Empirical Scaling of Single Oral Lethal Doses Across Mammalian Species Based on a Large Database

Authors: Rhomberg L.R.; Wolff S.K.

Source: Risk Analysis, Volume 18, Number 6, 199812 , pp. 741-753(13)

Publisher: Springer

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Abstract:

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.

Keywords: Lethal doses; cross-species extrapolation; dose scaling; RTECS®; noncancer risk assessment

Document Type: Research article

Affiliations: 1: Harvard Center for Risk Analysis, Harvard School of Public Health, 718 Huntington Avenue, Boston, Massachusetts 02115-5924

Publication date: 1998-01-01