No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment
- Daniel M. Sheehan and Associates, 1422 Scott St., Little Rock, AR 72202 (United States)
We tested the hypothesis that no threshold exists when estradiol acts through the same mechanism as an active endogenous estrogen. A Michaelis-Menten (MM) equation accounting for response saturation, background effects, and endogenous estrogen level fit a turtle sex-reversal data set with no threshold and estimated the endogenous dose. Additionally, 31 diverse literature dose-response data sets were analyzed by adding a term for nonhormonal background; good fits were obtained but endogenous dose estimations were not significant due to low resolving power. No thresholds were observed. Data sets were plotted using a normalized MM equation; all 178 data points were accommodated on a single graph. Response rates from {approx}1% to >95% were well fit. The findings contradict the threshold assumption and low-dose safety. Calculating risk and assuming additivity of effects from multiple chemicals acting through the same mechanism rather than assuming a safe dose for nonthresholded curves is appropriate.
- OSTI ID:
- 20775299
- Journal Information:
- Environmental Research, Vol. 100, Issue 1; Other Information: DOI: 10.1016/j.envres.2005.09.002; PII: S0013-9351(05)00126-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0013-9351
- Country of Publication:
- United States
- Language:
- English
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