Il-Je Yu

Risk assessment of low-level cadmium and arsenic on the kidney.

Cadmium (Cd) and arsenic (As) are widely distributed in the environment and are known human carcinogens. Several studies reported that chronic exposure to Cd and As produced renal injuries in humans. As one of the mechanisms, oxidative stress was suggested to play a role in the early process of Cd- and/or As-induced tubular damage in the kidney. This study was performed to evaluate the significance of urinary biomarkers, role of oxidative stress, and effect of coexposure to environmental low-level exposure to Cd and/or As in the general population. Urine samples were collected from 290 adults (86 males and 204 females). Urinary concentrations of Cd and As were measured, and kidney biomarkers of toxicity such as ß2-microglobulin and N-acetyl-β-D-glucosaminidase (NAG) activity determined in urine. Urinary malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured as oxidative stress indices. The mean concentration of Cd was 1.21 μg/L, 0.84 μg/g creatinine, and As was 5.7 μg/L, 3.95 μg/g creatinine in urine. NAG, MDA, and 8-OHdG were positively correlated with both Cd and As in urine. Positive correlations were also observed between NAG and oxidative indices. The effects of coexposure to Cd and As on biomarkers are more pronounced than for exposure to each metal alone. These findings suggest that chronic exposure to low levels of Cd and/or As might produce tubular damage in the kidney through oxidative stress in humans.

Evaluation of factors associated with cadmium exposure and kidney function in the general population.

Cadmium (Cd) is a nonessential toxic metal which is widely distributed in the environment. The general population is exposed to low levels of Cd and the kidney is the organ most sensitive to Cd toxicity. This study was performed to simultaneously evaluate Cd exposure, kidney function, and oxidative stress biomarkers in the general population. A total of 643 adults were interviewed to document demographic characteristics, lifestyles, past‐medical history, and diet during the last 24 h. We estimated daily Cd intake based on the diet of study subjects who had not been exposed to Cd occupationally. Whole blood and urine samples were collected and analyzed to determine Cd concentrations and kidney function indices (β2‐microglobulin [β2‐MG], N‐acetyl‐β‐D‐glucosaminidase [NAG], metallothionein [MT]). The oxidative stress index (malondialdehyde [MDA]) was determined from the urine. The daily Cd intake from diet was established as 7.07 μg/day. The mean concentration of Cd measured in the blood was 1.22 μg/L and urine was 0.95 μg/g creatinine. The concentrations of Cd in blood and urine were higher in females than in males. The blood levels of Cd were affected by sex, age, and smoking, and urine Cd was influenced by sex, age, and blood Cd. The urine Cd was positively correlated with MT, NAG activity, and MDA in females, but with NAG only in males. The blood Cd was associated with MT in males. Increased NAG activity was observed when Cd in urine reached 1.0 μg Cd/g creatinine and was also affected by age, hypertension, and diabetes mellitus. Urinary MT only responded to Cd in urine or blood. In summary, exposure to Cd in the general population was influenced by various factors including sex, age, and smoking habits. Such exposure might eventually cause tubular damage in the kidneys through the oxidative stress mechanism, and females might be more susceptible than males to Cd exposure under the environment.

Toxicity and clearance of intratracheally administered multiwalled carbon nanotubes from murine lung.

Carbon nanotubes (CNT) are known to have widespread industrial applications; however, several reports indicated that these compounds may be associated with adverse effects in humans. In this study, multiwalled carbon nanotubes were administered to murine lungs intratracheally to determine whether acute and chronic pulmonary toxicity occurred. In particular, pristine multiwalled carbon nanotubes (PMWCNT) and acid-treated multiwalled carbon nanotubes (TMWCNT) were used in this study. In broncheoalveolar lavage fluid (BALF) cell analysis, PMWCNT induced more severe acute inflammatory cell recruitment than TMWCNT. Histopathologically, both PMWCNT and TMWCNT induced multifocal inflammatory granulomas in a dose-dependent manner. The observed granulomas were reversible, with TMWCNT-induced granulomas diminishing faster than PMWCNT-induced granulomas. Although the area of granuloma reduced with time, hyperplasia and dysplastic characteristics such as mitotic figures, anisokaryosis, and anisocytosis were still observed. These findings demonstrate that MWCNT induces granulomatous inflammation, and the duration and pattern of inflammation seem to vary depending upon the types of MWCNT to which mice are exposed. Therefore, toxicity studies on various types of CNT are needed as the responsiveness to these compounds differs.

Effect of lifestyles on the blood mercury level in Korean adults

Mercury (Hg) is widely distributed in the environment and oral exposure is a main route in the general population. In this study, we estimated the dietary intake of Hg and its relationship with blood Hg levels in Korean adults. The study subjects were recruited from three different districts (rural: 189, coastal: 208 and urban: 184). We used a general questionnaire to collect information about demographic factors, lifestyles and diet. Dietary habits were studied using the 24-h recall method. The estimation of Hg intake was performed using the database of Hg contents in 128 Korean foods based on the previous studies. Blood Hg was analyzed using Direct Mercury Analyzer with the gold-amalgam method. Daily intake of Hg by diet was estimated at 13.57 μg (0.22 μg/kg body weight). The geometric mean Hg concentration in whole blood was 3.92 μg/L. Blood Hg level and Hg intake by diet was higher in coastal areas than in urban or rural areas, respectively. Blood Hg level correlated with the intake of Hg consumed from diet. Seafood was highly responsible and account for 75.6% of total dietary Hg intake. In this study, blood Hg concentrations were found to be significantly affected by sex, age, individual lifestyles and especially the amount of seafood intake, which might play an important role in determining blood Hg levels in Korean adults.

