No-threshold dose-response curves for nongenotoxic chemicals: findings and applications for risk assessment.
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 approximately 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.
Sheehan
Daniel M
DM
Daniel M. Sheehan and Associates, 1422 Scott St., Little Rock, AR 72202, USA. dansheeh@swbell.net
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004958:Estradiol / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D008297:Male; D018570:Risk Assessment; D012744:Sex Ratio; D018675:Toxicity Tests; D014426:Turtles
D004967:Estrogens; D004958:Estradiol