Objectives Cadmium is widely used, leading to extensive environmental and occupational exposure. Unlike other organs, for which the harmful and carcinogenic effects of cadmium have been established, the hepatotoxicity of cadmium remains unclear. Some studies detected correlations between cadmium exposure and hepatotoxicity, but others concluded that they were not associated. Thus, we investigated the relationship between cadmium and liver damage in the general population.
Methods In total, 11 838 adult participants from National Health and Nutrition Examination Survey 1999-2015 were included. Urinary cadmium levels and the following liver function parameters were measured: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin (TB), and alkaline phosphatase (ALP). Linear and logistic regression analyses were performed to assess the associations between urinary cadmium concentrations and each liver function parameter after adjusting for age, sex, race/ethnicity, annual family income, smoking status, alcohol consumption status, physical activity, and body mass index.
Results The covariate-adjusted results of the linear regression analyses showed significant positive relationships between log-transformed urinary cadmium levels and each log-transformed liver function parameter, where beta±standard error of ALT, AST, GGT, TB, and ALP were 0.049±0.008 (p<0.001), 0.030±0.006 (p<0.001), 0.093±0.011 (p<0.001), 0.034±0.009 (p<0.001), and 0.040±0.005 (p<0.001), respectively. Logistic regression also revealed statistically significant results. The odds ratios (95% confidence intervals) of elevated ALT, AST, GGT, TB, and ALP per unit increase in log-transformed urinary cadmium concentration were 1.360 (1.210 to 1.528), 1.307 (1.149 to 1.486), 1.520 (1.357 to 1.704), 1.201 (1.003 to 1.438), and 1.568 (1.277 to 1.926), respectively.
Conclusions Chronic exposure to cadmium showed positive associations with liver damage.
Summary
Korean summary
카드뮴은 사회 전반에서 널리 쓰이고 있어 직업적인 노출은 물론 환경적인 노출이 빈번히 일어나고 있다. 본 연구는 미국 국민건강영양조사 데이터를 이용하였으며 소변 내 카드뮴의 증가는 알라닌 아미노전이효소 (ALT), 아스파테이트 아미노전이효소 (AST), 감마 글루타밀전이효소 (GGT), 총 빌리루빈, 알칼리 인산분해효소 (ALP)의 상승과 관련이 있었다. 따라서 만성적인 카드뮴 노출은 간 손상과 연관이 있다고 할 수 있다.
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Objectives Prenatal cadmium (Cd) exposure may be associated with attention-deficit/hyperactivity disorder (ADHD) in children. Therefore, the objective of this study was to examine the relationship between Cd exposure during gestation and ADHD at 6 years of age.
Methods As part of an ongoing cohort study (the Environment and Development of Children study), 479 mother-child pairs from Seoul, Korea were included for analysis between 2008 and 2011. The whole blood concentration of Cd was analyzed using atomic absorption spectrophotometry. The parents were surveyed about ADHD behaviors in their children at age 6. Multivariable linear regression models were used to investigate the relationship between prenatal exposure to Cd and ADHD at 6 years of age.
Results Increased prenatal Cd concentrations were associated with increased scores for ADHD for girls, but not for boys, at age 6. A 2-fold increase in the prenatal Cd level was significantly associated with a 22.3% (95% confidence interval, 11.6 to 34.1) increase in ADHD in girls at 6 years of age, as indicated by the linear regression model.
Conclusions Our results identified significant associations between prenatal Cd exposure and ADHD scores in 6-year-old girls.
Summary
Korean summary
이 연구의 목적은 산모와 아이의 코호트 추적조사 상 임신 중 혈중의 중금속 카드뮴 농도가 6세 아이의 주의력결핍 과잉행동 장애(ADHD)와 연관이 있는지를 확인하는 것이다. 자료원으로는 환경부와 식약처 지원 어린이 코호트인 환경노출과 어린이 성장 코호트 (EDC)를 이용하였다. 총 479쌍의 산모-아이 쌍을 대상으로 다변수 선형 회귀분석을 통해 연관성을 살펴보았다. 연구 결과, 임신 중 산모의 혈중 카드뮴 농도가 2배 증가함에 따라 6세 여아의 한국어판 주의력결핍장애(ADHD) 평점척도 (K-ARS) 점수가 22.3% 증가하는 것으로 나타났다.
