Regulatory Cancer Risk Assessment Based on a Quick Estimate of a Benchmark Dose Derived from the Maximum

REGULATORY TOXICOLOGY AND PHARMACOLOGY 28, 222–225 (1998)ARTICLE NO. RT981258Regulatory Cancer Risk Assessment Based on a Quick Estimate1of a Benchmark Dose Derived from the Maximum Tolerated DoseDavid W. Gaylor* and Lois Swirsky Gold†*National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079; and†Lawrence Berkeley National Laboratory and University of California at Berkeley, Berkeley, California 94720Received February 9, 1998of cancer risk would be low regardless of the results ofa 2-year bioassay. Linear extrapolation to a risk of lessThe proposed U.S. Environmental Protection Agencythan 1 in 100,000 and use of an uncertainty factor, e.g.,carcinogen risk assessment guidelines employ aof 10,000, would give the same regulatory “safe dose.”benchmark dose as a point of departure (POD) forLinear extrapolation to a virtually safe dose associ-low-dose risk assessment. If information on the carci-ated with a cancer risk estimate of less than one in anogenic mode of action for a chemical supports a non-million would be 10 times lower than the referencelinear dose–response curve below the POD, a margin-dose based on the LTD /10,000.of-exposure ratio between the POD and anticipated 10human exposure would be considered. The POD wouldbe divided by uncertainty (safety) factors to arrive at areference dose that is likely to produce no, or at mostINTRODUCTIONnegligible, cancer risk for humans. If nonlinearity be-low ...