Annals of Occupational and Environmental Medicine

Original Article

The effect of blood cadmium levels on hypertension in male firefighters in a metropolitan city: Ye-eun Jeon, Min Ji Kim, Insung Chung, Jea Chul Ha; Ann Occup Environ Med 2022;34:e37. Published online November 8, 2022; DOI: https://doi.org/10.35371/aoem.2022.34.e37

Abstract Abstract in Korean PDF Supplementary Material PubReader ePub

Background

This study investigated the effect of dispatch frequency on blood cadmium levels and the effect of blood cadmium levels on hypertension in male firefighters in a metropolitan city.

Methods

We conducted a retrospective longitudinal study of male firefighters who completed the regular health checkups, including a health examination survey and blood cadmium measurements. We followed them for 3 years. To investigate the effect of dispatch frequency on blood cadmium levels and the effect of blood cadmium levels on hypertension, we estimated the short-term (model 1) and long-term (model 2) effects of exposure and hypothesized a reversed causal pathway model (model 3) for sensitivity analysis. Sequential conditional mean models were fitted using generalized estimating equations, and the odds ratios (ORs) and the respective 95% confidence intervals (CIs) were calculated for hypertension for log-transformed (base 2) blood cadmium levels and quartiles.

Results

Using the lowest category of dispatch frequency as a reference, we observed that the highest category showed an increase in blood cadmium levels of 1.879 (95% CI: 0.673, 3.086) μg/dL and 0.708 (95% CI: 0.023, 1.394) μg/dL in models 2 and 3, respectively. In addition, we observed that doubling the blood cadmium level significantly increased the odds of hypertension in model 1 (OR: 1.772; 95% CI: 1.046, 3.003) and model 3 (OR: 4.288; 95% CI: 1.110, 16.554). Using the lowest quartile of blood cadmium levels as a reference, the highest quartile showed increased odds of hypertension in model 1 (OR: 2.968; 95% CI: 1.121, 7.861) and model 3 (OR: 33.468; 95% CI: 1.881, 595.500).

Conclusions

We found that dispatch frequency may affect blood cadmium levels in male firefighters, and high blood cadmium levels may influence hypertension in a dose-response manner.

대도시 남성 소방관에서의 혈중 카드뮴 농도가 고혈압에 미치는 영향
목적
본 연구에서는 대도시 남성 소방관에서 출동빈도가 혈중 카드뮴 농도에 미치는 영향과 혈중 카드뮴 수치가 고혈압에 미치는 영향을 조사하였다.
방법
남성 소방관들을 대상으로 설문조사와 혈중 카드뮴 농도 및 혈압 측정을 포함하는 건강검진을 실시하였다. 2015년부터 2017년까지 3년 간 추적하였으며, 최종 연구 대상자는 215명이었다. 출동빈도가 혈중 카드뮴 농도에 미치는 영향과 고혈압에 대한 혈중 카드뮴 농도의 영향을 조사하기 위해 단기간 노출 효과 (모델1), 장기간 노출 효과 (모델2), 역방향 노출 효과(모델3)를 가정하여 분석하였다. 순차적 조건부 평균 모델 (sequential conditional mean model)을 적용하였고, 일반화 추정 방정식 (generalized estimating equations)을 사용하여 오즈비와 95% 신뢰구간을 계산하였다.
결과
가장 낮은 사분위의 출동 빈도 그룹을 기준으로 가장 높은 사분위수 그룹은 모델 2와 모델3에서 혈중 카드뮴 수치가 각각 1.879 (95% CI 0.673-3.086) μg/dL, 0.708 (95% CI 0.023-1.394) μg/dL 증가하였다. 혈중 카드뮴 농도가 두 배로 증가할 때마다 모델 1과 3 (OR [95% CI] 1.772 [1.046–3.003], 4.288 [1.110–16.554])에서 고혈압 발생 위험이 증가한다는 것을 관찰했다. 혈중 카드뮴 농도가 가장 낮은 사분위수 그룹을 기준으로 할 때, 가장 높은 사분위수 그룹은 모델 1과 3(OR [95% CI] 2.968 [1.121–7.861], 33.468 [1.881–595.500])에서 고혈압 발생 위험이 증가하였다. 혈중 카드뮴 농도와 고혈압 발생 사이의 용량-반응 관계는 모든 시나리오에서 관찰되었다.
결론
본 연구에서는 출동 빈도가 혈중 카드뮴 농도에 영향을 미칠 수 있고, 높은 혈중 카드뮴 농도가 고혈압에 영향을 미칠 수 있다는 것을 발견했다. 다양한 연구모집단에 대해 카드뮴의 다양한 생체지표를 사용하여 추가 연구가 수행되어야 할 것이다. 또한 일반적으로 단일 중금속 노출보다는 복합 중금속 노출의 가능성이 높으므로, 향후 연구에서는 중금속의 상호작용에 대해 평가하여야 할 것이다.

Citations

Citations to this article as recorded by

Internal Flames: Metal(loid) Exposure Linked to Alteration of the Lipid Profile in Czech Male Firefighters (CELSPAC-FIREexpo Study)
Nina Pálešová, Katarína Řiháčková, Jan Kuta, Aleš Pindur, Ludmila Šebejová, Pavel Čupr
Environmental Science & Technology Letters.2024; 11(7): 679. CrossRef
Heavy metal exposure linked to metabolic syndrome in Korean male firefighters: FRESH cohort cross-sectional analysis
Jee Eun Choi, Mun-Joo Bae, Mi-Ji Kim, Sung Soo Oh, Ki Soo Park, Chan Joo Lee, Sungha Park, Sang-Baek Koh, Jaelim Cho, Changsoo Kim
Scientific Reports.2023;[Epub] CrossRef

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Research Articles

The effects of exposure to lead, cadmium and mercury on follicle-stimulating hormone levels in men and postmenopausal women: data from the Second Korean National Environmental Health Survey (2012–2014): Tae-Woo Lee, Dae Hwan Kim, Ji Young Ryu; Ann Occup Environ Med 2019;31:e21. Published online August 28, 2019; DOI: https://doi.org/10.35371/aoem.2019.31.e21

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Background

Follicle-stimulating hormone (FSH), a gonadotropin secreted by the pituitary gland, is a representative secondary sex hormone and an important indicator of reproductive function. The effects of heavy metals such as lead, cadmium, and mercury on humans have been studied, but reports on their effects on sex hormone levels are lacking. Therefore, we investigated the relationship between heavy metal exposure and FSH levels in Korean men and postmenopausal women.

Methods

A total of 4,689 adults (2,763 men and 1,926 postmenopausal women aged 50 years or over) who participated in the Second Korean National Environmental Health Survey (2012–2014) were included. We compared differences in serum FSH levels by demographic characteristics using the t-test and analysis of variance. Multiple linear regression analysis was used to determine the relationship between the blood levels of lead and mercury and the urine cadmium level, and serum FSH levels.

Results

On multiple linear regression analysis, lead exposure was positively associated with serum FSH concentrations in postmenopausal women (β = 2.929, p = 0.019). However, we found no significant association between serum FSH concentration and blood lead and mercury levels, or urine cadmium level, in men.

Conclusions

This study suggests that lead exposure can affect the FSH level in postmenopausal women. Further studies are needed to evaluate the effects of low-dose long-term exposure to heavy metals on sex hormones.

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N. B. Hryntsova, A. M. Romaniuk, V. I. Bumeister, K. O. Sikora
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Hormonal profile changes under the influence of environmental factors in children residing in the Aral environmental disaster region
Valerii O. Erkudov, Kenzhabek Umar ugli Rozumbetov, Azat T. Matchanov, Andrey P. Pugovkin, Symbat N. Nisanova, Madina A. Kalmuratova, Andrey V. Kochubeev, Sergey S. Rogozin
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Exposure to mixed chemicals elevated triiodothyronine (T3) and follicle-stimulating hormone (FSH) levels: epidemiology and in silico toxicogenomic involvement
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Association between cadmium and anti-Mullerian hormone in premenopausal women at particular ages: Yu min Lee, Hye Won Chung, Kyungah Jeong, Yeon-Ah Sung, Hyejin Lee, Shinhee Ye, Eun-Hee Ha; Ann Occup Environ Med 2018;30:44. Published online July 9, 2018; DOI: https://doi.org/10.1186/s40557-018-0255-7

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Background

Anti-Mullerian hormone (AMH) in women is secreted by granulosa cells of antral follicles. AMH appears to be a very stable marker for ovarian function. It may be used to diagnosis cases of premature ovarian failure, polycystic ovary syndrome (PCOS), and ovarian tumors. It has been suggested that cadmium exposure can reduce female fecundity. The purpose of this study was to investigate whether environmental exposure to cadmium was associated with alterations in AMH with regards to age.

Methods

In a cross-sectional study, the data of premenopausal women living in Seoul, ranging from 30 to 45 of age was collected. The study included a total of 283 women who completed serum AMH and whole blood cadmium assessments. Linear regression analyses were used in order to examine the association between cadmium and AMH. Given that age was the strongest confounder in both cadmium and AMH concentrations, we stratified subjects by 5 years old and analyzed their data.

Results

Geometric mean concentrations of blood cadmium and AMH were 0.97 μg/L and 3.02 ng/ml, respectively. Total association between cadmium and AMH was statistically significant (adjusted coefficient = − 0.34 (0.15), p = 0.02). After stratification, the only age group with a negative association between cadmium and AMH were the women raging between 30 and 35 years (adjusted coefficient = − 0.43 (0.18), p = 0.01).

