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

JangWoo Lee,YoungLim Kho,SungKyoon Kim,Kyungho Choi,SeongHee Hwang,Jeeyeon Jeong,Pangyi Ki 한국환경보건학회 2013 한국환경보건학회지 Vol.39 No.5

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 ug/L, 24.8 ug/g creatinine (cr)). Concentrations were also high for MEHHP (median: 24.1 ug/L, 19.0 ug/g cr), followed by MEOHP (median: 22.8 ug/L, 17.9 ug/g cr). In individual cases, the maximum level reached up to 348 ug/L, and 291 ug/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 μg/kg bw/day, 3.5 μg/kg bw/day for DEHP and 4.9 μg/kg 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.

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

Lee, JangWoo,Kho, YoungLim,Kim, SungKyoon,Choi, Kyungho,Hwang, SeongHee,Jeong, Jeeyeon,Kim, Pangyi Korean Society of Environmental Health 2013 한국환경보건학회지 Vol.39 No.5

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 ug/L, 24.8 ug/g creatinine (cr)). Concentrations were also high for MEHHP (median: 24.1 ug/L, 19.0 ug/g cr), followed by MEOHP (median: 22.8 ug/L, 17.9 ug/g cr). In individual cases, the maximum level reached up to 348 ug/L, and 291 ug/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 ${\mu}g/kg$ bw/day, 3.5 ${\mu}g/kg$ bw/day for DEHP and 4.9 ${\mu}g/kg$ 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

Lee, Jiyun,Kho, Younglim,Kim, Pan-Gyi,Ji, Kyunghee Elsevier 2018 Toxicology and applied pharmacology Vol.338 No.-

<P><B>Abstract</B></P> <P>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 50μg/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 50μg/L BPS, six targeted <I>cyp19a1b</I> 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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BPS-induced miRNA regulation was related to the immune system and hematopoiesis. </LI> <LI> BPS exposure induced significant changes in miRNAs related to the <I>cyp19a1b</I> gene. </LI> <LI> Most of miRNAs are inversely correlated with their corresponding target mRNAs. </LI> </UL> </P>

Effects of chronic exposure to cefadroxil and cefradine on <i>Daphnia magna</i> and <i>Oryzias latipes</i>

Kim, Bokyung,Ji, Kyunghee,Kho, Younglim,Kim, Pan-Gyi,Park, Kyunghwa,Kim, Kyungtae,Kim, Youngsuk,Kim, Ki-Tae,Choi, Kyungho Pergamon Press 2017 Chemosphere Vol.185 No.-

<P><B>Abstract</B></P> <P>Cefadroxil and cefradine have frequently been detected in surface waters, however toxicological studies in aquatic organisms have mostly been limited to acute lethal effects. In the present study, endocrine disruption caused by cefadroxil and cefradine, and its underlying mechanism were investigated by chronic exposure of <I>Daphnia magna</I> (21 d) and <I>Oryzias latipes</I> (120 d). In medaka fish, the effects on growth, mortality, and reproduction, as well as on the levels of hormones and genes related to the hypothalamic-pituitary-gonad (HPG) axis, were investigated after 120 d exposure. In <I>D. magna</I>, the chronic effects on growth were observed at the highest concentration of 83.0 mg L<SUP>−1</SUP> cefadroxil and 80.8 mg L<SUP>−1</SUP> cefradine. The growth of juvenile fish was significantly impaired by exposure to cefradine. Following exposure to cefadroxil and cefradine for 120 d, sex-dependent changes in E2 hormones were observed and their levels were supported by the regulation of genes along the HPG axis. We found that chronic exposure to cefadroxil and cefradine impaired growth and reproduction in a freshwater invertebrate and fish, and altered the levels of sex hormones and genes associated with the HPG axis in fish.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cefadroxil and cefradine impaired growth in a freshwater invertebrate and a fish. </LI> <LI> Cephalosporin antibiotics altered gene transcriptions of the HPG axis in fish. </LI> <LI> Cefadroxil and cefradine modulated sex hormones and genes in a sex-dependent way. </LI> </UL> </P>

Effects of Bisphenol S Exposure on Endocrine Functions and Reproduction of Zebrafish

Ji, Kyunghee,Hong, Seongjin,Kho, Younglim,Choi, Kyungho American Chemical Society 2013 Environmental science & technology Vol.47 No.15

