Inter- and intra-species extrapolation in risk assessment of different classes of pesticides

Risk assessors routinely use the reference dose (RfD) approach for noncance r risk assessment. In this approach, No-Observed-Adverse-Effect-Level (NOAE L) is divided by the product of uncertainty factors (UFs) and, occasionally , an additional modifying factor (MF), each usually employed by default as factors of 10. In the present investigation, kinetic and dynamic data have been used in order to reduce uncertainties when establishing exposure guide lines for examples of chemicals representing four classes of pesticides (wa rfarin, lindane, carbaryl and parathion). An intensive search of databases was conducted for these pesticides, and toxicokinetic and toxicodynamic par ameters in inter- and intra-species were evaluated. The kinetic and dynamic subfactors were less than the proposed values of Renwick and the Internati onal Programme on Chemical Safety (IPCS). The composite factors for all the examined pesticides were less than 100. The present study indicated that i n setting exposure levels it is important to incorporate kinetic and dynami c data, as they become available, rather than rely on default uncertainty f actors, which are imprecise in many cases.