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Background: We aimed to determine relationship diabetes according to urinary phthalate metabolites using adult data from Korean National Environmental Health Survey cycle 3 (2015-2017)., Method: This study was conducted on 3,781 adults aged 19 years and older (1,648 men and 2,133 women) based on KoNEHS cycle 3. Participants' data were analyzed by gender; Relationship between phthalate metabolites in the urine and diabetes was analyzed by dividing the sociodemographic variables, health behavior-related variables, and urinary phthalate metabolite concentrations into quartiles. To determine the relationship between urinary phthalate metabolites and the prevalence of diabetes, the odds ratio (OR) was calculated using logistic regression analysis., Results: Based on the 1st quartile of each metabolite, the ORs for di-2-ethylhexyl phthalate (DEHP) (4th quartile), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (2nd quartile, 3rd quartile and 4th quartile), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) (4th quartile), mono-(2-ethyl-5-carboxypentyl) phthalate (MECCP) (4th quartile), mono-n-butyl phthalate (MnBP) (3rd quartile and 4th quartile), mono-benzyl phthalate (MBzP) (2nd quartile) and 4th quartile), and mono (3-carboxypropyl) phthalate (MCPP) (3rd quartile and 4th quartile) were significantly higher after the adjustment in men. The ORs for DEHP (2nd quartile, 3rd quartile and 4th quartile), MEHHP (2nd quartile, 3rd quartile and 4th quartile), MEOHP (4th quartile), MECCP (4th quartile), MBzP (4th quartile), and MCPP (4th quartile) were significantly higher after the adjustment in women., Conclusion: This study investigated relationship between urinary phthalate metabolites and diabetes. The higher urinary phthalate metabolites, the higher the prevalence of diabetes. Further regulation of phthalate may be needed, and further studies are warranted to confirm the association between phthalate concentration and other chronic diseases (such as hypertension, hyperlipidemia, and cardiovascular disease)., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2020 Korean Society of Occupational & Environmental Medicine.)

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007-2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6-49 year old survey respondents (n=3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age×creatinine, age×sex and fasting status×creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population., (Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.)

