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1.
J Appl Toxicol ; 41(3): 470-482, 2021 03.
Article in English | MEDLINE | ID: mdl-33022792

ABSTRACT

Cetylpyridinium chloride (CPC), a quaternary ammonium compound and cationic surfactant, is used in personal hygiene products such as toothpaste, mouthwash, and nasal spray. Although public exposure to CPC is frequent, its pulmonary toxicity has yet to be fully characterized. Due to high risks of CPC inhalation, we aimed to comprehensively elucidate the in vitro and in vivo toxicity of CPC. The results demonstrated that CPC is highly cytotoxic against the A549 cells with a half-maximal inhibitory concentration (IC50 ) of 5.79 µg/ml. Following CPC exposure, via intratracheal instillation (ITI), leakage of lactate dehydrogenase, a biomarker of cell injury, was significantly increased in all exposure groups. Further, repeated exposure of rats to CPC for 28 days caused a decrease in body weight of the high-exposure group and the relative weights of the lungs and kidneys of the high recovery group, but no changes were evident in the histological and serum chemical analyses. The bronchoalveolar lavage fluid (BALF) analysis showed a significant increase in proinflammatory cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α levels. ITI of CPC induced focal inflammation of the pulmonary parenchyma in rats' lungs. Our study demonstrated that TNF-α was the most commonly secreted proinflammatory cytokine during CPC exposure in both in vitro and in vivo models. Polymorphonuclear leukocytes in the BALF, which are indicators of pulmonary inflammation, significantly increased in a concentration-dependent manner in all in vivo studies including the ITI, acute, and subacute inhalation assays, demonstrating that PMNs are the most sensitive parameters of pulmonary toxicity.


Subject(s)
A549 Cells/drug effects , Anti-Infective Agents, Local/toxicity , Cell Survival/drug effects , Cetylpyridinium/toxicity , Pneumonia/chemically induced , Pneumonia/physiopathology , Animals , Disease Models, Animal , Humans , Male , Rats , Rats, Sprague-Dawley
2.
Int Arch Occup Environ Health ; 93(3): 337-344, 2020 04.
Article in English | MEDLINE | ID: mdl-31732794

ABSTRACT

PURPOSE: This cross-sectional study aimed to assess the effect of environmental cadmium (Cd) exposure and essential metal imbalance on renal tubular damage and oxidative stress in 979 adults living in a Cd-polluted area near an abandoned copper (Cu) refinery. METHODS: We analyzed urinary Cd concentrations, renal tubular damage and oxidative stress markers, such as beta-2 microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) activity and urine malondialdehyde (MDA) levels. The serum copper-to-zinc ratio (CZR) was used as an essential metal imbalance indicator. We divided the subjects into two Cd exposure groups based on the reference level of urinary Cd for renal dysfunction (2 µg/g creatinine). RESULTS: The geometric mean concentration of urinary Cd in all subjects was 2.25 µg/g creatinine. In both low and high Cd exposure groups, urinary Cd levels were positively correlated with urinary NAG activity, but not with serum CZR. After multivariate adjustment, serum CZR was strongly associated with urinary ß2-MG levels in the low Cd exposure group (ß = 1.360, P = 0.019) and was significantly associated with urinary MDA levels, regardless of Cd exposure level. In addition, the risk of renal tubular damage was significantly associated with urinary Cd level, particularly in the lowest or highest CZR tertile groups. CONCLUSIONS: Essential metal imbalance may be a determinant of oxidative stress and renal tubular damage in a chronically Cd-exposed population, and proper zinc supplementation will be effective in preventing adverse health effects due to Cd exposure.


Subject(s)
Cadmium/adverse effects , Copper/blood , Environmental Exposure/adverse effects , Kidney Diseases/chemically induced , Kidney Tubules/drug effects , Zinc/blood , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Kidney Diseases/blood , Kidney Tubules/pathology , Male , Oxidative Stress/drug effects , Republic of Korea
3.
J Korean Med Sci ; 31(4): 489-96, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27051230

ABSTRACT

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.


