• Safety and Health at Work
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• v.2 no.1
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• pp.57-64
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• 2011

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.

• Journal of Environmental Health Sciences
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• v.34 no.4
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• pp.271-278
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• 2008

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 children's 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 children's 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 children's age (months) was negatively correlated to the concentration of phthalate metabolites. The geometric mean concentration of phthalate metabolites (mg/g creatinine) in children's 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 (${\mu}g$/kg bw/day) were 0.8 for DEP, 5.0 for DnBP, 1.9 for DiBP and $8.9{\sim}14.2$ 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.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.53.1-53.15
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• 2023

Background: Plastics are high-molecular-weight materials composed of long carbon chains. They are prevalent in daily life, present in various items such as food containers and microwavable packaging. Phthalates, an additive used to enhance their flexibility, are endocrine-disrupting chemicals. We utilized the data from the Korean National Environmental Health Survey (KoNEHS) cycle 3, representing the general South Korean population, to investigate the relationship between the use of plastics in refrigerator food storage and phthalate exposure. Methods: We assessed 3,333 adult participants (aged ≥ 19 years) including 1,526 men and 1,807 women, using data from KoNEHS cycle 3. Using the 75th percentile concentration, urine phthalate metabolites were categorized into high and low-concentration groups. χ² test was conducted to analyze variations in the distribution of each variable, considering sociodemographic factors, health-related factors, food intake, the use of plastics, and the concentration of urine phthalate metabolites as the variables. To calculate odds ratios (ORs) for the high-concentration group of urine phthalate metabolites based on the use of plastics in refrigerator food storage, logistic regression analysis was conducted. Results: In men, the use of plastics in refrigerator food storage had significantly higher adjusted ORs compared to those using the others. The adjusted ORs were calculated as follows: mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) had an OR of 1.35 (95% confidence interval [CI]: 1.05-1.72), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) had an OR of 1.48 (95% CI: 1.16-1.88), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) had an OR of 1.32 (95% CI: 1.04-1.66), ∑di(2-ethylhexyl) phthalate (∑DEHP) had an OR of 1.37 (95% CI: 1.08-1.74) and mono-n-butyl phthalate (MnBP) had an OR of 1.44 (95% CI: 1.13-1.84). Conclusion: The concentrations of urine phthalate metabolites (MEHHP, MEOHP, MECPP, ∑DEHP, and MnBP) were significantly higher in men who used plastics in refrigerator food storage compared to those using the others.

• Advances in environmental research
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• v.2 no.1
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• pp.9-17
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• 2013

Urine is a widely used matrix in biomonitoring studies on the assessment of human exposure to environmental chemicals such as phthalate esters and bisphenol A (BPA). In addition to the need to apply valid analytical techniques, assurance of specimen integrity during collection and storage is an important prerequisite for the presentation of accurate and precise analytical data. One of the common issues encountered in the analysis of non-persistent contaminants is whether shipping and storage temperature and time since collection have an effect on sample integrity. In this study, we investigated the stability of phthalate metabolites and BPA in spiked and unspiked urine samples stored at room temperature ($20^{\circ}C$) or at $-80^{\circ}C$ for up to 8 weeks. Concentrations of phthalate metabolites declined, on average, by 3% to 15%, depending on the compounds, and BPA declined by ~30% after 4 weeks of storage of spiked urine samples at $20^{\circ}C$. In a test of 30 unspiked urine samples stored at $20^{\circ}C$ and at $-80^{\circ}C$ for 8 weeks, the concentrations of phthalate metabolites and BPA decreased by up to 15% to 44%, depending on the compound and on the samples. It was found that the small reduction in phthalate concentrations observed in urine, varied depending on the samples. In a few urine samples, concentrations of phthalate metabolites and BPA did not decline even after storage at $20^{\circ}C$ for 8 weeks. We found a significant relationship between concentrations of target analytes in urine stored at $20^{\circ}C$ and at $-80^{\circ}C$ for 8 weeks. We estimated the half-lives of phthalate metabolites and BPA in urine stored at $20^{\circ}C$. The estimated half-life of monoethyl phthalate (mEP) and mono (2-ethyl-5-carboxyphentyl) phthalate (mECPP) in urine stored at $20^{\circ}C$ was over two years, of mono (2-ethyl-5-oxohexyl) phthalate (mEOHP) and monobenzyl phthalate (mBzP) was approximately one year, and of other phthalate metabolites was approximately 6 months. The estimated half-life of BPA in urine stored at $20^{\circ}C$ was approximately 3 months, which is much longer than that reported for aquatic ecosystems.

• Journal of Environmental Health Sciences
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• v.36 no.6
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• pp.510-517
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• 2010

Phthalates, such as di (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) have been proved to be teratogenics and endocrine disruptors, metabolized rapidly and excreted in the urine. In this study, a simultaneous analytical method for 10 phthalate metabolites, MnBP, MiBP, MBzP, MCHP, MEHP, MEHHP, MEOHP, MnOP, MiNP and MiDP, in human urines, based on switching system with on-line pretreatment column using HPLC-MS/MS has been developed. This method was validated according to the guideline of bioanalytical method validation of National Institute of Toxicological Research. Limits of detection range between 0.2 and 0.9 ng/ml for 10 phthalate metabolites. The calibration curves showed linearity in the range 0.997~0.999, and the results of the intra- and inter-day validations were in the range from 0.4 to 14.7% RSD and from 0.3 to 9.4% RSD, respectively. Recoveries of phthalate metabolites varied from 87.0 to 116.1%. This analytical method showed high accuracy and stable precision for all metabolites, and seems to be suitable for biomonitoring of phthalates in human urine.

