinc superoxide dismutase (Cu/Zn-SOD) in 22 male inhabitants of the Cd-polluted Jinzu River basin in Toyama Prefecture, Japan (Cd group). The reference group consisted of 21 male inhabitants from an area that was not polluted with Cd (reference group). Urinary Cd levels and two renal tubular dysfunction markers in urine, α 1-microglobulin (α 1-m) level and N-acetyl-β- d-glucosaminidase (NAG) activity, were significantly elevated in the Cd group. Catalase and Cu/Zn-SOD activities were significantly reduced in the Cd group as compared to the reference group. Significant negative correlation was observed between the activities of these two antioxidant enzymes and urinary Cd levels. We also observed significant negative correlations between activities of these two antioxidant enzymes and the renal tubular dysfunction markers. Our results indicate that erythrocyte catalase and Cu/Zn-SOD activities are reduced as a result of long-term Cd exposure. This may be linked to renal tubular dysfunction in the inhabitants of the Cd-polluted area.

Dietary cadmium intake in polluted and non-polluted areas in Japan in the past and in the present.

The purpose of this data compilation is to overview past and current dietary exposure (primarily via rice) of general populations to cadmium (Cd) in environmentally polluted and non-polluted areas in Japan, and to compare the levels with counterpart levels in other areas in Asia. A literature survey was conducted for publications on this subject, in either Japanese or international languages, since the early 1970s. Most of the studies identified employed the food-duplicate method in combination with atomic absorption spectrometry for Cd determination, although a few studies utilized other methods, such as the market basket method and dithizon-colorimetry. The highest estimate of dietary Cd intake (Cd-D), 600 microg Cd/day, was reported in the late 1960s for the local population in the Jinzu river basin, where Itai-itai disease had been endemic, and the Cd-D levels were 300 microg/day or higher in other polluted areas. Cd-D dropped to well below 100 microg/day when the polluted soil was replaced in the late 1970s and thereafter. In non-polluted areas, the Cd-D was reported to be approximately 100 microg/day in 1969, followed by a gradual decrease to approximately 40 microg/day in the late 1970s, to reach the current level of less than 30 microg/day. There is a trend of gradual reduction at the rate of 0.3 to 0.6 microg/day per year. Cd from rice accounted for 30 to 40% of the Cd-D in non-polluted areas, but a higher contribution was observed in some polluted areas. Nevertheless, the current Cd-D is still higher than the levels in other rice-dependent populations in east and south-east Asia. The Cd-D levels reported for polluted areas were in excess of 300 microg Cd/day. Substantial reduction in Cd-D to the level below 100 microg/day was observed after remediation, such as replacement of polluted paddy soil. In non-polluted areas, there has been a gradual decrease in Cd-D in the past 25 years. Nevertheless, the levels in the current intake of the general population in Japan (25 to 30 microg/day, or <1/10 of the levels in polluted areas in the past) is still higher than the levels in other rice-dependent areas in Asia.

Total cadmium intake and mortality among residents in the Jinzu River Basin, Japan.

This study investigated the relationship between total cadmium intake and mortality among rural inhabitants of the Jinzu River Basin, Japan. A follow-up survey was conducted for 6,128 days on 3,236 inhabitants. The rural communities were divided into 2 groups, one with a total cadmium intake of < 2.0 gm and the other > or = 2.0 gm. Standardized mortality ratios and a Cox's proportional hazard model indicated mortality risk was greater in the > or = 2.0 gm group, compared with the < 2.0 gm group. In the Jinzu River Basin, a total cadmium intake > or = 2.0 gm exerts an adverse influence on life prognosis.

Allowable level of lifetime cadmium intake calculated from the individuals in the Jinzu River basin of Japan.

We investigated a dose-response relationship between renal dysfunction and lifetime cadmium intake in individual subjects using logistic regression analysis and calculated the allowable level of lifetime cadmium intake among the inhabitants of the Jinzu River basin. From the participants of 1967 and 1968 health examinations, target subjects in whose hamlet the cadmium concentration in rice was known and whose history of residence was also known were selected. Cadmium concentrations in rice from data analyzed by the Toyama Prefecture from 1971 to 1976 were used. The urinary examination was done by semiquantitative determination of protein and glucose. All odds ratios for lifetime cadmium intake obtained from logistic regression analysis were more than 1 in both males and females who had resided in their current hamlet since birth with and without subjects who moved from nonpolluted areas and with or without the control group. The allowable levels of lifetime cadmium intake were calculated by substituting the abnormality rates of urinary findings of the controls 40, 50, 60, and 70 yr old into the logistic regression formula. The allowable levels of lifetime cadmium intake were less than 1.58 g for both sexes and each age group using proteinuria with glucosuria measurements.

