Kakehashi River Research Articles

Estimation of benchmark doses for urinary cadmium based on β2-microglobulin excretion in cadmium-polluted regions of the Kakehashi River basin, Japan

A benchmark dose low (BMDL) is used as a replacement for the no observed adverse effect level. The threshold levels of urinary cadmium (Cd) as BMDL were estimated using data from the Kakehashi River basin. The target population (≥50 years) comprised 3178 and 294 participants inhabiting Cd-polluted and non-polluted areas, respectively. Cut-off values for β2-MG-uria were defined as the 84 and 95% upper limit values calculated from control subjects, and 1000 µg/l or µg/g cr of β2-MG. Using these cut-off values, the BMDL at which the excess risk is 0.05 was determined to be 2.9 – 4.0 µg/g cr (males) and 1.5 – 3.6 µg/g cr (females). The present study demonstrated that a BMD approach is useful to estimate the threshold level of urinary Cd in Cd-exposed subjects and people living in general environment without any known Cd-pollution since a BMD approach does not need abnormality rates of urinary findings in the controls.

Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment

Objectives: To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment. Methods: A 15 year follow up study was performed with...

Tolerable Level of Lifetime Cadmium Intake Estimated as a Benchmark Dose Low, Based on Excretion of ;2-Microglobulin in the Cadmium-Polluted Regions of the Kakehashi River Basin, Japan

Tolerable Level of Lifetime Cadmium Intake Estimated as a Benchmark Dose Low, Based on Excretion of ;2-Microglobulin in the Cadmium-Polluted Regions of the Kakehashi River Basin, Japan

Urinary cadmium and mortality among inhabitants of a cadmium-polluted area in Japan

The influence of cadmium (Cd) body burden on mortality remains controversial. Excess mortality and the dose–response relationship between mortality and urinary cadmium excretion were investigated in this study among environmentally exposed subjects. A 15-year follow-up study was carried out on 3119 inhabitants (1403 men and 1716 women) of the Cd-polluted Kakehashi River basin, whose urinary Cd concentration was examined in a 1981–1982 health impact survey. The mortality risk of high urinary Cd (⩾10 μg/g Cr) subjects after adjustment for age using Cox's proportional hazard model was higher than that of moderate urinary Cd (<10 μg/g Cr) subjects in both sexes. When the subjects were divided into five groups according to the amount of urinary Cd (<3, 3–5, 5–10, 10–20, ⩾20 μg/g Cr), the mortality risk was significantly increased among the subjects with urinary Cd⩾3 μg/g Cr in proportion to the increases in the amount of urinary Cd concentration after adjustment for age, especially in women. Furthermore, special causes of death among high and moderate urinary Cd were investigated, and mortality risk ratio for heart failure, which is a cause of death often diagnosed in cases with a gradual deterioration culminating in death, was significantly increased in both sexes, compared with the moderate urinary Cd subjects. Also, in women the mortality risk for renal diseases in the high urinary Cd subjects was significantly higher than that in the moderate urinary Cd subjects. These results suggest that a causal association between Cd body burden and mortality exists among inhabitants environmentally exposed to Cd but that no special disease may be induced except renal diseases.

Excretion of Urinary Cadmium, Copper, and Zinc in Cadmium-Exposed and Nonexposed Subjects, with Special Reference to Urinary Excretion of β&lt;SUB&gt;2&lt;/SUB&gt;-microglobulin and Metallothionein

The objectives of this study were to examine the association between urinary excretion of cadmium (U-Cd), copper (U-Cu), and zinc (U-Zn) and the severity of two different indicators of renal toxicity (urinary excretion of beta2-microglobulin [U-beta2-MG] and metallothionein [U-MT]) in Cd-exposed subjects compared to controls, and to assess the physiologic mechanisms by which the exposure to environmental Cd affects U-Cd, U-Cu, and U-Zn. The target population included 3508 Cd-exposed and 294 nonexposed participants who received a health survey conducted among the population of the Kakehashi River basin. Increases of U-Cd, U-beta2-MG, and U-MT in the Cd-exposed population were observed relative to excretion of these substances in controls. Regression analysis using a general linear model revealed that the correlations between U-Cd or U-Cu, and U-beta2-MG and between U-Cd, U-Cu or U-Zn, and U-MT were statistically significant in both sexes, but the correlation between U-Zn and U-beta2-MG excretion was significant only in men. These results suggest U-Cd and U-Cu is affected by dysfunction in renal tubular absorption (indicated by U-beta2-MG), whereas not only U-Cd and U-Cu but also U-Zn appear to be a function of renal cellular desquamation (indicated by U-MT).

