2- Naphthylamine bladder cancer

Historically, bladder tumors have been associated with exposures in the aniline dye industry. However, conclusive evidence for any one particular exposure could not be obtained in these studies since the workers were exposed to many chemicals within the same work area. For example, Case et al. (1954) investigated the incidence of bladder tumors among British workers in the chemical dye industry. In addition to aniline, the workers were exposed to other aromatic amines, including a- and P-naphthylamine, benzidine, and auramine. Although exposures could not be quantified, there was insufficient evidence to suggest that aniline was a cause of bladder cancers. More recent studies indicate that P-naphthylamine, 4-aminodiphenyl, 4-nitrodiphenyl, 4,4-diaminodiphenyl, or o-toluidine may be involved in increased cancers in the dye industry (Ward et al. 1991 Benya and Cornish 1994). 

Stern FB, Murthy LI, Beaumont JJ, et al Notification and risk assessment for bladder cancer of a cohort exposed to aromatic amines. III. Mortality among workers exposed to aromatic amines in the last 3-naphthylamine manufacturing facility in the United States. Occup Med27-.495-500, 1985... 

Toxicology of Certain Azo Dyes. It has been known for over 100 years that certain amines used to manufacture synthetic dyes caused bladder cancer, especially 2-naphthylamine, benzidine and 4-aminodiphenyl. All the major dyestuff manufacturers abandoned the use of these amines in the production of dyes in the early 1970s. 

Although the data are not sufficient to define the shapes of the dose incidence curves in most instances, a markedly increased risk of cancer has been noted in a number of more heavily exposed populations (Ikble 6.5). In 2-naphthylamine distillers, for example, the latency and incidence of bladder cancer have been observed to vary systematically in relation to the duration of exposure (Figure 6.2). In those with exposures lasting more than five years, the cumulative incidence approached 100 percent (Figures 6.2 6.3). 

DOT CLASSIFICATION 6.1 Label KEEP AWAY FROM FOOD SAFETY PROFILE Confirmed carcinogen with experimental tumorigenic data. Along with p-naphthylamine and benzidine, it has been incriminated as a cause of urinary bladder cancer. Poison by subcutaneous and intraperitoneal routes. Moderately toxic by ingestion. Mutation data reported. Combustible when exposed to heat or flame. Incompatible with nitrous acid. To fight fire, use dry chemical, CO2, mist, spray. When heated to decomposition it emits toxic fumes of NOx. See also 2-NAPHTHYLAMINE and AROMATIC AMINES. 

The toxic nature of some dyes and intermediates has long been recognized. Dermatologists have reported cases of skin reactions suspected to be caused by textile dyes. The positive link between benzidine derivatives and 2-naphthylamine with bladder cancer is also well documented. In fact, these studies prompted the introduction of stringent government regulations to control the exposure of workers to dye dust and the discharge of chemicals, colors, and other effluents. 

Bladder cancer in Chinese women may be linked to the oil fumes in the kitchen air, which were shown to be mutagenic and to contain up to about 50 p,g m-3 of 4-aminobiphenyl (7a) and 2-naphthylamine (9a). The concentration of these PAA was substantially reduced on adding the antioxidant catechin (42) to the oil43. 

Chemical carcinogenesis emerged as an established field of scientific enquiry after carcinogenic constituents in coal tar were identified by Japanese workers in 1915, and British workers isolated and identified coal-tar 3,4-benzo[a]pyrene as a carcinogen. Wignall (1929) reported the prevalence of bladder cancer among workers exposed to 8 and 10a (studies on 10b, 10c and lOd were not reported) and 1-naphthylamine (ll)24. Unlike... 

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... 

Specific studies have definitively established the relationship between exposures and cancer. In one example of this phenomenon, all 15 workers in a chemical plant who were exposed 2-naphthylamine during its distillation developed bladder cancer. 

P-Naphthylamine Dye makers and rubber workers Bladder cancer... 

The presence of P-naphthylamine in cigarette smoke has been demonstrated [Hoffmann et al. (1747)], along with other carcinogenic aromatic amines [Patrianakos et al. (2900)]. The yield was so low that [the researchers] did not believe these agents contributed significantly to the risk of bladder cancer in smokers [see p. 41 in (4009)]. 

Presented in Table 9.1 are toxicity data for some commercially used aromatic amines. These substances exhibit low toxicity and may cause bladder cancer (NIOSH 1986). The carcinogenicity is much weaker than benzidine or a- or /6-naphthylamine. The toxicity data on many of these substances are too little. These compounds are noncombustible liquids or solids. Any explosive reactions exhibited by these amines are not known. These may, however, undergo vigorous to violent reactions if mixed with strong oxidizers. 

Epidemiological studies have indicated that several aromatic amines were causative factors in occupational bladder cancer in man (64, 65, 215, 334). Among the aromatic amines which were implicated, 2-naphthylamine and 4-aminobiphenyl were bladder carcinogens in dogs (209, 478). Because aromatic amines are widely used in industry, extensive animal experiments have been performed to evaluate their potential as carcinogens. In general, aromatic amines induce tumors distant from their site of application. The differences in suscepti-... 

There have also been disasters associated with the manufacture of chemicals. The most notorious was the accident at Bhopal in India in 1984, which resulted in approximately 3000 deaths when leakage occurred from an agrochemical plant. Some workers in chemical factories have contracted occupational diseases as a result of exposure to chemicals. A well known example was the high incidence of bladder cancer among workers coming into contact with bicyclic aromatic amines such as 2-naphthylamine. 

Most substances absorbed will be carried by the blood stream to the liver where they may be rendered less harmful by a change in their chemical composition. However, some may be made more toxic, e.g. naphthylamine which is responsible for bladder cancer and tetra-ethyl lead which is converted into the tri-ethyl form and is toxic to the central nervous system. 

---