Manganese Mangles Mice Experiments

Moreno Paolini, Gian Luigi Biagi and Giorgio Cantelli-Forti
Journal of the National Cancer Institute 1997;89:736 (letter)


Is it possible that the risk assessment practice of extrapolating the results of laboratory animal experiments (called "bioassays" by the toxicologically hip) to humans is even less reliable than common sense dictates? Incredibly, the answer is "yes!"

Most standard risk assessment experiments expose rodents (generally Sprague-Dawley rats, Fischer rats, or B6C3F1 mice) to large doses of a test chemical for about 2 years (i.e., the natural life-span of rodents). The rodents are used because they are prone to cancer. It is theorized if a test chemical could possibly cause cancer, then such a possibility is more likely to show up in susceptible rodents.

Then in 1995, Science magazine editor Dr. Phil Abelson described how "genetic drift" in the rodents was making interpretation of bioassays more difficult. For example, in less than 10 years, spontaneous liver tumors in the B6C3F1 mice (i.e., liver tumors resulting solely from being genetically prone to cancer) had increased from 32 percent to 50 percent. Body weight in adult rodents had increased by 20-30 percent. In the 1970s, 58 percent of Sprague Dawley rats would be alive after two years; by the 1990s, survival rate had dropped to 24 percent.

Now comes news from Italian researchers that bioassay diets may be further clouding results.

Specifically, Paolini et al. say that the element manganese, supposedly a well-known mutagen and carcinogen, is contained in most standard rodent diet formulations. But so what? Everyone knows "the dose that makes the poison." Just because manganese is part of the diet doesn't mean it is increasing the number of cancers observed in rodent bioassays.

Well here's the "so what."

According to Paolini et al., the level of manganese in bioassay diet formulations is the same AND EVEN UP TO NINE TIMES HIGHER than the level of manganese in bioassays where manganese is the tested chemical!

Paolini et al. concluded that

To increase the reliability of long-term bioassays, the EPA should simply establish protocols in which animal diet constituents should be more carefully considered to avoid invalidating cancer bioassays.

Question: does this mean bioassays are invalid where dietary constituents were not carefully considered (i.e., most bioassays ever conducted)? Imagine the implications for the EPA's regulatory programs!

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