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.

Mortality in a cadmium polluted area in Japan

A 15-year follow-up study of 3178 inhabitants (1424 men and 1754 women) living in the cadmium (Cd) polluted Kakehashi River basin was conducted. The results clarified effects on mortality of renal dysfunction induced by Cd indicated by urinary beta-2-microglobulin (beta2-MG), total protein, glucose, and total amino acids. This study used Cox's proportional hazard model. The mortality risk ratio of urinary beta2-MG positive (>= 1000 microg/gCr) subjects was significantly increased in both sexes: 1.35 for men and 1.73 for women. The increased mortality ratio of the urinary protein positive (>= 10 mg/dl) subjects was also significant for both sexes, with risk ratios of 1.82 for men and 2.01 for women. Only the women showed significantly increased mortality of the urinary glucose positive (>= 20 mg/dl) subjects and amino acids positive (> = 300 microg/gCr) subjects. When the subjects were divided into four categories according to urinary beta2-MG, <300, 300-1000, 1000-10000, >= 10000 microg/gCr, the mortality risk ratios were increased in proportion to the increase of urinary beta2-MG in both sexes. These results suggest that mortality of Cd-exposed subjects increased with increasing excretion of four urinary markers of renal tubular dysfunction, and in proportion to increases in the amount of urinary beta2-MG excretion including under 1000 microg/gCr.

The relation of individual cadmium concentration in urine with total cadmium intake in Kakehashi River basin, 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.

Heavy-metal pollution and its state in algae in Kakehashi river and Godani river at the foot of Ogoya mine, Ishikawa Prefecture.

Alga as Achnanthes minutissima among diatoms is a widely adaptable taxon on the state of an aquatic environment. In this study, it was found that diatom had a specific tolerance to heavy metals (Cu, Zn, Pb, and Cd etc.) in river water samples, because the diatom assemblage consisted of almost only Achnanthes minutissima in Kakehashi river and Godani river, which were polluted with waste water from Ogoya copper mine. The relationship between the concentrations of heavy metals (Cu, Zn, Pb and Cd) in river water and the attached substances (algae and silt etc.) and the relative abundances of diatom taxa were investigated in detail. The results indicated that the higher is the concentration of heavy metals in the river environment, the higher is only the relative abundances of Achnanthes minutissima. Thus, the taxon can be used as a bioindicator of heavy metal pollution. The relative rates of toxic chemical forms of copper in algae were 61 - 92% in the attached substances and 49-70% in the sediment on the river bed, respectively. Therefore, it was found that diatom as Achnanthes minutissima had a tolerance to heavy metals in river water, being able to live in such an environment. Since the water treated with calcium hydroxide from the deposition reservoir of Ogoya mine enters in Godani river, the river is polluted by heavy metals (Cu, Zn, Pb and Cd etc.). From the viewpoint of both biological and chemical analyses, Godani river is still polluted with heavy metals, because their concentrations in the river samples were very high. On the other hand, in Kakehashi river, the concentrations of heavy metals were very low and the distributions of some diatoms appeared in an unpolluted Nishimata river were observed. Therefore, Kakehashi river seems to be considerably recovered from heavy-metal pollution after closing the Ogoya mine.

Excretion levels of urinary calcium and phosphorus among the inhabitants of Cd-polluted Kakehashi River basin of Japan.

Bone damage caused by exposure to cadmium (Cd) is often seen in Cd-polluted areas, and increased excretion of calcium (Ca) in urine is thought to be an important factor affecting bone damage. In order to clarify the significance of urinary Ca excretion in bone damage, we investigated the urinary excretion levels of Ca and phosphorus (P) of inhabitants of a Cd-polluted area and compared them to those of nonexposed subjects, and explored the possible association between urinary Ca or P and beta2-microglobulin (beta2-MG). The target subjects were 3164 inhabitants of the Cd-polluted Kakehashi River basin. Ca and Ca/P measurements were significantly higher in the Cd-polluted area than in the controls. In multiple-regression analysis, where either Ca or P was used as the criterion variable, and age, Cd, and beta2-MG were used as explanatory variables, there were positive associations between Ca and Cd and beta2-MG in both sexes. Therefore, the increased excretion level of Ca was the result of renal dysfunction. Bone damage is not thought to be caused by increased excretion of Ca alone because urinary excretion levels of Ca do not differ greatly between people with and without bone damage.

