Prenatal Exposure to Perfluorinated Compounds Affects Birth Weight Through GSTM1 Polymorphism.

OBJECTIVE: The aim of this study was to investigate the effect of genetic polymorphisms on the association of prenatal exposure to perfluorinated compounds (PFCs) with birth weight. METHODS: We analyzed the level of eight PFCs in cord blood and two genetic polymorphisms in maternal blood of 268 subjects. RESULTS: Concentrations of perfluorooctanoic acid, perfluorooctane sulfonate, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) showed significant association with a decrease in birth weight (P < 0.05). In mothers with glutathione S-transferase M1 (GSTM1) null genotype, concentrations of PFNA, PFDA, and PFUnDA showed significantly negative association with birth weight (P < 0.05). CONCLUSION: Our findings indicated that GSTM1 polymorphism might affect the association between exposure to PFCs and birth weight, suggesting the effect of genetic susceptibility on the relationship between prenatal PFCs exposure and birth outcomes.

Urinary phthalate metabolites among elementary school children of Korea: sources, risks, and their association with oxidative stress marker.

Phthalates have been used in a variety of consumer products and hence frequently been detected in humans. Children are susceptible to endocrine disrupting chemicals such as phthalates, but only limited information is available on the sources of exposure and potential adverse health effects among children. In this study, elementary school students (n=39, aged 9-12 years) were recruited in Seoul, and first void urine samples were collected twice in three-day intervals. Then six phthalate metabolites were analyzed by high performance liquid chromatography with triple quadrupole tandem mass spectrometry. In addition, malondialdehyde (MDA) as an oxidative stress marker was measured. A questionnaire was conducted and information on food consumption and the use of plastic packaging or storage materials was gathered. The concentrations of phthalate metabolites varied substantially by sampling time even within the same subject, but all target metabolites were detected in 100% of the samples with the highest geometric mean of 107 µg/g-creatinine for mono-n-butyl phthalate (MnBP). Urinary levels of mono-isobutyl phthalate (MiBP), and MnBP among Korean children were 8 and 3 times greater than those reported for US children, but those of monoethyl phthalate (MEP) were about 5 times lower than those of US children. Estimated phthalate intakes were generally in safe range, but in 3-8% of the participating children, the hazard quotients greater than one were noted. Urinary MDA concentrations were significantly associated with several metabolite levels after adjusting covariates in regression model. Consumption of dairy products or meat, and use of a plastic material were significantly associated with the DEHP metabolites or MnBP levels in multivariate model. The results of this study provide evidence of the association between phthalate exposure and oxidative stress especially among the early teenagers, and identified major sources that can be applied to development of management plan for phthalate exposure among children.

Urinary paraben concentrations among pregnant women and their matching newborn infants of Korea, and the association with oxidative stress biomarkers.

Parabens have been used in multiple products including personal care products, pharmaceuticals, and foods for more than 50 years but increasing numbers of studies have raised concerns on their safety. The present study was designed to determine urinary paraben levels among pregnant women and their matching newborn infants (<48 h after delivery), and the association between paraben levels and stress markers. Pregnant women (n=46) and their matching newborn infants were recruited from four university hospitals located in Seoul, Ansan and Jeju of Korea, 2011. Parabens including methyl paraben (MP), ethyl paraben (EP), n-propyl paraben (PP), and n-butyl paraben (BP) were measured in the urine using an automatic, high throughput online SPE-LC-MS/MS method. Urinary concentrations were normalized with specific gravity (SG). Free cortisol, malondealdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in the urine as stress marker. Urinary MP was detected as the highest, and BP was detected as the lowest paraben in the urine samples of both pregnant women and their infants. Significant correlations between paraben concentrations of maternal and their newborn infant's urine were observed. The levels of urinary parabens among Korean pregnant women are comparable to those reported elsewhere, except for EP which were 4-9 folds higher than pregnant women of other countries. The ratios of infant to maternal urinary paraben concentrations varied between 0.5 and 0.6 for MP and PP, but approximately 10 fold lower for EP. Urinary MP or EP levels were associated with several oxidative stress related biomarkers such as urinary 8-OHdG and MDA, even after the adjustment of relevant covariates such as maternal age, mode of delivery, pre-pregnancy BMI, gestational age and parity. This is the first study that reported the levels of major parabens in the first urine of newborn infants. Further studies are warranted to understand the implications of paraben exposure among biologically susceptible human populations.

