The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats
Autor: | Tong Yu, Linlin Sai, Zhaobin Zhang, Junyu Li, Xuan Xiao, Han Xiao, Jilong Guo, Desheng Zhu, Yingli Sun, Jun Li, Ying Hu, Libei Sun |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
medicine.medical_specialty No-observed-adverse-effect level Acceptable daily intake Estrogen receptor Parabens Urine 010501 environmental sciences Pharmacology Real-Time Polymerase Chain Reaction 01 natural sciences Article Gas Chromatography-Mass Spectrometry Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Estradiol Congeners In vivo Internal medicine medicine Animals Ethylparaben 0105 earth and related environmental sciences No-Observed-Adverse-Effect Level Multidisciplinary Methylparaben Gene Expression Profiling Uterus Estrogen Receptor alpha Estrogens Molecular Docking Simulation 030104 developmental biology Endocrinology chemistry Female Estrogen receptor alpha Protein Binding |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
Popis: | The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT–PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography–mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα). |
Databáze: | OpenAIRE |
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