Carcinogenicity risk assessment

United States Environmental Protection Agency (2005). Guidelines for Carcinogen Risk Assessment EPA/630/P-03/001F. Risk Assessment Forum, U.S. Environmental Protection... 

Crump, K.S., and R.B.Howe. 1984. The multistage model with a time-dependent dose pattern Applications to carcinogenic risk assessment. Risk Anal 4 163-176. 

Ramsey JC, Park CN, Ott MG, et al. 1979. Carcinogenic risk assessment Ethylene dibromide. Toxicol AppI Pharmacol 47 411-414. 

Guidelines for Carcinogen Risk Assessment Guidelines for Chemical Mixtures Risk Assessment... 

Carmichael, N.G., H. Enzmann, I. Pate, and F. Waechter, 1997. The significance of mouse hver tumor formation for carcinogenic risk assessment results and conclusions from a survey of ten years of testing by the agrochemical industry. Environ. Health Perspect. 105 1196-1203. 

US-EPA. 1986b. Guidelines for carcinogen risk assessment. Federal Register 51(185) 33992-34003. http // cfpub.epa.gov/ncea/raf/rafguid.cfm... 

In its 1986 Guidelines for Carcinogen Risk Assessment, the US-EPA introduced the LMS model into the U.S. regulatory framework. The multistage model was chosen for regulatory... 

The US-EPA has in its 1996 Proposed Guidelines for Carcinogen Risk Assessment (US-EPA 1996) adopted the dose descriptor LEDio (the 95% lower confidence limit on a dose associated with a 10% extra tumor risk) whereas in its 2005 Guidelines for Carcinogen Risk Assessment (US-EPA 2005), no defined incidence has been recommended (see Section 6.3.2). Within the EU chemical s regulation, the dose descriptor T25 has been proposed (see Section 6.3.3). In the newly proposed MOE approach, the JECFA and the EFSA have recommended the dose descriptor BMDLio (see Section 6.4). 

In 1996, the US-EPA published their Proposed Guidelines for Carcinogen Risk Assessment (US-EPA 1996). These Proposed Guidelines were a revision of the 1986 Guidelines for Carcinogen Risk Assessment (US-EPA 1986) and introduced, among others, a new approach for the quantitative risk assessment. A revised draft Guidelines was launched in 1999 (US-EPA 1999) and the final version was published in 2005 (US-EPA 2005). 

The following overview of the US-EPA revised quantitative approach for cancer risk assessment is based on the final version of the Guidelines for Carcinogen Risk Assessment (US-EPA 2005). 

Krewski, D., T. Thorslund, and J. Withey. 1989. Carcinogenic risk assessment of complex mixtures. Toxicol. Ind. Health 5 851-867. 

Thorslund, T.W. and D. Farrar. 1990. Development of relative potency estimates for PAH and hydrocarbon combustion product fractions compared to benzo[a]pyrene and their use in carcinogenic risk assessment. EPA/600/R-92/134, Dept. Commerce, NTIS. 

The Monographs represent the first step in carcinogenic risk assessment, which involves examination of all relevant information in order to assess the strength of the available evidence that certain exposures could alter the incidence of cancer in humans. The second step is quantitative risk estimation. Detailed, quantitative evaluations of epidemiological data may be made in the Monographs, but without extrapolation beyond the range of the data available. Quantitative extrapolation from experimental data to the human situation is not undertaken. 

The elements involved in risk assessment and risk management are depicted schematically in Figure 8.1. The procedure by which carcinogenic risk assessments are generally performed, and the ways in which data of the various types discussed above are utilized in performing such assessments have been reviewed elsewhere (Krewski and Brown, 1981), and are outlined below. 

In view of the foregoing, carcinogenic risk assessments for chemicals generally involve greater imcertainty than 4o carcinogenic risk assessments for radiation. 

In carcinogenic risk assessments for chemicals, as in those for radiation, risks should be expressed in ways that place them in perspective and make them broadly intelligible. Such an approach will facilitate their interpretation and use. 

Crouch, E.A.C. (1983b). Carcinogenic risk assessment — the consequences of believing models, Basic Life ScL 24,653. 

Crump, K.S. (1981). An improved procedure for low-dose carcinogenic risk assessment from animal data, J. Environ. Pathol. TbidcoL 5,675. 

Krewski, D. and Brown, C. (1981). Carcinogenic risk assessment a guide to the literature, Biometrics 37,353. 

Krewski, D., Withey, J.R., Ku, L.F. and Andersen, M.E. (1994) Applications of physiologic pharmacokinetic modeling in carcinogenic risk assessment. Environ. Health Perspect., 102, (Suppl 11) ... 

Carcinogen Risk Assessments New Directions in the Qualitative and Quantitative Aspects. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 33-4-1. 

EPA (1996a). U.S. Environmental Protection Agency. Proposed guidelines for carcinogen risk assessment, 61 FR 17960 (U.S. Government Printing Office, Washington). 

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