Conclusions

The results of this study suggest that environmental exposure to cadmium may alter the AMH level of premenopausal women, depending on their age group.

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Environmental exposure of heavy metal (lead and cadmium) and hearing loss: data from the Korea National Health and Nutrition Examination Survey (KNHANES 2010–2013): Gu Hyeok Kang, Jun Young Uhm, Young Gon Choi, Eun Kye Kang, Soo Young Kim, Won Oh Choo, Seong Sil Chang; Ann Occup Environ Med 2018;30:22. Published online April 17, 2018; DOI: https://doi.org/10.1186/s40557-018-0237-9

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Background

Lead and cadmium have been identified as risk factors for hearing loss in animal studies, but large-scale studies targeting the general human population are rare. This study was conducted to investigate the link between heavy metal concentrations in blood and hearing impairment, using a national population-based survey.

Methods

The study participants comprised 6409 Koreans aged 20 or older, who were included in the Fifth and Sixth Korea National Health and Nutrition Examination Surveys (KNHANES 2010–2013). Hearing impairment was categorized into two types, low- and high-frequency hearing impairment, using pure tone audiometry. Low-frequency hearing impairment was defined as having a binaural average of hearing thresholds for 0.5, 1, and 2 kHz exceeding 25 dB, and high-frequency hearing impairment was defined as having a binaural average of hearing thresholds for 3, 4, and 6 kHz exceeding 25 dB. The blood levels of heavy metals (lead and cadmium) were classified into quartiles. Cross-sectional association between hearing impairment and the level of heavy metals (lead and cadmium) was examined in both sexes. Multivariate logistic regression was used to obtain adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Among men, the prevalence of low- and high- frequency hearing impairment was 13.9% and 46.7%, respectively, which was higher than the prevalence among women (11.8% and 27.0%, respectively). Regarding lead, the adjusted OR of high-frequency hearing impairment for the highest blood level group versus the lowest group was significant in both men (OR = 1.629, 95% CI = 1.161–2.287) and women (OR = 1.502, 95% CI = 1.027–2.196), after adjusting for age, body mass index, education, smoking, alcohol consumption, exercise, diagnosis of diabetes mellitus, hypertension, and noise exposure (occupational, loud, firearm noises). No links were found between blood lead levels and low-frequency hearing impairment, or between blood cadmium levels and low- or high-frequency hearing impairment in either sex.

Conclusions

The present study findings suggest that even exposure to low-level lead is a risk factor for high-frequency hearing loss. A prospective epidemiologic study should be conducted to identify the causal relationship between human health and exposure to heavy metals, and efforts to reduce heavy metal exposure in the general population should continue.

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Yeungnam University Journal of Medicine.2019; 36(2): 141. CrossRef

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The association between cadmium and lead exposure and blood pressure among workers of a smelting industry: a cross-sectional study: Hyun Chan An, Joo Hyun Sung, Jiho Lee, Chang Sun Sim, Sang Hoon Kim, Yangho Kim; Ann Occup Environ Med 2017;29:47. Published online October 4, 2017; DOI: https://doi.org/10.1186/s40557-017-0202-z

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Background

Lead and cadmium are harmful heavy metals that are used for a variety of occupational purposes. Considering their potentially hazardous effects on health, studies on the association between exposure to these two heavy metals and health disorders have been actively conducted. This study aimed to determine the association between blood lead and cadmium levels and blood pressure in workers exposed to lead and cadmium in a smelter.

Methods

Nine hundred and sixty-three male workers who worked in a smelter, and underwent medical examinations at the Ulsan University Hospital between January 1 and December 31, 2014, were selected as participants. Among them, 310 subjects whose data on height, weight, blood pressure, fasting blood glucose, lipid profile, and blood lead and cadmium levels were available and who answered the questionnaire were selected as the final participants. We investigated the drinking habit, smoking status, exercise adequacy, and family history of hypertension of these workers using formal questionnaires. A statistical analysis was conducted using Student’s t-test, analysis of variance, and linear or logistic regression.

Results

The association between blood lead and cadmium levels and blood pressure was analyzed through statistical adjustment of the risk factors of hypertension. Results showed an association between blood cadmium level and blood pressure elevation. However, blood lead level was found to be not correlated with blood pressure elevation.

Conclusions

This study shows the association between blood cadmium level and systolic blood pressure (SBP) and diastolic blood pressure (DBP) elevation.

Trial registration

IRB No. 2017–03-037. Retrospectively Registered 30 March 2017.

Citations

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Levels of blood lead and urinary cadmium in industrial complex residents in Ulsan: Sang Hoon Kim, Yang Ho Kim, Hyun Chan An, Joo Hyun Sung, Chang Sun Sim; Ann Occup Environ Med 2017;29:26. Published online June 26, 2017; DOI: https://doi.org/10.1186/s40557-017-0179-7

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Background

Populations neighboring industrial complexes are at an increased health risk, due to constant exposure to various potentially hazardous compounds released during industrial production activity. Although there are many previous studies that focus on occupational exposure to heavy metals, studies that focused on environmental exposure to lead and cadmium are relatively rare. The purpose of this study is to evaluate the extent of the environmental exposure of heavy metals in residents of industrial area.

Methods

Four areas in close proximity to the Ulsan petrochemical industrial complex and the Onsan national industrial complex were selected to be included in the exposure group, and an area remotely located from these industrial complexes was selected as the non-exposure group. Among the residents of our study areas, a total of 1573 subjects aged 20 years and older were selected and all study subjects completed a written questionnaire. Blood and urine samples were obtained from about one third of the subjects (465 subjects) who provided informed consent for biological sample collection. Total 429 subjects (320 subjects from exposure area, 109 subjects from non-exposure area) were included in final analysis.

Results

The geometric mean blood lead level among the subjects in the exposed group was 2.449 μg/dL, which was significantly higher than the non-exposure group’s level of 2.172 μg/dL. Similarly, the geometric mean urine cadmium levels between the two groups differed significantly, at 1.077 μg/g Cr. for the exposed group, and 0.709 μg/g Cr. for the non-exposure group.

In a multiple linear regression analysis to determine the relationship between blood lead level and related factors, the results showed that blood lead level had a significant positive correlation with age, the male, exposure area, and non-drinkers. In the same way, urine cadmium level was positively correlated with age, the female, exposure area, and smokers.

Conclusions

This study found that blood lead levels and urine cadmium levels were significantly higher among the residents of industrial areas than among the non-exposure area residents, which is thought to be due to the difference in environmental exposure of lead and cadmium. Furthermore, it was clear that at a low level of exposure, differences in blood lead or urine cadmium levels based on age, gender, and smoking status were greater than the differences based on area of residence. Therefore, when evaluating heavy metal levels in the body at a low level of exposure, age, gender, and smoking status must be adjusted, as they are significant confounding factors.

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Assessment of heavy radionuclides in blood samples for workers of a cement factory by X-ray fluorescence
Zakariya A. Hussein
Journal of Radiation Research and Applied Sciences.2023; 16(2): 100553. CrossRef
Urinary concentrations of heavy metals in pregnant women living near a petrochemical area according to the industrial activity
Xiruo Kou, Lucía Iglesias-Vázquez, Martí Nadal, Josep Basora, Victoria Arija
Environmental Research.2023; 235: 116677. CrossRef
The Protection of Zinc against Acute Cadmium Exposure: A Morphological and Molecular Study on a BBB In Vitro Model
Jacopo J. V. Branca, Donatello Carrino, Ferdinando Paternostro, Gabriele Morucci, Claudia Fiorillo, Claudio Nicoletti, Massimo Gulisano, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Matteo Becatti, Alessandra Pacini
Cells.2022; 11(10): 1646. CrossRef
Relationship between renal function and metal exposure of residents living near the No. 6 Naphtha Cracking Complex: A cross-sectional study
Tzu-Hsuen Yuan, Ming-Jie Jhuang, Yen-Po Yeh, Yi-Hsuan Chen, Sasha Lu, Chang-Chuan Chan
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Blood lead level and Helicobacter pylori infection in a healthy population: A cross-sectional study
Won-Ju Park, Soo-Hyeon Kim, WonYang Kang, Ji-Sung Ahn, Seunghyeon Cho, Dae-Young Lim, Suwhan Kim, Jai-Dong Moon
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Ram B. Jain
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Air pollution and urinary n-acetyl-B-glucosaminidase levels in residents living near a cement plant: Min Soo Jung, Jae Yoon Kim, Hyun Seung Lee, Chul Gab Lee, Han Soo Song; Ann Occup Environ Med 2016;28:52. Published online September 29, 2016; DOI: https://doi.org/10.1186/s40557-016-0138-8

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Background

To identify adverse renal effects due to air pollution derived from a cement plant in Korea. Urinary n-acetyl-B-glucosaminidase (U-NAG) levels in residents living near a cement plant were compared to those in a group who lived farther away from the plant.

Methods

From June to August 2013 and from August to November 2014, laboratory tests for U-NAG and heavy metal were conducted on 547 study participants. Based on the level of air pollution exposure, subjects were divided into the “less exposed group,” (LEG) which consisted of 66 persons who lived more than 5 km away from the cement plant, the “more exposed group from the rural area” (MEG-R), which consisted of 272 persons, and the “more exposed group from downtown area” (MEG-D), which consisted of 209 persons who lived within a 1 km radius of the cement plant. U-NAG levels >5.67 U/L were defined as “higher U-NAG” levels. We compared the prevalence of higher U-NAG levels and estimated the adjusted odds ratio (OR) by air pollution exposure using a chi-square test and multiple logistic regression analysis. Further, we estimated the interaction between air pollution exposure and heavy metal exposure in renal toxicity.

