Chlorothalonil: Mechanism for the Formation of
Renal and Forestomach Tumors

The Agency poses the following questions to the SAP regarding Chlorothalonil: Mechanism for the Formation of Renal and Forestomach Tumors.

Based on our review of the dose-response data, mode of action studies and mutagenicity data, does the Panel agree with our conclusion that we can use a nonlinear method for risk assessment? Does the Panel agree that the point of departure for this nonlinear risk assessment should be 1.5 mg/kg/day? Does the Panel agree that the margin of exposure (MOE) method is appropriate for expressing the risk?
We are assuming that the enzyme GGTP in infants and children is similar in activity to that in rats even though it has been shown the enzyme activity in adult humans is much less than in the rat. Is this a prudent assumption? Does the panel have comments on the relative activity of this enzyme among rodents, adult humans and children, and potential differences in the response of kidney tissue to chlorothalonil exposure that may be expected among these groups?

Scientific Advisory Panel (SAP) July 1998 Meeting Questions for Session 4