Risk Assessment in the Genomic Era

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The sequencing of the human and mouse genomes, and soon that of the rat, offers a foundation to evaluate biological phenomena, including toxicologic effects. Numerous tools are being developed to evaluate aspects of biology based on the DNA sequence. These tools can be utilized to evaluate absorption, distribution, metabolism and excretion, and effects of the toxicologically active product on the target organ. The genes involved can be broadly categorized as those affecting susceptibility to a toxicologic effect and those that are involved in the biologic response. For risk assessment to be performed in a rational manner, fundamental mechanisms of toxicologic processes must be ascertained. Based on successes already achieved, such as development of transgenic and knockout mouse strains, the application of aspects of the genomics revolution could be useful in developing a better understanding of mechanisms, and possibly in identifying specific markers of responses. In addition, genomics are likely to be useful in translating effects between species. However, genomics are being portrayed as the ultimate solution to all of toxicology. This is hardly the case. Basic chemistry, biochemistry, toxicokinetics, pharmacology, and pathology will continue to be needed in the overall weight of evidence approach to risk assessment. Genomics are likely to be of limited usefulness in predicting individual, in contrast to population susceptibility to various toxicological responses. Concordance of various diseases in identical twins, for example, different cancers, is rarely greater than 20% over the lifetime of these individuals. Similarly, genomics are likely to be of limited usefulness in screening for toxicologic end points. As with other tools of biology, those to be developed based on the genome are likely to provide greater usefulness in dissecting the mechanistic processes involved and defining the basis for susceptibility.

Original languageEnglish (US)
Pages (from-to)3-8
Number of pages6
JournalToxicologic Pathology
Volume32
Issue numberSUPPL. 1
DOIs
StatePublished - Mar 1 2004

Keywords

  • Carcinogenesis
  • Dose response
  • Genetics
  • Species extrapolation
  • Toxicity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

Fingerprint Dive into the research topics of 'Risk Assessment in the Genomic Era'. Together they form a unique fingerprint.

  • Cite this