Metabolism of Azo Dyes

With regard to metabolism, azo dyes are the most widely investigated class of dyes. According to metabolic pathway two groups of azo dyes can be distinguished (1) water-soluble dyes, mostly bearing sulfo groups, and (2) solvent-soluble dyes with nonpolar substituents. 

By far the most predominant metabolic pathway for water-soluble azo dyes is cleavage of the azo linkage by azoreductase of the liver and extrahepatic tissue or by intestinal microflora in the body [25,26], Oxidative metabolism occurs for lipid-soluble dyes, e.g., solvent dyes. Three oxidation pathways are known for such dyes (1) C-(ring-)hydroxylation, (2) A-hydroxylation at a primary or secondary amino group or (3) by stepwise oxidation of the methyl groups of dimethylamino compounds (demethylation). All three oxidative degradation ways leave the azo bond intact. For further details of the mechanisms, see [27,28], 

The metabolism of the benzidine-based dyes C.I. Direct Red 28, C.I. Direct Blue 6, C.I. Direct Brown 95, and C.I. Direct Black 38 was studied in Rhesus monkeys. After ingestion of the dyes, benzidine and monoacetylbenzidine could be detected as metabolites in the urine. This indicated that the dyes had been converted to benzidine [29], Recent in vitro studies on C. I. DirectBlue 14 show that bacteria isolated from healthy human skin have reductase activity and are able to cleave the dye into the corresponding arylamine, in this case 3,3 -dimethylbenzi-dine [30], 

The possible release of the aromatic amines, which are carcinogenic in rodents, and subsequent metabolic activation in the organism is assumed to be the reason for the carcinogenic effect of some members of this dye class in animal testing. These findings support the conclusion that dyes which could be metabolized to a carcinogenic aromatic amine should be considered to be carcinogenic. 

In Germany bladder cancer is recognized as an existing occupational disease for textile workers [34], This knowledge is the reason for the recommendation of the German MAK Kommission to handle the dyes in the same way as the amines, which can be released under reducing conditions. In the next step the German, Austrian, and Dutch authorities prohibited their use in some consumer articles [35] (see Section 8.4.3). 

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Seesuriyachan P, Takenaka S, Kuntiya A (2007) Metabolism of azo dyes by Lactobacillus casei TISTR 1500 and effects of various factors on decolorization. Wat Res 41 985-992... 

Levine WG (1991) Metabolism of azo dyes implications for detoxification and activation drug. Metabol Rev 23(3-4) 253-309... 

NCTR. 1979. Metabolism of azo dyes to potentially carcinogenic amines. National Center for Toxicological Research Technical Report, Experiment No. 196. 

M. Boeniger, The Carcinogenicity and Metabolism of Azo Dyes, Especially those derived from Benzidine, DHHS (NIOSH) Publication No. 80 119, US Department of Health and Human Services, Ohio 1980. 

Aromatic amines are released during biodegradation and metabolism of azo dyes. More recently, they have been detected as AIAs following the cooking of meat and fish. Bioactivation of heterocyclic amines leading to AIA-DNA adducts, involving activation through phase I and phase II, and mutations, is almost identical with the processes found with other aromatic amines. 

Reid TM, Morton KC, Wang CY et al (1984) Mutangencity of azo dyes following metabolism by different reductive/oxidative systems. Environ Mutagen 6 705-717... 

In recent years, a growing interest in the research devoted to the biodegradation of azo dyes have been putting in evidence both the feasibility of yeast-mediated decolorization and the metabolic versatility exhibited by yeasts. Taken together, these are very encouraging findings, since the majority of yeast species have never been screened for azo dyes bioremediation. 

In metabolism studies of azo dyes and pigments in the hamster, in vivo cleavage of the benzidine-based dye, Direet Black 38, to benzidine was shown by analysis of the urine. However, studies of the 3,3 -diehlorobenzidine-based pigment. Pigment Yellow 12, showed no evidenee for in vivo cleavage to release 3,3 -diehlorobenzidine (Nony et al. 1980). 

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. 

In 1966-1967, we demonstrated that treatment of rats with certain polycyclic hydrocarbons or aromatic azo derivatives stimulated the in vitro and in vivo metabolism of 7,12-dimethylbenz[a]anthracene (9,10), which provided a mechanistic explanation for earlier research indicating an inhibitory effect of these compounds on 7,12-dimethylbenz[a]anthracene-induced mammary cancer and adrenal toxicity in rats (11-15). These early studies on mechanisms of inhibition of azo dye and polycyclic hydrocarbon carcinogenesis as well as subsequent studies suggested that induction of carcinogen detoxifying enzymes may be a useful strategy for cancer chemoprevention [reviewed in Refs. (16-18)]. 

McLean, P., Reid, E., and Gurney, M. W., Effect of azo-dye carcinogenesis on enzymes concerned with urea synthesis in the rat. Biochem. J. 91, 464-473 (1964). McLean, P., and Rossi, F., Changes in the activities of urea-cycle enzymes after the administration of carbon tetrachloride. Biochem. J. 91, 261-270 (1964). McMurray, W. C., Mohyuddin, F., Bayer, S. M., and Rathbun, J. C., Citrul-linuria a disorder of amino acid metabolism associated with mental retardation. Int. Copenhagen Congr. Sci. Study Meat. Retard., Proc. 3rd 1, 117 (1964). McMurray, W. C., Rathbun, J. C., Mohyuddin, F., and Koegler, S. J., Citrul-linuria. Pediatrics 32, 347-357 (1963). 

Work supported in part by Grant AM 06231 from the National Institute of Arthritis and Metabolic Diseases. Azo dyes graciously provided by R. Walker, National College of Food Technology, Weybridge, Surrey, England. 

Uses Mfg. of diaminophenol, picric acid, picramic acid herbicide reagent for detection of potassium and ammonium ions chemical synthesis biochemical research acid-base indicator polymerization inhibitor in styrene prod. intermediate for prod, of azo dyes. Cl sulfur black 1, Cl sulfur black 2, explosives, photographic developers fungicide for metalcutting oil emulsions, railroad ties, wood, pressure-treated wood wood preservative insecticide, miticide to control mosquitoes formerly as metabolic stimulator to aid in weight reduction... 

Some related antibacteiials are also included with the sulfonamides. The azo dye, Piontosil (3) is metabolized to sulfanilamide in and was the piogenitoi of the sulfa dmgs. Also, the antibacteiial sulfones, eg, dapsone (4), are believed to act in a similai fashion on enzymes involved with synthesis of fohc acid, leading to bacterial growth inhibition. 

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