Subject(s)
Arsenic/urine , Cadmium/blood , Environmental Exposure , Environmental Pollutants/analysis , Lead/blood , Acetylglucosaminidase/urine , Adult , Aged , Bone Density , Case-Control Studies , Chemical Industry , Creatinine/urine , Environmental Pollutants/blood , Environmental Pollutants/urine , Female , Humans , Male , Middle Aged , Regression Analysis , Republic of Korea , Spectrophotometry, Atomic
4.
J Occup Environ Hyg ; 11(5): 314-25, 2014.
Article in English | MEDLINE | ID: mdl-24219421

ABSTRACT

This study aimed to estimate the status of secondhand smoke (SHS) exposure through urine cotinine analysis among nonsmoking workers in Korea and to analyze factors affecting urine cotinine concentrations. Data were based on "The 2008 Korea National Survey for Environmental Pollutants in the Human Body," a cross-sectional study of the National Institute of Environmental Research of Korea. We selected 1448 nonsmoking adult workers from 200 localities to participate in this survey. Urine cotinine concentrations were analyzed using a gas chromatograph-mass selective detector. We calculated separate covariate-adjusted geometric means for socio-demographic variables for males, females, and total subjects by analysis of covariance (ANCOVA). Statistical analyses were performed using SPSS version 18.0 (SPSS Inc., Chicago, Ill.). The prevalence of self-reported exposure to SHS was 36.9%. The geometric mean (95% confidence interval) of urine cotinine concentrations among all participants was 16.50 (14.48-18.80) µg/L. Gender, living area, education, and SHS exposure showed significant differences in urine cotinine concentrations. The urine cotinine concentrations of farmworkers and blue-collar workers such as skilled agricultural, forestry, and fishery workers, and elementary occupations were higher than those of white-collar workers such as clerical support workers, technicians, and associate professionals. Such a high proportion of the population having high urine cotinine levels indicates widespread exposure to SHS among nonsmoking workers in Korea. Furthermore, the urine cotinine levels among nonsmoking workers exposed to SHS varied by occupation. The measured urine cotinine concentration is suggested to be a valuable indication of SHS exposure in Korea.


Subject(s)
Air Pollutants, Occupational/analysis , Cotinine/urine , Occupational Exposure/statistics & numerical data , Tobacco Smoke Pollution/analysis , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Occupations/classification , Prevalence , Republic of Korea , Self Report , Tobacco Smoke Pollution/statistics & numerical data
5.
Environ Monit Assess ; 186(8): 5209-20, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24744211

ABSTRACT

We analyzed national data on blood lead levels (BLL) and blood cadmium levels (BCL) in residents living near 38 abandoned metal mining areas (n = 5,682, 18-96 years old) in Korea that were collected by the first Health Effect Surveillance for Residents in Abandoned Metal mines (HESRAM) from 2008 to 2011. The geometric mean BCL and BLL were 1.60 µg/L (95 % CI = 1.57-1.62 µg/L) and 2.87 µg/dL (95 % CI = 2.84-2.90 µg/dL), respectively, notably higher than levels in the general population in Korea and other countries. We found significantly higher BLL and BCL levels in people living within 2 km of an abandoned metal mine (n = 3,165, BCL = 1.87 µg/L, BLL = 2.91 µg/dL) compared to people living more than 2 km away (n = 2,517, BCL = 1.31 µg/L, BLL = 2.82 µg/dL; P < 0.0001) and to the general population values reported in the literature.


Subject(s)
Cadmium/blood , Environmental Exposure/statistics & numerical data , Environmental Pollutants/blood , Lead/blood , Mining , Adolescent , Adult , Aged , Aged, 80 and over , Environmental Monitoring , Female , Humans , Male , Metals/blood , Middle Aged , Republic of Korea , Young Adult
6.
Environ Toxicol ; 28(10): 563-70, 2013 Oct.
Article in English | MEDLINE | ID: mdl-21786387

ABSTRACT

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 (ß2 -microglobulin [ß2-MG], N-acetyl-ß-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.


