home edit2 whole TSD November 2002 PDF format - OEHHA

incidences for each of the dose levels employed for sites where significant responses were observed,
dosing period, length of study and histopathology. Average daily dose levels were calculated assuming
100% absorption. Dose calculations follow procedures similar to those of Cal/EPA and US EPA;
details on methods used and standard values for animal lifespans, body weights, and diet, water and air
intake are listed in Gold et al. (1984). RCHAS (1992) reviewed the quality assurance, literature
review, and control procedures used in compiling the data and found them to be sufficient for use in an
expedited procedure. Cancer potency estimates were derived by applying the mathematical approach
described in the section below to dose response data in the Gold et al. database. The following criteria
were used for data selection:
1. Data sets with statistically significant increases in cancer incidence with dose (p ≤ 0.05) were used.
(If the authors of the bioassay report considered a statistically significant result to be unrelated to the
exposure to the carcinogen, the associated data set was not used.)
2. Data sets were not selected if the endpoint was specified as "all tumor-bearing animals" or results
were from a combination of unrelated tissues and tumors.
3. When several studies were available, and one study stood out as being of higher quality due to
numbers of dose groups, magnitude of the dose applied, duration of study, or other factors, the
higher quality study was chosen as the basis for potency calculation if study results were consistent
with those of the other bioassays listed.
4. When there were multiple studies of similar quality in the sensitive species, the geometric mean of
potencies derived from these studies was taken. If the same experimentalists tested two sexes of the
same species/strain under the same laboratory conditions, and no other adequate studies were
available for that species, the data set for the more sensitive sex was selected.
5. Potency was derived from data sets that tabulate malignant tumors, combined malignant and benign
tumors, or tumors that would have likely progressed to malignancy.
Cancer potency was defined as the slope of the dose response curve at low doses. Following the
default approach, this slope was estimated from the dose response data collected at high doses and
assumed to hold at very low doses. The Crump linearized multistage polynomial (Crump et al., 1977)
was fit to animal bioassay data:
Probability of cancer = 1- exp[- (q 0 + q 1 d + q 2 d 2 + ...)]
Cancer potency was estimated from the upper 95 % confidence bound on the linear coefficient q 1 ,
which is termed q 1 * .
For a given chemical, the model was fit to a number of data sets. As discussed in the section above, the
default was to select the data for the most sensitive target organ in the most sensitive species and sex,
unless data indicated that this was inappropriate. Deviations from this default occur, for example, when
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