Results

The OR of higher U-NAG levels by MEG-D and MEG-R compared to LEG was 2.13 (95 % CI 0.86–4.96) and 4.79 (95 CI 1.65–10.01), respectively. Urinary cadmium (U-Cd), urinary mercury (U-Hg), age, occupation, hypertension, and diabetes had a significant association with higher U-NAG levels. However, blood lead (B-Pb), sex, and smoking were not associated with higher U-NAG. Especially, concurrent exposure to heavy metals (U-Hg or/and U-Cd) and air pollution had an additive adverse effect. In the group with both 4^th quartile heavy metal exposure (U-Cd or/and U-Hg) and air pollution exposure, the OR in MEG-R and MEG-D was 6.49 (95 % 1.42–29.65) and 8.12 (95 % CI 1.74–37.92), respectively, after adjustment for age, occupation, hypertension, diabetes.

Conclusions

U-NAG levels seem to be affected by air pollution exposure as well as age, hypertension, diabetes, and even low levels of cadmium and low levels of mercury. Moreover, concurrent exposure to heavy metals and air pollution can have additive cytotoxic renal effects.

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The association between blood cadmium level, frequency and amount of gejang (marinated crab) intake: Chang Yul Choi, Gun Il Park, Young Seok Byun, Man Joong Jeon, Kwang Hae Choi, Joon Sakong; Ann Occup Environ Med 2016;28:23. Published online May 14, 2016; DOI: https://doi.org/10.1186/s40557-016-0109-0

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Background

Gejang (marinated crab) is a favorite traditional food and a main source of crab intake among Koreans. The present study aimed to identify the possibility of cadmium inflow to the body through gejang; accordingly, the relationship between gejang intake frequency and amount, and blood cadmium concentrations was investigated.

Methods

Using data from the first Korea National Health and Nutrition Examination Survey in the sixth period in 2013, means and standard errors of blood cadmium concentrations in relation to gejang intake frequency and amount, as well as the monthly intake of gejang, were obtained from 1381 participants for whom data regarding blood cadmium concentration measurements was available.

Results

After adjustment for confounding factors, a gejang intake frequency of four or fewer times per week and a monthly intake of 200 cm³ or less had no significant effect on blood cadmium concentrations. However, participants with gejang intake of at least five times per week had a weighted mean cadmium concentration of 2.12 μg/L (p < 0.001), and participants who had a gejang monthly intake of more than 200 cm³ had a weighted mean cadmium concentration of 1.76 μg/L (p < 0.001).

Conclusion

These results suggest that to minimize the effect of gejang consumption on blood cadmium level, gejang intake should be limited to four or less times per week and 200 cm³ or less per month. Weekly intake of at least five times and monthly intake of more than 200 cm³ may increase blood cadmium levels.

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Karlee N. Dyck, Shabina Bashir, Graham W. Horgan, Alan A. Sneddon
Journal of Trace Elements in Medicine and Biology.2019; 52: 22. CrossRef

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Association of cadmium with diabetes in middle-aged residents of abandoned metal mines: the first health effect surveillance for residents in abandoned metal mines: Hee-seung Son, Soo-geun Kim, Byung-seong Suh, Dong-uk Park, Dae-seon Kim, Seung-do Yu, Yeong-seoub Hong, Jung-duck Park, Byung-kook Lee, Jai-dong Moon, Joon Sakong; Ann Occup Environ Med 2015;27:20. Published online August 24, 2015; DOI: https://doi.org/10.1186/s40557-015-0071-2

Abstract PDF PubReader ePub

Objective

The aim of this study was to determine the association between urinary cadmium (U-cd) concentration and diabetes in middle-aged Korean residents of abandoned mines using the first Health Effect Surveillance for Residents in Abandoned Metal mines (HESRAM).

Methods

This study was cross-sectional study conducted on 719 residents between 40–70 years in 38 abandoned metal mines in Korea. Data was collected by HESRAM from 2008 to 2011. The correlation coefficient of U-cd and fasting blood glucose, odds ratio in urinary cadmium tertiles and diabetes prevalence was analyzed according to the sex category.

Results

The correlation coefficient U-cd concentration and fasting blood glucose was 0.182 in male. Logistic regression analysis in male revealed a third tertile odds ratio of U-cd (2 μg/g creatinine < U-cd) while diabetes prevalence was 1.81 (95 % CI 1.05-3.12) with adjusted age, BMI, smoking and alcohol consumption, region, family income. On the other hand, the odds ratio for third tertile of U-cd (3 μg/g creatinine < U-cd) between diabetes prevalence in female was 1.39 (95 % CI 0.52-3.72) in addition to adjusted menopausal status.

Conclusions

Environmental exposure to cadmium in abandoned mine residents was associated with diabetes in male. Closed monitoring and periodic evaluation of the health effects of chronic environmental exposure on abandoned mines residents will be needed.

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Food and Chemical Toxicology.2017; 106: 430. CrossRef
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Alexey A. Tinkov, Tommaso Filippini, Olga P. Ajsuvakova, Jan Aaseth, Yordanka G. Gluhcheva, Juliana M. Ivanova, Geir Bjørklund, Margarita G. Skalnaya, Eugenia R. Gatiatulina, Elizaveta V. Popova, Olga N. Nemereshina, Marco Vinceti, Anatoly V. Skalny
Science of The Total Environment.2017; 601-602: 741. CrossRef
Association between cadmium exposure and diabetes mellitus risk: a prisma-compliant systematic review and meta-analysis
Ming Wu, Jukun Song, Chen Zhu, Yadong Wang, Xinhai Yin, Guanglei Huang, Ke Zhao, Jianguo Zhu, Zhuhui Duan, Lingkai Su
Oncotarget.2017; 8(68): 113129. CrossRef

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Iron Deficiency is Not Associated with Increased Blood Cadmium in Infants: Jung-Hun Park, Sangkyu Park, Yangho Kim; Ann Occup Environ Med 2014;26:3-3. Published online February 10, 2014; DOI: https://doi.org/10.1186/2052-4374-26-3

Abstract PDF PubReader ePub

Objectives

To determine whether blood cadmium concentration is elevated in iron-deficient infants.

Methods

Blood cadmium and serum ferritin concentrations, serum iron/total iron-binding capacity (Fe/TIBC) and complete blood counts were measured in 31 iron deficient and 36 control infants, aged 6–24 months. All 31 iron-deficient infants received iron supplementation for 1–6 months.

Results

Blood cadmium concentrations were measured again in 19 of the iron deficient infants after their ferritin levels returned to the normal range. The mean blood cadmium concentration did not differ significantly in iron deficient and control infants. The mean blood cadmium concentration in the 19 iron-deficient infants was not significantly altered by ferric hydroxide treatment, while their hemoglobin, ferritin, and Fe/TIBC (%) concentrations were significantly higher after than before treatment.

Conclusion

These findings indicate that iron deficiency does not increase blood cadmium concentrations in infants, in contrast with the effects of iron deficiency on manganese and lead concentrations.

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Kyoung Sook Jeong, Eunhee Ha, Ji Young Shin, Hyesook Park, Yun-Chul Hong, Mina Ha, Suejin Kim, Soo-Jeong Lee, Kyung Yeon Lee, Ja Hyeong Kim, Yangho Kim
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Original Articles

Association between Cadmium and Cognitive Function in the Elderly: Mo Yeol Kang, Soo Hun Cho, Youn Hee Leem, Jin Hee Kim, Sang Hyuk Bae, Yun Chul Hong; Korean Journal of Occupational and Environmental Medicine 2011;23(3):309-316. Published online September 30, 2011; DOI: https://doi.org/10.35371/kjoem.2011.23.3.309

Abstract PDF

OBJECTIVES
We conducted this study to investigate the relationship between the blood concentration of cadmium and cognitive function in elderly Koreans.
METHODS
This research is a part of the Korean Elderly Environmental Panel Study (KEEPS). A total of 403 subjects were enrolled and analyzed from August 2008 through August 2010. Demographic information and medical histories were obtained using a questionnaire. Blood concentration of cadmium and Mini-Mental State Examination (MMSE) with Functional Activities Questionnaire (FAQ) were evaluated for each subject.
RESULTS
The mean age of subjects was 70.67 (SD 5.18, n=403) and 72% were female. The mean blood cadmium level was 1.22 microg/dl (SD 0.56), mean MMSE score was 25.12 out of 30 and mean FAQ score was 2.03 out of 30. Using linear regression analysis to estimate the relationship between blood cadmium concentration and MMSE and FAQ, we observed a significant association between log transformed values of blood cadmium levels and MMSE (p<0.002) or FAQ (p=0.005) scores. After adjusting for age, sex, level of education, alcohol consumption and smoking habits, the relationship between blood cadmium concentration and MMSE and FAQ scores ramained statistically significant (p=0.033 and 0.029, respectively).
CONCLUSIONS
These results suggest that blood cadmium concentration is strongly associated with cognitive function and functional activity in the elderly.

