The mutagenicity of mono- and di-functional aromatic glycidyl compounds.
Although epoxides are very important compounds in today's technology, they are not as well investigated for their carcinogenic and mutagenic properties as their economical importance would suggest. The present study tried, on one hand, to bridge the gap between microbial testing of such compounds and the in vivo mammalian test system. On the other hand, the comparative testing of structurally related substances was expected to yield some clues as to the structural determinants of possible in vivo mutagenic activity. Our investigations with 4 compounds of similar structure, namely glycidylmethylaniline (GMA), diglycidylaniline (DGA), phenylglycidylether (PGE), and resorcinol diglycidyl ether (RDGE), first demonstrated that, in bacterial assays, all 4 epoxides acted as potent mutagens. Only the 2 difunctional epoxides, however, were active in an in vitro chromosomal aberration assay with CHO cells. That such in vitro results cannot be supposed to represent the in vivo situation is again demonstrated by discovery that only one of the two in vitro active substances (and in fact it is the less active one) also has a damaging effect in vivo. It, therefore, seems quite justifiable to conclude that two structural features must be combined in an aromatic glycidyl compound if it is to exert chromosome damaging activity in vivo: The substance must possess 2 epoxy functions, and they must be bound to the aromatic nucleus by an aminic nitrogen. The industrial use of aromatic glycidyl ethers might, therefore, be considered not to pose a great systemic risk for mutagenicity or carcinogenicity, without completely excluding the possibility of local effects.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects; D004852:Epoxy Compounds / Q000633:toxicity*; D004912:Erythrocytes / Q000187:drug effects; D004988:Ethers, Cyclic / Q000633:toxicity*; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009153:Mutagens