Abstract
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).
Highlights
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
The uterine weights were significantly increased in rats treated with 20 mg/kg bw/ day of MP and 4 and 20 mg/kg bw/day of EP (P < 0.05); based on the uterotrophic activities of MP and EP, the lowest-observed-effect levels (LOELs) were 20 mg/kg bw/day for MP and 4 mg/kg bw/day for EP, and the no-observed-effect levels were 4 mg/kg bw/day for MP and 0.8 mg/kg bw/day for EP
This study demonstrates the in vivo estrogenicity of MP and EP at doses close to the acceptable daily intake (ADI) in immature SD rats after intragastric administration
Summary
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. 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. Lemini et al studied the estrogenicity of parabens with uterotrophic assay in immature and adult ovariectomized CD1 mice and in immature female Wistar rats[21] They found the median effective dose (ED50) of parabens to increase the uterine weight in CD1 mice ranged from 18 to 74 mg/kg, and that of E2 was 7 μ g/kg; in Wistar rats, the ED50 ranged from 33 to 338 mg/kg[21]. In a review of studies on paraben toxicology, Darbre and Harvey[15] discussed whether “parabens [should] be termed ‘weak oestrogens’” and suggested that “the extent to which parabens can be labelled as ‘weak oestrogens’ needs further consideration”[15]
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