Subject(s)
Cadmium/toxicity , Kidney/drug effects , Acetylglucosaminidase/blood , Acetylglucosaminidase/urine , Adult , Age Factors , Aged , Biomarkers/blood , Biomarkers/urine , Cadmium/blood , Cadmium/urine , Creatinine/urine , Female , Humans , Kidney/physiopathology , Kidney Function Tests , Male , Malondialdehyde/urine , Metallothionein/blood , Metallothionein/urine , Middle Aged , Oxidative Stress , Sex Factors , beta 2-Microglobulin/blood , beta 2-Microglobulin/urine
7.
Environ Res ; 118: 25-30, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22939007

ABSTRACT

The Korea National Survey for Environmental Pollutants in the human body conducts representative Korean population studies, which were first initiated in 2005 in Korea. This study was conducted from 2008 to 2009 to determine the exposure levels of polycyclic aromatic hydrocarbons and nicotine in the Korean general population. The study population consisted of 4702 adult subjects from 196 sampling locations including coastal, rural, and urban areas. The urinary levels of 1-hydroxypyrene, 2-naphthol, and cotinine were measured for exposure of polycyclic aromatic hydrocarbons and nicotine. The geometric means of the urinary 1-hydroxypyrene, 2-naphthol and cotinine concentrations in the Korean general population were 0.15 µg/L (95% confidence interval (CI): 0.13-0.17), 3.84 µg/L (95% CI: 3.57-4.11) and 47.42 µg/L (95% CI: 40.52-54.32) respectively. When these values were compared with reference ranges for the United States and Germany, the levels of 1-hydroxypyrene, 2-naphthol, and cotinine were very similar for Korea and Germany, however, these levels were slightly lower in the United States. This study is the first nationwide survey of exposure to polycyclic aromatic hydrocarbons and nicotine in Korea and provides a background reference range for exposure to polycyclic aromatic hydrocarbons and nicotine in the Korean general population.


Subject(s)
Biomarkers/urine , Cotinine/urine , Environmental Pollutants/urine , Naphthols/urine , Pyrenes/analysis , Adult , Aged , Female , Humans , Male , Middle Aged , Republic of Korea , Smoking/urine
8.
J Environ Monit ; 14(8): 2270-4, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22739933

ABSTRACT

Although the global positioning system (GPS) has been suggested as an alternative way to determine time-location patterns, its use has been limited. The purpose of this study was to evaluate a new analytical method of classifying time-location data obtained by GPS. A field technician carried a GPS device while simulating various scripted activities and recorded all movements by the second in an activity diary. The GPS device recorded geological data once every 15 s. The daily monitoring was repeated 18 times. The time-location data obtained by the GPS were compared with the activity diary to determine selection criteria for the classification of the GPS data. The GPS data were classified into four microenvironments (residential indoors, other indoors, transit, and walking outdoors); the selection criteria used were used number of satellites (used-NSAT), speed, and distance from residence. The GPS data were classified as indoors when the used-NSAT was below 9. Data classified as indoors were further classified as residential indoors when the distance from the residence was less than 40 m; otherwise, they were classified as other indoors. Data classified as outdoors were further classified as being in transit when the speed exceeded 2.5 m s(-1); otherwise, they were classified as walking outdoors. The average simple percentage agreement between the time-location classifications and the activity diary was 84.3 ± 12.4%, and the kappa coefficient was 0.71. The average differences between the time diary and the GPS results were 1.6 ± 2.3 h for the time spent in residential indoors, 0.9 ± 1.7 h for the time spent in other indoors, 0.4 ± 0.4 h for the time spent in transit, and 0.8 ± 0.5 h for the time spent walking outdoors. This method can be used to determine time-activity patterns in exposure-science studies.


