J 2019

A review of phthalate pharmacokinetics in human and rat: what factors drive phthalate distribution and partitioning?

DOMINGUEZ ROMERO, Elena and Martin SCHERINGER

Basic information

Original name

A review of phthalate pharmacokinetics in human and rat: what factors drive phthalate distribution and partitioning?

Authors

DOMINGUEZ ROMERO, Elena (724 Spain, belonging to the institution) and Martin SCHERINGER (756 Switzerland, guarantor, belonging to the institution)

Edition

Drug metabolism Reviews, ABINGDON, TAYLOR & FRANCIS LTD, 2019, 0360-2532

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.956

RIV identification code

RIV/00216224:14310/19:00110375

Organization unit

Faculty of Science

DOI

UT WoS

000472775700001

Keywords in English

Phthalate; partition coefficient; distribution; pharmacokinetic; algorithm; experiment; binding; hydrophobicity; ionization; metabolism

Tags

Tags

International impact, Reviewed
Změněno: 11/5/2020 16:09, Mgr. Marie Šípková, DiS.

Abstract

V originále

Phthalates are a class of compounds that have been extensively used as plasticizers in different applications. Several phthalates have been recognized as substances of very high concern (SVHCs) in the EU, because of their toxicity for reproduction. However, high amounts of other phthalates are still produced and imported in the European Economic Area. In China and the US, recent studies show increasing concentrations of several phthalates in the air and in human urine, respectively. The understanding of phthalate absorption, distribution, metabolism, and elimination ('pharmacokinetics') in the organism is still limited. Specifically, phthalate partitioning among tissues is insufficiently understood. Here, we estimate partition coefficient (PC) values for different phthalates by using five algorithms and compare them to experimental (in-vivo and in-vitro) PC values. In addition, we review all pharmacokinetic steps for phthalates in human and rat, based on data from 133 peer-reviewed publications. We analyze the factors that determine phthalate partitioning and pharmacokinetics. Four processes are particularly relevant to phthalate distribution: protein binding, ionization, passive partitioning, and metabolism in different tissues. The interplay of these processes needs to be better represented in methods for determining the PC values of phthalates. The hydrophobicity of phthalates affects all pharmacokinetic steps. The exposure route has an influence on specific steps of phthalate pharmacokinetics but generally does not affect the pattern of metabolites in urine. The age of the organism has an influence on phthalate metabolism. More studies on the protein-bound fraction of phthalates in plasma and pharmacokinetic studies following inhalation and dermal exposure are desirable.

Links

EF16_013/0001761, research and development project
Name: RECETOX RI
LM2015051, research and development project
Name: Centrum pro výzkum toxických látek v prostředí (Acronym: RECETOX RI)
Investor: Ministry of Education, Youth and Sports of the CR
733032, interní kód MU
Name: European Human Biomonitoring Initiative (Acronym: HBM4EU)
Investor: European Union, Health, demographic change and wellbeing (Societal Challenges)