Commentary: further comments on Mycoplasma pulmonis and lymphoma in bioassays of rats.
The authors recently assessed the likelihood that lifetime cancer bioassays of aspartame, methanol, and methyl tertiary butyl ether conducted with conventional (not specific pathogen free) Sprague-Dawley rats were compromised by Mycoplasma pulmonis disease. From the tumor data and other information, the authors concluded that the rats used in these bioassays likely had M pulmonis disease and that lesions of the disease were plausibly interpreted as lymphoma. Subsequently, they analyzed the nonneoplastic lesion data from these bioassays for occurrence of inflammatory lesions and found that 2,267 of 2,960 rats (76.6%) were reported to have bronchitis, the signature lesion of M pulmonis disease, and that 633 rats (21.4%) were reported to have otitis, another common lesion of the disease. Also, documentation is now available containing serologic evidence of mycoplasma infection in the rats. In contrast, the reports of 6 National Toxicology Program bioassays based on specific pathogen-free Sprague-Dawley rats listed no instances of bronchitis or otitis. These findings provide substantial additional evidence that the bioassays in question were compromised by M pulmonis disease. Therefore, the reported induction of lymphoma in these studies should not be considered in cancer risk assessments. The authors also found that inflammatory lesions were prevalent in lymph nodes, thymus, pleura, and brain. Finally, they found that of all 328 cases of lymphoimmunoblastic lymphoma affecting the lung (the primary form of lymphoma reported), 218 (66.5%) occurred within the first 104 weeks of the studies, showing that occurrence of such lesions was not due to appearance in rats surviving beyond that interval.
Schoeb
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TR
UAB Department of Genetics, Birmingham, AL 35294, USA. trs@uab.edu
McConnell
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EE
D000818:Animals; D000830:Animals, Laboratory; D001218:Aspartame / Q000633:toxicity; D001681:Biological Assay / Q000379:methods / Q000592:standards*; D008168:Lung / Q000473:pathology*; D008223:Lymphoma / Q000473:pathology*; D000432:Methanol / Q000633:toxicity; D008738:Methyl Ethers / Q000633:toxicity; D009175:Mycoplasma Infections / Q000473:pathology / Q000662:veterinary*; D045803:Mycoplasma pulmonis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012376:Rodent Diseases / Q000382:microbiology* / Q000473:pathology*
D008738:Methyl Ethers; C043243:methyl tert-butyl ether; D000432:Methanol; D001218:Aspartame