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OBJECTIVES To obtain basic data on blood lead level and urinary level of arsenic and cadmium of children living near a petrochemical estate and a suburban area in Ulsan, Korea and to observe the trend of the changes in the level of these metals in these children. METHODS: The study subjects comprised 626 children living near a petrochemical estate and 299 children living in a suburban area of Ulsan. We analyzed the level of lead, arsenic and cadmium using atomic absorption spectrometer. RESULTS: The mean levels of blood lead in children living near the petrochemical estate were 5.25 microgram/dl, 5.24 microgram/dl, and 7.24 microgram/dl in the years 1997, 1999, and 2000, respectively, whereas those of children living in the suburban area were 3.81 microgram/dl, 4.75 microgram/dl, and 7.19 microgram/dl respectively. The mean levels of urinary arsenic in children living near the petrochemical estate were 4.57 microgram/g creatinine, 4.78 microgram/g creatinine, and 6.02 microgram /g creatinine in the year 1997, 1999, and 2000 respectively, whereas those of children living in suburban area were 2.35 microgram/g creatinine, 4.75 microgram/g creatinine, and 7.07 microgram/g creatinine, respectively. The mean levels of urinary cadmium in children living near the petrochemical estate were 1.15 microgram/g creatinine, 1.05 microgram/g creatinine, and 1.71 microgram/g creatinine in the year 1997, 1999, and 2000, respectively, whereas those of the children living in the suburban area were 0.74 microgram/g creatinine, 1.29 microgram/g creatinine, and 1.48 microgram/g creatinine, respectively. There were increasing trends in the level of blood lead, urinary arsenic and cadmium of children in Ulsan, and the differences in the level of these metals were disappearing between the children living in other areas year by year. CONCLUSIONS: These results suggest that the amount of exposure to lead, arsenic, and cadmium is increasing from year to year, and there is a need for periodic biological and atmospheric monitoring of these metals in Ulsan.
OBJECTIVE To verify the separate and combined effects of cadmium and nickel on blood pressure in rats. METHODS: Following the daily administration of cadmium chloride(CdCl2) and nickel chloride(NiCl2) to rats both individually and in combination with intraperitoneal injection method for one week, systolic blood pressure of the tail was measured at 1 day and 5, 10, 20, 30 days after administration. Each substance was injected into the rats with 0.1 mg/kg bw and 1.0 mg/kg bw concentration. RESULTS: After 0.1 mg/kg bw CdCl2 was injected, a statistically significant difference was found as compared with the control group(only saline) after 1, 5 and 10 days. After 0.1 mg/kg bw NiCl2 was injected, a statistically significant difference was not found compared with the control group. After 0.1 mg/kg bw CdCl2 and 0.1 mg/kg bw NiCl2 were injected simultaneously, a statistically significant difference was found as compared with the control group after 1, 5 and 10 days and compared with 0.1 mg/kg bw CdCl2 group after 5 days and as compared with 0.1 mg/kg bw NiCl2 group after 5 and 10 days. After 1.0 mg/kg bw CdCl2 was injected, a statistically significant difference was found as compared with the control group after 1, 5, 10 and 20 days. After 1.0 mg/kg bw NiCl2 was injected, a statistically significant difference was found as compared with the control group after 1 day and 5 days. After 1.0 mg/kg bw CdCl2 and 1.0 mg/kg bw NiCl2 were injected in combination, a statistically significant difference was found after 1, 5, 10, 20 and 30 days as compared with 1.0 mg/kg bw CdCl2 after 10, 20 and 30 days and as compared with 1.0 mg/kg bw NiCl2 after 5, 10, 20 and 30 days. CONCLUSION: It was found that the effect of CdCl2 on blood pressure was much more than NiCl2 and a high concentration CdCl2 and NiCl2 in combination delayed the recovery of blood pressure.
OBJECTIVES It is the objective of this study to compare hepatotoxicity of nickel chloride and cadmium chloride with each other through IPRL(Isolated Perfused Rat Liver) method. METHODS: Biochemical indicator of hepatic function such as AST(aspartate aminotransferase), ALT(alanine aminotransferase), LDH(lactate dehydrogenase) and perfusion flow rate were used as the indicator of hepatotoxicity. Oxygen consumption rate were used as viability indicator. 300(+/-50) g - weighted rats were allocated randomly to each group(0 micrometer, 50 micrometer, 200 micrometer NiCl2 and CdCl2 exposure) by 5, totally 25. After Krebs-Ringer bicarbonate buffer solution flowed into the portal vein and passed the liver cell, it flowed out of vena cava. Liver was administered with each NiCl2 and CdCl2 of each concentration and observed with buffer solution sampling time. Buffer which got out of liver was sampled and then biochemical indicator of hepatotoxicity was measured. RESULTS: AST, ALT, and LDH in buffer increased with sampling time much more in CdCl2 exposure group than NiCl2 exposure group in both 50 and 200 micrometer and statistical significance was verified with 2-way repeated ANOVA. Viability was decreased more and more in all substances during passed time. CONCLUSIONS: It is inferred that CdCl2 has stronger hepatotoxicity than NiCl2. IPRL method would be used widely for acute hepatotoxicity when considerating the benefit of it.
