Infantile phthalate metabolism and toxico/pharmacokinetic implications within the first year of life. (November 2020)

• Record Type: Journal Article
• Authors: Liu, Liangpo; Wang, Heng; Li, Xueyan; Tian, Meiping; Huang, Qingyu; Zhang, Jie; Pan, Hong; Wen, Kai; Huang, Qiansheng; Yan, Jianbo; Tong, Zhendong; Zhang, Yongli; Zhang, Tongjie; Zhang, Yingying; Li, Ben; Wang, Tong; Shen, Heqing
• Is Part Of: Environment international. Volume 144(2020)
• Publication Date: 2020-11
• Subjects: Infant -- Phthalate exposure -- Urinary exposure biomarkers -- Variability -- Development stage specific clearance; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2020.106052
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: Urine samples were collected serially from infants within the first year of life. Free and total phthalate metabolites were measured by LC/MS/MS. Time series variability in phthalate metabolites and their metabolism was characterized. Most phthalate metabolites changed and their trends increased significantly over age. Infant phthalate exposure is highly prevalent, but cannot metabolize as efficiently as adults. 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.