Metabolism of phthalates in humans

Abstract

Phthalates are synthetic compounds widely used as plasticisers, solvents and additives in many consumer products. Several animal studies have shown that some phthalates possess endocrine disrupting effects. Some of the effects of phthalates seen in rats are due to testosterone lowering effects on the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to phthalates via maternal exposure is a matter of concern. The metabolic pathways of phthalate metabolites excreted in human urine are partly known for some phthalates, but our knowledge about metabolic distribution in the body and other biological fluids, including breast milk, is limited. Compared to urine, human breast milk contains relatively more of the hydrophobic phthalates, such as di-n-butyl phthalate and the longer-branched, di(2-ethylhexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP); and their monoester metabolites. Urine, however, contains relatively more of the secondary metabolites of DEHP and DiNP, as well as the monoester phthalates of the more short-branched phthalates. This differential distribution is of special concern as, in particular, the hydrophobic phthalates and their metabolites are shown to have adverse effects following in utero and lactational exposures in animal studies.

Phthalates and other additives in plastics: human exposure and associated health outcomes

“…Metabolism of phthalates depends on the size and structure of the diester, and can occur via two steps: phase I (e.g. hydrolysis, oxidation) followed by phase II (conjugation) (Frederiksen et al 2007). Since the monoester metabolite may be the more bioactive form of the phthalate, individuals who are predisposed to form and retain more monoester may have a heightened sensitivity to phthalate exposure.…”

Exposure Marker Discovery of Phthalates Using Mass Spectrometry

“…7. 65) Oxidative metabolites are more water soluble than the corresponding hydrolytic monoesters, which, in turn, have decreased water solubility when the length of the alkyl chain increases. erefore, low-molecular weight phthalates mostly metabolize to their hydrolytic monoesters.…”

“…Biotransformation pathways for phthalates. 65) extensively transformed to oxidative products. [68][69][70][71][72][73][74][75][76][77] erefore, using the hydrolytic monoester metabolites as sole biomarkers to assess the exposure of phthalates can be misleading, especially when comparing the hydrolytic monoester concentrations of high-versus low-molecular weight phthalates.…”

Interference of pollutants with PPARs: endocrine disruption meets metabolism

“…Although phthalates are nonpersistent chemicals that are rapidly metabolized, contamination of the environment is significant due to their widespread use. 17 Humans are exposed to phthalates through ingestion, inhalation or dermal absorption throughout their entire life. The long-branched di-ethyl-hexylphthalate (DEHP) is one of the most widespread phthalate plasticizers used as a major component in polyvinyl chloride plastics, which are frequently used in medical devices and consumer products.…”

“…Earlier studies have indeed shown that both in utero and adult exposure to phthalates have various effects on endocrine functions, in some cases mediated by PPARs. 17,19,40,49,66 Embryogenesis is a very sensitive period and several studies Figure 1 Schematic representation of the effects of MEHP on adipogenesis through selective PPARg modulation. MEHP, compared to the specific PPARg agonist rosiglitazone, only partially abolishes the interaction between PPARg and the corepressor NCoR.…”