Wen-Qian Wang,Hai-Xin Duan,Zhou-Tao Pei,Rou-Rou Xu,Ze-Tian Qin,Guang-Can Zhu,Li-Wei Sun
Ultraviolet absorbing chemicals (UV filters) are widely used in personal care products for protecting human skin and hair from damage by UV radiation. Although these substances are released into the environment during production and consumption processes, little is known about their genotoxicity effects. Our previous studies have shown that benzophenone-type UV filters exhibited acute toxicity on three species of aquatic organisms. Mutagenesis by benzophenone (BP) and benzophenone-1(BP-1) was tested in the present study by theSalmonella typhimurium/reverse mutation assay (Ames assay). All the positive reverse mutations occurred in the absence of the S9 liver extract system for both chemicals. From BP, positive mutation effects on the TA102 strain at doses of 0.05 μg/plate and 0.5 μg/plate were detected. From BP-1, positive mutation effects on the TA97 strain at doses of 0.05 μg/plate and 0.5 μg/plate, and on the TA100 strain at a dose of 0.5 μg/plate, were detected. A mixture of BP and BP-1 exhibited mutagenicity on the TA97 and TA100 strains. For the TA97 strain, the positive mutation results were detected at 10% and 50% of the mixture. For the TA100 strain, the results were detected when the mixture was at 5% and 10%. In the mixture at 5%, the concentrations of BP and BP-1 were 3.5 μg/plate and 14 μg/plate, respectively. In the 10% mixture, the doses of BP and BP-1 were 7 μg/plate and 28 μg/plate, respectively. In the 50% mixture, the doses of BP and BP-1 were 35 μg/plate and 140 μg/plate, respectively. The mixture test results suggested that there was antagonism in mutagenicity between BP and BP-1.
Tingjie Zhan,Shixuan Cui,Xujun Liu,Chunlong Zhang,Yu-ming M. Huang,Shulin Zhuang
Benzophenone-1 (BP-1), one of the commonly used ultraviolet filters, has caused increasing public concern due to frequently detected residues in environmental and recreational waters. Its susceptibility to residual chlorine and the potential to subsequently trigger endocrine disruption remain unknown. We herein investigated the chlorination of BP-1 in swimming pool water and evaluated the endocrine disruption toward the human androgen receptor (AR). The structures of monochlorinated (P1) and dichlorinated (P2) products were separated and characterized by mass spectrometry and 1H–1H NMR correlation spectroscopy. P1 and P2 exhibited significantly higher antiandrogenic activity in yeast two-hybrid assays (EC50, 6.13 μM and 9.30 μM) than did BP-1 (12.89 μM). Our 350 ns Gaussian accelerated molecular dynamics simulations showed the protein dynamics in a long-time scale equilibrium, and further energy calculations revealed that although increased hydrophobic interactions are primarily responsible for enhanced binding affinities between chlorinated products and the AR ligand binding domain, the second chloride in P2 still hinders the complex motion because of the solvation penalty. The mixture of BP-1–P1–P2 elicited additive antiandrogenic activity, well fitted by the concentration addition model. P1 and P2 at 1 μM consequently downregulated the mRNA expression of AR-regulated genes, NKX3.1 and KLK3, by 1.7–9.1-fold in androgen-activated LNCaP cells. Because chlorination of BP-1 occurs naturally by residual chlorine in aquatic environments, our results regarding enhanced antiandrogenic activity and disturbed AR signaling provided evidence linking the use of personal care products with potential health risks.
危险品化学品经营许可证（带存储）