Subject(s)
Environmental Monitoring/instrumentation , Geographic Information Systems , Documentation/methods , Environmental Monitoring/methods , Humans , Time
9.
Environ Res ; 111(3): 394-9, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21367405

ABSTRACT

Although ambient particulate pollutants have been shown to exacerbate existing allergic symptoms of mucous membranes including rhinitis and asthma, the effects on skin such as atopic dermatitis in childhood deserve further study. We investigated the effects of urban particulate pollutants including ultrafine particles on atopic severity in children with atopic dermatitis. We included 41 schoolchildren, 8-12 years old, who had been diagnosed with atopic dermatitis. For 67 consecutive days, all of them measured their symptoms in a diary. To assess exposure, the daily ambient mass concentrations of particulate matter less than 10, 2.5 and 1 µm (PM(10), PM(2.5) and PM(1), respectively) and concentrations of submicron particles (0.01- 1 µm) were measured at a local school. The mean mass concentrations of PM(10), PM(2.5) and PM(1) were 74.0, 57.8 and 50.8 µg/m(3), respectively. The mean concentrations were 41,335/cm(3) ultrafine particles (UFPs) and 8577/cm(3) accumulation mode (0.1-1 µm) particles. Significant associations were found between the concentrations of ultrafine particles and the itchiness symptom in children with atopic dermatitis. An interquartile range (IQR) increase in previous day ultrafine particles concentration (IQR: 28-140/m(3)) was significantly associated with a 3.1% (95% confidence interval, 0.2-6.1) increase in the itch symptom score for children with atopic dermatitis. The results suggested that the concentration of ambient ultrafine particles may exacerbate skin symptoms in children with atopic dermatitis.


Subject(s)
Dermatitis, Atopic/immunology , Environmental Exposure/adverse effects , Particulate Matter/immunology , Particulate Matter/poisoning , Child , Dermatitis, Atopic/epidemiology , Female , Humans , Korea/epidemiology , Linear Models , Male , Particle Size , Pruritus/immunology , Surveys and Questionnaires , Urban Population
10.
Toxics ; 9(7)2021 Jul 14.
Article in English | MEDLINE | ID: mdl-34357910

ABSTRACT

Ambient particulate matter 2.5 (PM2.5) and total suspended particles (TSPs) are common airborne pollutants that cause respiratory and cardiovascular diseases. We investigated the differences of cytotoxicity and mechanism between PM2.5 and TSP activity in human alveolar epithelial A549 cells. Atmospheric samples from the central district of Seoul were collected and their chemical compositions were analyzed by inductively-coupled plasma mass spectrometry and ion chromatography. PM2.5 and TSP contained high concentrations of heavy metals (Cu, Fe, Zn, and Pb). The most abundant ions in PM2.5 were SO42-, NH4+, and NO3-. A549 cells were exposed to PM2.5 and TSP (25-200 µg/mL) for 24 h. TSP was more cytotoxic than PM2.5 per unit mass. PM2.5 induced oxidative stress, as evidenced by increased levels of a glutamate-cysteine ligase modifier, whereas low-concentration TSP increased hemeoxygenase-1 levels. PM2.5 and TSP did not affect c-Jun N-terminal kinase expression. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in PM2.5- and TSP-treated cells decreased significantly in the cytosol and increased in the nucleus. Thus, Nrf2 may be a key transcription factor for detoxifying environmental airborne particles in A549 cells. TSP and PM2.5 could activate the protective Kelch-like ECH-associated protein 1/Nrf2 pathway in A549 cells.

