strates or inhibitors of human DMEs, both the oxidases and the converting enzymes, in biochemical assays or in cell lines carrying a variety of human DMEs. Such approaches have begun (for a review, see Crespi and Miller 1999). Thus far, this information has found limited use in risk assessment for several reasons. First, many assays have not utilized consistently stabilized transfected cell lines, and therefore the responses have been variable. (This variability has also been problematic for the EDSP.) Second, gene-induction profiles for specific compounds have shown tremendous variability when inducers are compared across established human cell lines. Thus, although comparisons can be made across compounds within some cell assays, comparisons across cell lines and with animals remain problematic.
Ongoing research efforts in these areas should help clarify and resolve these issues. However, risk assessors need to understand what types of information these assays can provide for assessment. Recent conferences have summarized key information available from the use of human cell- and tissue-based assays (Society of Toxicology (SOT) Workshop on In Vitro Human Tissue Models in Risk Assessment, September 1999). Additional work on such systems would prove especially useful, as such recent conferences attest.
As data are obtained, they would be entered in a widely accessible database (e.g., the recent Science magazine Web site for cell signaling pathways, www.stke.org). Compounds with high activity in such tests could be prioritized for higher levels of testing, especially if human exposure is current or pending. Compounds that do not show effects in these assays would still need testing at other levels of assessment if human exposure or environmental release is likely. At this information level, false positives are preferable to false negatives, and high sensitivity is preferable to low sensitivity (see discussions on how to use such information to strategize test applications by Lave and Omenn 1986).
It is expected that comprehensive gene expression assays will soon become routinely available with DNA microarrays. Some arrays now include 6,000-10,000 DNA sequences in order to detect changes in messenger ribonucleic acid (mRNA) levels (after conversion to complementary (c) DNAs) in cells or tissues exposed to a chemical. Libraries of yeast strains, each carrying one of the 6,000 genes on a plasmid with a reporter gene, will soon be available. These libraries will represent a full-spectrum profile of the effects of chemicals on gene expression. The committee expects that the assays at this level will be better and broader in the near future and emphasizes the need to expeditiously put the results from these assays in the context of temporal patterns, and dose and downstream responses.
At this level, nonmammalian animals should be used to assess the potential for chemicals to affect developmental processes. The animals are small, inexpen-