四个α,β-不饱和醛,2-苯基-2-丁烯醛,nona-2-反式-6-顺式二烯醛,2-甲基-2-戊烯醛,和对甲氧基肉桂醛,用作香料,使用鸡蛋遗传毒性试验(CEGA)和鸡蛋微核试验(HET-MN)进行评估,分别。材料的选择是基于它们的化学结构和它们先前在调节性体外和/或体内遗传毒性测试电池中的评估结果。三种测试材料,2-苯基-2-丁烯醛,nona-2-反式-6-顺式二烯醛,和2-甲基-2-戊烯醛,两者都是阴性的,CEGA和HET-MN测定。这些发现与调节体内遗传毒性测定的结果一致。相比之下,对甲氧基肉桂醛,在体内遗传毒性试验中也是阴性的,产生了DNA损伤的证据,包括CEGA中的DNA链断裂和DNA加合物。然而,在HET-MN研究中没有报道血液中微核形成的增加.CEGA和HET-MN测定之间的这种响应变化可归因于给药方案的差异。用谷胱甘肽前体预处理,N-乙酰半胱氨酸,对甲氧基肉桂醛在CEGA中产生的否定阳性结果,表明在鸡蛋和啮齿动物模型中观察到的反应差异可归因于谷胱甘肽的快速消耗。总的来说,我们的研究结果支持以下结论:CEGA和/或HET-MN可被视为动物试验的潜在替代方法,作为评估芳香材料遗传毒性潜力的后续策略,并有体外遗传毒性证据.
The genotoxic and clastogenic/aneugeneic potentials of four α,β-unsaturated aldehydes, 2-phenyl-2-butenal, nona-2-trans-6-cis-dienal, 2-methyl-2-pentenal, and p-methoxy cinnamaldehyde, which are used as fragrance materials, were assessed using the Chicken Egg
Genotoxicity Assay (CEGA) and the Hen\'s egg micronucleus (HET-MN) assay, respectively. Selection of materials was based on their chemical structures and the results of their previous assessment in the regulatory in vitro and/or in vivo
genotoxicity test battery. Three tested materials, 2-phenyl-2-butenal, nona-2-trans-6-cis-dienal, and 2-methyl-2-pentenal, were negative in both, CEGA and HET-MN assays. These findings were congruent with the results of regulatory in vivo
genotoxicity assays. In contrast, p-methoxy cinnamaldehyde, which was also negative in the in vivo
genotoxicity assays, produced evidence of DNA damage, including DNA strand breaks and DNA adducts in CEGA. However, no increase in the micronucleus formation in blood was reported in the HET-MN study. Such variation in responses between the CEGA and HET-MN assay can be attributed to differences in the dosing protocols. Pretreatment with a glutathione precursor, N-acetyl cysteine, negated positive outcomes produced by p-methoxy cinnamaldehyde in CEGA, indicating that difference in response observed in the chicken egg and rodent models can be attributed to rapid glutathione depletion. Overall, our findings support the conclusion that CEGA and/or HET-MN can be considered as a potential alternative to animal testing as follow-up strategies for assessment of genotoxic potential of fragrance materials with evidence of
genotoxicity in vitro.