EVALUATION OF THE GENOTOXICITY OF 4-DIETHYLAMINO-4'-NITROAZOBENZENE AND 7 ANALOGS

A series of eight nitroaromatic azo compounds based on 4-diethylamino- 4'-nitroazobenzene has been examined for genotoxic activity in a colla borative study conducted under the auspices of the Ecological and Toxi cological Association of Dyes and Organic Pigments Manufacturers (ETAD ). The evaluation has been conducted in two parts, firstly an examinat ion in vitro to assess any intrinsic genotoxic activity of the compoun d. The chemicals were examined in the Salmonella assay in a standard p late incorporation protocol in both the presence and absence of S9 and in a minimum of the four tester strains recommended in the OECD guide line for this assay, i.e. TA1535, TA1537, TA98 and TA100. All of the c ompounds were mutagenic in one or more of the Salmonella tester strain s, and all were positive in TA98 with S9. A considerable range of pote ncy was seen in this assay. The chemicals were further examined in vit ro for mammalian cell gene mutation at either the HGPRT or TK locus in a standard (CHO, V79 or L5178Y) cell system. Only one of the chemical s was mutagenic and only with S9. This chemical also showed the most p otent response in the Salmonella assay. The second part of the study w as an examination in vivo to see whether any genotoxic activity was ex pressed in the whole animal. The in vivo rat liver DNA repair (unsched uled DNA synthesis; UDS) assay was chosen as being the most likely to be sensitive to aromatic nitroazo compounds. All of the materials were negative when tested alongside a structurally related positive contro l. The chemicals were also examined in the mouse bone marrow micronucl eus assay in order to provide a second in vivo assessment. Seven of th e chemicals were negative in this assay, however, one produced a posit ive response. This compound was also the only one detected as positive in the in vitro mammalian cell gene mutation assay. The data obtained in this study show how genotoxic nitroazo compounds can be evaluated using a structured combination of in vitro and in vivo assays.