Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate.

Abstract

Exposure to di-(2-ethylhexyl) phthalate (DEHP) is prevalent based on the measurement of its hydrolytic metabolite mono-(2-ethylhexyl) phthalate (MEHP) in the urine of 78% of the general U.S. population studied in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). However, despite the high level of production and use of DEHP, the urinary MEHP levels in the NHANES samples were lower than the monoester metabolites of phthalates less commonly used than DEHP, suggesting metabolic differences between phthalates. We measured MEHP and two oxidative DEHP metabolites, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) to verify whether these other metabolites account for a greater proportion of DEHP metabolic products in 127 paired human urine and serum samples. We found that the urinary levels of MEHHP and MEOHP were 10-fold higher than levels of MEHP; concentrations of urinary MEOHP and MEHHP were strongly correlated (r = 0.928). We also found that the serum levels of MEOHP and MEHHP were comparatively lower than those in urine. Furthermore, the glucuronide-bound conjugates of the oxidative metabolites were the predominant form in both urine and serum. MEOHP and MEHHP cannot be formed by serum enzymes from the hydrolysis of any contamination from DEHP potentially introduced during blood collection and storage. Therefore, concentrations of MEHHP and MEOHP in serum may be a more selective measure of DEHP exposure than is MEHP. However, additional data on the absorption, distribution, metabolism, and elimination of these oxidative metabolites are needed to completely understand the extent of DEHP exposure from the serum concentrations of oxidative DEHP metabolites.

Assessing exposure to phthalates – The human biomonitoring approach

“…For all these reasons, in most of the subsequent biomonitoring studies, oxidative phthalate metabolites of DEHP and DiNP have been implemented in the parameter spectrum [16,19,106,[140][141][142]. The two oxidative DEHP metabolites mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) and mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) are excreted in at least three times higher concentrations than MEHP in the general population, proving these oxidative metabolites as much more sensitive biomarkers of DEHP exposure than MEHP.…”

Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes

“…In the airways, DEHP is absorbed as the parent compound and thereafter metabolized to MEHP (Shea 2003). Serum MEHP levels are generally low in the population (50th percentileZ4 ng/ml), but markedly higher levels of exposure occur in, for example, patients undergoing intensive care (Kato et al 2004). Infants are particularly exposed and plasma MEHP levels as high as 15.1 mg/ml (z54 mM) have been recorded (Sjoberg et al 1985).…”

Exposure to Di-(2-Ethylhexyl) Phthalate Among Premature Neonates in a Neonatal Intensive Care Unit

“…The median percentages (and SDs) of the free DEHP oxidative metabolites in the neonates' samples (mEHHP: 22% [17%]; mEOHP: 21% [18%]) were higher than those found in 127 urine samples collected during 2001 from a demographically diverse population group (mEHHP: 5% [21%]; mEOHP: 12% [23%]). 37 The percentage of free mEHP in the urine of the neonates was not calculated because of the low frequency of detection of free mEHP. Additional studies are warranted to confirm the percentages of glucuronidation of the DEHP metabolites in individuals, including infants and young children, who are exposed to elevated levels of DEHP.…”