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Title: No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

Abstract

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.

Authors:
 [1]
  1. Daniel M. Sheehan and Associates, 1422 Scott St., Little Rock, AR 72202 (United States). E-mail: dansheeh@swbell.net
Publication Date:
OSTI Identifier:
20775299
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environmental Research; Journal Volume: 100; Journal 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)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL EFFECTS; ESTRADIOL; HYPOTHESIS; RISK ASSESSMENT; THRESHOLD DOSE; TURTLES

Citation Formats

Sheehan, Daniel M. No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment. United States: N. p., 2006. Web. doi:10.1016/j.envres.2005.09.002.
Sheehan, Daniel M. No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment. United States. doi:10.1016/j.envres.2005.09.002.
Sheehan, Daniel M. Sun . "No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment". United States. doi:10.1016/j.envres.2005.09.002.
@article{osti_20775299,
title = {No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment},
author = {Sheehan, Daniel M.},
abstractNote = {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.},
doi = {10.1016/j.envres.2005.09.002},
journal = {Environmental Research},
number = 1,
volume = 100,
place = {United States},
year = {Sun Jan 15 00:00:00 EST 2006},
month = {Sun Jan 15 00:00:00 EST 2006}
}