On ‘toxicity equivalent factors’ and ‘relative potency’ to account for differential toxicity and carcinogenicity: concerns about uncommon effects of dose in animal experiments and environmental exposures to humans

A number of historical experiments have been conducted to determine whether mixtures of chemical compounds can be treated as if their ingredients act by joint toxicological mechanisms. For mixtures comprised of pairs and combinations of 42 different organic compounds, the LD 50 or LC 50 could be predicted accurately from the Finney harmonic-mean concept which defines joint toxicity as a potency-adjusted concept in which one compound can be substituted for another. This analysis revisits data from those classic experiments that serve as the basis for Threshold Limit Value (TLV) applications to mixtures, to determine whether the potency-adjustment can be based on comparisons of bioassay data as published in the Registry of Toxic Effects of Chemical Substances instead of requiring the LD 50 (or LC 50 ) for each ingredient as used by the Finney model. This study has found that the toxicity of a mixture can be predicted accurately from a variety of bioassay data for each component of the mix and an LD 50 (or LC 50 ) for only one ingredient of the mixture. Finally, concerns are described about transforming high-dose data from laboratory experiments to low-dose human environmental exposures.