11.
Sci Total Environ ; 707: 135334, 2020 Mar 10.
Article in English | MEDLINE | ID: mdl-31874399

ABSTRACT

Perfluoroalkyl acids (PFAAs) have been widely used in many industrial and consumer products. They have been detected ubiquitously in ambient water along with other environmental matrices, and their adverse effects on aquatic organisms have been a subject of active investigation. Here, we intended to summarize and synthesize the existing body of knowledge on PFAA toxicity through an extensive literature review, and shed light on areas where further research is warranted. PFAA toxicity appears to be influenced by the sex and developmental stages of aquatic organisms, but not significantly by exposure route. PFAA-induced aquatic toxicity could be classified as metabolism disturbance, reproduction disruption, oxidative stress, developmental toxicity, thyroid disruption, etc. At the molecular level, these responses can be initiated by key events, such as nuclear receptor activation, reactive oxygen species induction, or interaction with a membrane, followed by a cascade of downstream responses. PFAA-induced toxicity involves diverse metabolic processes, and therefore elucidating crosstalk or interactions among diverse metabolic pathways is a challenging task. In the presence of other chemicals, PFAAs can function as agonists or antagonists, resulting in different directions of combined toxicity. Therefore, mixture toxicity with other groups of chemicals is another research opportunity. Experimental evidence supports the trans-generational toxicity of PFAAs, suggesting that their long-term consequences for aquatic ecosystems should become of concern. A recent global ban of several PFAAs resulted in an increasing dependence on PFAA alternatives. The lack of sufficient toxicological information on this emerging group of chemicals warrant caution and rigorous toxicological assessments.


Subject(s)
Aquatic Organisms , Animals , Ecosystem , Fishes , Fluorocarbons , Seafood , Water Pollutants, Chemical
12.
Toxics ; 8(3)2020 Sep 22.
Article in English | MEDLINE | ID: mdl-32971939

ABSTRACT

The toxicity profiles of the widely used guanidine-based chemicals have not been fully elucidated. Herein, we evaluated the in vitro and in vivo toxicity of eight guanidine-based chemicals, focusing on inhalation toxicity. Among the eight chemicals, dodecylguanidine hydrochloride (DGH) was found to be the most cytotoxic (IC50: 0.39 µg/mL), as determined by the water soluble tetrazolium salts (WST) assay. An acute inhalation study for DGH was conducted using Sprague-Dawley rats at 8.6 ± 0.41, 21.3 ± 0.83, 68.0 ± 3.46 mg/m3 for low, middle, and high exposure groups, respectively. The levels of lactate dehydrogenase, polymorphonuclear leukocytes, and cytokines (MIP-2, TGF-ß1, IL-1ß, TNF-α, and IL-6) in the bronchoalveolar lavage fluid increased in a concentration-dependent manner. Histopathological examination revealed acute inflammation with necrosis in the nasal cavity and inflammation around terminal bronchioles and alveolar ducts in the lungs after DGH inhalation. The LC50 of DGH in rats after exposure for 4 h was estimated to be >68 mg/m3. Results from the inhalation studies showed that DGH was more toxic in male rats than in female rats. Overall, DGH was found to be the most cytotoxic chemical among guanidine-based chemicals. Exposure to aerosols of DGH could induce harmful pulmonary effects on human health.

13.
J Toxicol Environ Health A ; 72(21-22): 1493-8, 2009.
Article in English | MEDLINE | ID: mdl-20077223

ABSTRACT

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 beta(2)-microglobulin and N-acetyl-beta-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 microg/L, 0.84 microg/g creatinine, and As was 5.7 microg/L, 3.95 microg/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.


Subject(s)
Arsenic/toxicity , Arsenic/urine , Cadmium/urine , Kidney Diseases/chemically induced , Adult , Biomarkers , Female , Humans , Male , Oxidative Stress/drug effects , Risk Assessment
14.
Article in English | MEDLINE | ID: mdl-31405250

ABSTRACT

Association between short-term exposure to fine particulate matter (PM2.5) and mortality or morbidity varies geographically, and this variation could be due to different chemical composition affected by local sources. However, there have been only a few Asian studies possibly due to limited monitoring data. Using nationwide regulatory monitoring data of PM2.5 chemical components in South Korea, we aimed to compare the associations between daily exposure to PM2.5 components and mortality across six major cities. We obtained daily 24-h concentrations of PM2.5 and 11 PM2.5 components measured from 2013 to 2015 at single sites located in residential areas. We used death certificate data to compute the daily counts of nonaccidental, cardiovascular, and respiratory deaths. Using the generalized additive model, we estimated relative risks of daily mortality for an interquartile range increase in each pollutant concentration, while controlling for a longer-term time trend and meteorology. While elemental carbon was consistently associated with nonaccidental mortality across all cities, nickel and vanadium were strongly associated with respiratory or cardiovascular mortality in Busan and Ulsan, two large port cities. Our study shows that PM2.5 components responsible for PM2.5-associated mortality differed across cities depending on the dominant pollution sources, such as traffic and oil combustion.