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Hai Duc Nguyen, Hojin Oh, Ngoc Hong Minh Hoang, Min-Sun Kim
Scientific Reports.2021;[Epub] CrossRef
Associations between Cadmium Exposure and Taste and Smell Dysfunction: Results from the National Health and Nutrition Examination Survey (NHANES), 2011–2014
Yi Zheng, Yun Shen, Zheng Zhu, Hui Hu
International Journal of Environmental Research and Public Health.2020; 17(3): 943. CrossRef
The association between cadmium and lead exposure and blood pressure among workers of a smelting industry: a cross-sectional study
Hyun Chan An, Joo Hyun Sung, Jiho Lee, Chang Sun Sim, Sang Hoon Kim, Yangho Kim
Annals of Occupational and Environmental Medicine.2017;[Epub] CrossRef
Does cadmium exposure contribute to depressive symptoms in the elderly population?
Changwoo Han, Youn-Hee Lim, Yun-Chul Hong
Occupational and Environmental Medicine.2016; 73(4): 269. CrossRef

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The Effects of Smoking and Drinking on Blood Lead and Cadmium Levels: Data from the Fourth Korea National Health and Nutrition Examination Survey: Boram Lee, Jaehyeok Ha; Korean Journal of Occupational and Environmental Medicine 2011;23(1):31-41. Published online March 31, 2011; DOI: https://doi.org/10.35371/kjoem.2011.23.1.31

Abstract PDF

OBJECTIVES
The purpose of this study is to assess the effects of smoking and drinking on blood lead and cadmium levels based on a dose-response relationship in the general Korean adult population.
METHODS
The study population consisted of 1,901 Koreans, who took part in the 2008 Korean National Health and Nutrition Examination Survey, in which blood lead and cadmium levels were measured. Geometric mean concentrations and their 95% confidence intervals of metals in blood were estimated by analysis of covariance (ANCOVA) adjusting for demographic and lifestyle factors.
RESULTS
We observed a statistically significant dose-response relationship with daily smoking amount/alcohol intake and blood lead/cadmium levels. While daily smoking amount was more consistent with blood cadmium level (0.1-0.2 microg/L per 5 cigarettes), blood lead concentrations were higher as daily alcohol intake increased (0.1-0.2 microg/dL per 10 gram of alcohol).
CONCLUSIONS
Our findings clearly support a relationship between daily smoking amount/alcohol intake and blood lead/cadmium levels, suggesting an additional reason towards efforts to reduce smoking and drinking habits.

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Sunmi Kim
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Yosub Joo, Sangchul Roh
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Ho-Ki An, Jae-Yong Park, Hee-Jung Yoon
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Se Young Jung, Suyeon Kim, Kiheon Lee, Ju Young Kim, Woo Kyung Bae, Keehyuck Lee, Jong-Soo Han, Sarah Kim
BMJ Open.2015; 5(7): e008218. CrossRef
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Heejin Park, Kyoungho Lee, Chan-Seok Moon, Kyungsook Woo, Tack-Shin Kang, Eun-Kyung Chung, Bu-Soon Son
International Journal of Environmental Research and Public Health.2015; 12(6): 5905. CrossRef
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Ji-Young Im, Eun-Kyung Chung, Hee-Jin Park, Seungdo Yu, Bong-Ki Jang, Bu-Soon Son
Journal of Environmental Science International.2013; 22(1): 59. CrossRef
Smoking Prevalence and the Association between Smoking and Sociodemographic Factors Using the Korea National Health and Nutrition Examination Survey Data, 2008 to 2010
Sungroul Kim
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Ji-Ye Shin, Ji-Myung Kim, Yuri Kim
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The Concentration of Cadmium in Urine, and Its Role in Health-risk Assessment of Residents in the Vicinity of Abandoned Mines in Gyeongsangbuk-do, Korea: Sung Ho Yun, Chang Yoon Kim, Tae Yoon Hwang, Kyu Chang Won, Jun Young Do, Se Jin Lee, Yeong Mog Park, Kwan Soo Jun, Gae Ho Lee, Do Young Lee, Kwang Seub Park, Joon Sakong; Korean Journal of Occupational and Environmental Medicine 2010;22(3):251-261. Published online September 30, 2010; DOI: https://doi.org/10.35371/kjoem.2010.22.3.251

Abstract PDF

OBJECTIVES
This study was conducted to assess the concentration of urine cadmium and health risks of residents in the vicinity of abandoned metal mines in Gyeongsangbuk-do.
METHODS
The concentration of cadmium in the soil, water, and agricultural crops was measured in Gyeongsangbuk-do, Butdeun and Suksan, which have abandoned metal mines. We measured the concentration of cadmium in the urine of residents from the following areas: 78 from village A, 99 from village C and 147 from control areas. Other health-risk assessments were performed on each resident, such as measuring the concentration of beta2-MG and a bone density test.
RESULTS
In abandoned mine areas, the mean concentration of cadmium was higher in agricultural soil and in the crops than in that of control areas. The concentration of cadmium in the stream exceeded the guideline level. In regard to provisional tolerable daily intake (PTDI) of cadmium, the actual intake rate through crops was 33.81%, 72.74% in abandoned mine areas and 5.03%, 6.16% in control areas. Residents in abandoned mine areas, A village and C village had a geometric mean of urine Cd of 1.90 microgram/g cr and 1.45 microgram/g cr. These measurements were significantly higher than those of residents in control areas, B village and D village, 0.59 microgram/g cr and 0.65 microgram/g cr (p<0.01). Following adjustments for age, sex, smoking habit, and occupational history, the concentration of urine cadmium of residents in the Butdeun abandoned meta mine was higher by 1.62 microgram/g cr as compared with the control group (p<0.01). Residents from the Suksan abandoned metal mine also had a higher concentration by 1.07 microgram/g cr (p<0.01). A multiple linear regression analysis was performed for the factors associated with T-score, and this showed that the concentration of urine cadmium was not an influential factor.
CONCLUSIONS
Based on these measurements, areas with abandoned metal mines contaminated streams, agricultural soil, and crops of the adjacent areas, with cadmium. Because residents in the adjacent areas intake contaminated crops, their urine cadmium was increased. Despite a lack of evidence demonstrating the detrimental effect of increased urine cadmium in residents, an additional study is needed to assess the health risks of residents in the vicinity of abandoned metal mines.

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Jung-Yeon Kwon, Seungho Lee, Ulziikhishig Surenbaatar, Hyoun-Ju Lim, Byoung-Gwon Kim, Sang-Yong Eom, Yong Min Cho, Woo Jin Kim, Byeng-Chul Yu, Kwan Lee, Young-Seoub Hong
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HyeJeong Jo, GeunBae Kim, JunYoung Chang, Kwan Lee, ChulWoo Lee, BoEun Lee
International Journal of Environmental Research and Public Health.2021; 18(4): 1731. CrossRef
A study on the correlation between upper airway diseases and urinary heavy metals concentration in household residents
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Comparative Analysis of Offensive Odorants in Urine Samples in Relation to Sample Treatment Conditions
Min-Hee Lee, Yong-Hyun Kim, Sang-Hee Jo, Si-On Choi, Inyoung Sa, Ki-Hyun Kim
Journal of Korean Society for Atmospheric Environment.2014; 30(5): 492. CrossRef

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Blood and Urinary Cadmium Concentration of Residents around Abandoned Metal Mines in Busan and Gyeongsangnam-do: Hyo Jun Kim, Byoung Gwon Kim, Dae Seon Kim, Jeong Wook Seo, Byeng Chul Yu, Young Wook Kim, Young Seoub Hong; Korean Journal of Occupational and Environmental Medicine 2010;22(1):1-10. Published online March 31, 2010; DOI: https://doi.org/10.35371/kjoem.2010.22.1.1

Abstract PDF

OBJECTIVES
To evaluate the blood and urinary cadmium concentration levels of around abandoned metal mines in comparison with a control group.
METHODS
Blood and urinary cadmium concentration levels were analyzed through investigations of the dietary habits and dietary water of subjects living near abandoned metal mines (exposure group) (n=190) in comparison with those living in designated control areas (control group) (n=256).
RESULTS
The blood cadmium (1.93 microgram/l) and urinary cadmium (2.41 microgram/g cr) concentrations of the exposure group were significantly higher than those of the control group (blood cadmium: 1.19 microgram/l, urinary cadmium: 1.94 microgram/g cr). Both concentrations were significantly higher in vegetarians in both groups.
CONCLUSIONS
The exposure group had higher blood and urinary cadmium concentrations than the control group. We attributed the elevated blood and urine cadmium levels in the abandoned mine residents to the influence of the abandoned mine sites.

