Search

The mutagenicity of N,N-dimethytaminoazobenzene (DAB) is difficult to demonstrate in Ames' test. Usually there are specific requirements for activation by post-mitochondrial supernatant fluid (S-9) from Aroclor-treated rat livers and the pre-incubation modification of the test. Results from this laboratory suggest, however, that pre-incubation is not essential; also, that, contrary to published reports, concentrations of S-9 >10% in S-9 mix do not reduce the mutagenic response. Induction of enzyme activity well above normal levels, on the other hand, is necessary, but this requirement can be substituted by the addition of norharman. If a competent S-9 mix is used, pre-incubation with or without shaking does not alter the response and supplementation with ATP or NADH similarly has no effect. It is concluded that interiaboratoiy differences in the ability to demonstrate DAB mutagenicity reflect differences in the level of induction of liver enzymes and, possibly, the concentration of endogenous co-factors. [ABSTRACT FROM PUBLISHER]

The detection of certain bis-azo biphenyl dyes (Trypan blue, Evans blue and Congo red) by a modification of the standard Ames test protocol is reported. Detection of a mutagenic response required both the inclusion of FMN in S-9 mix and use of a pre-incubation step prior to addition of topagar and pouring in the usual manner. Evidence is presented to substantiate the proposal that use of this protocol provides optimal conditions for the two stages of activation required for the production of mutagenic metabolites from these dyes. These are (i) initial flavin-mediated (hepatic) azo reduction resulting in the formation of proximate mutagenic metabolites followed by (ii) the oxidative metabolism by S-9 resulting in the formation of ultimately mutagenic products. [ABSTRACT FROM PUBLISHER]

Abstract: The occupational exposure assessment uses data from published sources, from Industry (most often from the producers), and from dedicated occupational exposure data bases, as well as evaluations using the EASE model (Estimation and Assessment of Substance Exposure). Atmospheric concentrations and characteristics of skin contacts are evaluated in different scenarios (such as manufacturing, formulating, main and most polluting uses) and sub-scenarios (e.g. warm water dilution). Air concentrations of EGBE are low during production (most often <0.5mg/m3), incidental excursions being <50mg/m3; the “worst-case” mean concentration is proposed as 9mg/m3. Skin contact, according to EASE, may be in the range of 0–0.1mg/cm2(day), and should be mitigated by the use of suitable gloves. For formulations of products containing EGBE, air concentrations are evaluated as 10mg/m3 and skin contact as 0.19mg/cm2(day). The “reasonable worst case” air concentrations (8-Hr TWA) are assessed at around 11mg/m3 (coating industry), from 5 to 20mg/m3 in printing activities (depending on the task), and in the 20–70mg/m3 range (upper limit 40mg/m3 in better controlled situations) for cleaning activities. Skin contact would be around twice the preceding level, i.e., 0.4mg/cm2(day) for coating as well as cleaning activities. EGBE and its major metabolites, 2-butoxyacetaldehyde (2-BAL) and 2-butoxyacetic acid (2-BAA) have been subjected to tests for genetic toxicity tests both in vitro and in vivo. While some positive responses have been obtained, the balance of the evidence indicates that EGBE does not express significant genotoxic activity. There are no epidemiological data investigating a relationship between exposure to EGBE and human cancer. Two carcinogenicity inhalation bioassays have been conducted in rodents, one in rats and one in mice. Significant increases were found in forestomach tumours in female mice and haemangiosarcomas in male mice. No increases in tumour incidences were found in either male or female rats. Mechanistic studies have suggested the crucial involvement in the pathogenesis of haemangiosarcomas of a chain of events consisting of (1) haemolysis due to BAA, followed by (2) hepatic haemosiderin deposition and (3) the subsequent generation of reactive oxygen species within the endothelial cells from which haemangiosarcomas arise. Since human erythrocytes are particularly resistant to the haemolytic effects of BAA, it is extremely unlikely, according to this model, that the haemangiosarcomas observed in male mice will have human significance. Similarly, mechanistic studies on the female mouse forestomach tumours have suggested that these also are not important as an indication of human risk. In vivo, EGBE tested in a continuous breeding study and in repeated dose toxicity tests, did not produced specific effects on reproductive organs or fertility parameters. For developmental toxicity, rats, mice and rabbits were dosed via oral and/or inhalation routes. Foeto- and embryo-toxicity was observed in presence or maternal toxicity (haemolytic anaemia). The data available give plausible support to the hypothesis that this developmental toxicity is a direct consequence of maternal toxicity. There are no epidemiological data investigating a relationship between exposure to EGBE alone and human reproductive effects. [Copyright &y& Elsevier]