Assessment of bone metabolism in cadmium-induced renal tubular dysfunction by measurements of biochemical markers

Bone metabolism related to the severity of cadmium (Cd)-induced renal tubular dysfunction (RTD) was assessed by measuring several bone biochemical markers. Fifty-three female subjects with RTD aged 65–76 years (mean 70.0±3.3 years) and who lived in the Cd-polluted Jinzu River basin in Toyama, Japan were studied. Bone alkaline phosphatase (bone-ALP), intact bone Gla-protein (intact-BGP) and carboxy-terminal propeptide of type I collagen (PICP) in serum as bone formation markers and pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in urine as bone resorption markers were measured. All markers of bone turnover were increased and significantly correlated with each other, suggesting that bone formation and resorption were coupled and increased in Cd-induced RTD. Fractional excretion of β 2-microglobulin (β 2-m, FE β2-m) as an index of severity of Cd-induced RTD was extremely varied ranging from 0.45 to 53%. There were no significant correlations between FE β2-m and each of the five bone biochemical markers. The bone turnover in Cd-induced RTD appeared to be determined by the glomerular filtration rate (GFR): in subjects with GFRs above 50 ml/min, the levels of bone-ALP or intact-BGP tended to be inversely related to the GFRs, whereas in subjects with GFRs below 40 ml/min, those levels tended to decrease. These results suggest that the bone turnover, in particular the bone formation, was influenced by renal tubular function as assessed by the levels of GFR in Cd-induced RTD.

Influence of years engaged in agriculture and number of pregnancies and deliveries on mortality of inhabitants of the Jinzu River basin area, Japan

Background: The occurrence of itai-itai disease is thought to be affected by such factors as pregnancy, lactation, hormonal disorders, aging, and calcium deficiency. Aims: To study the influence of years...

Association between Renal Dysfunction and Mortality among Inhabitants in the Region around the Jinzu River Basin Polluted by Cadmium

A follow-up study was conducted on 5725 inhabitants (men 2858, women 2867) in and around the Jinzu River basin to determine the influence of environmental Cd exposure on mortality. In the Jinzu River basin, standardized mortality ratios (SMRs) investigated according to urinary findings (protein, glucose, and protein+glucose) were significantly low in the urinary protein-, glucose-, and protein+glucose-negative groups. SMRs calculated after dividing urinary protein- and glucose-positive status into two levels were lowest in the proteinuria- and glycosuria-negative groups and tended to be high in the higher positive groups. In the Jinzu River basin, Cox's hazard ratios were significantly higher for men and women in the urinary protein, glucose and protein+glucose-positive-groups. In the same analysis where the urinary protein- and glucose-positive subjects were divided into two levels, mortality was demonstrated to be higher in the groups with the greater degrees of proteinuria and glycosuria. In the Jinzu River water system almost all SMRs and Cox's hazard ratios showed statistical significance. This was not the case in the other water systems. Mortality of inhabitants with Cd-induced renal injury is increased in the Jinzu River basin.

Cadmium overload and toxicity.

Studies suggest that cadmium is associated with several clinical complications, primarily renal dysfunction and bone disease, but also some cancers. Cadmium toxicity has been associated with clinical manifestations at exposure levels that are well below the limits set by the World Health Organization. Here I review the OSCAR study, which demonstrates an association between environmental and occupational cadmium exposure and renal tubular damage, as well as the Cadmibel study, a cross-sectional population study demonstrating an association of cadmium exposure with renal dysfunction. The paper also reviews the association of end-stage renal disease prevalence with occupational and environmental exposure to cadmium in the Swedish population of Kalmar County. Renal tubular damage was shown to develop at levels of exposure much lower than previously thought. Cadmium-induced tubular proteinuria is irreversible, and continued exposure may lead to glomerular damage with decreased glomerular filtration rate. Itai-itai disease in the Jinzu river basin is discussed, as are the implications of low-level cadmium exposure in the PheeCad project. Cadmium accumulates in bone and is associated with osteomalacia and osteoporosis. Other bone-seeking trace elements, such as chromium, lanthanum, strontium and zinc, are of concern because of low level environmental, occupational or clinical exposure. As techniques are perfected for detecting smaller amounts of trace elements in various tissues in the body, investigators are finding that the threshold for toxicity from trace elements is much lower than expected. Further research on cadmium is necessary to reveal the mechanisms of toxicity and true environmental and occupational exposure limits.