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Association between levels of exposure to heavy metals and renal function indicators of residents in environmentally vulnerable areas
Jung-Yeon Kwon, Seungho Lee, Ulziikhishig Surenbaatar, Hyoun-Ju Lim, Byoung-Gwon Kim, Sang-Yong Eom, Yong Min Cho, Woo Jin Kim, Byeng-Chul Yu, Kwan Lee, Young-Seoub Hong
Scientific Reports.2023;[Epub] CrossRef
Health Effect and Blood Lead Concentration among Residents in Gwangyang and Yeosu
Heejin Park, Myung-Kyu Park, Tack-Shin Kang, Geun-Bae Kim, Jong-Wha Lee, Bong-Ki Jang, Bu-Soon Son
Korean Journal of Environmental Health Sciences.2016; 42(3): 205. CrossRef
Urinary Cadmium Concentration of Residents around Industrial Complex in Gwangyang and Yeosu
Heejin Park, Tack-Shin Kang, Jong-Dae Lee, Geun-Bae Kim, Seungdo Yu, Bong-Ki Jang, Jong-Wha Lee, Bu-Soon Son
Journal of Korean Society of Occupational and Environmental Hygiene.2015; 25(3): 338. CrossRef
Relationship between Urine Cadmium and Bone Mineral Density of Residents Around Abandoned Metal Mines
Kyung-Sick Jung, Nam-Soo Kim, Seung-Chul Ahn, Byung-Kook Lee
Korean Journal of Environmental Health Sciences.2012; 38(4): 323. CrossRef
Relationship between Heavy Metal Concentrations in the Soil with the Blood and Urine of Residents around Abandoned Metal Mines
Bong-Ki Jang, Sang-Il Park, Nam-Soo Kim, Kyung-Sick Jung, Byung-Kook Lee, Jong-Wha Lee
Korean Journal of Environmental Health Sciences.2011; 37(5): 348. CrossRef

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Blood Pb, Urine Cd and Health Assessment of Residents in the Vicinity of Abandoned Mines in Gyeongsangbuk-do: Jong Hak Chung, Pock Soo Kang, Chang Yoon Kim, Kyung Soo Lee, Tae Yoon Hwang, Gyu Tae Kim, Jong Seo Park, Si Young Park, Dae Seop Kim, Ou Taek Lim, Joon Sakong; Korean Journal of Occupational and Environmental Medicine 2005;17(3):225-237. Published online September 30, 2005; DOI: https://doi.org/10.35371/kjoem.2005.17.3.225

Abstract PDF

OBJECTIVES
The objective of this health assessment is to evaluate the health risks that may result from exposure to abandoned mine tailings in Gyeongsangbuk-do. The tailings are remnants from an earlier flotation mill and mining operation that was in business from the early 1930's until 1970.
METHODS
The soil, stream water, and drinking water in and around three abandoned mine areas, Soochul, Gumjang, Darock, and three control areas located in Gyeongsangbuk-do were analyzed for level of Cd, Pb, Cu, As, and Hg. Potential chronic health effects were evaluated by interview and medical examination.
RESULTS
Some soil and stream samples exceeded the Korean standard for soil contamination in farmland and the Korean standard of water contamination in streams respectively. Blood lead (5.37 microgram/dl) and urine cadmium (2.79 microgram/g Cr) levels of the residents in the vicinity of the abandoned mine sites were significantly higher than of the residents in the control areas (blood lead, 4.34 microgram/dl; urine cadmium, 1.62 microgram/g Cr). There were no significant differences between the mining and control areas in terms of blood pressure, Hb, BUN, creatinine, SGOT, SGPT, fasting blood sugar, and the prevalence of potential chronic diseases.
CONCLUSIONS
The results of the assessment suggested that the three abandoned mine sites do not pose an apparent health risk to nearby residents. Nevertheless, the elevated blood lead and urine cadmium levels in the residents of the abandoned mine site suggested that it might be an important source of heavy metals contamination. Therefore, a nationwide evaluation program is needed to assess the potential health risks of residents living in the vicinity of abandoned mine sites.

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Exposure factors of cadmium for residents in an abandoned metal mine area in Korea
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Seok-Jun Yoon, Hyeong-Su Kim, Jongsik Ha, Eun-Jung Kim
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Blood Cadmium Concentration of Residents Living near Abandoned Metal Mines in Korea
Young-Seoub Hong, Byung-Kook Lee, Jung-Duck Park, Joon Sakong, Jae-Wook Choi, Jai-Dong Moon, Dae-Seon Kim, Byoung-Gwon Kim
Journal of Korean Medical Science.2014; 29(5): 633. CrossRef
Association of arsenic levels in soil and water with urinary arsenic concentration of residents in the vicinity of closed metal mines
YongMin Cho, SungChul Seo, Seung-Hyun Choi, SeungKil Lee, KyungHee Kim, Hae-Joon Kim, Jae-Wook Choi
International Journal of Hygiene and Environmental Health.2013; 216(3): 255. CrossRef
Relationship between Urine Cadmium and Bone Mineral Density of Residents Around Abandoned Metal Mines
Kyung-Sick Jung, Nam-Soo Kim, Seung-Chul Ahn, Byung-Kook Lee
Korean Journal of Environmental Health Sciences.2012; 38(4): 323. CrossRef
The association of heavy metals in blood, fish consumption frequency, and risk of cardiovascular diseases among Korean adults: The Korean National Health and Nutrition Examination Survey (2008-2010)
Ji-Ye Shin, Ji-Myung Kim, Yuri Kim
Korean Journal of Nutrition.2012; 45(4): 347. CrossRef
Blood lead levels of residents living around 350 abandoned metal mines in Korea
Nam-Soo Kim, Joon Sakong, Jae-Wook Choi, Young-Seoub Hong, Jai-Dong Moon, Byung-Kook Lee
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Korean Journal of Environmental Health Sciences.2011; 37(5): 335. CrossRef
Relationship between Heavy Metal Concentrations in the Soil with the Blood and Urine of Residents around Abandoned Metal Mines
Bong-Ki Jang, Sang-Il Park, Nam-Soo Kim, Kyung-Sick Jung, Byung-Kook Lee, Jong-Wha Lee
Korean Journal of Environmental Health Sciences.2011; 37(5): 348. CrossRef
Blood Lead Level in Populations Resident in Some Abandoned Mine Area
Sun-Ho Song, Sang-Yong Eom, Yong-Dae Kim, Heon Kim, Jang-Soo Hong
Journal of Environmental Science International.2010; 19(4): 527. CrossRef
Investigation on Health Effects of an Abandoned Metal Mine
Soyeon Kim, Ho-Jang Kwon, Hae-Kwan Cheong, Kyungho Choi, Jae-Yeon Jang, Woo-Chul Jeong, Dae-Seon Kim, Seungdo Yu, Young-Wook Kim, Kwang-Young Lee, Seoung-Oh Yang, Ik Jae Jhung, Won-Ho Yang, Yun-Chul Hong
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Effects of Cadmium on Placental Function and Reproduction in Rats: Jin Hong Ahn, Kwang Soo Ko, Chae Kwan Lee, Deog Hwan Moon, Byung Chul Son, Dae Hwan Kim, Chang Hee Lee, Hwi Dong Kim, Jung Won Kim, Jong Eun Kim, Jin Ho Chun, Chae Un Lee; Korean Journal of Occupational and Environmental Medicine 2004;16(3):236-249. Published online September 30, 2004; DOI: https://doi.org/10.35371/kjoem.2004.16.3.236

Abstract PDF: OBJECTIVES
This study investigated the toxic effects of cadmium on placental function and reproduction in rats. For this study, the mRNA levels of the placental prolactin-growth hormone (PRL-GH) gene family, placental trophoblast cell frequemcy and reproductive data were analyzed.
METHODS
Pregnant F344 Fisher rats (200 g+/-23 g) were intraperitoneally injected with 0, 0.5, and 5.0 mg/kg B.W/day of cadmium (CdCl2) dissolved in saline from days 7-11 or 16-20 of pregnancy, and were sacrificed at days 11 or 20, respectively. The mRNA levels were analyzed by Northern blot hybridization and reverse transcription-polymerase chain reaction. The hormone concentration was analyzed by radioimmunoassay and the frequemcy of the placental trophoblast cells was observed by histochemical study. Reproductive data were surveyed at day 20 of the pregnancy and after the births. Statistical analysis was carried out using the SAS program (version 8.1).
RESULTS
The mRNA levels of the PRL-GH gene family were reduced dose dependently by cadmium. The mRNA levels of Pit-1a and -b isotype genes were also reduced by cadmium. The hormone concentration of PL-Iv and -II was decreased by cadmium. During the second half of pregnancy (days 11-21), a high dose of cadmium exposure significantly reduced the frequency of spongiotrophoblast and trophoblast giant cells that secrete the PRL-GH hormones. In the last stage of pregnancy (day 20), a high dose of cadmium exposure induced the apoptosis of spon-giotrophoblast cells in the junctional zone of the placenta. Reproductive data such as placental and infant weight, number of live fetuses were decreased, and number of resorptions and dead fetuses, post-implantation loss were increased significantly in the cadmium exposed group compared with the control.
CONCLUSIONS
Cadmium disrupts the functions of the placenta and these effects leads to reproductive disorders in rats.

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Cadmium-induced Apoptosis in HL-60 Cells Via Signal Transduction: Nam Song Kim, Gyung Jae Oh, Kwang Ho Cho, Mee Sun Hyun, Yoo Chang Kim, Tae Ho Sung, Jung Ho Youm, Keun Sang Kwon; Korean Journal of Occupational and Environmental Medicine 2002;14(1):1-12. Published online March 31, 2002; DOI: https://doi.org/10.35371/kjoem.2002.14.1.1

Abstract PDF

OBJECTIVES
Apoptosis is a process of active cell death, distinct from necrosis and characterized by specific morphological and biochemical features. Apoptosis induced by metals and metal-related deleterious conditions has only recently been studied. Although the toxic effects of heavy metals are well described, little is known about the mechanism of apoptosis via cadmium toxicity. Therefore, this study is designed to define the induction mechanism of apoptosis by which cadmium exerts its cytotoxic effect on human promyelocytic leukemic HL-60 cells. The cytotoxic effects of cadmium on HL-60 cells are studied in regards to apoptotic signal transduction pathways.
METHODS
The mode of cadmium-induced apoptosis was investigated in HL-60 cells. HL-60 cells were treated with various concentrations of cadmium and antioxidants after which the viability of the cells were measured by MTT assay. The morphological features of cadmium- induced apoptosis were evaluated by fluoromicroscopy and the DNA fragmentation was analyzed using 1.5% agarose gel electrophorosis. Kinase activity was assayed by autoradiography and activity of NF-kappaB and nuclear proteins were measured by EMSA.
RESULTS
Cadmium (125 microM) induces the characteristic morphological features of apoptosis, which are characterized by a shrinkage of the cytoplasm and a condensation of chromatin. In addition, cadmium induced the ladder pattern of DNA fragmentation. Antioxidants(Sodium nitroprusside, glutathione and N-acethylcysteine), which were not toxic to the cells, did not suppress apoptosis induced by cadmium. Cadmium enhances the expression of several classes of genes at elevated cytotoxic concentrations. Poly(ADP-ribose) polymerase(PARP) was predominantly in the fragmented form when doses of 125 microM were used. Since PARP is cleaved by CPP32 (caspase-3), we next determined if cadmium was capable of effecting changes in CPP32 activity. The results of these experiments showed that cadmium increased caspase-3 activity in a time dependent manner, corresponding to the time of appearance of fragmented PARP. Cadmium also increased the phosphotransferase activities of c-JUN N-terminal kinase (JNK). Furthermore, cadmium increased the activation of transcriptional factors including the activation of protein-1 (AP-1) and NF-kappaB .
CONCLUSIONS
These results suggest that cadmium induces the apoptotic death of HL-60 cells via the activation of a DEVD-specific caspase, JNK and transcriptional factors such as AP-1 and NF-kappaB .

