Benzidine congeners

Prival, M.J., Bell, S.J., Mitchell, VD., Peiperi, M.D. and Vaughn, VL. (1984). Mutagenicity of benzidine and benzidine-congener dyes and selected monoazo dyes in a modified Salmonella assay. Mutation Res. 136 33-47. 

Bimer G, Albrecht W, Neumann H-G. 1990. Biomonitoring of aromatic amines III. Hemoglobin binding of benzidine and some benzidine congeners. Arch Toxicol 64(2) 97-102. 

Reid TM, Morton KC, Wang CY, et al. 1984a. Mutagenicity of some benzidine congeners and their N-acetylated and N,N -diacetylated derivatives in different strains of Salmonella typhimurium. Environ Mutagen 6 145-151. 

A method for the determination of personal exposure to benzidine-based dyes has been developed. This procedure involved the reduction of benzidine-based dye filter samples to free benzidine with neutral buffered sodium hydrosulfite solution. The benzidine-containing reduction solution was then analyzed by high performance liquid chromatography. The reduction was found to be quantitative by visible-spectrum analysis. This reduction and analysis method was evaluated with four benzidine-based dyes over the range from 12 to 300 micrograms per sample. Precision for the reduction and analysis of the four dyes falls within % coefficient of variation. This method can differentiate between benzidine-and benzidine congener-based dyes. Results are reported in terms of free benzidine. 

Azo Compounds Azo dyes are widely used in the food, pharmaceutical, cosmetic, textile, and leather industry. They are synthetic compounds characterized by one (monoazo) or several intramolecular N = N bonds. Azo dyes, if they are systemically absorbed, can be metabolized by the way of azoreductases of intestinal microflora by liver cells and skin surface bacteria. This metabolism leads to aromatic amines that can be hazardous. In the 1930s, some azo derivatives like 4-dimethyl aminoazoben-zene (Butter Yellow, Cl Solvent Yellow 2, Cl 11020) and o-aminoazotoluene were experimentally found to be directly carcinogenic to liver and bladder after feeding. Other complex azo dyes like Direct Black 38 or Direct Blue 6 (Figure 28) release the aromatic amine benzidine. Some examples of azo dyes metabolized in benzidine and benzidine-congeners are listed in Table 3. 

Table 3 Benzidine and benzidine-congener-based dyes...

Bouzige, M., Legeay, P., Pichon, V., and Hennion, M. C., Selective on-line immunoextraction coupled to liquid chromatography for the trace determination of benzidine, congeners and related azo dyes in surface water and industrial effluents, J. Chromatogr., 846, 317-329, 1999. 

EPA (1979) TSCA Chemical assessment series preliminary risk assessment phase i benzidine, it s congeners and their derivative dyes and pigments. US Environmental Protection Agency, Washington DC, EPA-560/11-80-019... 

Bowman, M.C., King, J.R., and Holder, C.R. Benzidine and congeners analytical chemical properties and trace analysis in five substrates, Int. J. Environ. Anal. Chem., 4(3) 205-223, 1976. 

Riggin RM, Howard CC, Scott DR, et al. 1983. Determination of benzidine related congeners and pigments in atmospheric particulate matter. J Chromatogr 21 321-325. 

Leather can be dyed with acid, direct and mordant dyes. Many of the direct dyes were based on benzidine and its congeners but the German Ordinance, covered under the toxicity of certain azo dyes in section 2.3.1.1, has meant that this is no longer an option. To improve the light fastness of the dyed leathers, 1 2 premetallised azo dyes have also been used, but once again the use of metal complex dyes is becoming less favoured. ... 

Sandmeyer in 1884 found that replacement of the diazonium group by halogen was catalyzed by cuprous chloride or bromide. It is a good route to o- and p-chlorotoluenes and m-nitrochlorobenzene. Gattermann in 1890 used copper powder to permit milder conditions. Methods were available for synthesis of benzidine and its congeners, a variety of aminoanthraquinones and acyl derivatives of aryl amines. 

Subcutaneously injected benzidine (10a) induces liver tumors, ear duct carcinomas and a few adenocarcinomas of the intestine, in rats. A number of congeners, including o-tolidine (10b), 3,3 -dichlorobenzidine (10c) and o-dianisidine (3,3 -dimethoxybenzidine) (10d), initiate tumors in rats99 103. The metabolism of benzidine in the dog has also received attention104. The A-acetylated metabolites of benzidine have been detected in the urine of monkeys, rats and humans. Metabolism of both N,N - and A-acetylated derivatives has received extensive coverage105-117. 

In the US, a workplace study of exposure to benzidine and its congeners, such as 10b, 10c and lOd, at the chemical facility of Upjohn (previously Carwin Company), located at North Haven, Connecticut, between 1965 (when benzidine manufacture ceased) and 1989, indicated a statistically significant increase in the standardized incidence ratio125. The impact of interindividual variation in NAT2 activity on urinary metabolites and urothelial DNA adducts in workers has been examined126. Phenyl-2-naphthylamine (37), and perhaps chemicals used in its manufacture, have been implicated as possible causes of bladder cancer, based on studies of workers at a factory in North Wales. Other amines investigated... 

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