Detail of "16071-86-6"

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Metabolism of benzidine-based dyes and the appearance of mutagenic metabolites in urine of rats after oral or intraperitoneal administration

Metabolism of benzidine-based dyes and the appearance of mutagenic metabolites in urine of rats after oral or intraperitoneal administration. Bos, R. P.; Groenen, M. A. M.; Theuws, J. L. G.; Leijdekkers, C. M.; Henderson, P. T. (Inst. Pharmacol., Univ. Nijmegen, Nijmegen, Neth.). Toxicology, 31(3-4), 271-82 (English) 1984. CODEN: TXCYAC. ISSN: 0300-483X. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The azo redn. and acetylation in vitro and the mutagenic activation in vivo of 3 azo dyes were studied. In the presence of rat liver 9000 g supernatant, benzidine [92-87-5] was released from direct black 38 (I) [1937-37-7] and direct brown 95 [16071-86-6], whereas hardly any benzidine was produced during incubation of direct blue 6 [2602-46-2]. Incubation of benzidine with isolated rat hepatocytes resulted in the appearance of diacetylbenzidine [613-35-4]. No diacetylbenzidine was formed during incubation of benzidine with rat liver 9000 g supernatant, unless the cofactor for the acetylation reaction, acetyl CoA [72-89-9], was added to the incubation medium. Isolated rat hepatocytes were capable to produce diacetylbenzidine from I, direct blue 6, or direct brown 95 without supplementation with acetyl CoA. The administration of benzidine, I, or direct brown 95 to rats resulted in the appearance of mutagenicity in urine. For I, significantly higher mutagenic values were found in urine after oral administration than after i.p. treatment. Such differences were not obsd. for benzidine and direct brown 95. Thus, rat liver has a considerable capacity to reduce azo compds. Nevertheless, for some compds., like I, extrahepatic enzymes, most likely present in the intestinal flora, may also play a substantial role in the azo cleavage.

Induction of unscheduled DNA synthesis in primary rat hepatocytes by benzidine-congener-derived azo dyes in the in vitro and in vivo/in vitro assays

Induction of unscheduled DNA synthesis in primary rat hepatocytes by benzidine-congener-derived azo dyes in the in vitro and in vivo/in vitro assays. Joachim, Fred; Decad, Gary M. (Dep. Mater. Toxicol., IBM Corp., San Jose, CA, USA). Mutat. Res., 136(2), 147-52 (English) 1984. CODEN: MUREAV. ISSN: 0027-5107. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The genotoxicity of the benzidine-congener-derived azo dyes Direct Blue 1 (DB1)(I) [2610-05-1], Direct Blue 14 (DB14) [72-57-1], Direct Brown 95 (DB95) [16071-86-6], and Direct Red 46 (DR46) [6548-29-4] was studied in the in vitro and in vivo/in vitro unscheduled DNA synthesis (UDS) assays in primary rat hepatocytes to det. if in vivo metab. of these compds. was required for induction of UDS. Hepatocytes were isolated, cultured, and treated with the azo dyes and [3H]thymidine (in vitro assay); alternatively, in the in vivo/in vitro assay, rats were incubated with the azo dyes, the hepatocytes isolated at 17 h after dosing, and incubated in a medium contg. [3H]thymidine. UDS was quantified by an autoradiog. method. None of the azo dyes induced UDS in the in vitro assay. However, DR46 did induce marginal, but significant, UDS in 1 expt. (1.2 net grains at 500 mg/mL media). No significant UDS was obsd. when DR46 was tested in a subsequent in vitro assay. In the in vivo/in vitro assay, DB95 (100 mg/kg), DB14 (125 mg/kg), and DR46 (100 mg/kg) induced significant UDS (12, 2.1, and 3.5 net grains, resp.). None of the azo dyes tested was mutagenic in the Salmonella/microsome assay in the presence and absence of rat liver enzymes. Therefore, in vivo redn. of azo dyes, presumably by the gut microflora, is a requirement for the genotoxicity of these azo dyes in the primary rat hepatocyte UDS assay.