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. 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.
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.
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.
Authors: Fiorella Lucarini; Marc Blanchard; Tropoja Krasniqi; Nicolas Duda; Gaëlle Bailat Rosset; Alessandro Ceschi; Nicolas Roth; Nancy B Hopf; Marie-Christine Broillet; Davide Staedler Journal: Int J Environ Res Public Health Date: 2021-06-24 Impact factor: 3.390