National Water Quality Inventory Report to Congress (as required by 

 Section 305(b) of the Clean Water Act). The information presented in 

 this guidance manual can be used to support these activities through 

 the identification of guidelines on levels of contaminants in tissues that 

 correspond to a defined risk to human health (e.g., tolerable risk 

 levels). 



In addition to these ongoing monitoring activities, the 1987 amend- 

 ments to the Clean Water Act, in particular the new Section 304(1), 

 require states to develop Usts of impaired waters, identify point source 

 discharges of toxic substances and the amounts of pollutants present, 

 and develop individual control strategies (permits) for each point 

 source discharger. The information in this guidance manual may be 

 useful in evaluating data on concentrations of chemical contaminants 

 in fish and shellfish tissue and associated human health risks to identify 

 waters impaired by toxic contamination. 



Because of differences in legislative and regulatory responsibilities 

 among EPA, FDA, and state and local governments, these entities have 

 developed differing procedures for risk assessment and risk manage- 

 ment. As an EPA guidance manual, this document presumes the use 

 of standard EPA risk assessment procedures. However, certain pro- 

 cedures recommended in this manual can be modified to make the risk 

 assessment compatible with alternative approaches used by FDA and 

 some states. This section explains how conversion factors can be used 

 to make risk assessment procedures recommended herein compatible 

 with certain assumptions used in FDA risk assessments. 



A major difference between EPA and FDA risk assessment ap- 

 proaches concerns the methods for extrapolating the toxic potency of 

 chemicals in small experimental animals (e.g., rats and mice) to es- 

 timate potential effects in humans. U.S. EPA (1986a) pointed out 

 several species-specific factors that may influence the response to a 

 carcinogen, including life span, body size, genetic variability, concur- 

 rent diseases, and the rates and products of metabolism and excretion. 

 To account for at least some of the differences between experimental 

 animals and humans, the estimate of exposure in laboratory animals is 

 multiplied by a scaling factor to obtain an estimate of equivalent dosage 

 in humans. EPA uses the ratio of animal-to-human surface area, 

 whereas FDA uses the corresponding ratio of body weights as a scaling 

 factor. Thus, EPA uses mg of carcinogen per m body surface area per 

 day as a standardized scale for expressing dosages, whereas FDA uses 

 mg carcinogen per kg body weight per day. This difference in inter- 

 species extrapolation factors results in approximately a five- to ten-fold 

 difference in estimates of carcinogenic potency (and risk) derived by 

 the two agencies. 



In recognition of the difficulties that differences in interspecies 

 extrapolation procedures between EPA and FDA may pose for state 

 agencies and others who rely on federal guidance on risk assessment, 

 EPA's Risk Assessment Council and FDA reviewed the pros and cons 

 of their respective methods for dosage scaling. They concluded that 



Relationship of EPA Risk 

 Assessment Methods to FDA 

 Risk Assessment Methods 