Subject(s)
Air Pollutants/adverse effects , Air Pollution/adverse effects , Mortality , Particulate Matter/adverse effects , Air Pollutants/analysis , Carbon/adverse effects , Carbon/analysis , Cities , Humans , Particulate Matter/chemistry , Republic of Korea
15.
J Hazard Mater ; 367: 171-181, 2019 04 05.
Article in English | MEDLINE | ID: mdl-30594717

ABSTRACT

Metformin has been treated for diabetes (type 2). Nowadays, this compound is frequently found in ambient water, influent/effluent of a wastewater treatment plant. To evaluate the metformin aquatic toxicity under a multi-generational exposure regimen, we exposed Oryzias latipes to metformin for two generations (133 d) and investigated its adverse effects. In the F0 generation, metformin significantly elevated gene expression for cytochrome P450 19a (CYP19a) and estrogen receptor α (ERα) in male fish; in female fish, the treatment decreased gene expression of vitellogenin (VTG2) and ERß1, suggesting endocrine disruption (one-way ANOVA, p < 0.05). Intersex occurrence of F0 female fish were found in a concentration-dependent manner, whereas no significant changes in fecundity and hatching rate were observed (p < 0.05). Metformin increased the reactive oxygen species (ROS) content, and decreased the glutathione (GSH) content in F0 male fish compared with those of the control (one-way ANOVA, p > 0.05). In F0 female fish, metformin increased catalase activity compared with that of the control (p > 0.05). The results demonstrated that metformin leads to oxidative stress and two-generation endocrine disruption in O. latipes. These results may be useful for better understanding metformin toxicity mechanism.


Subject(s)
Endocrine Disruptors/toxicity , Hypoglycemic Agents/toxicity , Metformin/toxicity , Oryzias/genetics , Oryzias/metabolism , Water Pollutants, Chemical/toxicity , Animals , Catalase/metabolism , Cytochrome P450 Family 19/genetics , Disorders of Sex Development , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Female , Fish Proteins/genetics , Gene Expression Regulation/drug effects , Glutathione/metabolism , Glutathione Transferase/metabolism , Male , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Vitellogenins/genetics
16.
Front Pharmacol ; 9: 161, 2018.
Article in English | MEDLINE | ID: mdl-29541028

ABSTRACT

Many consumer products used in our daily lives result in inhalation exposure to a variety of chemicals, although the toxicities of the active ingredients are not well known; furthermore, simultaneous exposure to chemical mixtures occurs. Sodium metabisulfite (SM) and propylene glycol (PG) are used in a variety of products. Both the cytotoxicity and the sub-acute inhalation toxicity of each chemical and their mixtures were evaluated. Assays for cell viability, membrane damage, and lysosome damage demonstrated that SM over 100 µg/ml induced significant cytotoxicity; moreover, when PG, which was not cytotoxic, was mixed with SM, the cytotoxicity of the mixture was enhanced. Solutions of 1, 5, and 20% SM, each with 1% PG solution, were prepared, and the whole body of rats was exposed to aerosols of the mixture for 6 h/day, 5 days/week for 2 weeks. The rats were sacrificed 1 (exposure group) or 7 days (recovery group) after termination of the exposure. The actual concentration of SM in the low-, medium-, and high-exposure groups was 3.91 ± 1.26, 35.73 ± 6.01, and 80.98 ± 5.47 mg/m3, respectively, and the actual concentration of PG in each group was 6.47 ± 1.25, 8.68 ± 0.6, and 8.84 ± 1.77 mg/m3. The repeated exposure to SM and PG caused specific clinical signs including nasal sound, sneeze, and eye irritation which were not found in SM single exposure. In addition, the body weight of treatment group rats decreased compared to that of the control group rats in a time-dependent manner. The total protein concentration and lactate dehydrogenase activity in the bronchoalveolar lavage fluid (BALF) increased. Histopathological analysis of the lungs, liver, and nasal cavity was performed. Adverse effects were observed in the nasal cavity, with squamous cell metaplasia identified in the front of the nasal cavity in all high-exposure groups, which completely recovered 7 days after exposure was terminated. Whereas inhalation of SM for 2 weeks only reduced body weight in the high-dose group, inhalation of SM and PG mixtures for 2 weeks significantly decreased body weight and induced metaplasia of the respiratory epithelium into squamous cells in the medium- and high-dose groups. In conclusion, PG potentiated the toxicity of SM in human lung epithelial cells and the inhalation toxicity in rats.