Background: Di-2-ethylhexylphthalate (DEHP) is an ester of phthalic acid commonly found in processed foods. DEHP may contribute to obesity and insulin resistance in children and adolescents, yet dietary exposures have been not been studied in this vulnerable subpopulation., Objective: To assess diet and its relation to urinary phthalates in a nationally representative sample of US children and adolescents., Design: Cross-sectional analysis of 24-h dietary recall and urinary phthalate metabolites from 2743 6-19 year olds participating in the 2003-8 National Health and Nutrition Examination Surveys. Regression analyses examined relationships of food consumption with log-transformed metabolite concentrations, examined as low-molecular weight, high molecular weight and di-2-ethylhexylphthalate categories, controlling for urinary creatinine, age group, body mass index category, race/ethnicity, caloric intake and gender., Results: We identified a -0.04% (95% CI: -0.08, -0.01) increment in di-2-ethylhexylphthalate metabolite concentration/additional gram fruit consumption, a +0.01% increment/additional calorie dietary intake (95% CI: +0.003, +0.02), and a +0.09% (95% CI: +0.02, +0.17) increment/additional gram meat/poultry/fish consumption. Soy consumption (-0.40% increment/additional gram consumed, 95% CI: -0.66, -0.14) was inversely associated with di-2-ethylhexylphthalate, while poultry (+0.23% increment/additional gram consumed, 95% CI: +0.12, +0.35) was positively associated. Findings were robust to examination of metabolite concentrations per unit body mass index and weight, and inclusion of fasting time., Conclusions: Diet contributes to urinary phthalate concentrations in children and adolescents. Further study is needed to examine the implications of di-2-ethylhexylphthalate exposure, especially earlier in life, when more permanent metabolic changes may occur., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood., Objective: To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women., Methods: We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year., Results: The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1-0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ∑DEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant., Conclusions: Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To examine associations of urinary phthalate levels with blood pressure (BP) and serum triglyceride and lipoprotein levels in children., Study Design: We performed a cross-sectional analysis of a subsample of US children aged 6-19 years who participated in the National Health and Nutrition Examination Survey between 2003 and 2008. We quantified exposure to 3 families of phthalates--low molecular weight, high molecular weight and di-2-ethylhexylphthalate (DEHP)--based on molar concentration of urinary metabolites. We assessed descriptive, bivariate, and multivariate associations with BP and lipid levels., Results: Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass index, levels of metabolites of DEHP, a phthalate commonly found in processed foods, were associated with higher age-, sex-, and height-standardized BP. For each log unit (roughly 3-fold) increase in DEHP metabolites, a 0.041 SD unit increase in systolic BP z-score was identified (P = .047). Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products were not associated with BP. Phthalate metabolites were not associated with triglyceride levels, high-density lipoprotein level, or prehypertension., Conclusions: Dietary phthalate exposure is associated with higher systolic BP in children and adolescents. Further work is needed to confirm these associations, as well as to evaluate opportunities for intervention., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Human exposure to chemicals commonly encountered in our environment, like phthalates, is routinely assessed through urinary measurement of their metabolites. A particular attention is given to the specific population groups, such as obese, for which the dietary intake of environmental chemicals is higher. To evaluate the exposure to phthalates, nine phthalate metabolites (PMs) were analyzed in urine collected from obese individuals and a control population. Obese individuals lost weight through either bariatric surgery or a conservative weight loss program with dietary and lifestyle counseling. Urine samples were also collected from the obese individuals after 3, 6 and 12months of weight loss. Individual daily intakes of the corresponding phthalate diesters were estimated based on the urinary PM concentrations. A high variability was recorded for the levels of each PM in both obese and control urine samples showing the exposure to high levels of PMs in specific subgroups. The most important PM metabolite as percentage contribution to the total PM levels was mono-ethyl phthalate followed by the metabolites of di-butyl phthalate and di 2-ethyl-hexyl phthalate (DEHP). No differences in the PM levels and profiles between obese entering the program and controls were observed. Although paralleled by a significant decrease of their weight, an increase in the urinary PM levels after 3 to 6months loss was seen. Constant figures for the estimated phthalates daily intake were observed over the studied period, suggesting that besides food consumption, other human exposure sources to phthalates (e.g. air, dust) might be also important. The weight loss treatment method followed by obese individuals influenced the correlations between PM levels, suggesting a change of the intake sources with time. Except for few gender differences recorded between the urinary DEHP metabolites correlations, no other differences were observed for the urinary PM levels as a function of age, body mass index or waist circumference. Linear regression analysis showed almost no significance of the relationship between measured urinary PMs and serum free thyroxine, thyroid-stimulating hormone (TSH) for all obese individuals participating to the study, while for the control samples, several PMs were significantly associated with the serum TSH levels., (© 2013.)

Background: Previous studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life., Objectives: To evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24-36 months of age., Methods: This analysis was conducted on the first three years of life among a subsample of 136 mother-child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36 months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level., Results: No significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (β=-2.11 [95% CI: -3.73, -0.49]), MEHHP (β=-1.89 [95% CI: -3.64, -0.15]), MEOHP (β=-1.80 [95% CI: -3.58, -0.03]) MECPP (β=-2.52 [95% CI: -4.44, -0.61]), and ΣDEHP (β=-3.41 [95% CI: -5.26, -1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (β=1.79 [95% CI: 0.14, 3.45]) and MCPP (β=1.64 [95% CI: 0.15, 3.12]); there was no significant effect on PDI among girls., Conclusion: This study demonstrates that sex plays a role of an effect modifier in the association between prenatal phthalate exposure and neurodevelopment., (Copyright © 2013 Elsevier B.V. All rights reserved.)