Cancer slope factor

Did You Know?

• High-quality human data on carcinogens are preferable to animal data; when human data are limited, the most sensitive species is given the greatest emphasis.
• When no single study is judged most appropriate yet several studies collectively support the estimate, the geometric mean of estimates from all studies may be adopted as the slope.
• The CSF is also called a potency factor and is used to calculate the Incremental Lifetime Cancer Risk by multiplying the CSF by the chronic daily intake.

Toxicity Assessments for Carcinogenic Effects

For genotoxic carcinogens, scientists assume no safe exposure level exists, as even a single molecular change in a cell can potentially trigger uncontrolled growth and cancer. This is called a non-threshold effect. However, some non-genotoxic carcinogens may have a threshold, meaning doses below that point pose no cancer risk. Since a threshold cannot be estimated for genotoxic carcinogens, risk is quantified through a two-step process. First, the substance receives a weight-of-evidence classification. Then, a cancer slope factor is calculated to express the potency of the carcinogen.

Weight-of-Evidence Classification for Carcinogens

The cancer slope factor is a tool used in risk assessment to calculate the upper-bound probability that a person will develop cancer over a lifetime from exposure to a specific level of a possible carcinogen. It is usually determined for chemicals classified as A, B1, or B2 carcinogens. For class C chemicals, the factor is estimated individually. The slope factor must always be paired with a weight-of-evidence classification that shows how strong the evidence is that the substance causes cancer in humans. Class A means it is a known human carcinogen. B1 means limited human data exist. B2 means there is sufficient animal evidence but inadequate or no human evidence. C means it is a possible human carcinogen. D means it cannot be classified. E means there is evidence it does not cause cancer in humans.

Calculation of Cancer Risk

For each age interval i, the cancer risk for exposure by a specified pathway is computed using the concentration of the chemical in the contaminated environmental medium (C, in mg/kg for soil or mg/L for water), the intake rate of that medium (IRi, in kg/day for soil or L/day for water), the body weight of the exposed person (BWi), the exposure frequency (EFi, in days/year), the exposure duration (EDi, in years), the averaging time (AT, in days, using a lifetime of 70 years or 70 years times 365 days/year), the cancer slope factor (SF, in (mg/kg-day)^-1), and the age-dependent adjustment factor (ADAF, unitless). The formula incorporates these terms to yield the cancer risk estimate.

Risk Specific Dose (RSD)

The cancer slope factor helps calculate the risk specific dose, or RSD, for carcinogens that directly mutate DNA. It is also the standard method for chemicals whose mode of action cannot be proven to be nonlinear. The RSD is typically set for an extra cancer risk of one in a million or, for people not heavily exposed, one in a hundred thousand. The term "extra" means the risk from environmental exposure to the chemical beyond the existing background risk. The formula for a one-in-a-million risk is RSD equals 0.000001 divided by the cancer slope factor.