We also compute optimal allocation to estimate the minimum effective and peak doses in discrete dose space using isotonic regression.
The two or three doses, spaced months apart, are administered by injection.
Two doses spaced at least 6 months apart appeared to have the same effect as three.
Vaccines against diseases such as polio and tetanus currently are given in several small doses spaced weeks or months apart.
Whereas geometric means of ratios were in a narrow range of 1.1 2.5, the geometric standard deviations and 95th percentiles increased with dose spacing of the involved studies.
Recently, study design parameters such as application route with related dose-decrements, dose-spacing and number of animals per group but not exposure duration were found to affect NOAEL distributions.
This study assessed the occurrence of hormetic dose responses from three previously published data sets [1 3] with 825 chemicals in three Ames assay tester strains (i.e., TA97, TA98, TA100) with and without the S9 fraction, using a five dose protocol and semi-log dose spacing.
Using NOAELs related to lowest LOAELs instead of lowest NOAELs, excluding studies with a dose spacing >8, and standardizing NOAELs to the initial dose animals received shifted the 5th percentile of NOAEL distributions from 0.22 to 0.5 mg/kg body weight per day.
The initial three doses were spaced two weeks apart, followed by 11 doses spaced four weeks apart, so that the treatment period lasted approximately one year.
In the present study, no damage was visualized by MRI in 4 control rats irradiated by intersecting, non-interlacing arrays which created 700Gy microplanar peak doses spaced by 200 µm on-center (valley dose of 12.5 Gy at 1 cm depth).
Additionally, the dose spacing in the animal study may have confounded the ratio.
