The use of biochemical and molecular parameters to estimate dose-response relationships at low levels of exposure

Environmental Health Perspectives
M E Andersen, H A Barton

Abstract

Biomarkers based on alterations in molecular and biochemical parameters may be useful in chemical risk assessment for establishing the presence of an exposure, ranking relative risks among exposed individuals, and estimating risks at low levels of exposure. Because it is unlikely that the relation between toxic responses and the degree of alteration in the biomarker is equivalent at all doses, quantification of risks at low levels is not necessarily more accurate using these biomarkers for extrapolation. The application of response biomarkers for risk evaluation at low levels of exposure is discussed in relation to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a compound that causes induction of cytochromes CYP1A1 and CYP1A2 in liver and other tissues. CYP1A1 induction in liver increases monotonically with TCDD dosage; however, several of the dose-response curves for hepatic effects of TCDD are U-shaped. The U-shaped dose-response curve for hepatic tumor promotion appears to result because the integrated toxicologic response depends on multiple underlying processes--mitosuppression, toxicity, and cell proliferation--each of which has a different dose-response relationship with respect to TCDD. Although dose-response relationships...Continue Reading

References

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Citations

Mar 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Manabu NukayaChristopher A Bradfield
Jan 1, 1999·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals· Leonard I Sweet Dora R Passino-Reader Peter G Meier Geneva M Omann
Jan 19, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Tomasz GrabowskiWalerian Piotrowski
Jul 24, 2008·Dose-response : a Publication of International Hormesis Society·John F ReichardAlvaro Puga
Mar 12, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·C Tenley FrenchMelvin E Andersen
Mar 27, 2004·Experimental Biology and Medicine·Hirohisa TakanoToshikazu Yoshikawa
Nov 20, 2020·Bulletin of Environmental Contamination and Toxicology·Tash-Lynn L ColsonValerie S Langlois

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