A simple approach to performing quantitative cancer risk assessment using published results from occupational epidemiology studies
Introduction
Quantitative risk assessment provides formalized scientific input for setting occupational and environmental standards for potentially toxic exposures. Risk assessment using well-conducted human studies provides distinct advantages over the use of animal data: errors resulting from interspecies extrapolation are eliminated (Smith, 1988), and errors from differences in exposure patterns are reduced (Hertz-Picciotto, 1995). Nevertheless, cancer and reproductive risk assessment continues to rely heavily on animal bioassays sometimes even when epidemiological data are available. Methods used for risk assessment based on bioassay data are commonly used (Gart et al., 1986, Crump, 1996), whereas methods for risk assessment based on human studies have received much less attention. We describe the concepts and methods used to perform cancer risk assessment based on published data from occupational epidemiology studies, and illustrate these methods for some suspected or known human carcinogens. The methods presented can be applied using a hand calculator or spreadsheet. This paper should help clarify some of the methods used in human-based risk assessment by those without access to original data from epidemiologic studies, and should facilitate the use of published data in the estimation of cancer risk in the general or working population.
Section snippets
Methods
To perform risk assessment based on published epidemiological studies, several steps are required: (a) identification of appropriate epidemiologic data; (b) exposure determination in units of daily intake (e.g. milligram per day) or lifetime cumulative exposure (e.g. cumulative milligram); (c) determination of the carcinogenic potency; and (d) calculation of tumorigenic dose (TD), i.e. the estimated daily dose corresponding to a specified additional lifetime risk (e.g. TD1 is the daily dose
Results
We illustrate our methods for quantitative risk assessment using the epidemiological literature for several chemicals: perchloroethylene (PCE) (Vaughan et al., 1997), formaldehyde (Vaughan et al., 2000), benzene (Hayes et al., 1997), and nickel (Andersen et al., 1996). Vaughan and colleagues conducted a population-based case-control study of 1130 primary cancers of the oral cavity, larynx, and esophagus and 724 controls (Vaughan et al., 1997). Work history information was obtained through
Discussion
Uncertainties from human studies are unlikely to be as great as those resulting from interspecies extrapolation based on animal data, which can be highly inappropriate. Therefore, use of epidemiological data for quantitative risk assessment reduces uncertainty in both the potencies and associated TDs, as compared with the use of animal data alone (Smith, 1988, Hertz-Picciotto, 1995, Stayner et al., 1995).
That said, the results of risk assessment based on epidemiological data must be interpreted
Acknowledgements
This work was partially supported by National Institute for Occupational Safety and Health (NIOSH) cooperative agreement U60/CCU-415922.
References (16)
- et al.
Exposure to nickel compounds and smoking in relation to incidence of lung and nasal cancer among nickel refinery workers
Occup Environ Med
(1996) The linearized multistage model and the future of quantitative risk assessment
Hum Exp Toxicol
(1996)- et al.
Model fitting
- et al.
Human interindividual variability in parameters related to health risks
Risk Anal
(1999) - et al.
Benzene and the dose-related incidence of hematologic neoplasms in China. Chinese Academy of Preventive Medicine—National Cancer Institute Benzene Study Group
J Natl Cancer Inst
(1997) Epidemiology and quantitative risk assessment: a bridge from science to policy
Am J Public Health
(1995)- et al.
Observations on the dose-response curve for arsenic exposure and lung cancer
Scand J Work Environ Health
(1993) Human respiratory tract model for radiological protection. A report of a task group of the International Commission on Radiological Protection
(1994)
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