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Advisory Committee on Health Effects of Endocrine Disruptors
The Supplement II to the Intermediary Report
1.3.3

 

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(4) Endocrine disruptor study using genomic techniques
Identification of gene profiles which serve as biomarkers has achieved considerable advance. A further step to biomarker identification based on proteomics will be advantageous for administrative purposes58. Candidate approaches are developing of a chip specifically designed for markers of possible problems caused by endocrine disruptors59, or regarding gene expression as a phenotype (reverse science)60.
Each of these approaches has advantages according to applications. The following problems should also be taken into account.

  1. Possibility of long-term prediction from effects initially observed
  2. Adequate approach to dose-effect relationship, dose-specific gene profiling
  3. Possibility of prediction of combined effects (for which they will be useful)
  4. Possibility of extrapolation to different animal species (gene profiling concerning homologous phenotype)
  5. Correlation between the gene expressions in cells and tissues in vitro and in individuals61
A considerable part of these topics overlap the low-dose issue.
Along with genomics, informatics is considered to play an important role in future studies. Introduction of these "omics" techniques was discussed in a WHO/IPCS workshop in Berlin62 and an OECD workshop in Kyoto63 to identify major technical problems.
 
 
58 Watanabe H, Suzuki A, Mizutani T, Kohno S, Lubahn DB, Handa H, Iguchi. Genome-wide analysis of changes in early gene expression induced by estrogen. Genes Cells, 7: 497-507, 2002.
59 ChineChipTM Probe Array Technology, Copyrihgt 2000, Affymetrix, Inc.
60 T. Inoue & W.D.Pennie (eds) Toxicogenomics. Springer, Tokyo, Berlin 2003, pp.3-11.
61 Inoue T, Igarashi K, Sekizawa J. JMAJ (Japan Medical Association Journal) 46: 97-102, 2003.
62 Held at the Federal Institute for Risk Assessment, Berlin, Nov. 17-19, 2003, Proceedings in press
63 Held at Kyoto International Conference Center, Oct. 13-15, 2004, Proceedings in press

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