Decreased formation of ethoxyacetic acid from ethylene glycol monoethyl ether and reduced atrophy of testes in male rats upon combined administration with toluene and xylene.

Male painters are commonly exposed to ethylene glycol monoethyl ether (EGE), a well known reproductive toxic agent causing testicular atrophy, in the form of solvent mixture containing toluene (TOL) and xylene (XYL). This study was carried out to determine the effect of exposing male rats to solvent mixture containing TOL and XYL on the EGE (200 mg/kg) on testicular atrophy and production of toxic metabolite, ethoxyacetic acid (EAA) from EGE. Compared to the extent of testes atrophy observed upon EGE administration alone, the combined administration of EGE (200 mg/kg) with TOL (250 mg/kg) and XYL (500 mg/kg) for 4 weeks has reduced the extent of testes atrophy by 25%. The combined administration delayed the time for appearance of the highest plasma concentration (t(max)) of EAA from 3 to 6 h and also decreased the highest concentration (Cmax) as well as the total amount of plasma EAA (AUC(0-18 h)) by 45 and 29%, respectively. This explained the diminished testicular atrophy in male rats observed when EGE was administered in a solvent mixture containing TOL and XYL. This study suggested that testicular toxicity observed in male painters caused by EGE may be decreased when they are exposed to EGE in the form of solvent mixture containing TOL and XYL.

Co-administration of toluene and xylene antagonized the testicular toxicity but not the hematopoietic toxicity caused by ethylene glycol monoethyl ether in Sprague–Dawley rats

Occupational painters are exposed to ethylene glycol monoethyl ether (EGEE), a widely used emulsifying solvent known to cause testicular degeneration and bone marrow depression, together with toluene (TOL) and xylene (XYL) as a mixture. In the previous study (Chung et al., Tox. Lett. 104:143, 1999), testicular atrophy caused by EGEE (200 mg/kg) was shown to be antagonized by co-administration of TOL (250 mg/kg) and XYL (500 mg/kg). This study was conducted to provide histological support for the previously observed antagonistic protective effect of TOL + XYL on EGEE inducible testicular toxicity and to determine whether a similar antagonistic effect can be demonstrated against the EGEE derived hematopoietic toxicity. Compared to the extent of seminiferous tubule degeneration caused by EGEE (150 mg/kg, six times per week for 4 weeks), testes of rats given co-administration of TOL (250 mg/kg) + XYL (500 mg/kg) showed dramatically reduced tubular degeneration. Hyperplasia of Leydig cells in the interstitium was observed in both EGEE and EGEE + TOL + XYL-treated rats. Although a minimal dose of EGEE causing testicular atrophy was used, WBC and platelet counts were decreased significantly. In the TOL + XYL-treated control group, the WBC and platelet counts were not decreased. However, the bone marrow depression caused by EGEE was not reversed by the combined administration of TOL + XYL. In all experimental groups (EGEE alone, TOL + XYL, EGEE + TOL + XYL), plasma levels of creatinine and alkaline phosphatase were significantly decreased. In addition to the marked testicular atrophy, EGEE also decreased the weights of adrenal glands and epididymis. In conclusion, while the testicular degeneration caused by EGEE was antagonized by TOL + XYL, the EGEE derived hematopoietic suppression was not reversed.

Arsenic exposure and seafood intake in Korean adults.

Arsenic (As) is widely distributed in the environment, and humans can be exposed to As from various sources such as air, water, soil, and food. This study was performed to evaluate the As exposure levels in Korean adults by measuring total As in urine and its relation with the consumption of seafood, a favorite food in Korea. A total of 2077 adults were the study subjects; they ranged in age from 19 to 83, and they were recruited by probability sampling stratified by area, sex, and age. None of the subjects had been exposed to As occupationally. We collected information about the demographic characteristics, lifestyles, and food consumption of study subjects using a questionnaire and followed urine sampling. Diet was assessed in individual interviews using the 24-h recall method. Total As in urine was analyzed using inductively coupled plasma mass spectrometry (PerkinElmer NEXION 300S; Concord, Ontario, Canada). The geometric mean concentration of total As in urine was observed to be 97.6 µg/L and was higher in males (103.9 µg/L) than in females (93.0 µg/L). Total As levels in urine were affected by sex, age, seafood intake, and geographic location. In this study, total As in urine was positively correlated with fish and shellfish consumption, and was mainly determined by As intake through fish and shellfish/grains/flavors. These findings suggest that seafood consumption might be a major contributor to urinary As levels in Korean adults.