Evaluation of the genotoxicity of 4-diethylamino-4'-nitroazobenzene and seven analogues.
A series of eight nitroaromatic azo compounds based on 4-diethylamino-4'-nitroazobenzene has been examined for genotoxic activity in a collaborative study conducted under the auspices of the Ecological and Toxicological Association of Dyes and Organic Pigments Manufacturers (ETAD). The evaluation has been conducted in two parts, firstly an examination in vitro to assess any intrinsic genotoxic activity of the compound. The chemicals were examined in the Salmonella assay in a standard plate incorporation protocol in both the presence and absence of S9 and in a minimum of the four tester strains recommended in the OECD guideline for this assay, i.e. TA1535, TA1537, TA98 and TA100. All of the compounds were mutagenic in one or more of the Salmonella tester strains, and all were positive in TA98 with S9. A considerable range of potency was seen in this assay. The chemicals were further examined in vitro 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 chemicals was mutagenic and only with S9. This chemical also showed the most potent response in the Salmonella assay. The second part of the study was an examination in vivo to see whether any genotoxic activity was expressed in the whole animal. The in vivo rat liver DNA repair (unscheduled 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 control. The chemicals were also examined in the mouse bone marrow micronucleus assay in order to provide a second in vivo assessment.(ABSTRACT TRUNCATED AT 250 WORDS)
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
B M
BM
Elliott
R
R
Jackh
R
R
Jung
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D015197:Carcinogenicity Tests; D002478:Cells, Cultured / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004260:DNA Repair; D005069:Evaluation Studies as Topic; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D008322:Mammals; D051379:Mice; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D051381:Rats; D017208:Rats, Wistar; D012475:Salmonella / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D001391:Azo Compounds; C092020:4-diethylamino-4'-nitroazobenzene