Color vision impairments among shipyard workers exposed to mixed organic solvents, especially xylene.

OBJECTIVES: We evaluated color vision impairment in workers exposed to organic solvents, especially xylene. METHODS: Three groups of subjects, comprising 63 workers occupationally exposed to organic solvents, 122 non-exposed workers in the same industry, and 185 subjects from the general population as controls, were evaluated for color vision. Exposure to solvents was indirectly evaluated by measuring the concentration of a urinary metabolite. Color vision was assessed using the Lanthony Desaturated 15-hue (Lanthony D-15) panel. RESULTS: Color confusion index (CCI) values in the exposed group were significantly higher than in the non-exposed workers or the general population, after adjustment for age and education, and significantly correlated with the concentration of methylhippuric acid. Color vision impairments were detected more frequently among the exposed group, and the most common types were type III and complex impairments. The rate of type III impairments was 9.52% in the exposed group, 1.64% in the non-exposed group, and 1.62% in the general population. CONCLUSION: Our results support the hypothesis that acquired color vision impairments could be induced by exposure to xylene. Testing for color vision impairment is a relatively simple, non-invasive and sensitive diagnostic method for relatively low-level exposures to xylene.

Risk assessment of chlortetracycline, oxytetracycline, sulfamethazine, sulfathiazole, and erythromycin in aquatic environment: are the current environmental concentrations safe?

To understand potential risks of major pharmaceutical residues in waters, we evaluated ecotoxicities of five major veterinary pharmaceuticals, i.e., chlortetracycline, oxytetracycline, sulfamethazine, sulfathiazole, and erythromycin, which have been frequently detected in freshwater environment worldwide. We conducted acute and chronic toxicity tests using two freshwater invertebrates (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). In general, D. magna exhibited greater sensitivity than M. macrocopa, and chronic reproduction was the most sensitive endpoints for both organisms. The population growth rate was adversely influenced by exposure to chlortetracycline, sulfamethazine, or sulfathiazole in water fleas, but reduction in population size was not expected. In O. latipes, the tested pharmaceuticals affected several reproduction related endpoints including time to hatch and growth. Based on the toxicity values from the present study and literature, algae appeared to be the most sensitive organism, followed by Daphnia and fish. Hazard quotients derived from measured environmental concentrations (MECs) and predicted no effect concentrations (PNECs) for erythromycin and oxytetracycline exceeded unity, suggesting that potential ecological effects at highly contaminated sites cannot be ruled out. Long-term consequences of veterinary pharmaceutical contamination in the environment deserve further investigation.

Lung function decline and blood lead among residents nearby to industrial complex.

PURPOSE: This study was to ascertain the risk factors of pulmonary function decline (forced expiratory volume in 1 s [FEV(1)], forced vital capacity [FVC]) among those exposed to lead in the vicinity of industrial complex. METHODS: In total, 263 men and women, aged over 30, were recruited from two cities during a 2-year follow-up. Spirometry testing was conducted first at baseline and then after 2-years of follow-up. The change in FVC and FEV(1) during the study period was analyzed according to blood lead (BPb), urinary cotinine, and 1-hydroxypyrene, after controlling for sex, height, baseline FVC or FEV(1), and airway hyperresponsiveness. RESULTS: With increase in age, both FEV(1) and FVC declined. More marked decline in FVC was noted for men than for women (p < 0.05), while the decline in FEV(1) was not. Biological variables, especially height (p < 0.05) and pulmonary status (p < 0.0001), were associated with the decline in both FEV(1) and FVC. Even after controlling these other variables, blood lead level was also significantly associated with the decline of FVC. CONCLUSIONS: Even though the decline in FEV(1) and FVC with aging was within a normal range, people with smaller height were more vulnerable to the decline of both FEV(1) and FVC and especially higher level of BPb was accompanied with larger decline of FVC. Oxidative stress in relation to lead accumulation in adult may contribute to rapid aging of pulmonary function.

Occurrence of perfluorooctanoate and perfluorooctanesulfonate in the Korean water system: implication to water intake exposure.

