Using Human Data to Develop Risk Values

One of the criticisms of industry-sponsored human subject testing of toxicants is based on the perception that it is often motivated by an attempt to raise the acceptable exposure limit for the chemical. When Reference Doses (RfDs) or Reference Concentrations (RfCs) are based upon no-effect levels from human rather than animal data, an animal-to-human uncertainty factor (usually 10) is not required, which could conceivably result in a higher safe exposure limit. There has been little in the way of study of the effect of using human vs. animal data on the development of RfDs and RfCs to lend empirical support to this argument. We have recently completed an analysis comparing RfDs and RfCs derived from human data with toxicity values for the same chemicals based on animal data. The results, published in detail elsewhere, are summarized here. We found that the use of human data did not always result in higher RfDs or RfCs. In 36% of the comparisons, human-based RfDs or RfCs were lower than the corresponding animal-based toxicity values, and were more than 3-fold lower in 23% of the comparisons. In 10 out of 43 possible comparisons (23%), insufficient experimental animal data are readily available or data are inappropriate to estimate either RfDs or RfCs. Although there are practical limitations in conducting this type of analysis, it nonetheless suggests that the use of human data does not routinely lead to higher toxicity values. Given the inherent ability of human data to reduce uncertainty regarding risks from human exposures, its use in conjunction with data gathered from experimental animals is a public health protective policy that should be encouraged.