Artifacts Due to Secondary Pathology: Case Study Examples

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Abstract
The manuscript presents a summary of both biochemical and morphological information that has led to proposed mechanisms by which nitrilotriacetate (NTA) causes urinary tract toxicity that is a necessary precondition for NTA's reported tumorigenidty. These models ascribe urinary tract toxicity to site specific changes in divalent metal distributions between urinary tract tissue and urine that accompany renal clearance of NTA. The proposed models show definable NTA concentration thresholds that must be exceeded before NTA can induce the divalent metal perturbations that are the initiating steps in tissue toxicity, which is a necessary precondition for subsequent carcinogenicity. The proposed mechanisms are consistent with all of the known NTA effects, including urinary tract tumorigenicity noted in chronic exposure studies with high doses of NTA.

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