ENVIRONMENTAL
NEWS
Proposed cancer risk guidelines open door to use of new data
N
ew proposed guidelines for cancer risk assessments will allow scientists to provide more relevant information on dose-response, route of exposure, and chemical structure of regulated chemicals and pollutants, according to EPA officials. But critics question whether this influx of information will help government agencies such as EPA make more scientifically justifiable decisions or simply tie UD the regulatory process. The complex guidelines, unveiled in April, will expand the agency's cancer risk assessment process to include mode of action discoveries in biochemistry and cell biology and recent advances in molecular biology, according to Jeannette Wiltse, associate director for health at EPAs National Center for Environmental Assessment. By embracing mechanistic data on cancers the agency will reduce its reliance on the linearized multistage model (LMS) to extrapolate the risk to humans from high-dose t o loW""doSC CXDo The proposed guidelines also replace the current alphanumeric cancer classification with a more descriptive weight-of-evidence narrative. "The whole idea is to throw out the cookbook and instead use judgment," said Arnold Kuzmack, a senior scientist in EPAs Office of Water. The most important aspect of the proposal is the inclusion of mode of action data, which consider how a substance causes cancer, scientists said. "This is significant because it takes us away from the automatic use of the default option that all chemicals that have some carcinogenicity are all affecting DNA," said Roger McClellan, president of the Chemical Industry Institute of Toxicology. When the current
guidelines were finalized in 1986, McClellan said, researchers were confident that radiation, for instance, caused cancer by affecting DNA and wreaking havoc with cells. "But what we now know is that not all cancers are necessarily caused by direct damage to DNA," McClellan added. EPAs retreat from an automatic reliance on the LMS will also lessen the need for risk assessors to make "intergalactic extrapolations," according to a scientist familiar with the guidelines. EPA has proposed using a new standardized number for calculating an equivalent human dose level when extrapolating from animal test data. The new number will more accurately consider the weight difference between humans and test rodents. Chris Portier, acting chief of the Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, said the agency's willingness to move away from the LMS should result in regulations with fewer instances in
EPA's proposed cancer risk guidelines call for increased reliance on mechanistic data. A Chemical Industry Institute of Toxicology scientist evaluates tissue slides for chemically induced toxicity and regenerative cell proliferation.
2 3 8 A • VOL. 30, NO. 6, 1996 / ENVIRONMENTAL SCIENCE & TECHNOLOGY / NEWS
which a cancer risk is assumed. The inclusion of mode of action information, for example, will allow risk assessors to use studies on metabolism, hormone-type actions, cell killing, and genotoxicity. With this data in hand, the agency can undertake simpler, less expensive analyses that will paint a clearer picture of the relationship between the original dose and the response, he said. Portier also praised the agency's proposal to accept that there might be a threshold 3.t which SL compound does not csuse csneer in humans a theory not u.su