<P>While bisphenol S (BPS) has been frequently detected both in environment and biota, limited information is available on their effects of endocrine system. In the present study, adult zebrafish pairs were exposed to 0.5, 5, and 50 μg/L of BPS for 21 d, and the effects on reproduction, sex steroid hormones, and transcription of the genes belonging to the hypothalamic-pituitary-gonad (HPG) axis were investigated. The adverse effects on performances of F1 generation were further examined with or without subsequent exposure to BPS. Egg production and the gonadosomatic index in female fish were significantly decreased at ≥0.5 μg/L BPS. Plasma concentrations of 17β-estradiol were significantly increased in both male and female fish. In male fish, however, significant decreases of testosterone concentration were observed along with up-regulation of <I>cyp19a</I> and down-regulation of <I>cyp17</I> and <I>17βhsd</I> transcripts. Parental exposure to BPS resulted in delayed and lesser rates of hatching even when they were hatched in clean water. Continuous BPS exposure in the F1 embryos resulted in worse hatchability and increased malformation rates compared to those without BPS exposure. Our observations showed that exposure to low level BPS could affect the feedback regulatory circuits of HPG axis and impair the development of offspring.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/esthag/2013/esthag.2013.47.issue-15/es400329t/production/images/medium/es-2013-00329t_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/es400329t'>ACS Electronic Supporting Info</A></P>

Phototoxicity and chronic toxicity of methyl paraben and 1,2-hexanediol in Daphnia magna

Lee, Jiyun,Park, Nayeon,Kho, Younglim,Lee, Kiyoung,Ji, Kyunghee Springer-Verlag 2017 Ecotoxicology Vol.26 No.1

<P>Parabens are used as antimicrobial preservatives in consumer products. Exposure to methylparaben (MP) has been associated with adverse health outcomes, therefore, an alternative compound, 1,2-hexanediol (1,2-H), has been applied for cosmetics. In the present study, the phototoxicity of MP and 1,2-H, as well as the toxic effect caused by chronic exposure, were investigated using Daphnia magna. The 48 h acute toxicity tests with D. magna were conducted under indoor or ultraviolet (UV) light irradiation conditions, i.e., exposure to 4 h/d sunlight. Changes in the transcription of genes related to oxidative stress were determined in D. magna juveniles, to investigate the underlying mechanism of phototoxicity. The 21 d chronic toxicity tests of MP and 1,2-H were performed under indoor light irradiation. Exposure to MP under environmental level of UV light was more detrimental to D. magna. Transcripts of catalase and glutathione-S-transferase genes in D. magna was significantly increased by co-exposure to MP and UV light. After 21 d of chronic exposure to MP and 1,2-H, the reproduction no-observed effect concentrations for D. magna were 1 and > 10 mg/L, respectively. The present study showed that exposure to UV could magnify the toxicity of MP on daphnids. Although acute and chronic toxicities of 1,2-H were generally lower than those of MP, its effects on other aquatic organisms should not be ignored. Further studies are needed to identify other mechanisms of MP phototoxicity.</P>

Levels of Perfluorinated Compounds in Liquid Milk Products in Korea

Park, Na-youn,Kho, Younglim,Kim, Junghoan The Korean Society of Food Hygiene and Safety 2021 한국식품위생안전성학회지 Vol.36 No.4

본 연구는 국내 유통되는 액상 유제품에 함유된 17종의 과불화화합물 (PFCs) 함량에 대한 모니터링을 위해 수행되었다. 샘플을 액체-액체 추출을 통해 추출하고 LC-MS/MS로 정량 분석하였다. 시중에 유통중인 98개의 액상 유제품 샘플에서 PFCs의 모니터링을 진행하였으며 그 결과, PFTeDA를 제외한 16종의 PFCs가 검출되었다. 총 PFCs의 함량은 0.9037 ng/mL로 액상 우유에서 가장 높았으며, PFPeA, PFDS, PFHxA도 액상우유에서 0.1 ng/mL 이상의 농도 수준을 보였다. 미국과 이탈리아에서 수행한 연구와 비교했을 때 PFOA와 PFOS의 잔류 패턴은 유사한 것으로 나타났으며, 농도 수준은 0.1 ng/mL 미만이었다. 액상 유제품은 다양한 가공단계(살균, 혼합, 지방제거 등)를 거쳐 총 PFCs의 함량이 감소하는 것으로 보여 지며, 특히 짧은 탄소 사슬을 가진 PFCs가 크게 감소하거나 검출되지 않았다. 이는 식품 안전에서 원료의 PFOS와 PFOA의 잔류정도가 중요하다는 것을 의미한다. This study was carried out to monitor the level of 17 perfluorinated compounds (PFCs) present in liquid milk products sold on the Korean market. The liquid milk samples were extracted via liquid-liquid extraction and analyzed by LC-MS/MS. Excellent linearity over the calibration range (r²>0.99), and the limit of quantification of perfluorooctane sulfonate (PFOS) was 0.021 ng/g, and perfluorotetradecanoic acid (PFOA) was 0.057 ng/g. The accuracy was in the range of 72.5-115.3%, and the precision was under 20%. The preprocessing method for this experiment is considered appropriate for analysis of milk samples. The proposed analytical method was applied for the determination of PFCs in 98 liquid milk product samples, and the average content of total PFCs was 0.6576 ng/mL. PFOA and PFOS were detected in most samples, and their levels were less than 0.1 ng/mL, which was lower than those in other studies.