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The association between blood cadmium level, frequency and amount of gejang (marinated crab) intake
Chang Yul Choi, Gun Il Park, Young Seok Byun, Man Joong Jeon, Kwang Hae Choi, Joon Sakong
Annals of Occupational and Environmental Medicine.2016;[Epub] CrossRef

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Changes of Superoxide Dismutase Activity in Cadmium-induced Acute Nephrotoxicity of Rats: Soo Jin Lee, Hyun Chul Koh, Chung Yill Park; Korean Journal of Occupational and Environmental Medicine 2001;13(4):393-400. Published online December 31, 2001; DOI: https://doi.org/10.35371/kjoem.2001.13.4.393

Abstract PDF: OBJECTIVES
To investigate the role of superoxide dismutase(SOD) in the pathogenesis of cadmium-induced acute nephrotoxicity.
METHODS
Rats treated with a single intraperitoneal injection of cadmium(as CdCl2, 1 mg/kg) were included in the cadmium-treated group; the control group comprised untreated rats. 24-hour urine samples were obtained prior to sacrifice on days 1, 2, 4, 8 and 16(N = 10 per group), respectively. The activity of SOD and concentration of cadmium were measured in the homogenates of the renal cortex. Nephrotoxicity indices such as N-acetyl-beta-D-glucosaminidase(NAG) activity, total protein, and 24-hour urine volume, and the cadmium concentrations in the urine were measured.
RESULTS
The cadmium injection caused a significant increase of cadmium concentration in the renal cortex on days 1 and 2, and in the urine on days 1, 2 and 4. The NAG activities and total protein concentrations in urine were significantly increased on days 1, 2 and 4, and on days 1, 4 and 8, respectively. The peak values of NAG activity and total protein in urine were observed on days 1 and 4, respectively. A significant decrease of 24- hour urinary volume was induced on day 1. Renal SOD activity was significantly inhibited on day 1. Finally, on day 8, SOD activity was significantly increased and all nephrotoxicity indices except urinary total protein returned to the control level.
CONCLUSIONS
These results suggest that cadmium induces initial depression of SOD enzyme activities in the renal cortex followed by a later activation, and that the initial depression of this enzyme plays an important role in mediating the proteinuric injury of cadmium-induced acute nephrotoxicity.

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Induction of Apoptosis by Heavy Metals in HL-60 Cells: Nam Song Kim, Tae Ho Seong, Kwang Ho Cho, Jung Ho Youm, Dai Ha Koh; Korean Journal of Occupational and Environmental Medicine 1999;11(4):557-568. Published online December 31, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.4.557

Abstract PDF: OBJECTIVES
Apotosis induced by metals and metal-related deleterious conditions has only recently been studied. Although the toxic effects of heavy metal are well described, little is known about the mechanism of apoptosis by heavy metal toxicity. This study is designed to define the induction of apoptosis by which heavy metals exert the cytotoxic effect on human promyelocytic leukemic HL-60 cells.
Methods
After the incubation with CdC12, Na2SeO3 and HgC12, viability of the cells were measured by MTT assay. DNA fragmentation was analyzed by electrophoresis. For measurement of caspase 1 and 3-like proteases activity, the whole lysates were subjected to the proteolytic cleavage and then measured by using fluorospectrometry. c-JUN N-terminal kinase (JNK) activity was detected by an in vitro kinase assay. Transcriptional activities of activating protein-1 (AP-1) and nuclear factor-kB (NF-kB) were measured by elec trophoresis mobility shift assay (EMSA).
RESULTS
Cadmium (l2OuiN/I) and selenium (30,iM) induce the apoptosis of HL-60 cells which is characterized by the ladder pattern of DNA fragmentation. Cadmium and selenium induce the activation of caspase-3 in a time dependent manner. They also increase the phosphotransferase activities of c-JUN N-terminal kinase (JNK) in cadmium and selenium treated HL-60 cells. Furthermore, cadmium and selenium increase the activation of transcriptional factors including AP-i and NF-kB.
CONCLUSIONS
These results suggest that cadmium and selenium induce the apoptotic death of HL-60 cells via activation of DEVD-specific caspase, JNK and transcriptional factors such as AP-1 and NF-kB.

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Reference Value of Cadmium in Myocardium in Korean: Jung Duck Park, Heon Bang Lim, Byung Sun Choi, Il Hoon Kweon, Sang Yeon Lee, Eun Yong Kang, Yeon Pyo Hong, Im Won Chang; Korean Journal of Occupational and Environmental Medicine 1999;11(1):24-32. Published online March 31, 1999; DOI: https://doi.org/10.35371/kjoem.1999.11.1.24

Abstract PDF: Cadmium(Cd) is an ubiquitous, toxic and non-essential metal which is controversial about the association with a cardiovascular disease. In this study, we investigated the reference level of Cd in myocardium in Korean general population. The level of Cd and zinc(Zn) concentration in myocardium of 252 cases of "sudden and unexpected death" autopsies(male 172, female 60) aged 0 to 87 years was analyzed. The concentration of Cd and Zn was determined with atomic absorption spectrophotometer(Perkin-Elmer Model 5100) by flameless and flame method, respectively. The content of Cd and Zn in myocardium showed the log-normal distribution rather than normal distribution. Geometric mean concentration of Cd was 0.19 microgram/g wet weight in myocardium. The level of Cd in myocardium was not significantly different between male(0. 18 microgram/g wet weight) and female(0.22 microgram/g wet weight). Geometric mean concentration of Zn in myocardium was 25.25 microgram/g wet weight. The level of Zn between male(25.13 microgram/g wet weight) and female(25.57 microgram/g wet weight) was not different. The deposit of Cd in myocardium was age-dependent of biphasic pattern, but the Zn level by age was not significantly different. The level of Cd in myocardium was increased to the fifties of age, thereafter a leveling-off was shown. The regression model of Cd deposit in myocardium by age was predicted as the following equation Log Heart-Cd = -1.2726 + 0.0234 Age - 0.0002 Age2. The maximum Cd deposit in myocardium was estimated to be 0.26 microgram/g wet weight at the age of 58.5 in Korean general population. In addition, the total Cd burden in heart by age was predicted as a following equation Total Cd burden in Heart = -10.165 + 2.891 Age - 0.0258 Age2. The maximum heart burden of Cd was estimated to be 70.7 microgram at age of 55.4. The positive correlation between Cd and Zn was observed in myocardium. The linear regression equation was Log Heart-Zn = 1.4195 +/- 0.0262- Log Heart-Cd.

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Concentration of Lead, Cadmium, and Mercury in Scalp Hair, Cerebellum, Cerebrum, Heart, Kidney, Liver, Lung and Spleen from Autopsy Subjects : Relationship between Scalp Hair and Internal Organs: Jong Hak Chung, Chang Yoon Kim, Joon Sakong, Joong Jung Lee, Man Joong Jeon, Seong Kuk Lee, Jeung Sik Kwak, Sung Hwa Park; Korean Journal of Occupational and Environmental Medicine 1998;10(4):571-586. Published online December 31, 1998; DOI: https://doi.org/10.35371/kjoem.1998.10.4.571

