NIEHS/NTP Initiatives

The National Toxicology Program has broad responsibilities for expanding the toxicological database on the cor impact of chemical interactions with biological systems, providing data that strengthen the scientific foundation P .# for regulatory decisions, developing and validating alternative test systems, and communicating strategies and C i g c findings to the scientific community, regulatory agencies, and the public. NTP strategies and approaches are evolving in a number of ways to meet these responsibilities and to take advantage of the emerging opportunities presented by the tools of molecular biology. The overall objective of NTP initiatives is to protect public health by more efficiently testing chemicals for toxic effects using a broad array of test systems and by generating data that can make risk assessments more reliable. Current risk assessment approaches frequently use default assumptions which reflect an inadequate scientific foundation for assessing risk.and create an unacceptable amount of uncertainty. This uncertainty can lead to both over-and under-regulation. The costs of regulatory decisions are enormous in terms of industry compliance, health costs, and litigation, yet relatively little money is spent to develop strategies for reducing uncertainties in risk assessment. Traditional toxicity tests such as the two-year chronic bioassay to detect carcinogens have been the basis for most regulatory decisions regarding the safety of environmental chemicals. However, only a limited number of the thousands of chemicals present in the environment, for which we have little or no toxicological data, can be studied by these conventional approaches. Increased application of knowledge of the mechanisms of toxicity can help in several ways. First, hazard identification, which is currently done using animal bioassays to determine whether an environmental agent has the potential to produce an adverse health effect, can be streamlined by appropriate use of mechanistic information. The emerging tools of molecular biology, which can characterize interactions of chemicals with critical target genes, offer tractable approaches for developing more accurate and inexpensive methods to perform this step. Examples include methods for detecting receptor-mediated toxi-cants, use of transgenic animals, and other alternative/complementary in vivo tests to the rodent bioassay. Promising mechanistic and predictive methods to identify environmental health risks must be developed, validated, and accepted for regulation. These approaches could dramatically increase the number of environmental agents evaluated for toxicity. Although mechanistic approaches should be more frequently incorporated into toxicity testing, the chronic bioassay in rodents must be used in many cases, especially those where mechanistic data …