Association Between Urinary Calcium Excretion Level and Mortality in Inhabitants of the Jinzu River Basin Area of Japan

A follow-up study on 5442 inhabitants (2699 men, 2743 women) was conducted to determine the association between urinary Ca excretion level and mortality of the general population of three different areas of the Jinzu River basin area, namely, non-Jinzu River, mixed, and the Jinzu River water systems, over a period of 6127 d. More than 98% of the subjects were followed completely in each area. In comparison with the low- and high-Ca-excretion groups (cutoff values; 25.1 mg/dL in men, 20.4 mg/dL in women), the mortality rates per 1000 person-years and standardized mortality ratios (SMRs) tended to be greater in the low-Ca-excretion groups than in the high-Ca-excretion groups in both sexes for each of the three areas. Moreover, Cox's hazard ratios in men and women of the three areas exhibited negative values, 0.99 except for men of the mixed water system. These values were statistically significant in both sexes for the Jinzu River water system and in women for the non-Jinzu River water system. We conclude that the life-span becomes shorter as urinary Ca excretion levels become lower.

Association between total cadmium intake calculated from the cadmium concentration in household rice and mortality among inhabitants of the cadmium-polluted Jinzu River basin of Japan

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 the ≥2.0 g group and 0.68 in men and 0.29 in women for the <2.0 g group (significant in the women). Cox's hazard ratios for men, women, and men+women for the ≥2.0 g group relative to those in the <2.0 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.

Relationship between cadmium concentration in rice and renal dysfunction in individual subjects of the Jinzu River basin determined using a logistic regression analysis

We investigated the association between the Cd concentration in rice and renal dysfunction in individuals living in the Cd-polluted Jinzu River basin, using a logistic regression analysis. In the cases of logistic regression analysis for people (1) who had either resided in the present hamlet since birth or who had moved there from a non-polluted area and for those (2) who had resided in the present hamlet since birth, except for glucosuria in males, all partial correlation coefficients between the Cd concentration in rice and occurrence of abnormal urinary findings were statistically significant in both sexes. The allowable level of Cd concentration in rice was calculated by substituting the abnormality rates of urinary findings of the controls in the 40–49, 50–59 and 60–69 year age groups into the logistic regression formula for people (3). The value for subjects aged 50 years was 0.13 and 0.17 ppm for males and females, respectively, with regard to proteinuria and 0.15 and 0.10 ppm for males and females, respectively, with regard to proteinuria+glucosuria.

Association between cadmium concentration in rice and mortality in the Jinzu River basin, Japan

A follow-up survey on 2101 inhabitants (1566 men, 535 women), who participated in a 1967 health survey and had resided in their present rural community since birth was conducted to determine the influence of environmental cadmium exposure on the mortality of the general population in the Jinzu River basin. The survey was conducted over 6128 days from August 1, 1967 to May 10, 1984. The rural communities were divided into two groups, one with a cadmium concentration in rice of <0.30 ppm and the other ≥0.30 ppm. The influence of cadmium concentration in rice on mortality was analyzed using SMRs and a Cox's proportional hazards model. In both sexes, SMRs tended to be greater in the ≥0.3 ppm group as compared to <0.3 ppm group. The Cox hazard ratios for males and females in the ≥0.30 ppm group, to those in the <0.30 ppm group, were 1.42 and 1.10, respectively (significant in the men). Since the mean cadmium concentration in rice in each rural community was closely related to the development of renal injury, in regions with high cadmium concentrations in rice, the development of renal injury induced by cadmium is believed to be the factor underlying the increased mortality observed.