OBJECTIVES To evaluate the protective effects of glutathione (GSH) on the cytotoxicity of mercurial compounds(CH3HgCl, HgCl2) or cadmium chloride(CdCl2) in EMT-6 cells. METHODS: The compounds investigated were CH3HgCl, HgCl2, CdCl2, GSH, buthionine sulfoximine(BSO), L-2-oxothiazolidine-4-carboxylic acid(OTC). Cytotoxicity analysis consist of nitric oxide(NO) production, ATP production and cell viability. RESULTS: Mercurial compounds and cadmium chloride significantly decreased cell viability and the synthesis of NO and cellular ATP in EMT-6 cells. GSH was not toxic at concentrations of 0 - 1.6 mM. In the presence of GSH, mercurial compounds and cadmium did not decrease the production of ATP and nitrite in EMT-6 cells. The protective effects of GSH against the cytotoxicity of mercurial compounds and cadmium depended on the concentration of added GSH to the culture medium for EMT-6 cells. We evaluated the effects of intracellular GSH level on mercury- or cadmium-induced cytotoxicity by the pretreatment experiments. Pretreatment of GSH was not changed NO2- and ATP production, and pretreatment of BSO was decreased in dose- and time-dependent manner. Pretreatment of OTC was increased NO2- and ATP production in dose- and time-dependent manner. Because intracellular GSH level was increased by OTC pretreatment, the protective effect on mercury- and cadmium-induced cytotoxicity was increased. CONCLUSIONS: These results indicated that sulfhydryl compounds had the protective effects against mercury-induced cytotoxicity by the intracellular GSH levels.
OBJECTIVES We conducted this study to obtain basic data of urinary levels of arsenic, cadmium, and zinc in children of Ulsan industrial area and to evaluate the difference in urinary levels of these metals between industrial area and suburban area. METHODS: The study subjects were composed of 348(male 182, female 166) school children residing in industrial area and 100(male 50, female 50) school children of suburban area. We analyzed urinary levels of arsenic, cadmium, and zinc using atomic absorption spectrophotometer. RESULTS: The geometric means of urinary levels of arsenic, cadmium, and zinc of study participants were 3.69, 0.99, 282.49 microgram/L respectively. The adjusted geometric means of urinary levels of arsenic, cadmium, and zinc of study participants were 3.92, 1.05, 299.92 microgram/g creatinine respectively. CONCLUSIONS: The children residing in industrial area had the higher urinary levels of arsenic and cadmium than suburban children with statistical significance(p<0.01).
Urinary cadmium is used as a sensitive indicator for internal Cd dose, and increased excretion of N-acetyl-beta-D-glucosaminidase(NAG), beta(2)microglobulin(MG) and total protein are useful indices for renal dysfunction by chronic exposure to Cd. The target group was 184 inhabitant(82 men and 102 women) in an abandoned mine area known as exposure to low level Cd. The control group was took 160 individuals(64 men and 96 women) in Cd not-exposed area. Urinary Cd concentration was significantly higher in the target group than the control. The geometric mean of urinary Cd for male was 2.56ng/l, 2.80ng/g creatinine and 2.50ng/S.G. in the target group and 1.19ng/l, 1.36ng/g creatinine and 1.17ng/S.G. in the control. For female 2.69ng/l, 3.94ng/g creatinine and 2.63ng/S.G. in the target group and 1.27ng/l, 1.97ng/g creatinine and 1.25ng/S.G. in the control, respectively. In addition, urinary Cd of the target group had affected by the period of residence and dietary habit for the rice and the vegetables from the target area. These findings suggest the chronic exposure to Cd of the target population. Mean excretion of urinary NAG, beta(2)MG and total protein were not significant between two groups. In the target group, urinary NAG activity and total protein were significantly correlated with urinary Cd, but beta(2)MG was not related. Urinary excretion of NAG, beta(2)MG and total protein were significantly increased in 10 than in <2 of urinary Cd level. In 2~10 group of urinary Cd level, the excretion of NAG significantly increased while not showed for beta(2)MG. In present study, urinary excretion of NAG was relatively sensitive than beta(2)MG in chronic exposure population to low level Cd.
