Benzidine carcinogenicity

M. p. 168-169 C. This reagent has superseded benzidine for blood detection, showing same sensitivity and specificity but it is non-carcinogenic in doses at which benzidine produces a high incidence of neoplasms. 

Care. Benzidine is carcinogenic, and strict care should be taken not to absorb it eitlier by inhalation or by contact with the skin. 

Direct dyes are defined as anionic dyes substantive to ceUulosic fibers (cotton, viscose, etc), when applied from an aqueous bath containing an electrolyte. Before the discovery of Congo Red in 1884, only mordanted cotton could be dyed. Congo Red [573-58-0] (62) (Cl Direct Red 28 Cl 22120) a primary symmetrical disazo dye, which is made readily from bisdiazotized benzidine and naphthionic acid [84-86-6] (4-arnino-l-naphthalenesulfonic acid), was the precursor of a most important line of dyes, including all shades, derived from benzidine and its homologues. Today, no benzidine dye is produced because benzidine is carcinogenic. 

The past experience of the dyestuff industry in its use of dye intermediates such as ( -naphthyl amine and benzidine (4), known human bladder carcinogens (334—343), have led to studies as to whether or not handlers of dyes are exposed to medical ha2ards such as cancer, dermatitis, and other disorders (344-360). 

Carcinogens Cancer-producing agents Skin Respiratory Bladder/urinary tract Liver Nasal Bone marrow Coal tar pitch dust crude anthracene dust mineral oil mist arsenic. Asbestos polycyclic aromatic hydrocarbons nickel ore arsenic bis-(chloromethyl) ether mustard gas. p-naphthylamine benzidine 4-am i nodi pheny lam ine. Vinyl chloride monomer. Mustard gas nickel ore. Benzene. 

The benzidine rearrangement is of interest for mechanistic considerations. The preparative applicability may be limited because of the many side products, together with low yields. Furthermore benzidine is a carcinogenic compound. ... 

Warning The substances benzidine and o-dianisidine, which are classified as carcinogenic, react in a similar manner to o-tolidine, which is also suspected of causing cancer. 

Sphingolipids (ceramids, sphingomyelin, cerebrosides, sulfatides, gangliosides) and lipids with secondary amines produce blue spots on a white backgound (CAUTION benzidine is a carcinogen)... 

The carcinogenicity of aromatic amines, such as benzidine and 2-naph-thylamine, was first recognized by Rehn in the 1890s as an occupational hazard in the German dyestuffs industry. Compounds in this class induce... 

The metabolic formation of N-sulfonyloxy-N-acetyl-2-aminofluorene (N-sulfonyloxy-AAF) and its observed electrophilic reactivity, provided the first evidence for the importance of enzymatic conjugation reactions in chemical carcinogenesis (23,24). This reaction was shown to be catalyzed by PAPS-dependent sulfotrans-ferases that are located predominantly in liver cytosol and has been subsequently demonstrated for N-hydroxy arylamide metabolites of several other carcinogens, including N-acetyl-4-aminobiphenyl (AABP), benzidine, N-acetyl-2-aminophenanthrene and phenacetin. 

Benzidine is a known carcinogen and should be handled with extreme caution (Fourth Annual Report on Carcinogens NTP 85-002, 1985, p. 37). The solid and its vapors may be rapidly absorbed through skin. Protective clothing and the use of a fume hood are... 

Caution Both o-tolidine and benzidine are potential carcinogens. Protective clothing, gloves, and the use of a fume hood are recommended. Avoid all contact of the compounds with skin or clothing and do not inhale vapors or dust. 

Lu, P.Y., Metcalf, R.L., Plummmer, N., Mandel, D. (1977) The environmental fate of three carcinogens benzol a Ipyrene, benzidine, and vinyl chloride evaluated in laboratory model ecosystems. Arch. Environ. Contam. Toxicol. 6, 129-142. 

Numerous linear diamines, such as many of those in the survey mentioned above, have been evaluated as potential replacements for benzidine, an inexpensive and highly versatile intermediate that was banned in the 1970s because it posed a carcinogenic threat. Two trisazo dyes have been synthesised recently using 4,4, diaminodiphenyl thioether instead of the benzidine component of Cl Direct Black 38 (3.112 X = Y = NH2) and Cl Direct Green 1 (3.112 X = OH, Y = H). These new dyes exhibited higher substantivity and fastness to washing than the two traditional products on cellulosic fibres [119]. 

It is of more than a little interest to note that the sites of tumor formation do not always match across species. Benzidine, a substance once widely used in dye manufacture, was shown many years ago to be a carcinogenic risk for the bladder in workers exposed to excessive levels. The rat bladder is not responsive to this substance, but its liver is. It wasn t until Wilhelm Hueper turned to the dog that bladder cancer could be reproduced in a laboratory animal. It is now understood that benzidine metabolism is similar in dogs and people, and that metabolism in the rat takes a different course. It is also understood that certain benzidine metabolites, and not benzidine itself, are the proximate causes of tumors. Knowledge of metabolic differences helps explain the species similarities and differences in tumor response. If we had available the rat data and no human data, we would be in error to conclude that benzidine was a cause of human liver cancer. 

The NCI (1978) bioassay, which demonstrated carcinogenicity in two species, provides sufficient evidence of carcinogenicity of 1,2-diphenylhydrazine in animals. Biotransformation products of 1,2-diphenylhydrazine include aniline and benzidine, which are known carcinogens in animals (both chemicals) and humans (benzidine) (ERA 1988b,c). Based on the animal evidence for carcinogenicity from the NCI (1978) bioassay and the carcinogenicity of its metabolites,... 

---