Pan-Gyi Kim

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.

Korea National Survey for Environmental Pollutants in the human body 2008: 1-hydroxypyrene, 2-naphthol, and cotinine in urine of the Korean population

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.

Effect of chronic exposure to acetaminophen and lincomycin on Japanese medaka (Oryzias latipes) and freshwater cladocerans Daphnia magna and Moina macrocopa, and potential mechanisms of endocrine disruption.

Chronic toxicity of acetaminophen and lincomycin were evaluated using freshwater organisms including two crustaceans (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). H295R, a human adrenal cell was also used to understand the effects on steroidogenesis. In 21 d D. magna exposure, survival NOEC was found at 5.72 mg L(-1) and no reproduction related effects were noted at this level of exposure to acetaminophen, while 21 d survival or growth effects were not observed even at the highest exposure levels (153 mg L(-1)) for lincomycin. In the chronic fish toxicity test, significant reduction in juvenile survival was observed at 30 d post-hatch (dph) at 95 mg L(-1) of acetaminophen, and 0.42 mg L(-1) of lincomycin. After the exposure to both pharmaceuticals, vitellogenin levels tended to increase in male fish at 90 dph. In the eggs which were prenatally exposed to 9.5 mg L(-1) of acetaminophen, reduced hatchability was observed. The results of H295R cell assay showed that both pharmaceuticals could alter steroidogenic pathway and increase estrogenicity. Endocrine disruption potentials and their ecological implication may deserve further studies. Our observations suggest however that ecological risks of both pharmaceuticals are negligible at the concentrations currently found in the environment.

Determination of Phthalate Metabolites in Korean Children's Urine by High Performance Liquid Chromatography with Triple Quadrupole Tandem Mass Spectrometry

Dialkylated phthalates have been commonly used as plasticizers and a variety of applications. Phthalate diesters have been shown to be developmental and reproductive toxicants. It is very difficult to exactly estimate the dose of dialkylated phthalates taken up by the general population because of environmental contamination. Urinary metabolites of phthalates enabled to estimate internal exposure. The objective of this study was quantitative determination of phthalate metabolites by LC/MS/MS with on-line cleanup method to analyze phthalate metabolites in Korean childrens urine. We employed LC/MS/MS with on-line enrichment and column-switching techniques for this biological monitoring. Metabolites determined were 4 primary metabolites; MEHP, MnBP, MiBP, MEP and 2 secondary metabolites of DEHP; 5-OH-MEHP), 5-oxo-MEHP. We analyzed childrens urine from 30 boys and 30 girls. The method detection limit of phthalate metabolites were 0.03 ng/mL for MEP, 1.05 ng/mL for MBP, 0.22 ng/mL for MEHP, 0.15 ng/mL for 5-OHMEHP and 0.16 ng/mL for 5-oxo-MEHP, respectively. Switching Column LC/MS/MS was proven to be a useful tool to determine metabolites of phthalate diesters in human urine. The correlation among phthalate metabolites was very high and statistically significant, except MEP. The childrens age (months) was negatively correlated to the concentration of phthalate metabolites. The geometric mean concentration of phthalate metabolites (mg/g creatinine) in childrens urine were 25.5 for MEP, 130.3 for MnBP, 56.8 for MiBP, 19.5 for MEHP, 85.6 for 5-OH-MEHP and 83.1 for 5-oxo-MEHP, respectively. Levels of estimated daily intake of parent phthalate compounds (/kg bw/day) were 0.8 for DEP, 5.0 for DnBP, 1.9 for DiBP and for DEHP, respectively. Estimated daily intake for DEP and DiBP were lower than those of other studies but the value for DEHP was higher than that of other study.

Thyroid endocrine disruption in male zebrafish following exposure to binary mixture of bisphenol AF and sulfamethoxazole.

