Phthalate metabolites: Characterization, toxicities, global distribution, and exposure assessment

Ying-Jie Zhang; Jia-Liang Guo; Jing-Chuan Xue; Cui-Lan Bai; Ying Guo

doi:10.1016/j.envpol.2021.118106

Phthalate metabolites: Characterization, toxicities, global distribution, and exposure assessment

Environ Pollut. 2021 Dec 15:291:118106. doi: 10.1016/j.envpol.2021.118106. Epub 2021 Sep 4.

Authors

Ying-Jie Zhang¹, Jia-Liang Guo¹, Jing-Chuan Xue², Cui-Lan Bai¹, Ying Guo³

Affiliations

¹ Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 510632, China.
² Key Laboratory for City Cluster Environmental Safety and Green Development of the Ministry of Education, Institute of Environmental and Ecological Engineering, Guangdong University of Technology, Guangzhou, 510006, China.
³ Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 510632, China. Electronic address: yingguo2004@jnu.edu.cn.

PMID: 34520948
DOI: 10.1016/j.envpol.2021.118106

Abstract

Phthalates are plasticizers in various products and regarded as endocrine disruptors due to their anti-androgen effects. Environmental occurrence and toxicities of parent phthalates have been widely reported, while the current state of knowledge on their metabolites is rarely summarized. Based on the available literature, the present review mainly aims to 1) characterize the potential metabolites of phthalates (mPAEs) using the pharmacokinetics evidences acquired via animal or human models; 2) examine the molecular and cellular mechanism involved in toxicity for mPAEs; 3) investigate the exposure levels of mPAEs in different human specimens (e.g., urine, blood, seminal fluid, breast milk, amniotic fluid and others) across the globe; 4) discuss the models and related parameters for phthalate exposure assessment. We suggest there is subtle difference in toxic mechanisms for mPAEs compared to their parent phthalates due to their alternative chemical structures. Human monitoring studies performed in Asia, America and Europe have provided the population exposure baseline levels for typical phthalates in different regions. Urine is the preferred matrix than other specimens for phthalate exposure study. Among ten urinary mPAEs, the largest proportions of di-(2-ethylhexyl) phthalate (DEHP) metabolites (40%), monoethyl phthalate (mEP) (43%) and DEHP metabolites/mEP (both 29%) were observed in Asia, America and Europe respectively, and mono-5-carboxy-2-ethypentyl phthalate was the most abundant compounds among DEHP metabolites. Daily intakes of phthalates can be accurately calculated via urinary mPAEs if the proper exposure parameters were determined. Further work should focus on combining epidemiological and biological evidences to establish links between phthalates exposure and biological phenotypes. More accurate molar fractions (F_UE) of the urinary excreted monoester related to the ingested diesters should be collected in epidemiological or pharmacokinetic studies for different population.

Keywords: EDI model; Global distribution; Human exposure profile; Human matrix; Phthalate metabolite; Toxicity.

Publication types

Review

MeSH terms

Diethylhexyl Phthalate* / toxicity
Endocrine Disruptors*
Environmental Exposure / analysis
Environmental Pollutants* / toxicity
Female
Humans
Milk, Human / chemistry
Phthalic Acids* / analysis
Phthalic Acids* / toxicity
Plasticizers / toxicity

Substances

Endocrine Disruptors
Environmental Pollutants
Phthalic Acids
Plasticizers
phthalic acid
Diethylhexyl Phthalate