Empirical scaling of single oral lethal doses across mammalian species based on a large database.

The scaling of administered doses to achieve equal degrees of toxic effect in different species has been relatively poorly examined for noncancer toxicity, either empirically or theoretically. We investigate empirical patterns in the correspondence of single oral dose LD50 values across several mammalian species for a large number of chemicals based on data reported in the RTECS database maintained by the National Institute for Occupational Safety and Health. We find a good correspondence of LD50 values across species when the dose levels are expressed in terms of mg administered per kg of body mass. Our findings contrast with earlier analyses that support scaling doses by the 3/4-power of body mass to achieve equal subacute toxicity of antineoplastic agents. We suggest that, especially for severe toxicity, single- and repeated-dosing regimes may have different cross-species scaling properties, as they may depend on standing levels of defenses and rate of regeneration of defenses, respectively.

Selecting experimental data for use in quantitative risk assessment: an expert-judgement approach.

In many cancer risk assessments the experimental data used in statistical modeling are selected by applying generic guidelines. The guidelines exclude use of some types of experimental data and often appear arbitrary since rules rather than scientific judgments guide selection of data. This paper implements an alternative approach in which data are selected based on the judgments of practicing scientists. Eight such scientists were identified through an explicit selection procedure to help select data for use in a dose-response assessment of formaldehyde. Judgements about appropriate data sets were then elicited in personal interviews using a formal interview protocol. Appropriate data sets were fit to the multistage model and used as the basis for low-dose extrapolation. Low-dose risk estimates are shown to be sensitive to the selection of data, especially the treatment of benign tumors. The recommendations of the experts also differ in some respects from the choices made in previously published risk assessments. This suggests that scientific judgement may be an appropriate method to augment guidelines when a broad range of data is available. The paper argues that the expert judgment approach has some advantages that are worth considering.