• Annals of Occupational and Environmental Medicine
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• v.35
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• pp.2.1-2.15
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• 2023

Background: Phthalates are endocrine disrupting chemicals that are widely used in the production of items of daily life such as in polyvinylchloride plastics, insecticides, and medical devices. This study aimed to determine the association between phthalate exposure and shellfish consumption using data from the Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017), which is a nationally representative survey. Methods: In this study, we analyzed the KoNEHS cycle 3 data of 3,333 (1,526 men and 1,807 women) adults aged more than 19 years. Data related to the variables of sociodemographic factors, health-related behaviors, dietary factors, seafood consumption frequency, and urinary phthalate metabolites concentrations were collected. The concentrations of urinary phthalate metabolites of all the participants were divided into quartiles to define high and low concentration groups based on the 75th percentile concentration. A χ² test was conducted to analyze the distribution of independent variables. To analyze the relationship between shellfish consumption and phthalate exposure, the odds ratios (ORs) were calculated using logistic regression analysis. Results: Total adults with shellfish consumption frequency of over once a week showed the following adjusted ORs for high concentrations of the following metabolites compared with the group that consumed shellfish once a week or less: 1.43 (95% confidence interval [CI]: 1.01-2.06) for mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), 1.43 (95% CI: 1.01-2.03) for mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), 1.57 (95% CI: 1.10-2.24) for ∑di-2-ethylhexyl phthalate (∑DEHP), 2.01 (95% CI: 1.46-2.77) for mono-carboxyoctyl phthalate (MCOP), 1.56 (95% CI: 1.11-2.18) for mono-carboxy-isononly phthalate (MCNP), and 2.57 (95% CI: 1.85-3.56) for mono (3-carboxypropyl) phthalate (MCPP). Conclusions: The concentrations of urinary phthalate metabolites (MEOHP, MECPP, ∑DEHP, MCOP, MCNP, and MCPP) were higher in adults with a higher frequency of shellfish consumption.

• Environmental Mutagens and Carcinogens
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• v.25 no.3
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• pp.110-117
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• 2005

DEHP is one of well known endocrine disrupter and it is used as additives for the production of PVC. There has been contradictional result on the genotoxicity of DEHP. In order to examine genotoxicity of a endocrine disruptors, DEHP (Di-2-EthylHexyl Phthalate) and it's metabolites, EHA (2-EthylHexanoic Acid) and DEP (Di-2-Ethyl Phthalate), chromosome aberration (CA), sister chromatid exchange (SCE), micronuclei (MN) and single cell gel electrophoresis were analysised. No increase of the frequency of CA was observed by DEHP and its two metabolites. DEHPincreased the frequency of SCE and MN whereas EHA only increased the frequency of SCE. DEP increased the frequency of SCE but the increase was not statistically significant. DEHP and DEP, also induced DNA damage. It is suggested that combination of different methods were recomended to find the genotoxicity of DEHP and its metabolites.

• Journal of Environmental Health Sciences
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• v.39 no.5
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• pp.408-417
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• 2013

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.

• Journal of Environmental Health Sciences
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• v.48 no.6
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• pp.315-323
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• 2022

Background: Socioeconomical disadvantaged communities are more vulnerable to environmental chemical exposure and associated health effects. However, there is limited information on chemical exposure among vulnerable populations in Korea. Objectives: This study investigated chemical exposure among underprivileged populations. We measured urinary metabolites of phthalates in urban disadvantaged communities and investigated their correlations with residential environment factors and relative socioeconomic vulnerability. Methods: Urine samples were collected from 64 residents in a disadvantaged community in Seoul. A total of eight phthalate metabolites were analyzed by liquid chromatography-mass spectroscopy. Analytical method used by the Korean National Environmental Health Survey (KoNEHS) was employed. Covariate variance analysis and general linear regression adjusted with age, sex and smoking were performed. Results: Several phthalate metabolites, namely monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-n-butyl phthalate (MnBP) had higher levels than those reported in the adults of 4th KoNEHS. Notably, the MnBP level was higher in the lower socioeconomic group (geometric mean [GM]=47.3 ㎍/g creatinine) compared to non-recipients (GM=31.9 ㎍/g creatinine) and the national reference level (GM=22.0, 28.2 and 32.2 ㎍/g creatinine for adults, 60's and 70's, respectively.). When age, sex and smoking were adjusted, MEP and MnBP were significantly increased the lower socioeconomic group than non-recipients (p=0.014, p=0.023). The lower socioeconomic group's age of flooring were higher than non-recipients, not statistically significant. Conclusions: These results suggest that a relatively low income and aged flooring could be considered as risk factors for increased levels of phthalate metabolites in socioeconomic vulnerable populations.

• Journal of Environmental Health Sciences
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• v.44 no.5
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• pp.433-443
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• 2018

Objectives: The purpose of this study was to examine the relationship between dietary habits and concentrations of urinary phthalate metabolite in elementary school children. Methods: This study was conducted in Seoul, South Korea. We collected urine samples from 156 children from a single school in September 2016. Information on dietary habits was obtained from the parents of the children. Five types of urinary phthalate metabolites were analyzed using a high-performance liquid chromatography tandem mass spectrometer. Multiple linear regression analysis was used to determine the factors affecting the concentrations of urinary phthalate metabolite. Results: Girls had a significantly lower concentration of urinary mono-n-butyl phthalate (MnBP) (p=0.006) than did boys. When the consumption of bean processed food and wrapped delivery food were more than once a week, urinary MnBP (p=0.021) and monobenzyl phthalate (MBzP) (p=0.032) concentrations were the highest, respectively. Conclusion: Several urinary phthalate metabolite concentrations were associated with demographic and dietary habits. Particularly, urinary MnBP and MBzP were associated with several processed foods. The findings of this study might be useful as basic data for establishing and educating on environmental health policy.