the most appropriate method for interspecies dosage extrapolation 

 may vary depending on exposure conditions and chemicals involved. 

 For example, one procedure may be more realistic for lipophilic 

 chemicals, whereas the other would be more appropriate for 

 hydrophilic chemicals. Differences in target organs (i.e., primary site 

 of toxicity) also affect the preferred extrapolation procedure. 



Because the EPA extrapolation procedure results in a higher estimate 

 of risk than the FDA procedure (by approximately an order of mag- 

 nitude), the former is considered more protective. For most EPA 

 assessments, the surface-area based extrapolation is appropriate. The 

 technical basis for EPA's approach relies primarily on a demonstrated 

 relationship between pharmacological effects (e.g., balance of rates of 

 metabolism and excretion) and body surface area (Pinkel 1958; 

 Freireich et al. 1966; Dedrick 1973). If state or local policymakers 

 decide that the body-weight based extrapolation is more appropriate 

 for local risk management needs, then procedures recommended in 

 this manual can be modified by converting EPA's dose-response data 

 using a ratio of human body weight to surface area. This would allow 

 the risk assessor to use carcinogenic potency factors in EPA's com- 

 puterized database, IRIS (U.S. EPA 1987a). IRIS is a database main- 

 tained by EPA to provide regularly updated toxicological data for use 

 in risk assessment. The use of IRIS would greatly increase the ability 

 of a state to perform risk assessments for chemicals of local concern 

 while increasing consistency among jurisdictions sharing responsibility 

 for common waters. 



Although the conversion of EPA estimates of toxic potency to es- 

 timates based on equivalent dosage scales related to body weight is not 

 technically complex, the modified procedure should preferably be 

 carried out only by experienced toxicologists. The conversion factor 

 will vary depending on whether the dose-response data were derived 

 from rats or from mice. Thus the original data set must be reviewed to 

 determine an appropriate conversion factor. In general, an EPA es- 

 timate of carcinogenic potency would be multiplied by a factor equal 

 to the ratio of surface area per unit body weight (m /kg) of the 

 laboratory animal to that of humans. For example, if the EPA car- 

 cinogenic potency factor is C and the surface area per unit body weight 

 is X for the laboratory animal and Y for humans, the corresponding 

 potency factor based on dosage scaled to body weight is C multiplied 

 by X divided by Y. Because specific data on surface area are often 

 unavailable, body weight to the two-thirds power is typically used as an 

 estimate of surface area. Note that some EPA carcinogenic potency 

 factors are derived from epidemiological studies and therefore do not 

 require conversion. 



Other steps in the process to estimate carcinogenic potencies may vary 

 somewhat among regulatory agencies. For example, different agencies 

 may choose different data sets to derive a carcinogenic potency factor 

 for the same chemical. The mathematical expression used to model the 

 dose-response relationship may also differ among agencies. Hogan and 

 Hoel (1982) and Cothern et al. (1986) discuss various models for 

 extrapolating data from high doses used in laboratory experiments to 

 the low doses of concern in carcinogenic risk assessment. At low doses 

 corresponding to risks of 10" to 10 or less, different models may 

 produce results that vary by as much as several orders of magnitude. 



