TESTING GUIDELINES FOR EVALUATION OF THE IMMUNOTOXIC POTENTIAL OF DIRECT FOOD-ADDITIVES

Immunotoxicity testing is a new addition to the safety assessment guidelines for direct food and color additives. The approaches and philosophy for this area of specialized testing are consistent with the case-by-case strategy applied in the regulatory approval process, which is based on structure-activity relationships, preexisting knowledge, and projected exposure estimates. Specialized testing such as immunotoxicity is not part of the basic testing requirements, but would be applied when indicators are positive. Concepts for immunotoxicity testing have evolved, in part, from research for evaluating various testing methods as well as specific study designs. This research, conducted over the last decade, has focused mainly on the rat as the rodent species of choice. The miniature swine was evaluated as a nonrodent model. Testing is defined by type 1 and type 2 tests, which differ in that type 1 tests are performed on the same animals used in the core study design. Sets of type 1 and type 2 tests, with reference to the indicators, define various testing levels. Retrospective testing, expansion of basic testing (such as histopathology and serum chemistry profiles), and alternative study designs, which include satellite groups for evaluation of the functional capacity of the immune system, can be considered in the evaluation of immunotoxic potential.