Thyroid endocrine disruption by bisphenol AF (BPAF) alone or in combination with sulfamethoxazole (SMX) exposure was evaluated in adult male zebrafish. Changes in thyroid gene transcription were examined using microarrays and were linked to effects on thyroxine hormone production and transcription of genes related to the hypothalamic-pituitary-thyroid axis. BPAF alone or in combination with SMX affected genes related to thyroid hormone production and receptor activity, thyroid gland development, and deiodinase activity. Increases in thyroxine levels, and gene transcription were more pronounced in the BPAF and SMX mixture group than in the BPAF group. Significant down-regulation of trh and tshβ genes in the brain suggested a negative feedback response resulting in increased thyroxine levels. The present study indicated that BPAF exposure alone alters transcription of genes associated with the thyroid endocrine system, and combination with SMX could increase the endocrine disrupting effect of BPAF.

Major benzophenone concentrations and influence of food consumption among the general population in Korea, and the association with oxidative stress biomarker

Benzophenones (BPs) have been used as sunscreen agents and as ultraviolet stabilizers in plastic surface coatings for food packaging. However, few studies have been performed to examine the level of human exposure to BPs and the potential sources of such exposure. We evaluated the exposure levels to six major BPs (BP-1, BP-2, BP-3, BP-4, BP-8, and 4-hydroxybenzophenone (4-OH-BP)) among the adult population in two cities in Korea, and investigated the potential dietary sources of the BPs. Urinary levels of malondialdehyde (MDA) as an oxidative stress biomarker as well as their association with the levels of BPs were also analyzed. Among the six BPs analyzed, 4-OH-BP, BP-1, BP-3, and BP-4 were detected in 77%, 49%, 27%, and 21% of the population, respectively. BP concentrations were relatively higher in younger (people in their 20s and 30s) cosmetic users and leaner women. Even after the adjustment of age, body mass index, and cosmetic use, the consumption of frozen storage food, instant noodles, and instant coffee was significantly correlated with urinary BPs, and these associations were sex-dependent. No significant correlation was observed between the levels of BPs and levels of MDA. The results of the present study will be useful for developing plans of public health management of BPs.

DEHP, DEP and DBP Exposure Analysis using Urinary Metabolites of Gyonggi Province University Students

Objectives: Phthalates are used as plasticizers in polyvinyl chloride (PVC) plastics. As phthalate plasticizers are not chemically bound to the PVC, they can leach, migrate or evaporate into indoor air and atmosphere, foodstuffs, other materials, etc. Therefore, humans are exposed through ingestion, inhalation, and dermal exposure over their entire lifetime, including during intrauterine development. In particular, university students have a great number of opportunities to contact products including phthalates during campus life (food packaging, body care products, cosmetic, lotions, aftershave, perfume etc.). The purpose of this study was to examine levels of phthalate exposure as undergraduate students begin to use pharmaceuticals and personal care products including phthalates. Methods: Phthalate metabolites, mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-2- ethylhexyl phthalate (MEHP), {(mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP}, and mono-(2-ethlyl-5-oxohexyl) phthalate (MEOHP} were examined. 80 urine samples collected from university students were analyzed using LC/MS/MS(API 4000, Applied Bioscience) with on-line enrichment and columnswitching techniques. This study was carried out at Y university located in Gyonggi Province from 2008 to 2011. Results: The detection limit of phthalate metabolites were 0.03 ng/mL for MEP, 0.11 ng/mL for MnBP, 0.08 ng/mL for MiBP, 0.93 ng/mL for MEHP, 0.19 ng/mL for MEOHP and 0.16ng/mL for MEHHP. MnBP showed the highest urinary levels (median: 31.6 ㎍/L, 24.8 ug/g creatinine (cr)). Concentrations were also high for MEHHP (median: 24.1 ㎍/L, 19.0 ㎍/g cr), followed by MEOHP (median: 22.8 ㎍/L, 17.9 ㎍/g cr). In individual cases, the maximum level reached up to 348 ㎍/L, and 291 ㎍/g cr, respectively. The urinary and creatinine adjusted levels of MEP were lower than those for DBP and DEHP metabolites, but were higher in 95th percentiles. As a result, the mean daily DEP intake value was 2.3 ㎍/㎏ bw/day, 3.5 ㎍/㎏ bw/day for DEHP and 4.9 ㎍/㎏ bw/day for DBP. Conclusion: These students’ phthalate exposure levels were below the international safe level set by the EU, but higher than the 2012 KFDA survey of the age group from 3 to 18.