This study was carried out to assess the present level of atmospheric metals. Five metals-lead, cadmium, chromium, manganese, vanadium-were checked on the industrial(Sasang) and residental area(Daeshindong) in the city of Pusan sampling period was the year of 1986, 1990, and 1994, and the sampling time was 2 days of each site. As the result of comparison with the atmospheric standard of ASHRAE(1980) the average concentrations of lead was above the standard, the average concentrations of chromium was around the standard, and the average concentrations of cadmium and vanadium was below the standard. The average concentrations of manganese was above the standard of industrial environment. And the average concentrations of five metals was higher in the industrial area than the residental area The average concentrations of lead cadmium and chromium showed the increase tendency by the year, and the average concentrations of vanadium showed no change, and the average concentrations of manganese showed the decrease tendency. As a result of correlation analysis, lead and cadmium(r=0.31), vanadium and manganese(r=0.24), vanadium and chromium(r=0.19) showed significance.
Thirty five male Sprague-Dawley rats were treated with cadmium chloride solution ranging from 0.2 to 3.2mg CdCl2/kg by intravenous single injection. At 48 hours after administration of cadmium, total cadmium, MT bound cadmium and histopathologic finding in liver, kidney, lung, heart, testis, metallothionein in liver, kidney and total cadmium in blood were examined. Tissue cadmium concentration was highest in liver, followed by in kidney, heart, lung and testis. Cadmium bound to metallothionein(MT-Cd) and ratio of MT-Cd to total cadmium were increased in liver and kidney dependently of cadmium exposure dose, but not significantly changed in other organs. On histopathologic finding, the most susceptible organ was heart in considering cadmium exposed dose, but testis in considering cadmium concentration. Blood cadmium concentration was increased with dose-dependent pattern, and significantly correlated with tissue cadmium concentration, so that we may estimate tissue cadmium concentration by measurement of blood cadmium concentration. Metallothionein in liver and kidney was increased with dose-dependent pattern, higher in liver than in kidney, and was significantly correlated with tissue cadmium concentration. However, metallothionein induction efficiency of tissue cadmium(microgram MT/microgram Cd) was greater in liver than in kidney, and reverse to tissue concentration or exposed dose of cadmium.
A case-control study was conducted to investigate the relationship between blood cadmium, blood zinc and cadmium/zinc ratio and hypertension. Eighty-three hypertensive and seventy-seven normotensive study subjects matched for age and sex were selected from the workers who had no history of job-related cadmium exposure, in Ulsan city and it's vincinity, Korea. The blood cadmium in hypertensive group was 2.90 etag/mL, which was significantly higher than that of control group, 1.99 etag/mL(P<0.01). After stratifing for smoking and age variables, the relationship was still remained. The blood cadmium/zinc ratio in hypertensive group was 2.46, which was significantly higher than that of control group, 1.65(P<0.01). After stratifing for smoking and age variables, the relationship was still remained. There was no significant difference in blood zinc between hypertensive and control group. On multiple logistic regression analysis, the blood cadmium/zinc ratio is highly significant than blood cadmium. In conclusion, there is the possible relationship between blood cadmium level which has been known to be within normal limits and hypertension. But, further cohort studies to define the effect of cadmium on human hypertension are required.
Tolerance to several toxic effects of cadmium, including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats (A, B, C), each consisting of 16 rats, were studied and each group was divided into four subgroups (1, 2, 3, 4), 4 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), CdCl2(0.5 mg/kg, B), and ZnCl2 (13.0 mg/kg, C) during time periods of 1~6 weeks. At the end of the period, rats were challenged with CdCl2 (3.0, 6.0 and 9.0 mg/kg, ip). After giving the challenge dose, cadmium and metallothionein (MT) concentrations were determined and also observed the histologic change in liver and kidney. The concentration of cadmium in liver and also observed the increased dose-dependently to the challenge dosage. These data indicate the kidney is a major target organ of chronic cadmium poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play and important role in the nephrotoxicity observed in response to long-term exposure to cadmium. In addition, histologic examination of group A2, A3 and A4 revealed moderate to severe cadmium toxicity, evidenced by infiltration of inflammatory cells, cell swelling, pyknosis, enlarged sinusoids and necrosis in liver, and tubule cell necrosis and degeneration in kidney. However, MT concentrations in liver and kidney were increased by the pretreatment of CdCl2 and ZnCl2 and their morphological findings were not significantly changed, comparing with control group. Higher MT concentration in liver and kidney observed in the pretreated groups constitutes a plausible explanation of the protective effects of pretreatment against the cadmium toxicity after challenge dosing.