Perfluorinated compounds (PFCs) measured in surface running waters indicated the existence of different emission sources in eight main city basins. The tap water reflected the contamination pattern and levels in their corresponding source water basins. The daily intakes through tap water consumption ranged from <0.01 to 0.73 ng kg(-1) d(-1) for perfluorooctanoate (PFOA) and <0.01 to 0.08 ng kg(-1) d(-1) for perfluorooctanesulfonate (PFOS). Tap water intake-derived exposure accounted for 8.6%-101% (for PFOA) and while <10% (for PFOS) of total daily exposure, which was estimated from Korean serum concentrations using a pharmacokinetic model. Our findings indicate that tap water intake could be an important contributor to PFOA exposure in Korean populations; accordingly, additional efforts are necessary to improve the removal efficiency of perfluorinated compounds (PFCs) in the water purification process. However, more fundamentally the aim would be to reduce the discharge of PFCs from potential sources within the basin.

Determination of Phthalate Metabolites in Human Serum and Urine as Biomarkers for Phthalate Exposure Using Column-Switching LC-MS/MS.

OBJECTIVES: Although phthalates like dibutyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) are commonly used as plasticizers and their metabolites are especially suspected of reproductive toxicity, little is known about occupational exposure to those phthalates. The aim of this study was to assess the utility of measuring the metabolite concentrations of DBP and DEHP in serum and urine samples as an indicator of occupational exposure to those phthalates. METHODS: Phthalate metabolites were analyzed by using column-switching high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: We detected phthalate metabolites in serum and urine matrices at approximately 10-fold lower than the limit of detection of those metabolites in the same matrix by LC-MS/MS without column switching, which was sufficient to evaluate concentrations of phthalate metabolites for industrial workers and the general population. CONCLUSION: The accuracy and precision of the analytical method indicate that urinary metabolite determination can be a more acceptable biomarker for studying phthalate exposure and adverse health outcomes.

Extensive changes to occupational exposure limits in Korea.

Occupational exposure limits (OELs) are used as an important tool to protect workers from adverse chemical exposures and its detrimental effects on their health. The Ministry of Labor (MOL) can establish and publish OELs based on the Industrial Safety and Health Act in Korea. The first set of OELs was announced by the MOL in 1986. At that time, it was identical to the Threshold Limit Values of the American Conference of Governmental Industrial Hygienists. Until 2006, none the first OELs except for those of three chemicals (asbestos, benzene, and 2-bromopropane) were updated during the last twenty years. The Hazardous Agents Review Committee established under the MOL selected 126 chemicals from 698 chemicals covered by OELs using several criteria. From 2005 to 2006, the MOL provided research funds for academic institutions and toxicological laboratories to gather the evidence documenting the need to revise the outdated OELs. Finally, the MOL notified the revised OELs for 126 chemicals from 2007 to 2008. The revised OELs of 58 substances from among these chemicals were lowered to equal or less than half the value of the original OELs. This is the most substantial change in the history of OEL revisions in Korea.

Pharmacological stimulation of NADH oxidation ameliorates obesity and related phenotypes in mice.

OBJECTIVE: Nicotinamide adenine dinucleotides (NAD+ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD+-to-NADH ratio is implicated in metabolic syndrome. However, it is still unknown whether a modulating intracellular NAD+-to-NADH ratio is beneficial in treating metabolic syndrome. We tried to determine whether pharmacological stimulation of NADH oxidation provides therapeutic effects in rodent models of metabolic syndrome. RESEARCH DESIGN AND METHODS: We used beta-lapachone (betaL), a natural substrate of NADH:quinone oxidoreductase 1 (NQO1), to stimulate NADH oxidation. The betaL-induced pharmacological effect on cellular energy metabolism was evaluated in cells derived from NQO1-deficient mice. In vivo therapeutic effects of betaL on metabolic syndrome were examined in diet-induced obesity (DIO) and ob/ob mice. RESULTS: NQO1-dependent NADH oxidation by betaL strongly provoked mitochondrial fatty acid oxidation in vitro and in vivo. These effects were accompanied by activation of AMP-activated protein kinase and carnitine palmitoyltransferase and suppression of acetyl-coenzyme A (CoA) carboxylase activity. Consistently, systemic betaL administration in rodent models of metabolic syndrome dramatically ameliorated their key symptoms such as increased adiposity, glucose intolerance, dyslipidemia, and fatty liver. The treated mice also showed higher expressions of the genes related to mitochondrial energy metabolism (PPARgamma coactivator-1alpha, nuclear respiratory factor-1) and caloric restriction (Sirt1) consistent with the increased mitochondrial biogenesis and energy expenditure. CONCLUSIONS: Pharmacological activation of NADH oxidation by NQO1 resolves obesity and related phenotypes in mice, opening the possibility that it may provide the basis for a new therapy for the treatment of metabolic syndrome.