17.
Environ Health Toxicol ; 33(1): e2018004, 2018.
Article in English | MEDLINE | ID: mdl-29370680

ABSTRACT

Several epidemiological studies have reported an association between environmental pollution and various health conditions in individuals residing in industrial complexes. To evaluate the effects of pollution from industrial complex on human health, we performed a pooled analysis of environmental epidemiologic monitoring data for residents living near national industrial complexes in Korea. The respiratory and allergic symptoms and the prevalence of acute and chronic diseases, including cancer, were used as the outcome variables for health effects. Multiple logistic regression analysis was used to analyze the relationship between exposure to pollution from industrial complexes and health conditions. After adjusting for age, sex, smoking status, occupational exposure, level of education, and body mass index, the residents near the industrial complexes were found to have more respiratory symptoms, such as cough (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.06 to 1.31) and sputum production (OR, 1.13; 95% CI, 1.03 to 1.24), and symptoms of atopic dermatitis (OR, 1.10; 95% CI, 1.01 to 1.20). Among residents of the industrial complexes, the prevalence of acute eye disorders was approximately 40% higher (OR, 1.39; 95% CI, 1.04 to 1.84) and the prevalence of lung and uterine cancer was 3.45 times and 1.88 times higher, respectively, than those among residents of the control area. This study showed that residents living in the vicinity of industrial complexes have a high risk of acute and chronic diseases including respiratory and allergic conditions. These results can be used as basic objective data for developing health management measures for individuals residing near industrial complexes.

18.
Environ Health Perspect ; 115(3): 430-4, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17431494

ABSTRACT

BACKGROUND: The contribution of the metal components of particulate pollutants to acute respiratory effects has not been adequately evaluated. Moreover, little is known about the effects of genetic polymorphisms of xenobiotic metabolism on pulmonary function. OBJECTIVES: This study was conducted to assess lung function decrement associated with metal components in particulate pollutants and genetic polymorphisms of glutathione S-transferase M1 and T1. METHODS: We studied 43 schoolchildren who were in the 3rd to 6th grades. Each student measured peak expiratory flow rate three times a day for 42 days. Particulate air concentrations were monitored every day, and the concentrations of iron, manganese, lead, zinc, and aluminum in the particles were measured. Glutathione S-transferase M1 and T1 genetic polymorphisms were determined using DNA extracted from participant buccal washings. We used a mixed linear regression model to estimate the association between peak expiratory flow rate and particulate air pollutants. RESULTS: We found significant reduction in the peak expiratory flow rate after the children's exposure to particulate pollutants. The effect was shown most significantly 1 day after exposure to the ambient particles. Manganese and lead in the particles also reduced the peak expiratory flow rate. Genetic polymorphisms of glutathione S-transferase M1 and T1 did not significantly affect peak expiratory flow rate. CONCLUSIONS: This study demonstrated that particulate pollutants and metals such as manganese and lead in the particles are associated with a decrement of peak expiratory flow rate. These effects were robust even with consideration of genetic polymorphisms of glutathione S-transferase.