APPLICATION OF PATH ANALYSIS TO URINARY FINDINGS OF CADMIUM-INDUCED RENAL DYSFUNCTION

In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, β2-microglobulin (β2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure → increase of β2-m and/or MT excretion → increase of amino-N and/or total protein excretion → increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of β2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

Preconcentration and determination of trace amounts of lead (II) as thenoyltrifluoroacetone complex with dibenzo-18-crown-6 by synergistic extraction and atomic absorption spectrometry

A new method for the preconcentration and determination of trace amounts of lead at the μg/L level in natural waters has been established based on the formation of the thenoyltrifluoroacetone (TTA) complex with dibenzo-18-crown-6 (DB18C6) by means of synergistic extraction and back-extraction combined with atomic absorption spectrometry (AAS). The effect of various factors (synergism with TTA and DB18C6, shaking time, preconcentration factor, composition of the extracted species, and foreign ions etc.) on the extraction and back-extraction of lead has been investigated in detail. The lead-TTA chelate in o-dichlorobenzene forms a stable adduct with DB18C6 as Pb(TTA)2 DB18C6. The stability constant (β) of the adduct determined by curve fitting method was log β = 4.2. The amount of lead in natural waters such as tap water (Kanazawa University) and Kakehashi river (Komatsu City) determined by the present method was found to be 0.64 ± 0.02 μg/L and 5.10 ± 0.03 μg/L, respectively.

Concentration of cadmium in rice and urinary indicators of renal dysfunction.

OBJECTIVES: (1) To examine the relation between concentrations of cadmium (Cd) in rice and urinary concentrations of indicators of renal dysfunction and the prevalence of abnormalities in urine in areas...

A case study of flood control schemes for the Kakehashi river and their socio-cultural consequences

SUMMARY This paper is concerned with a twenty-five year campaign against the relocation of the Komatsu-Tenmangu shrine as a result of the enlargement of the Kakehashi river. The Komatsu-Tenmangu shrine is an important cultural property of Japan, and was constructed by Toshitsune Maeda, the third dynasty of the Kaga clan in 1657. It is suggested that the primary reason why it took so long to settle this issue is a flaw in our social system for managing public works. It is concluded that preservation of cultural property is not always contrary to land development, and that the proposed procedures or something like them must be put into practice for the real expansion of our culture.

Mortality of inhabitants in an area polluted by cadmium: 15 year follow up.

To assess the influence of environmental exposure to cadmium (Cd) on long term outcome of inhabitants living in an area polluted by Cd. A follow up study for 15 years (from 1974-5 to 1991) was carried out on 2408 inhabitants (amounting to 95% of the target population, 1079 men and 1329 women) of the Kakehashi River basin in Ishikawa Prefecture, Japan. These inhabitants had been the subjects of the health impact survey in 1974-5 to evaluate (by measurement of urinary retinol binding protein (RBP)) renal dysfunction induced by Cd. Analysis of mortality was performed by dividing subjects into a urinary RBP positive (> or = 4 mg/l) group and RBP negative (< 4 mg/l) group. After adjustment for age with Cox's proportional hazard model, RBP > or = 4 mg/l showed a significant relation to mortality in both sexes. At this time, the mortality risk ratio of the RBP positive to negative group was 1.71 in the men and 1.42 in the women. When the SMRs according to causes of deaths in the RBP positive group were compared with those of the RBP negative group or the overall Japanese population increases of SMR for cardiovascular diseases, especially heart failure, and renal diseases were found in both sexes. These results suggest that the prognosis of the exposed inhabitants with renal tubular dysfunction is unfavourable, and these increases of mortality are due to heart failure and renal diseases.

Our Ten Years Campaign against Relocation of the Komatsu-Tenmangu Shrine accempanied with Enlargement of the Kakehashi River, Japan

Our Ten Years Campaign against Relocation of the Komatsu-Tenmangu Shrine accempanied with Enlargement of the Kakehashi River, Japan

