home edit2 whole TSD November 2002 PDF format - OEHHA

US EPA Calculation of Carcinogenic Potency Based on Human Data
US EPA states that existing human epidemiologic studies with sufficiently valid exposure characterization
are always used in evaluating 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 ( equivalent to the factor q 1 * ). If no carcinogenic effect is demonstrated and carcinogenicity has
been demonstrated in animals, then it is assumed that a risk does exist, but it is smaller than could have
been observed in the epidemiologic study. An upper limit of cancer incidence is calculated assuming
that the true incidence is just below the level of detection in the cohort studied, which is largely
determined by the cohort size. Whenever possible, human data are used in preference to animal data.
In human epidemiologic studies, the response is measured as the relative risk of the exposed cohort of
individuals compared to the control group. The excess risk (R(X) - 1, where R(X) is relative risk) is
assumed to be proportional to the lifetime average exposure X, and to be the same for all ages. The
carcinogenic potency is equal to [R(X) - 1]/X multiplied by the lifetime risk at that site in the general
population. The confidence limit for the excess risk is not usually calculated due to the difficulty in
accounting for inherent uncertainty in the data (exposure and cancer response).
Office of Environmental Health Hazard Assessment (OEHHA), California Environmental
Protection Agency
Office of Environmental Health Hazard Assessment cancer risk assessment procedures are outlined in
“Guidelines for Chemical Carcinogen Risk Assessments and their Scientific Rationale” (referred to
below as the Guidelines) (CDHS, 1985). These procedures are generally used in generating Toxic Air
Contaminant (TAC) cancer potency values (Air Toxicology and Epidemiology Section, Office of
Environmental Health Hazard Assessment), standard Proposition 65 cancer potency values
(Reproductive and Cancer Hazard Assessment Section (RCHAS), Office of Environmental Health
Hazard Assessment) and ATES cancer potency values (Air Toxicology and Epidemiology Section,
Office of Environmental Health Hazard Assessment). Expedited Proposition 65 cancer potency values
(Reproductive and Cancer Hazard Assessment Section (RCHAS), Office of Environmental Health
Hazard Assessment) depart somewhat from those procedures and are discussed separately below.
OEHHA cancer risk assessment methodology (CDHS, 1985) generally resembles that used by US
EPA (Anderson et al., 1983; US EPA, 1986). The Guidelines state that both animal and human data,
when available, should be part of the dose-response assessment.
OEHHA Calculation of Carcinogenic Potency Based on Animal Data
The procedures used to extrapolate low-dose human cancer risk from animal carcinogenicity data
assume that a carcinogenic change induced in a cell is transmitted to successive generations of cells
descended from that cell, and that the initial change in the cell is an alteration (e.g. mutation,
rearrangement, etc.) in the cellular DNA. Non-threshold models are used to extrapolate to low-dose
human cancer risk from animal carcinogenicity data.
12