Subject(s)
Air Pollutants/toxicity , Metals/toxicity , Particulate Matter/toxicity , Peak Expiratory Flow Rate/drug effects , Air Pollutants/analysis , Child , Female , Genotype , Glutathione Transferase/genetics , Humans , Korea , Male , Metals/analysis , Particle Size , Particulate Matter/analysis , Polymorphism, Genetic
19.
Int J Hyg Environ Health ; 220(2 Pt A): 29-35, 2017 03.
Article in English | MEDLINE | ID: mdl-27816434

ABSTRACT

National biomonitoring program can offer solid scientific evidence on exposure profiles of environmental chemicals at a national level, and provide a snapshot of changing exposure level over time. Therefore, several countries have maintained such programs for developing environmental health policies. The Korean National Environmental Health Survey (KoNEHS) was designed to understand the level of human exposure to environmental chemicals by time and location, and to identify possible sources of such exposure. The 2nd stage of KoNEHS, which was conducted between 2012 and 2014, examined a total of 6478 adult subjects over 19 years of age, and measured 21 environmental chemicals of major policy concern. Compared to the findings from the first stage monitoring (2009-2011), slightly higher levels of blood lead were observed, while those of mercury remained similar. Blood metal concentrations, however, were higher than those reported from national biomonitoring programs of United States, Germany and Canada. The urinary concentrations of phthalates metabolites were lower, but those of t,t-muconic acid and BPA were higher than those reported in the first stage survey. The urinary cotinine level decreased perhaps reflecting general declining patterns of first- and second-hand smoking. The results of the second stage survey were made available for public use since April 2016. Some policy efforts appear to be at least in part effective on mitigating chemical exposure among people, e.g., urinary phthalate metabolites and cotinine, while further confirmations are warranted. In-depth assessments will be conducted to identify vulnerable groups and important exposure pathways.


Subject(s)
Environmental Pollutants/blood , Environmental Pollutants/urine , Adult , Aged , Arsenic/urine , Asian People , Environmental Monitoring , Female , Health Surveys , Humans , Male , Metals, Heavy/blood , Metals, Heavy/urine , Middle Aged , Pesticides/urine , Phenols/urine , Phthalic Acids/urine , Polycyclic Aromatic Hydrocarbons/urine , Republic of Korea , Tobacco Smoke Pollution , Volatile Organic Compounds/urine , Young Adult
20.
Article in English | MEDLINE | ID: mdl-27447653

ABSTRACT

Spatial interpolation is employed to improve exposure estimates and to assess adverse health effects associated with environmental risk factors. Since various studies have reported that high ozone (O3) concentrations can give rise to adverse effects on respiratory symptoms and lung function, we investigated the association between O3 levels and lung function using a variety of spatial interpolation techniques and evaluated how different methods for estimating exposure may influence health results for a cohort from an industrial complex (Gwangyang Bay) in South Korea in 2009. To estimate daily concentrations of O3 in each subject, four different methods were used, which include simple averaging, nearest neighbor, inverse distance weighting, and kriging. Also, to compare the association between O3 levels and lung function by age-groups, we explored ozone's impacts on three age-related groups: children (9-14 years), adults (15-64 years), and the elderly (≥65 years). The overall change of effect size on lung function in each age group tended to show similar patterns for lag and methods for estimating exposure. A significant negative association was only observed between O3 levels and FVC and FEV1 for most of the lag and methods in children. The largest effect of O3 levels was found at the average for the lung function test day and last 2 days (0-2 days). In conclusions, the spatial interpolation methods may benefit in providing individual-level exposure with appropriate temporal resolution from ambient monitors. However, time-activity patterns of residents, monitoring site locations, methodological choices, and other factors should be considered to minimize exposure misclassification.


Subject(s)
Air Pollutants/adverse effects , Air Pollution/adverse effects , Lung/drug effects , Ozone/adverse effects , Adolescent , Adult , Aged , Air Pollutants/analysis , Child , Female , Humans , Male , Ozone/analysis , Republic of Korea , Respiratory Function Tests , Risk Factors , Spatial Analysis
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