Infantile phthalate metabolism and toxico/pharmacokinetic implications within the first year of life

Liangpo Liu; Heng Wang; Xueyan Li; Meiping Tian; Qingyu Huang; Jie Zhang; Hong Pan; Kai Wen; Qiansheng Huang; Jianbo Yan; Zhendong Tong; Yongli Zhang; Tongjie Zhang; Yingying Zhang; Ben Li; Tong Wang; Heqing Shen

doi:10.1016/j.envint.2020.106052

Infantile phthalate metabolism and toxico/pharmacokinetic implications within the first year of life

Environ Int. 2020 Nov:144:106052. doi: 10.1016/j.envint.2020.106052. Epub 2020 Aug 18.

Authors

Liangpo Liu¹, Heng Wang², Xueyan Li³, Meiping Tian⁴, Qingyu Huang⁴, Jie Zhang⁵, Hong Pan⁵, Kai Wen⁵, Qiansheng Huang⁴, Jianbo Yan², Zhendong Tong², Yongli Zhang², Tongjie Zhang⁶, Yingying Zhang⁷, Ben Li⁷, Tong Wang⁷, Heqing Shen⁸

Affiliations

¹ School of Public Health, Shanxi Medical University, Taiyuan 030001, PR China; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China. Electronic address: lpliu@sxmu.edu.cn.
² Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, Zhoushan Municipal Center for Disease Control and Prevention, Zhoushan, Zhejiang 316021, PR China.
³ Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China; Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, Zhoushan Municipal Center for Disease Control and Prevention, Zhoushan, Zhejiang 316021, PR China.
⁴ Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China.
⁵ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, PR China.
⁶ Daishan County Center for Disease Control and Prevention, Daishan, Zhejiang 316200, PR China.
⁷ School of Public Health, Shanxi Medical University, Taiyuan 030001, PR China.
⁸ Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, PR China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, PR China. Electronic address: hqshen@xmu.edu.cn.

PMID: 32822925
DOI: 10.1016/j.envint.2020.106052

Abstract

Background: Infantile development of phthalate metabolism is crucial for risk assessment of endocrine disruption and has important toxico/pharmacokinetic implications.

Objectives: To characterize temporal variability in urinary phthalate metabolites in infants and to examine their growth-dependent detoxification.

Methods: In this cohort study, urine samples (n = 876) from 155 healthy Chinese infants were collected serially at eight time points from birth to one year old. Free and total (i.e., free plus glucuronide conjugated) phthalate metabolites (PMEs) were measured by LC/MS/MS. Time variability in PMEs and PME metabolism capacity was characterized using intraclass correlation coefficients (ICCs) and linear mixed regression models.

Results: Concentrations of most PMEs changed significantly, with ICCs ranging from 0.213 to 0.318, and trends increased significantly over time (p < 0.001), while MEHP showed fair reproducibility (ICC = 0.480). Glucuronidation increased considerably (ICC ≤ 0.250; p < 0.001) for most PMEs but not for MMP or MEHP. Ester-chain ω-/ω-1-oxidation and α-/β-oxidation patterns of MEHP steeply increased from 3 months to 8 months, where they peaked, resulting in a molar percentage of MEHP in ΣDEHP showing the inversion pattern. MEHP detoxification through oxidation of the hydrophobic ester-chain is apparently a priority for carboxyl glucuronidation in infants.

Conclusions: Infant phthalate exposure is prevalent, but they cannot metabolize or eliminate these compounds as efficiently as adults, especially during the first 6 months of life. From an environmental biomonitoring view, age-dependent phthalate metabolism provides crucial implications for infantile ontogeny and health risk assessment within the first year of life.

Keywords: Development stage specific clearance; Infant; Phthalate exposure; Urinary exposure biomarkers; Variability.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cohort Studies
Diethylhexyl Phthalate* / toxicity
Environmental Exposure / analysis
Environmental Pollutants* / toxicity
Humans
Infant
Phthalic Acids* / toxicity
Reproducibility of Results
Tandem Mass Spectrometry

Substances

Environmental Pollutants
Phthalic Acids
phthalic acid
Diethylhexyl Phthalate