MANY COMMERCIAL DYES HAVE A BENZIDINE BASE.

MANY COMMERCIAL DYES HAVE A BENZIDINE BASE. EVIDENCE SUGGESTS A CAUSAL RELATIONSHIP BETWEEN THESE DYES AND BLADDER CANCER IN HUMANS. ROUTINE SHORT-TERM TESTS ARE INEFFICIENT FOR DETECTION OF THE BENZIDINE BASE DYES WITHOUT MODIFICATIONS. SHORT-TERM TESTS COUPLED TO ACTIVATION SYSTEMS FROM RODENT CELLS OR FRACTIONS MAY NOT BE GERMANE FOR EXTRAPOLATION TO HUMAN RISK. RECOGNIZING A NEED FOR RELEVANT METHODS TO ASSESS THE METABOLIC FATE AND BIOLOGICAL CONSEQUENCES OF BENZIDINE BASE DYES IN HUMANS, NIEHS HAS ELECTED TO DEVELOP ALTERNATIVE ACTIVATION SYSTEMS THAT MORE ACCURATELY REFLECT THE OUTCOME OF METABOLISM OF THESE DYES IN MAN. SPECIFIC OBJECTIVES OF PHASE I ARE TO DEVELOP CELL-MEDIATED ACTIVATION SYSTEMS WITH RODENT LIVER, BLADDER, KIDNEY, AND INTESTINAL CELLS FOR BENZIDINE BASE DYES IN THE MOUSE LYMPHOMA L5178Y TK/ ASSAY AND TO DETERMINE THE METABOLITE PROFILE OF THESE DYES IN THE SPECIFIC TISSUE. FUTURE STUDIES (PHASE II) WILL DETERMINE THE CAPACITY OF HUMAN CELLS FROM THESE TISSUES TO ACTIVATE BENZIDINE BASE DYES TO A MUTAGENIC/CLASTOGENIC FORM. INFORMATION WILL BE OBTAINED ON THE METABOLIC ACTIVATION OF THESE DYES BY HUMAN CELLS AND VARIATION NOTED IN METABOLIC CAPABILITY RELATED TO AGE, SEX, GENETIC COMPOSITION, AND EXPOSURE TO MODIFIERS. DEVELOPMENT OF HUMAN CELL-MEDIATED ASSAYS FOR THE MOUSE LYMPHOMA ASSAY WOULD PROVIDE A RELEVANT TESTING PROGRAM FOR BENZIDINE DYES THAT COULD BE MARKETED TO THE TEXTILE, RUBBER, LEATHER, AND PAPER INDUSTRIES TO EVALUATE THE POTENTIAL HAZARD OF THESE WORKPLACE CHEMICALS.