Dearfield K L, Millis C S, Harrington-Brock K, Doerr C L, Moore M M
Health Effects Division, US Environmental Protection Agency, Washington, DC 20460.
Mutagenesis. 1989 Sep;4(5):381-93. doi: 10.1093/mutage/4.5.381.
Nine acrylate/methacrylate esters were tested for the induction of mutations, aberrations and micronuclei in cultured L5178Y mouse lymphoma cells without exogenous activation. With the exception of 2-ethylhexyl acrylate, and dicyclopentenyloxyethyl methacrylate which produced equivocal mutagenic responses, the other seven compounds (2-hydroxyethyl acrylate, dicyclopentenyloxyethyl acrylate, tetraethylene glycol diacrylate, tetraethylene glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, and pentaerythritol triacrylate) produced positive mutagenic responses with different potencies. For the mutagenic acrylates/methacrylates, primarily small-colony, trifluorothymidine (TFT)-resistant mutants were induced, suggesting a clastogenic mechanism that was supported by increased aberrations and micronucleus frequencies (except for trimethylolpropane trimethacrylate which was positive for aberration but not micronucleus induction). Generally, it was found that multifunctional compounds (esters with greater than 1 functional vinyl group) required lower concentrations than monofunctional compounds to induce maximal cytotoxic, mutagenic, and clastogenic responses. In addition, acrylates were generally more potent than their corresponding methacrylates. This information and these comparative activities will provide some guidance for setting priorities of concern for hazard consideration for acrylate/methacrylate ester compounds.
在无外源性活化的情况下,对9种丙烯酸酯/甲基丙烯酸酯进行了测试,以检测其在培养的L5178Y小鼠淋巴瘤细胞中诱导突变、畸变和微核的能力。除丙烯酸2-乙基己酯和甲基丙烯酸二环戊烯氧基乙酯产生不明确的诱变反应外,其他7种化合物(丙烯酸2-羟乙酯、丙烯酸二环戊烯氧基乙酯、四甘醇二丙烯酸酯、四甘醇二甲基丙烯酸酯、三羟甲基丙烷三丙烯酸酯、三羟甲基丙烷三甲基丙烯酸酯和季戊四醇三丙烯酸酯)产生了不同强度的阳性诱变反应。对于诱变的丙烯酸酯/甲基丙烯酸酯,主要诱导出小菌落、抗三氟胸苷(TFT)的突变体,这表明一种断裂剂机制,该机制得到了畸变增加和微核频率增加的支持(除三羟甲基丙烷三甲基丙烯酸酯仅对畸变呈阳性而对微核诱导呈阴性外)。一般来说,发现多功能化合物(具有大于1个官能乙烯基的酯)比单功能化合物诱导最大细胞毒性、诱变和断裂反应所需的浓度更低。此外,丙烯酸酯通常比其相应的甲基丙烯酸酯更具活性。这些信息和这些比较活性将为确定丙烯酸酯/甲基丙烯酸酯化合物危害考虑的关注重点提供一些指导。