2-NAPHTHYLAMINE

2-Naphthylamine is a known human carcinogen formerly used commercially as an intermediate in the manufacture of dyes, as an antioxidant in the rubber industry, and to produce 2-chloronaphthylamine(IARC 1974, HSDB 2003)

It was First Listed in the First Annual Report on Carcinogens (1980) after sufficient evidence of carcinogenicity in humans was established. Epidemiological studies have shown that occupational exposure to 2-naphthylamine, either alone or present as an impurity in other compounds, causes bladder cancer. Studies of dyestuff workers and of chemical workers exposed mainly to 2-naphthylamine found increased risks of bladder cancer. At one of the dyestuff plants, the risk increased with increasing exposure to 2-naphthylamine, which gives us information on the dose response relationship that this toxic chemical has. In these studies, the increased risk of bladder cancer could not be explained by workers’ smoking habits (IARC 1974, 1987).

Additional Information Relevant to Carcinogenicity has also been found. 2-Naphthylamine caused genetic damage in various test systems, including mutations in bacteria, yeast, insects, plants, cultured human and other mammalian cells, and experimental animals. Other types of genetic damage observed in some of these systems included DNA strand breaks, chromosomal aberrations (changes in chromosome structure or number), micronucleus formation (a sign of chromosome damage or loss), aneuploidy (extra or missing chromosomes), sister chromatid exchange, and cell transformation (a step in tumor formation) (IARC 1987, Gene-Tox 1998). The mechanism by which 2-naphthylamine causes cancer is thought to require its metabolism to a reactive form. When arylamines, such as 2-naphthylamine, are metabolized, they can be either activated via N-hydroxylation (by cytochrome P-450 liver enzymes) or detoxified via pathways such as N-acetylation. The Nhydroxylamine metabolites can form adducts with blood-serum proteins (such as hemoglobin), which circulate freely, or they can undergo further metabolism (conjugation) to form reactive compounds that can be transported to the bladder and can bind to DNA (Yu et al. 2002). 2-Naphthylamine DNA adducts have been found in bladder and liver cells from exposed dogs (IARC 1987)

2-Naphthylamine was commercially produced in the United States from at least the early 1920s to the early 1970s. In 1955 (the latest year for which production data were found), 581,000 kg (1.3 million pounds) were produced by four manufacturers (IARC 1974). Since its commercial manufacture and use were banned in the early 1970s, 2-naphthylamine has been available only in small quantities for laboratory research. Six U.S. suppliers of 2-naphthylamine were identified in 2003 (ChemSources 2003).

The potential for exposure is low since the commercial production and use of 2-naphthylamine are banned,. The general population may be exposed through inhalation of emissions from sources where nitrogen-containing organic matter is burned, such as coal furnaces and cigarettes (HSDB 2003). Mainstream cigarette smoke from eight different U.S. conventional market cigarettes contained 2-naphthylamine at concentrations of 1.5 to 14.1 ng per cigarette (Stabbert et al. 2003); other investigators reported levels as high as 35 ng per cigarette (Hoffman et al. 1997). In sidestream smoke, a concentration of 67 ng per cigarette was reported (Patrianakos and Hoffmann 1979). 2-Naphthylamine also occurs as an impurity (0.5% or less) in commercially produced 1-naphthylamine. At greatest risk of occupational exposure to 2-naphthylamine are laboratory technicians and scientists who use it in research. Before U.S. commercial production of 2-naphthylamine and its use in the dye and rubber industries were banned, workers in these industries potentially were exposed. The National Occupational Hazard Survey (1972–1974) estimated that 420 workers potentially were exposed to 2-naphthylamine in the workplace (NIOSH 1976), and the National Occupational Exposure Survey (1981–1983) estimated that 275 workers, including 265 women, potentially were exposed (NIOSH 1984).

Guidelines for 2-Naphthylamine are as follows:

ACGIH: Threshold Limit Value - Time-Weighted Average Limit (TLV-TWA) = as low as possible

NIOSH: Listed as a potential occupational carcinogen

REFERENCES: 

1) Wikipedia, the online encyclopedia: http://en.wikipedia.org/wiki/2-Naphthylamine

2) 11th ROC - 2-Naphthylamine: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s117naph.pdf