Abstract PDF

This study was conducted to measure the lead, cadmium and mercury levels in the scalp hair, cerebellum, cerebrum, heart, kidney, liver, lung, and spleen of the 60 Korean autopsy subjects and assess the relationship among those samples. The mean lead level in the scalp hair was 12.29+/-12.51 microgram/g and no significant difference was detected in lead concentrations between the two sexes. Among the internal organ tissues the cerebrum contained the highest level of lead. This is followed by the cerebellum, spleen and liver respectively. After which the kidney and lung showed a close similarity at relatively low concentrations and the heart contained the lowest concentration. There was also no significant variation found between sexes in a comparison of lead in the internal organ tissues. The concentrations of cadmium in kidney were 127.33+/-89.36 microgram/g and considerably higher than those in the other internal organs. The liver contained the next highest level of cadmium. In both sexes, the consistent difference was noted in the cadmium concentrations of the kidney, heart and spleen. Yet female cadmium level was higher than the male's. The concentrations of mercury in the kidney and liver were 1.26+/-2.89 microgram/g, 0.59+/-0.54 microgram/g and considerably higher than those in the other internal organs. The mean mercury level in the scalp hair was 1.29+/-0.64 microgram/g and no marked difference was noted in both sexes. The lead concentration in the spleen increased with advancing age, though not statistically significance, and most of the internal organ tissues that were examined showed no evidence of increased lead concentration with age. The kidney, cerebrum, spleen and cerebellum showed increased cadmium concentrations with age. Also as well as the internal organ tissues that were examined showed no evidence of increased mercury concentration with age. The lead concentrations in the liver and lung were higher in the urban area than in the rural area, but the lead concentration in the kidney was higher in the rural area. No difference was noted in tissue cadmium and mercury concentrations as to the area of residence either. The physical workers had greater concentrations of lead in cerebellum than did housewives or the unemployed. Yet no difference was noted in the other tissues between the two groups. In the cerebellum, cerebrum, heart, and spleen, the physical workers had greater concentrations of cadmium than students or mental workers. Also physical workers had greater concentrations of cadmium in lung than housewives or the unemployed. In contrast to lead and cadmium, both the housewives and the unemployed had higher concentrations of mercury in cerebellum and cerebrum than physical workers, but there was no difference was noted in the other tissues between the two groups. In the lead concentration, there was no statistically significant correlation between the scalp hair and examined internal organ tissues. There was a close relationship between lead levels in cerebellum and cerebrum (r=0.465, p<0.01), as well as a relationship between the cerebellum and the kidney(r=0.300, p<0.05). There was no statistically significant correlation between the cadmium levels in the scalp hair and in the examined internal organ tissues. Positive correlations were found between the cadmium concentrations in the cerebellum and the cerebrum(r=0.5543, p<0.01), heart(r=0.480, p<0.01), kidney(r=0.376, p<0.01) and spleen(r=0.408, p<0.01). Also positive correlation was found between in the cerebrum and the heart(r=0.377, p<0.01), kidney(r=0.484, p<0.01), liver(r=0.265, p<0.05), lung(r=0.458, p<0.01) and spleen (r=0.483, p<0.01). There was also no statistically significant correlation between the mercury levels in the scalp hair and in the examined internal organ tissues. Positive correlation was found between the mercury concentrations in the cerebellum and cerebrum(r=0.760, p<0.01), heart(r=0.270, p<0.05), liver(r=0.425, p<0.01), lung (r=0.488, p<0.01) and spleen (r=0.534, p<0.01), and also positive correlation was found between in the cerebrum and heart(r=0.376, p<0.01), liver(r=0.350, p<0.01), lung(r=0.554, p<0.01) and spleen (r=0.489, p<0.01). Various epidemiological studies reported usefulness and reliability of using scalp hair as a monitor of a environmental pollutants. In this study, there was statistically significant correlation of lead, cadmium and mercury levels in most of the tissues that were examined, but there was no statistically significant correlation between the lead, cadmium and mercury levels in the scalp hair and most of examined internal organ tissues. The findings of this study would suggest that it is still uncertain to using scalp hair as a biological monitoring.

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Human Exposure to Metals: Levels in Autopsy Tissues of Individuals Living Near a Hazardous Waste Incinerator
Montse Mari, Martí Nadal, Marta Schuhmacher, Eneko Barbería, Francisco García, José L. Domingo
Biological Trace Element Research.2014; 159(1-3): 15. CrossRef
Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population
Zeliha Kayaaltı, Görkem Mergen, Tülin Söylemezoğlu
Toxicology and Applied Pharmacology.2010; 245(2): 252. CrossRef

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Effect of Cadmium on Cytokine Gene Expression in a Human Monocytic Cell Line, THP-1: Mi Jung Kang, Seon Hee Yang, In Sung Chung, Dong Hoon Shin, Kwan Kyu Park, Suk Kwon Suh; Korean Journal of Occupational and Environmental Medicine 1997;9(2):320-331. Published online June 30, 1997; DOI: https://doi.org/10.35371/kjoem.1997.9.2.320

Abstract PDF: Cadmium, a potent toxic metal, poses a serious environmental threat but the mechanism of its toxicity remains unclear. Also, cadmium is a known immunotoxic agent in animal studies and induces pathophysiological effects by modulating components of immune system. Cytokines are being increasingly recognized as essential mediators of normal and pathologic immune response. Cells of mononuclear phagocytic system are strategically located at portals of entry in humans and therefore may be particularly at risk for cadmium exposure through contaminated air, food, and drinking water. In the present study, we investigated the effect of cadmium cytotoxicity for the monocyte and expression of cytokine gene in the control and cadmium treated human monocytic cell lines using RT-PCR method. The results showed that cadmium inhibited cell proliferation at 0.1mM cadmium treated cells for 24 hours. The TNF-alpha mRNA was expressed in both control and cadmium treated cells but not IL-6 and IL-1 beta The mRNA levels of TNF-alpha were examined during 24 hours culture period, at different time points. The expression of TNF-alpha mRNA increased in both 0.01mM and 0.1mM cadmium treated cells, but did not show dose-response relationship. According to cadmium treated duration, expression of TNF-alpha mRNA was more decreases in 24 hours than 6 hours. The decreased levels of mRNA of TNF-alpha that cadmium suppresses iris production at the transcription level.

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Biological Indices for Early Detection of Cadmium Poisoning: Significance of Urinary Metallothionein: Jung Duck Park, Yeon Pyo Hong, Im Won Chang; Korean Journal of Occupational and Environmental Medicine 1997;9(2):230-243. Published online June 30, 1997; DOI: https://doi.org/10.35371/kjoem.1997.9.2.230

Abstract PDF: Metallothionein(MT) is a low molecular weight protein that is induced as a defence mechanism for cadmium (Cd) toxicity. In present study, urinary MT was determined using a competitive ELISA in Cd-exposed rats. In addition, measures the urinary, blood and renal Cd concentration and the urinary excretion of total protein, beta 2-microglobulin (MG) and N-acetyl-beta-D-glucosaminidase(NAG) at 1, 3, 7, 14, 28 days after Cd injection in Cd-exposed rats with dosers of 0.8 and 1.6 mg Cd/kg body weight respectively. The urinary, blood and renal Cd were specific for Cd-exposure, that increased in proportional to dose of Cd. The urinary and blood Cd tended to slightly decrease, while renal Cd tended to increase by lapse of time after Cd exposure. this finding indicates that renal Cd is more specific than urinary and blood Cd for Cd exposure. The urinary excretion of MT showed a statistically significant increase in Cd exposed rats(0.8 and 1.6 no Cd/kg body weight). The increase of urinary excretion of MT was more evident at 7, 14, 28 lays after Cd exposure than the changes of urinary excretion of total protein, beta-MG and NAG. The Pearson's correlation coefficients between urinary Cd and urinary MT, beta-MG, NAG and total protein were 0.4344, 0.3727, 0.3307 and 0.2099, respectively. These findings indicate that the urinary MT is more sensitive and specific than total protein, beta-MG and NAG for Cd exposure. The present results suggest that the urinary MT, using a simple and rapid competitive ELISA, is a valuable index as screening test in epidemiologic study for Cd exposed group.

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Changes of Renal Cadmium Accumulation Levels and Urinary Cadmium Excretion Levels Induced by Long-term Cadmium Exposure in Rats: In Soon Song, Yong Chae Cho, Soo Young Kim, Am Park, Kyung Sun Son, Tae Yong Lee, Dong Bae Lee; Korean Journal of Occupational and Environmental Medicine 1997;9(1):109-121. Published online February 28, 1997; DOI: https://doi.org/10.35371/kjoem.1997.9.1.109

Abstract PDF: This study was performed to compare the cadmium accumulation levels in kidney with urinary cadmium excretion levels according to the duration of cadmium exposure in rats. Total 120 male rats, 6 weeks of age, were administered 0.5 mg/day of Cd to subcutaneously, intraperitoneally and orally 6 times per week for 12 weeks. The animals were sacrificed in the 1st day of 2nd, 4th, 6th, 8th, 10th and 12th week after beginning of cadmium administrations. Body weight, hematologic values, enzyme activities, renal Cd levels, urinary Cd and proteins were calculated and each value was compared according to the Cd administration routers. The Cd accumulation levels in the kidney of rats increased remarkably for 6-8th weeks which were experimented and urinary Cd excretion levels and urinary protein levels showed the tendency of increasing with the Cd accumulations in kidneys, especially in the subcutaneous injected rats. On the other hand, there was a significant positive correlation among the total Cd administration, the Cd accumulation in the kidneys, the urinary Cd excretion and protein.

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Biological Index for Cadmium Exposure: Assay of Metallothionein by Competitive ELISA: Jung Duck Park, Woo Suk Lee, Yoon Kong, Yeon Pyo Hong, Im Won Chang; Korean Journal of Occupational and Environmental Medicine 1996;8(2):258-271. Published online September 30, 1996; DOI: https://doi.org/10.35371/kjoem.1996.8.2.258

Abstract PDF

Metallothionein (MT) is a cadmium binding protein that played major' roles in protective mechanism for cadmium toxicity. In the present study, competitive ELISA was established to assay the MT expression utilizing monospecific antibody which was generated against MT-L A total of 10 Sprague-Dawley rats was injected with CdCl2 for two weeks to induce MT. The cytosolic fraction of rat liver was obtained by differential centrifugation. Two major MT isozymes (MT-I & MT-II) at ca. 10 kDa were purified by Sephadex G-75 gel filtration followed by DEAE-Trisacryl-M anion exchange column chromatogra-phy, respectively. Two rabbits were immunized 4 times consecutively with the conjugate of purified MT-L The sera were collected by heart puncture. When immunoblot was carried out, the immunized rabbit sera (anti-MT-I) exhibited specific immunoreactive band at MT-I while showed any cross reactions neither with MT-II nor with other cytosolic proteins.. By chequerboard titration using the monospecific antibody, the competitive ELISA was established. The dose-dependent relationship was observed between anti-MT-I antibody and the amount of MT in biological samples (r(2)=O.9980). These results suggested strongly that competitive ELISA is a simple, rapid and reproducible method for screening cadmium exposure.