Exposure to bisphenol S alters the expression of microRNA in male zebrafish

ABSTRACT Bisphenol S (BPS), an alternative compound of bisphenol A, has been found to affect reproduction, development, and immune system. Although microRNAs (miRNAs) play an important role in many metabolic activities, whether and how they are involved in the process of BPS‐induced toxicity is unknown. In the present study, BPS‐induced changes in miRNAs and target gene expression in male zebrafish gonad, and the potential mechanism was investigated. Male zebrafish were exposed to 0, 5, and 50 &mgr;g/L BPS for 21 d. miRNA was isolated from the gonad pool and the expression profiles of 255 known zebrafish miRNAs were analyzed using microarrays. Quantitative real‐time polymerase chain reaction was used to validate the expression of several miRNAs in the microarray data. The GO term analysis revealed that miRNAs significantly affected by BPS exposure were involved in hematopoiesis, lymphoid organ development, and immune system development. Among 14 miRNAs that were significantly regulated after exposure to 5 and 50 &mgr;g/L BPS, six targeted cyp19a1b gene, suggesting the role of BPS‐induced toxicity via the interference with the aromatization process. Our findings provide novel insight into the epigenetic regulatory mechanisms of BPS‐induced toxicity in male zebrafish, and identification of novel miRNA biomarkers for exposure to BPS. HighlightsBPS‐induced miRNA regulation was related to the immune system and hematopoiesis.BPS exposure induced significant changes in miRNAs related to the cyp19a1b gene.Most of miRNAs are inversely correlated with their corresponding target mRNAs.

Levels of perfluorinated compounds in prepared foods in Korea

Perfluorinated compounds (PFCs) are linked to adverse effect on human healths, therefore, the aim of this study was to determine the levels of PFCs in prepared food. One hundred and fifty-one samples of six prepared food groups were purchased from retail food establishments in Korea. Twelve PFCs were detected in the sample, the accuracy ranged between 80.8-119.4% and precision ranged between 2.2-2.89% high and low concentrations in PFCs spiked samples. The detection frequency of perfluoro-pentanoic acid (PFPeA) was and perfluorooctanoic acid (PFOA) above the limit of detection, which was 84.1 and 82.8%, respectively, but positive detection frequency of perfluorooctanesulphonic acid (PFOS) was as shown as low as 29.1%. Residual PFOA levels in most of the samples were higher than the PFOS levels. The average concentration of total PFCs in the samples was 1.68±1.79 ng/g, and PFPeA and PFOA were the predominant PFCs.

A Study on the Spatial Distribution of Medical Waste Generation and Treatment in Korea

Objectives: In Korea, the system of management of medical waste largely relies on the incineration method. Our study aimed to identify any regional imbalances between the generation and treatment of medical waste, and provide reference data for future policy in Korea. Methods: We analyzed data on the amount of medical waste from 2,000 hospitals in 2012, 2013, and 2014 obtained from the Korea Environment Corporation. In the Arc GIS program (version 10.2.3), the addresses of hospitals and incinerators were transformed into map coordinates. The amount of waste generated by each hospital and the amount incinerated were represented by density and size of a triangle symbol, respectively. Results: As of 2014, the total amount of medical waste from the top 2,000 hospitals was 136,073 tons, out of which about half (49%) was generated in the capital area. Eleven incineration companies (three in the capital area, two in the Chungcheong Provinces area, one in the Jeolla Provinces area, and five in the Gyeongsang Provinces area) treated this waste. For the years 2012, 2013, and 2014, about 60% of the medical waste generated from the hospitals in the capital area was treated within the capital area and about 40% was transported to other areas, especially the Gyeongsang Provinces area, for treatment. On the other hand, about 90% of the medical waste incinerated in the capital area originated from the capital area. Conclusion: Our results suggest a spatial imbalance between the generation and treatment of medical waste in Korea and warrants multilateral policies, including the expansion of on-site treatment, strengthening regulation of the containment of medical wastes, promoting reductions in medical waste and more.