CATEGORY*: IARC probable carcinogen, NTP reasonably anticipated carcinogen, Endocrine disruptor
FOUND IN: Tobacco smoke, diesel exhaust, formed in production of polyurethane foams, dyes, pesticides and pharmaceuticals
THE GIST: These carcinogens are found in a variety of substances including polyurethane foams, dyes, pesticides, pharmaceuticals and semiconductors. They are also found in environmental pollution from diesel exhaust, combustion of wood chips and rubber; tobacco smoke; and substances in grilled meats and fish. Studies of female rubber-factory workers show that aromatic amines are associated with an increased risk of breast cancer.
State of the Evidence on Aromatic Amines
Aromatic amines are a class of chemicals found in the plastic and chemical industries as byproducts of the manufacturing of compounds such as polyurethane foams, dyes, pesticides, pharmaceuticals and semiconductors. They are also found in environmental pollution such as diesel exhaust, combustion of wood chips and rubber, tobacco smoke, and substances in grilled meats and fish (DeBruin, 1999; 2002). There are three types of aromatic amines: monocylic, polycyclic and heterocyclic.
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Three monocyclic amines, including o-toluidine, have been identified in the breast milk of healthy lactating women (DeBruin, 1999); o-toluidine is known to cause mammary tumors in rodents (NTP, 2005d; Layton, 1995). These data indicate that the mother’s mammary tissue and the nursing child are exposed to environmental carcinogens during breast-feeding.
Occupational exposures of female rubber-factory workers to another set of monocyclic aromatic amines are associated with an increased risk of breast cancer in the following several years. The amount of increased risk was correlated with total cumulative exposure levels to the aromatic amines, with the lowest levels leading to a 3.7-fold increase in cancer and the highest levels of exposure increasing risk more than tenfold (de Vocht, 2009).
Heterocyclic aromatic amines (HAAs) are formed, along with the polycyclic type, when meats or fish are grilled or otherwise cooked at high temperatures. A recent questionnaire study found an association between higher lifetime consumption of grilled meats and fish and increased incidence of post-menopausal breast cancer (Steck, 2007). Higher exposures to HAAs were associated with the presence of more DNA adducts in studies of both milk and cells from the ducts of women’s breasts (Thompson, 2002; Turesky, 2007). These DNA adducts are indicators of problems in DNA repair in cells, one of the early hallmarks of tumor development.
Aromatic amines are metabolized by enzymes in the class called N-acetyltransferases. This metabolic process ultimately produces other compounds that are thought to be the actual carcinogenic chemicals. There is an extensive literature examining whether or not genetic profiles that alter the efficacy or speed of N-acetyltransferase activation, especially through the N-acetyltransferase 2 (NAT2) regulated pathway, might alter susceptibility to breast cancer. Several studies have reached differing conclusions about the role of possible polymorphisms of the NAT2 gene on breast cancer susceptibility. A recent report tried to disentangle many of the possible confounding factors and found that eating grilled meat (and drinking coffee) resulted in greater risk for diagnosis of estrogen-receptor-negative breast tumors in women with the “slow-acetylator” form of the NAT2 gene (Rabstein, 2010).
Laboratory studies of HAAs in systems using cultured breast cancer cells demonstrate that these chemicals can mimic estrogen, and they can also have direct effects on cell-division processes in ways that might enhance the development of tumors (Gooderham, 2006).
*For chemicals that have been shown to be carcinogens, we provide classifications from two authoritative bodies: the International Agency for Research on Cancer (IARC, an international body) and the National Toxicology Program (NTP, a division of the U.S. Department of Health and Human Services). We have categorized endocrine-disrupting compounds where the body of peer-reviewed research indicates a strong foundation for doing so.