home edit2 whole TSD November 2002 PDF format - OEHHA

exposure to a concentration of 1 µg/m 3 of a given chemical; the cancer potency factor describes the
excess cancer risk associated with exposure to 1 mg of a given chemical per kilogram of body weight.
The Guidelines recommend the use of the linearized 95% upper confidence interval of risk as a doseresponse
assessment guideline.
OEHHA Calculation of Carcinogenic Potency Based on Human Data
Human epidemiologic studies with adequate exposure characterization are used to evaluate the cancer
potency of a chemical. If they show a carcinogenic effect, the data are analyzed to provide an estimate
of the linear dependence of cancer rates on lifetime cancer dose. The Guidelines state that with
continuous exposure, age-specific incidence continues to increase as a power function (e.g., t 4 ) of the
elapsed time since initial exposure. Lifetime risks can be estimated by applying this power function to
the observed data and extrapolating beyond the actual followup period. The specific approaches used
in OEHHA risk assessments based on human epidemiologic studies vary on a case by case basis;
examples of the methods used can be observed in the Toxic Air Contaminant documents (these
documents are referenced in Appendix B).
Reproductive And Cancer Hazard Assessment Section (RCHAS), Office of Environmental
Health Hazard Evaluation (OEHHA), California Environmental Protection Agency (Cal/EPA):
Expedited Proposition 65 Cancer Risk Assessment Methodology
Expedited cancer potency values developed for several agents listed as carcinogens under Proposition
65 (California Health and Safety Code 25249.5 et seq.) by RCHAS were derived from selected data
sets of the Carcinogenic Potency Database (CPDB) of Gold et al. (1984, 1986, 1987, 1989, 1990)
using default procedures specified in the administrative regulations for Proposition 65 (Title 22 California
Code of Regulations [CCR] 12703). OEHHA hazard assessments usually describe all relevant data on
the carcinogenicity (including dose-response characteristics) of the chemical under examination,
followed by an evaluation of any pharmacokinetic and mechanistic (e.g. genotoxicity) data. An
evaluation of the data set for the chemical may indicate that adjustments in target dose estimates or use
of a dose response model different from the default are appropriate. The procedure used by RCHAS
to derive expedited Proposition 65 cancer potency values differs from the usual methodology in two
ways. First, it relies on cancer dose response data evaluated and extracted from the original literature
by Gold et al.. Second, the choice of a linearized multistage procedure for generating cancer potency
values is automatic, and pharmacokinetic adjustments are not performed. The methods used by
RCHAS to develop expedited cancer potency values incorporate the following assumptions:
1. The dose response relationship for carcinogenic effects in the most sensitive species tested is
representative of that in humans.
2. Observed experimental results can be extrapolated across species by use of the interspecies factor
based on "surface area scaling."
3. The dose to the tissue giving rise to a tumor is assumed to be proportional to the administered dose.
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