Benzidine derived azo dyes may be degraded metabolically in the gut or liver in man to free benzidine or monoacetylbenzidine. /Benzidine derived azo dyes/
Environmental and urine samples were collected at six factories where workers were potentially exposed to benzidine based dyes (two benzidine based dye manufacturers, two textile dyeing plants, a leather dyeing plant and a mill where paper was dyed). Monoacetylbenzidine was detected in the urine of 2/8 workers at one of the dye manufacturing plants at levels of 3 and 7 ppb. At the second factory, 4 workers exposed to average levels of 7.9, 5.2, 11.7 and 17.4 mg total particulate/cu m had corresponding urinary concentrations of 52, 11, 10 and 112 ppb benzidine; 590, 248 and 22 ppb monoacetylbenzidine were detected in urine samples containing 112, 52 and 11 ppb benzidine. Traces of diacetylbenzidine, ortho-tolidine and ortho-dianisidine were also detected. Benzidine (0-39 ppb) and/or monoacetylbenzidine was detected in the urine of workers in one textile dyeing factory where Direct Black 38 and Direct Blue 2 were being used. The total level of airborne particulates (measured gravimetrically) was 1-4 mg/cu m. Benzidine was not detected in the urine of workers from the other facilities. Minute levels of impurities in the dyestuffs could not account for the quantity of benzidine and its derivatives that were found in the urine samples.
Six azodyes derived from benzidine, o-tolidine or o-dianisidine were separately administered orally by gavage to rats. Urine was collected over a 24 hr period. All six dyes, direct black 38, direct brown 95, direct blue 6, Congo red, trypan blue and Chicago sky blue were found to be reduced, N-acetylated and N-conjugated. However, no N,N'-diacetylated metabolites were detected. After administration of the same dyes via injection into the hepatic portal vein, bile was collected over a 3 hr period by cannulation of the bile duct. Urine was withdrawn from the bladder by syringe at the end of the three hours. Both body fluids were analyzed for reduction products which were found only in the case of direct black 38, direct brown 95 and direct blue 6. Of the six dyes examined only the three direct dyes were mutagenic to S. typhimurium strains TA98 and TA1538 in the absence of flavin mononucleotide. The same three dyes were also substrates for rat liver microsomal azoreductase enzymes whereas Congo red, trypan blue and Chicago sky blue were shown to be inactive.
The azo reduction and acetylation in vitro and the mutagenic activation in vivo of three azo dyes were studied. In the presence of rat-liver 9000 g supernatant benzidine was released from direct black 38 and direct brown 95, whereas hardly any benzidine was produced during incubation of direct blue 6. Incubation of benzidine with isolated rat hepatocytes resulted in the appearance of diacetylbenzidine. No diacetylbenzidine was formed during incubation of benzidine with rat-liver 9000 g supernatant, unless the cofactor for the acetylation reaction, acetyl coenzyme A, was added to the incubation medium. Isolated rat hepatocytes were capable to produce diacetylbenzidine from direct black 38, direct blue 6 or direct brown 95 without supplementation with acetyl coenzyme A. Rat liver has a considerable capacity to reduce azo compounds.
Classification of carcinogenicity: 1) evidence in humans: inadequate; 2) No data for evidence in animals. Overall summary evaluation of carcinogenic risk to humans is Group 2A: The agent is probably carcinogenic to humans. /From table; Benzidine-based dyes/
Urine cytology surveillance has proved useful in evaluating tumors in dyestuff plant workers. The system consists of two-stage tests: periodic urine cytology, followed by, in suspicious cases, urological examinations. /Benzidine/
PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/
A strong association relating human exposure to benzidine based dyes with the subsequent development of bladder tumors was presented after a case control mortality study of 200 bladder cancer patients in Japan. The patients were found to have been predominantly kimono painters and dyers. The kimono painters had a habit of forming a point on their brushes by drawing the brush between their lips, which allowed for ingestion of the dyes. Several other case control mortality studies indicate an increased risk of developing bladder cancer in the textile and leather industries, both large users of direct dyes. However, only a few references have been made concerning benzidine derived dyestuffs. In Russia, a medical study concerning the early detection of bladder tumors among textile dyers using benzidine derived dyes revealed an unusual incidence of bladder lesions, some of which were suggested as being of a precancerous nature. The greatest number of such lesions were found in those workers with the highest potential exposure to these dyes. /Benzidine based dyes/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
恒河猴在通过灌胃接受两种不同剂量的Direct Blue 6染料后，尿液中平均排泄出1.25%的联苯胺加上单一乙酰联苯胺的联苯胺部分，而纯联苯胺的灌胃则产生了1.45%。
Rhesus monkeys excreted an average of 1.25% benzidine plus monoacetylbenzidine of the benzidine moiety in Direct Blue 6 in the urine after receiving two different doses by gavage, whereas gavage with pure benzidine yielded 1.45%.
