On Reference Dose (RFD) and Its Underlying Toxicity Data Base

Abstract

The toxicity data of pesticides were summarized and compared amongst different animal species and types of bioassays. These comparisons showed the expected inter-species and inter-bioassay variability. After quantitative and statistical analysis of these data, it was concluded that, on the average, a 2-year dog bioassay detected toxic responses at similar doses as a 2-year rat study, and that both of these bioassays detected toxic responses at lower doses than either a rat 2-generation bioassay, a rat developmental toxicity study, or a 2-year mouse bioassay. Although these chronic dog and rat bioassays were found to detect toxic responses at lower doses than the other studies listed, this analysis does not reflect the seriousness of the effects that were compared. Within the confines of this analysis, then, it appears that a 2-year dog and rat study, reproductive and developmental bioassays are a sufficient data base on which to estimate high confidence Reference Doses (RfDs), and furthermore, that an additional uncertainty factor is needed to estimate RfDs to account for this inter-species and inter-bioassay variability when fewer than this number of bioassays are available.

Allometric principles for interspecies extrapolation in toxicological risk assessment—empirical investigations

“…This increasing susceptibility with increasing body weight is clearly in agreement with the caloric demand scaling rule, albeit the rat appeared to be somewhat more susceptible on average than expected. Our overall results are thus in agreement with similar results obtained by two other evaluations of long-term studies on pesticides with rats, mice, and dogs (Dourson et al, 1992;Rennen et al, 2001). However, in interpreting the quantitative outcome it must be kept in mind that extrapolation factors derived from NOAEL ratios may be subject to substantial error due to the poor statistical properties of the NOAEL (Brand et al, 1999).…”

Overview: Uncertainty in noncancer risk assessment

“…Several reports describe the underlying scientific basis of uncertainty factors (Zielhuis and van der Kreek, 1979;Dourson and Stara, 1983). Research has also been conducted in this area (see, for example, Calabrese, 1985;Hattis, Erdreich, and Ballew, 1987;Renwick, 1991Renwick, , 1993Dourson, Knauf, and Swartout, 1992;Calabrese, Beck, and Chappell, 1992;Lewis, 1993;Calabrese and Gilbert, 1993;Kadry, Skowronski, and Abdel-Rahman, 1995). The following reports of the workshop enhance this existing research.…”

Development of acute exposure guideline levels for airborne exposures to hazardous substances

“…For example, Dourson et al (1992) conducted an analysis of chronic and subchronic toxicity data on 67 pesticides. They found that the rat NOAEL exceeded the dog NOAEL by greater than a factor of 10 in 10% of the cases and the dog NOAEL exceeded the rat NOAEL by more than a factor of 10 in 4% of the cases.…”