In order to exmaine the mutagenicity of cadmium dichloride the author studied the induction of sister chromatid exchanges in chinese hamster ovary K1 cells which treated with cadmium dichloride at various concentrations. The results obtained were as follows: 1. In cells treated with 10(-4) M cadmium dichloride, a small number of cells were visable but no mitosis was bound. 2. The frequencies of sister chromatid exchanges in cells treated with 10(-5) M and 10(-6) M cadmium dichloride as 10.7 +/- 1.9 and 8.3 +/- 2.1, respectively, were significantly increased for control (6.0 +/- 2.3). (p<0.05). 3. There were dose-dependent relationship between the concentration of cadmium dichloride and frequency of sister chromatid exchanges in cells treated with cadmium dichloride at concentration ranging from 10(-5) to 10(-7) M.
This study was carried out to clarify the effect of dietary calcium, casein, and suet on the accumulation of cadmium in mice. It was performed for 30 days, from April 11 to May 10 1988. 90 mice were divided into 4 experimental groups and control group with 6 mice each dietary group, and measured survival rate, body weight, and weight ratio of organ to body. The contents of cadmium in liver, kidney, spleen, muscle and skin with hair, and faces were analyzed by atomic absorption spectrophotometer after sacrifice by anesthesia. After 30 days, the survival rate of control group was 100%, but 66.7% in group IV(basal+Cd+Ca) with single dose of 100 microgram cadmium and with free-intake of water containing 50ppm cadmium, and group V(basal diet+Cd+suet) with free-intake of water containing 50ppm cadmium. The rate of weight gain in the case of single dose of 100 microgram cadmium was highest in group IV as 42.3% and lowest in group V as 26.0%, whereas in the cases of free intake group IV was highest as 24.0% and group II(basal diet+Cd) was lowest as 11.6%. The body weight, in the case of single dose of 100 microgram cadmium showed no increase until 5th day after acute poisoning. But in the case of free intake group, it showed very increase through all the breeding period. The weight ratio of organ to body were lowest in the liver of group II in both occasions. The most of cadmium administered were excreted through feces within 2 days after single dose of 100 microgram cadmium. The contents of cadmium in each group were significantly higher than those of control group. In the liver, kidney, spleen and muscle, group II showed the highest level in both occasions of 100 microgram single dose and free intake of water containing 50ppm cadmium. In the skin with hair, group II of the occasion with single dose of 100 microgram and group V with free intake showed the highest level. And the contents of cadmium in tissue were markedly higher in the occasion of free intake of water containing 50ppm cadmium. From the above results I would conclude that the addition of casein and calcium are effective in the inhibition of intension absorption of cadmium esp. by calcium.
In order to determine the contents of lead, cadmium and zinc, the tissues of the crussian carp, Carassius carassius, collected from the middle streams of the Nakdong river were examined. During the dry season from 8 to 15, March, 1987, six loci were selected to sample the fish and river water; five of them were the midstreams of the Nakdong river i.e., the vicinities of the Andong dam, the Nakdong bridge, the Waegwan bridge, Gangjung and Gaepori, the other one was the Kumho river around the Paldal bridge(see Fig.1). The microanalyses of lead and cadmium contents were undertaken by the atomic absorption spectrophotometer(Model IL-551) connected with CTF-IL 655, while that of zinc by the flame method with IL-551 only. The contents of lead and cadmium in water sampled from Gaepori distant from about 30km downward from the junction with the Kumho river were about 1.5 times higher than those from Gangjung distant about 0.5km upward from the junction, and the content of zinc from Gaepori was slightly higher than that from Gangjung. However, the contents of lead and cadmium in water sampled from Gaepori were three fifth of those from the vicinity of Paldal bridge far about 2km upperward from the junction. In the other words, the contents of lead and cadmium in the samples from the vicinity of the Paldal bridge were about 2.5 to 3 times higher than those from the Gangjung and 5 times higher than those from the Andong dam. The contents of the heavy metals in the tissues of Carassius carassius were relatively consistent to those of the aquatic environments were the fish were collected, with higher contents in the tissues of the crussian carp collected from the vicinity of Gaepori and the Paldal bridge which were so much polluted than in those from other loci in upper stream from the junction. And the contents of lead and cadmium in tissues were positively correlated with the age of the fish, however, that zinc was not. The contents of lead in bone of crussian carp from the vicinity of the Paldal bridge in the group of 0-1 year old fish were similar to those of 4-5 years old fish from Gaepori, and higher than those of 3-4 years old fish collected from the upper stream of the junction. It is likely that fishing from Gaepori and the paldal bridge is not recommended, and all the industrial producers have to pay intensive attention to the water pollution due to the sewage disposal.