Comparison of thyroid hormone disruption potentials by bisphenols A, S, F, and Z in embryo-larval zebrafish

Lee, Sangwoo,Kim, Cheolmin,Shin, Hyesoo,Kho, Younglim,Choi, Kyungho Elsevier 2019 CHEMOSPHERE - Vol.221 No.-

<P><B>Abstract</B></P> <P>Several structural analogues of bisphenol A (BPA), e.g., bisphenol F (BPF), bisphenol S (BPS), and bisphenol Z (BPZ), have been used as its substitutes in many applications and consequently detected in the environment, and human specimen such as urine and serum. While BPA has been frequently reported for thyroid hormone disruption in both experimental and epidemiological studies, less is known for the BPA analogues. In the present study, thyroid hormone disrupting effects of BPF, BPS and BPZ, were investigated, and compared with those of BPA, using embryo-larval zebrafish (<I>Danio rerio</I>). At 120 hpf, significant increases in T3 and/or T4 were observed in the larval fish following exposure to BPA, BPF, or BPS. Moreover, transcriptional changes of the genes related to thyroid development (<I>hhex</I> and <I>tg</I>), thyroid hormone transport (<I>ttr</I>) and metabolism (<I>ugt1ab</I>) were observed as well. Thyroid hormone (T4) disruption by BPF was observed even at the concentration (2.0 mg/L) lower than the effective concentration determined for BPA (>2.0 mg/L). Delayed hatching was observed by all tested bisphenols. Our results clearly show that these BPA analogues can disrupt thyroid function of the larval fish, and their thyroid hormone disruption potencies could be even greater than that of BPA. The concentrations which disrupt thyroid function of the larval fish were orders of magnitude higher than those occurring in the ambient environment. However, thyroid hormone disruption by longer term exposure and its consequences in the fish population, deserve further investigation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Thyroid disruption of three BPA substitutes was studied. </LI> <LI> BPA, BPF, and BPS significantly increased T3 and/or T4 levels in larval zebrafish. </LI> <LI> The genes related to TH synthesis were also up-regulated. </LI> <LI> Hatching delay was also observed in larval fish after exposure. </LI> <LI> Similar to BPA, several BPA analogues are thyroid disruptors. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

국내의 조리 식품 중 과불화화합물의 잔류 수준

신재호(Jae-Ho Shin),고영림(Younglim Kho),박나연(Nayoun Park),방선아(Sunah Bang),임초롱(Cho Rong Lim),김판기(Pan-Gyi Kim),김정환(Jung Hoan Kim) 한국식품과학회 2016 한국식품과학회지 Vol.48 No.6

국내에서 유통되는 조리식품 6종류, 151점의 시료를 수집하여 LC-MS/MS를 이용해 PFCs 잔류 수준을 측정하였다. 총 12종의 PFCs를 분석하였으며, PFBS를 제외한 PFCs의 회수율은 82.2-119.4%였으며, 정밀도는 2.2-28.9%였다. PFCs물질별로는 PFPeA(84.1%)와 PFOA (82.8%) 검출률이 높았고, PFOS의 검출률은 29.1%였으며, 대부분의 시료에서 PFOA가 PFOS보다 잔류 수준이 높은 경향을 보였다. 시료의 총 PFCs의 평균 농도는 1.68±1.79 ng/g이었으며, PFPeA와 PFOA의 비중이 높았다. 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.

Development and Validation of Gas Chromatography-Triple Quadrupole Mass Spectrometric Method for Quantitative Determination of Regulated Plasticizers in Medical Infusion Sets

Jeon, So Hyeon,Kim, Yong Pyo,Kho, Younglim,Shin, Jeoung Hwa,Ji, Won Hyun,Ahn, Yun Gyong Hindawi 2018 Journal of analytical methods in chemistry Vol.2018 No.-

<P>A method for the quantitative determination of dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), bis(2-ethylhexyl) adipate (DEHA), bis(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), dioctyl terephthalate (DOTP), diisononyl phthalate (DINP), and diisodecyl phthalate (DIDP) in medical infusion sets was developed and validated using gas chromatography coupled with triple quadrupole mass spectrometry (GC-MS/MS) in the multiple reaction monitoring (MRM) mode. Solvent extraction with polymer dissolution for sample preparation was employed prior to GC-MS/MS analysis. Average recoveries of the eight target analytes are typically in the range of 91.8–122% with the relative standard deviations of 1.8–17.8%. The limits of quantification (LOQs) of the analytical method were in the ranges of 54.1 to 76.3 ng/g. Analysis using GC-MS/MS provided reliable performance, as well as higher sensitivity and selectivity than GC-MS analysis, especially for the presence of minority plasticizers at different concentrations.</P>