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Evaluation of factors associated with cadmium exposure and kidney function in the general population
Mingai Huang, Seong‐Jin Choi, Dong‐Won Kim, Na‐Young Kim, Hye‐Sun Bae, Seung‐Do Yu, Dae‐Seon Kim, Heon Kim, Byung‐Sun Choi, Il‐Je Yu, Jung‐Duck Park
Environmental Toxicology.2013; 28(10): 563. CrossRef

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Expression of IL-6 mRNA by Human Lung Fibroblast Cell Line Treated with Cadmium: Dong Hoon Shin; Korean Journal of Occupational and Environmental Medicine 1996;8(1):34-42. Published online February 29, 1996; DOI: https://doi.org/10.35371/kjoem.1996.8.1.34

Abstract PDF

Cadmium is a highly toxic element responsible for acute and chronic toxicity in man and induces pathophysiological effects by modulating components of immune system, Cytokines are being increasingly recognized as essential mediators of normal and pathologic immune response. The present study has been investigated the effect of cadmium cyto toxicity for lung fibroblast and expression of cytokine gene in unstimulated and cadmiurn-treated lung fibroblast using reverse transcription-polymerase chain reaction showed that cadmium inhibited the cell proliferation and expression of IL-6, TGF-b-mRNA in both unstimulated and cadmium-treated cell. The expression of IL-6 mRNA increased at 0.8mM and l.OmM cadmium treated for 2 hours and more increased a 0. ImM cadmium treated for 24 hours than for 2 hours. This results suggest that cadmium stimulates expression of D-i-6 mRNA in lung fibroblast.

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Predicting Respiratory Toxicity Using a Human 3D Airway (EpiAirway™) Model Combined with Multiple Parametric Analysis
Jamin A. Willoughby
Applied In Vitro Toxicology.2015; 1(1): 55. CrossRef

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Assessment of Cadmium in Blood and Urine of Occupationally Exposed Workers and Renal Dysfunction by Cumulative Exposure Estimate: Seong Kyu Kang, Jeong Sun Yang, Ki Woong Kim, Jae Yeon Jang, Ho Keum Chung; Korean Journal of Occupational and Environmental Medicine 1995;7(1):101-110. Published online February 28, 1995; DOI: https://doi.org/10.35371/kjoem.1995.7.1.101

Abstract PDF

88 workers exposed to cadmium were examined at the 12 factories using or producing cadmium in order to know the present state of cadmium exposure and renal dysfunction in 1992. Cadmium in blood and in urine were measured and compared by the 3 exposure level of cadmium in air. Cadmium in blood of low, moderate and high exposure group were 2.5, 3,8 and 7.6 microgram/L, respectively. Cadmium in urine were 1.8(1.3), 3.8(2,6) and 7.9 microgram/L(6.1 microgram/g creatinine) , resrectively. However, there was no relationship between Urinary cadmium and beta(2)-microglobulin. Cumulative exposure estimate (CEE) was calculated by multiplying the mean ambient cadmium level of the factory and working duration. CEE has a high correlation with cadmium in blood and urine, but no relation to beta(2)-microglobulin. Because working durations were relatively shorter than European workers', the highest CEE was just 300 microgram. year/m(3), which was not enough to induce renal tubular dysfunction. This study, however, suggested the possibility that renal tubular dysfunction caused by cadmium could be happened in Korea in the near future.

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Chronic Cadmium Intoxication and Renal Injury Among Workers of a Small-scale Silver Soldering Company
Won-Jun Choi, Seong-Kyu Kang, Seunghon Ham, Wookyung Chung, Ae Jin Kim, Myunghee Kang
Safety and Health at Work.2020; 11(2): 235. CrossRef

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Changes of Cadmium in Blood and Urine of Cadmium Exposed Rats: Jung Duck Park, Mee Jung Kim, Byung Sun Choi, Yeon Pyo Hong, Im Won Chang; Korean Journal of Occupational and Environmental Medicine 1994;6(2):316-322. Published online September 30, 1994; DOI: https://doi.org/10.35371/kjoem.1994.6.2.316

Abstract PDF: The changes of Cadmium(Cd) in plasma, whole blood, erythrocyte and urine in Sprague-Dawley male rates exposed to intravenous single injection of 0.8 mg CdCl2/kg of body weight were investigated. Blood sample was taken at 0.5 to 672 hours, and 24 hour-urine was collected by using metabolic cage for the same period. The plasma level of Cd was reached to peak at 0.5 hour after injection and reduced rapidly in 1 hour. The Cd level in blood was the highest in plasma and the lowest in erythrocyte at 0.5 hour after injection. However, in one hour postinjection, the levels of Cd were higher in order of erythrocyte, whole blood and plasma, up to 4 weeks. The changes of urinary volume and creatinine were not significant between Cd-treated and saline-treated groups. However, urinary protein was slightly increased with time in Cd-treated group. Urinary Cd level was higher in Cd treated group than control. These results suggest that the measurement of Cd in erythrocyte and urine is valuable for the biological index to estimate recent Cd exposure.

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Assessment of Occupational Exposure to Cadmium in Korea: Seong Kyu Kang, Jeong Pyo Hong, Ki Woong Kim, Jae Yeon Jang, Ho Keun Chung, Kyou Chull Chung; Korean Journal of Occupational and Environmental Medicine 1994;6(2):252-258. Published online September 30, 1994; DOI: https://doi.org/10.35371/kjoem.1994.6.2.252

Abstract PDF

Twenty-four factories registered at the Ministry of Labor as factories using or producing cadmium in 1991 were investigated to know the present state of occupational exposure to cadmium in 1992. Nine factories among 24 stopped using or changed to other substances and 1 factory didn't produce any more, but delivered it to other factories through imports. Therefore, only 14 factories were producing or using cadmium. But, alloying materials were uspplied to about 20 and more factories, however, they couldn't be investigated because of limited information. Three factories had less than 50 workers were 3, 6 had 50-300 and 5 had more than 300. About 167 workers were exposed to cadmium. According to the classification by process, there were 4 alloy processes, 2 refinary, 2 elctroplating, 2 dry cell making, 1 industrial battery and 1 copper refinary. 8 factories used metal cadmium, 3 cadmium oxide, 2 cadmium sulfide, and 1 cadmium hyroxide. One factory was importing cadmium stearates only and supplying them to the PVC making factories. The amount of metal cadmium producing in 2 refinary factories was about 50-65 ton per month. The other cadmium compounds were imported. According to exposure level of cadmium in air of the 10 factories examined, each factory could be divided into high, moderate and low exposure groups. 1 battery recycling factory and 3 alloy factories were in the high exposure group and their mean air concentrations were 0.06679, 0.05481, 0.02492, and 0.003mg/m3, respectively. Refinary and industrial battery making factories were in the middle exposure group and their mean air concentrations were 0.00773 and 0.00613 mg/m3, respectively. Finally, low exposure group were copper smelting, dry cell case making, duplicator drum making and electroplating factory and their mean air concentrations were 0.00096, 0.00071, 0.00057 and 0.00054 mg/m3 respectively.

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Chronic Cadmium Intoxication and Renal Injury Among Workers of a Small-scale Silver Soldering Company
Won-Jun Choi, Seong-Kyu Kang, Seunghon Ham, Wookyung Chung, Ae Jin Kim, Myunghee Kang
Safety and Health at Work.2020; 11(2): 235. CrossRef
The association between cadmium and lead exposure and blood pressure among workers of a smelting industry: a cross-sectional study
Hyun Chan An, Joo Hyun Sung, Jiho Lee, Chang Sun Sim, Sang Hoon Kim, Yangho Kim
Annals of Occupational and Environmental Medicine.2017;[Epub] CrossRef

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Changes in Cadmium Deposit and Histopathologic Finding of Testis, Liver and Kidney in Cadmium Exposed Rats: Young Goo Lee, Jung Duck Park, Byung Sun Choi, Yeon Pyo Hong, Im Won Chang; Korean Journal of Occupational and Environmental Medicine 1994;6(1):56-68. Published online February 28, 1994; DOI: https://doi.org/10.35371/kjoem.1994.6.1.56

Abstract PDF: To assess the changes of cadmium deposit and histopathologic finding of testis, liver and kidney, different dose of cadmium (Cd) was administered into male Sprague-Dawley rat(purchased from KIST, Korea Institute of Science and Technology) by single intravenous injection. At 12, 24, 48, 168 and 672 hours after Cd injection, tissue cadmium concentration and histopathological change were examined. Cd exposed group showed lesser weight gain than the control. Renal Cd content tended to increase in time-dependent pattern, while hepatic and testicular Cd content tended to decrease. Mean of renal Cd content to hepatic Cd content (Cd K/Cd L) also progressively increased. These results suggest that Cd might be gradually transported to kidney fro other organs. In testis and liver, degenerative changes appeared relatively in acute phase. These changes became more pronounced in testis, while less prominent in liver. In kidney, swelling of proximal tubluar cells and thickening of glomerular basement membrane appeared relatively later and these changes were progressively aggravated.

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