Can the observed association between serum perfluoroalkyl substances and delayed menarche be explained on the basis of puberty-related changes in physiology and pharmacokinetics?
An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of...
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| Published in | Environment international Vol. 82; pp. 61 - 68 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
01.09.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0160-4120 1873-6750 1873-6750 |
| DOI | 10.1016/j.envint.2015.05.006 |
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| Abstract | An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association.
To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden.
We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association.
The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values.
The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances.
•Ability to simulate longitudinal trends in blood biomarkers in early life•Kinetic variation contributed to the association between PFAS and age at menarche.•MC-PBPK modeling can enhance interpretation of epidemiological associations. |
|---|---|
| AbstractList | Background An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association. Objectives To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden. Methods We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association. Results The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values. Conclusion The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association.BACKGROUNDAn association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association.To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden.OBJECTIVESTo assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden.We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association.METHODSWe developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association.The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values.RESULTSThe prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values.The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances.CONCLUSIONThe reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association. To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden. We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association. The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values. The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association.To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden.We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association.The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values.The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association. To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden. We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association. The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values. The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. •Ability to simulate longitudinal trends in blood biomarkers in early life•Kinetic variation contributed to the association between PFAS and age at menarche.•MC-PBPK modeling can enhance interpretation of epidemiological associations. |
| Author | Andersen, Melvin E. Longnecker, Matthew P. Verner, Marc-André Clewell, Harvey J. Luo, Man Wu, Huali Xue, Jianping Yoon, Miyoung |
| Author_xml | – sequence: 1 givenname: Huali surname: Wu fullname: Wu, Huali organization: The Hamner Institutes for Health Sciences, RTP, NC, USA – sequence: 2 givenname: Miyoung surname: Yoon fullname: Yoon, Miyoung organization: The Hamner Institutes for Health Sciences, RTP, NC, USA – sequence: 3 givenname: Marc-André surname: Verner fullname: Verner, Marc-André organization: Department of Environmental Health, Harvard School of Public Health, Boston, USA – sequence: 4 givenname: Jianping surname: Xue fullname: Xue, Jianping organization: US Environmental Protection Agency, RTP, NC, USA – sequence: 5 givenname: Man surname: Luo fullname: Luo, Man organization: The Hamner Institutes for Health Sciences, RTP, NC, USA – sequence: 6 givenname: Melvin E. surname: Andersen fullname: Andersen, Melvin E. organization: The Hamner Institutes for Health Sciences, RTP, NC, USA – sequence: 7 givenname: Matthew P. surname: Longnecker fullname: Longnecker, Matthew P. organization: National Institute of Environmental Health Sciences, RTP, NC, USA – sequence: 8 givenname: Harvey J. surname: Clewell fullname: Clewell, Harvey J. organization: The Hamner Institutes for Health Sciences, RTP, NC, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26043300$$D View this record in MEDLINE/PubMed |
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| Snippet | An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents.... Background An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of... |
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| SubjectTerms | Adolescent adolescents Age Alkanesulfonic Acids blood serum Caprylates Computer simulation Cross-Sectional Studies Environmental exposure epidemiological studies Epidemiology excretion Female females Fluorocarbons - blood Fluorocarbons - pharmacokinetics half life Humans Male Mathematical models Menarche Menarche - physiology menstruation PBPK Perfluoroalkyls perfluorooctane sulfonic acid perfluorooctanoic acid PFA PFOA PFOS pharmacokinetics Physiology Prevalence Puberty - physiology Serums Sexual Maturation toxicity |
| Title | Can the observed association between serum perfluoroalkyl substances and delayed menarche be explained on the basis of puberty-related changes in physiology and pharmacokinetics? |
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