There is insufficient evidence to conclude that the pharmaceutical causes bladder cancer in humans based upon findings in rats. Cancer will afflict 40% of all people in their lifetime. Bladder cancer is the fifth most common cancer. Cancer is caused by lifestyle, spontaneous alterations in genetic material and other endogenous processes rather than other exogenous factors.
The use of animal tests cannot be used to determine causation in humans without sufficient evidence in studies in humans, because the cancer mechanism in experimental animals may not be relevant for human cancer. Chemicals, including pharmaceuticals, that are known human bladder carcinogens are genotoxic and have been shown to cause cancer through genotoxic mechanisms, whereas studies of this pharmaceutical do not show that it is genotoxic.
Studies of this pharmaceutical in experimental animals have identified some increases in bladder tumors but the likely mechanism involves indirect toxic effects mediated by the formation of crystals in the urine causing tumor promotion. These crystals would not be expected to occur in humans due to differences in the urine biochemistry between rats and humans. Consequently, the findings of bladder tumors in rodents are not predictive of the development bladder cancer in humans.
The expert relied on his experience as a toxicologist, researcher and physician, published scientific and toxicology literature on this pharmaceutical and similar drugs.
The expert is a physician, biochemist and certified toxicologist with more than 40 years of toxicology research. He has authored peer-reviewed articles on carcinogenicity, tumor promotion, cancer mechanism, and DNA changes associated with chemical exposure.