Carcinogenesis nonlinear

Radiation is carcinogenic. The frequency of death from cancer of the thyroid, breast, lung, esophagus, stomach, and bladder was higher in Japanese survivors of the atomic bomb than in nonexposed individuals, and carcinogenesis seems to be the primary latent effect of ionizing radiation. The minimal latent period of most cancers was <15 years and depended on an individual s age at exposure and site of cancer. The relation of radiation-induced cancers to low doses and the shape of the dose-response curve (linear or nonlinear), the existence of a threshold, and the influence of dose rate and exposure period have to be determined (Hobbs and McClellan 1986). 

Hoel, D.G, Kaplan, N.L. Anderson, M.W. (1983) Implication of nonlinear kinetics on risk estimation in carcinogenesis. Science, 219, 1032-1037... 

Lutz WK. 1998. Dose-response relationships in chemical carcinogenesis superposition of different mechanisms of action, resulting in linear-nonlinear curves, practical thresholds, J-shapes. Mutat. Res. 405 117-24... 

While scientific advances are being made, political influences are also important. This can be seen in some cases such as the court-forced incorporation of the nonlinear method for EPA s assessment of chloroform instead of the linear extrapolation method. This brings to mind the importance of evaluation of carcinogenesis mechanisms by scientists rather then being settled in the courts. International decisions and deliberations are also affecting regulation of carcinogens (or at least the debate about them) in the United States. An example is the precautionary principle, which is often applied in the context of the impact of human actions on human health and the environment, in which the consequence of actions... 

Formaldehyde is another example of a mutagenic compound with evidence of nonlinearity. Based on limited evidence of respiratory cancer in humans and evidence of nasal tumors in rats and mice, ERA classifies formaldehyde as a probable human carcinogen. In rats, the most well-studied animal model for formaldehyde carcinogenesis, there is a threshold for tumor formation at 6 ppm. At levels below 6 ppm, formaldehyde induces DNA crosslinks in a dose-dependent manner wilh apparent low-dose linearity (Conolly et al. 2000 Slikko- et al. 2004). At doses above 6 ppm, concurrent with tumor formation, formaldehyde causes maiked cytotoxicity in the nasal passages of rats. 

Petito CT, Beck BD (1991) Evaluation of evidence of nonlinearities in the dose-response curve for arsenic carcinogenesis. Trace Subst Environ Health 24 143-176... 

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