potency ranking and low dose risk assessment. Other investigators have previously proposed linear extrapolation from the TD01 for low dose risk estimation (Mantel & Bryan, 1961; Van Ryzin, 1980; Farmer et al., 1982; Gaylor, 1983).
Another approach to estimating low dose risks is the model-free extrapolation (MFX) method proposed by Krewski et al. (1991a). This procedure assumes only that the dose-response curve is linear at low doses, and is based on a series of secant approximations to the slope of the dose-response curve obtained by linear interpolation between points in the low dose region and controls. Upper confidence limits on the slope of the dose-response curve based on MFX are generally close to the values of q1* obtained from the LMS model. If the dose-response curve is actually sublinear at low doses, the MFX method still provides an upper bound on low dose risks.
In practice, estimation of measures of carcinogenic potency such as the TD50 is not as straightforward as might appear from the preceding discussion. Ideally, estimation of the TD50 should take into account both intercurrent mortality in long-term animal studies and, when available, cause of death information (Finkelstein & Ryan, 1987; Finkelstein, 1991). Sawyer et al. (1984) propose methods for adjusting for intercurrent mortality with rapidly lethal tumors; Portier & Hoel (1987) show that estimates of the TD50 may be biased when the assumption of rapid tumor lethality is not satisfied. Dewanji et al. (1992) proposed a Weibull model that can be used for this purpose, provided that the survival times of individual animals are available for analysis. Bailar & Portier (1992) also use a Weibull model in estimating carcinogenic potency.
2.2 Carcinogenic Potency Database (CPDB)
Gold et al. (1984, 1986a, 1987, 1990) have tabulated the TD50 values for a large number of chemicals which have induced tumors in laboratory animals in their Carcinogenic Potency Database (CPDB). The TD50 values were calculated using statistical methods developed by Sawyer et al. (1984) and Peto et al. (1984) using a one-stage model. All TD 50 values are expressed in common units of mg/kg body weight/day, adjusted to a standard two year rodent lifetime, and corrected for intercurrent mortality whenever individual animal data was available (Gold et al.,