Di(2-ethylhexyl) phthalate (DEHP): human metabolism and internal exposure—an update and latest results. Int J Androl

Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Erlangen, Germany.
International Journal of Andrology (Impact Factor: 3.7). 03/2006; 29(1):155-65; discussion 181-5. DOI: 10.1111/j.1365-2605.2005.00607.x
Source: PubMed


Di(2-ethylhexyl)phthalate (DEHP) is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. There is widespread exposure to DEHP in the general population. Patients can be additionally exposed through DEHP-containing medical devices. Toxicokinetic and metabolic knowledge on DEHP in humans is vital not only for the toxicological evaluation of DEHP but also for exposure assessments based on human biomonitoring data. Secondary oxidized DEHP metabolites like mono-(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP), mono-(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) and mono-[2-(carboxymethyl)hexyl]phthalate (2cx-MMHP) are most valuable biomarkers of DEHP exposure. They represent the major share of DEHP metabolites excreted in urine (about 70% for these four oxidized metabolites vs. about 6% for MEHP); they are immune to external contamination and possibly the ultimate developmental toxicants. Long half-times of elimination make 5cx-MEPP and 2cx-MMHP excellent parameters to measure the time-weighted body burden to DEHP. 5OH-MEHP and 5oxo-MEHP more reflect the short-term exposure. We calculated the daily DEHP intake for the general population (n = 85) and for children (n = 254). Children were significantly higher exposed to DEHP than adults. Exposures at the 95th percentile (21 and 25 microg/kg/day, respectively) scooped out limit values like the Reference Dose (RfD, 20 microg/kg/day) and the Tolerable Daily Intake (TDI, 20-48 microg/kg/day) to a considerable degree. Up to 20-fold oversteppings for some children give cause for concern. We also detected significant DEHP exposures for voluntary platelet donors (n = 12, 38 microg/kg/apheresis, dual-needle technique). Premature neonates (n = 45) were exposed to DEHP up to 100 times above the limit values depending on the intensity of medical care (median: 42 microg/kg/day; 95th percentile: 1,780 microg/kg/day).

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    • "Measurement of phthalates exposure in humans is complicated by the rapid metabolism and excretion of these compounds. For example, after 24 h, 67% of an oral dose of di(2-ethylhexyl) phthalate (DEHP 3 ) is excreted as five major metabolites in urine (Koch et al., 2006). Previous studies have therefore typically quantified the urinary concentrations of monoester metabolites of phthalates to characterize recent exposure (Anderson et al., 2001; Koch and Calafat, 2009). "
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    ABSTRACT: Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5years [women] or 2.9years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients ≤0.3. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl) phthalate, had a Spearman rank correlation coefficient ≥0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population. Published by Elsevier Ltd.
    Full-text · Article · Aug 2015 · Environment international
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    • "Their ability to leak out from tubing during hemodialysis and blood transfusions represents a potential route of exposure of humans to relatively high concentrations of these environmental chemicals that can reach levels as high as 25 mg/kg/day in children during medical intensive care (Koch et al., 2006). It was reported that Europeans are predominantly exposed to the 2 major phthalates, di-n-butyl phthalate (DBP) and di-2- ethylhexyl phthalate (DEHP) in their day-to-day life (Wormuth et al., 2006). "
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    ABSTRACT: Numerous studies have reported on testicular toxicity of phthalates in different experimental paradigms and showed that Leydig cells (LCs) were one of the main targets of phthalate actions. Adverse effects of phthalates on LCs steroidogenesis have been attributed to their metabolites, mono-phthalates. The present study focuses on investigation whether LCs responsiveness to mono-phthalates action is associated with their potential to produce androgens. We found that of three mono-phthalates investigated (i.e., MEHP, MBP and MBeP) only MEHP caused biological effects on the mouse LCs function. This mono-phthalate stimulated basal steroidogenesis associated with upregulation of StAR protein expression with no effect on hCG-stimulated androgen production by LCs from CBA/Lac and C57BL/6j mouse genotypes were observed. Further, MEHP attenuated ATP production and increased superoxide generation by both phenotypes of mouse LCs that indicated on mitochondrial dysfunction induced by the mono- phthalate. All together, our data indicate that MEHP-mediated stimulation of steroidogenesis and perturbation in mitochondrial function are not associated with the capacity of the LCs to synthesize androgens. We suggest that this effect of MEHP observed in LCs of rodent origin needs to be taken into consideration in analysis of earlier start of puberty in boys and may highlight a possible influence of phthalates on reproductive health in males. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email:
    Full-text · Article · Feb 2015 · Toxicological Sciences
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    • "Many studies indicated that DEHP was a developmental toxicant and endocrine modulator in animals and humans. The results showed that DEHP might cause changes in fertility, pregnancy, and prenatal and postnatal survival of offspring or might reduce sperm counts and cause reproductive organ malformations [15]. Some data demonstrated that young rats exposed to DEHP exhibited the damage of spermatogenic cells which increased significantly with the increase in DEHP dose and exposure time. "
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    ABSTRACT: Background Curcumin is a phytochemical derived from rhizome of turmeric Curcuma longa, present in the curry spice. Recently, it has attracted the attention of researchers and clinicians as an anti-inflammatory and anti-oxidant agent with a potential use in therapy of many diseases with an inflammatory component. Interestingly, curcumin despite its very low bioavailability showed protective activity against many organ lesions. Methods In the present study we investigated the effects of curcumin treatment on mice semen quality parameters in vitro and on semen and testicular damage induced by di(2-ethylhexyl)phthalate in vivo. Results The study demonstrated protective effects of low concentrations (1–50 μM) of curcumin on mouse sperm motility in vitro and on DEHP-induced damage of seminiferous tubules in testes and its ability to diminish the decrease in sperm motility in vivo. In contrast, curcumin used in high concentration (100 μM) decreased sperm motility and viability in vitro. Conclusion The effects of curcumin were dependent on its concentration. In male germ cells in vivo the protective effect was seen despite the low bioavailability of curcumin. In contrast, high, unattainable in the organism, concentration of curcumin had a cytotoxic effect on male reproductive cells in vitro. Curcumin also had a protective effect against the harmful impact of DEHP on the male reproductive system.
    Full-text · Article · Oct 2014 · Pharmacological reports: PR
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