Studies on health effects of cadmium exposure in the general environment

Effects of exposure to cadmium (Cd) in the general environment on health have been studied in several Cd-polluted areas in Japan. In this paper, results of investigations in the Kakehashi River basin, Ishikawa, a Cd-polluted area, are mainly reviewed as follows. 1. In an epidemiological study, prevalences of beta 2-microglobulinuria (beta 2-MG-uria) were 14. 3 and 18.7% in Cd-exposed men and women over 50 years of age, respectively, when a cutoff level of beta 2-MG of 1000 micrograms/g.cr. was used. These values are significantly high compared with those of nonexposed subjects. 2. Using several urinary indicators of renal function, such as alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, human intestinal alkaline phosphatase, mucoprotein and albumin, levels of all indicators were significantly higher in Cd-exposed subjects than in nonexposed subjects. Furthermore, in a 5-year follow-up study, irreversibility of Cd-induced renal damage was shown after the level of beta 2-MG rose above 1000 micrograms/g.cr. 3. Exposure to Cd caused marked osteopenia, in particular in women, as assessed by microdensitometry, and this osteopenia was significantly associated with Cd-induced renal dysfunction. Serum 1 alpha, 25 dihydroxy-vitamin D levels were lower and serum parathyroid hormone (PTH) levels were higher in Cd-exposed subjects with renal damage than in nonexposed subjects. We assume that disturbances in vitamin D and PTH metabolism may be one of the causative factors for Cd-induced bone damage. 4. The dose-response relationships between Cd exposure and renal dysfunction were assessed using several statistical methods such as simple linear regression, probit linear regression, logistic regression analysis and general linear models. The prevalences of beta 2-MG-uria or metallothioneinuria were employed as indices of health effects, while urinary Cd and total Cd intake was used as indicators of Cd exposure. As the biological threshold, urinary Cd concentrations were calculated to be 3.8-4.2 micrograms/g.cr. in men and 3.8-4.8 micrograms/g.cr. in women, and a maximum allowable intake of about 2 g Cd is considered to be a reasonable estimate for preventing Cd-induced renal dysfunction. 5. A significant association was found between urinary beta 2-MG and mortality in a 9-year follow-up study of 3178 Cd-exposed inhabitants, using Cox's proportional hazards model. Moreover, mortality rates increased in proportion to increases in the amount of urinary beta 2-MG excreted. These results suggest that the prognosis for Cd-exposed subjects with renal tubular dysfunction is unfavorable.

Prognostic Factors of Renal Dysfunction Induced by Environmental Cadmium Pollution

To assess the influence of environmental cadmium (Cd) exposure on long-term outcome, a follow-up study was conducted from 1981-1982 to March 1991 on 3178 inhabitants living in the Cd-polluted Kakehashi River basin. The standardized mortality ratios of the urinary β 2-microgloburin (β2-MG)-, protein-, and amino acid-positive subjects of both sexes and the urinary glucose-positive female subjects were higher than those of the subjects with urinary-negative findings or the general Japanese population during the observation period. After adjusting for age using Cox′s proportional hazards model, significant associations were found between mortality and urinary indices. In multiple comparisons using all of the indices, urinary protein and β2-MG in the women and urinary protein in the men were the factors most contributing to the mortality rates. In the urinary protein-negative female group as well, a significant association was found between urinary β2-MG and mortality. These results suggest that the prognosis of subjects with Cd-induced renal dysfunction is unfavorable, with the mortality fate increasing even in the Early stage of proximal tubular dysfunction. Urinary protein and urinary β2-MG are important prognostic factors, with the latter, in particular, considered to be useful as an early index predictive of premature mortality.

A study of thyroid hormone levels of inhabitants of the cadmium-polluted Kakehashi River basin

We compared thyroid hormone levels of inhabitants (19 men and 16 women) of the cadmium (Cd)-polluted Kakehashi River basin in Ishikawa Prefecture, with those of subjects (23 men and 47 women) living in a non-polluted area. In addition, we investigated the relationships between the thyroid hormone levels and indices of renal dysfunction induced by Cd exposure. The following results were obtained: 1) The free T4 level of females was significantly lower than that of controls. 2) The T3 level of inhabitants of both sexes was significantly higher than that of controls. 3) The level of free T4 among females became lower with the increases of urinary beta 2-microglobulin (beta 2-MG), urinary protein, urinary sugar, urinary amino acids and serum creatinine (Cr) levels, and with decreases of creatinine-clearance (CCr) and %TRP. 4) We could not find any relationship between the increase of T3 and the indices of renal dysfunction induced by Cd exposure in either sex.

Dose-response relationship between total cadmium intake and β 2-microglobulinuria using logistic regression analysis

The dose-response relationship between total cadmium intake and β 2-microglobulinuria was investigated using logistic regression analysis in order to consider the effect of age on this association. The target population consisted of 1850 inhabitants of the cadmium-polluted Kakehashi River basin in Ishikawa prefecture, Japan. They were divided into 58 subgroups (27 in the men and 31 in the women) by four factors of sex, age, rice cadmium concentration and length of residence in cadmium-polluted areas. Logistic regression analysis was performed for this dose-response relationship, and both age and total cadmium intake were significantly associated with β 2-microglobulinuria. It was confirmed that total cadmium intake had a significant association with β 2-microglobulinuria, independent of the aging effect.