The vanishing zero revisited: Thresholds in the age of genomics

Helmut Zarbl, Michael A. Gallo, James Glick, Ka Yee Yeung, Paul Vouros

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


The concept of the vanishing zero, which was first discussed 50 years ago in relation to pesticide residues in foods and food crops, focused on the unintended regulatory consequences created by ever-increasing sensitivity and selectivity of analytical methods, in conjunction with the ambiguous wording of legislation meant to protect public health. In the interim, the ability to detect xenobiotics in most substrates has increased from tens of parts per million to parts per trillion or less, challenging our ability to interpret the biological significance of exposures at the lowest detectable levels. As a result the focus of risk assessment, especially for potential carcinogens, has shifted from defining an acceptable level, to extrapolating from the best available analytical results. Analysis of gene expression profiles in exposed target cells using genomic technologies can identify biological pathways induced or repressed by the exposure as a function of dose and time. This treatise explores how toxicogenomic responses at low doses may inform risk assessment and risk management by defining thresholds for cellular responses linked to modes or mechanisms of toxicity at the molecular level.

Original languageEnglish (US)
Pages (from-to)273-278
Number of pages6
JournalChemico-Biological Interactions
Issue number1-2
StatePublished - Mar 2010

All Science Journal Classification (ASJC) codes

  • Toxicology


  • Low dose-response
  • No observable transcriptional effect level
  • Risk assessment
  • Toxicogenomics


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