Table II.
Results of histopathological analysis of rats treated with NNN enantiomers or racemic NNN in drinking water for 17–19 months
| Addition to drinking water | ||||
|---|---|---|---|---|
| None | (S)-NNN 14 p.p.m. | (R)-NNN 14 p.p.m. | Racemic NNN 28 p.p.m. | |
| Number of rats analyzed | 22 | 20 | 24 | 11 or 12a |
| Number of rats with each type of lesion | ||||
| Tongue | ||||
| Atypical hyperplasiab | 0 | 15 | 1 | 10 |
| Squamous cell papilloma | 0 | 13 | 3 | 11 |
| Squamous cell carcinoma | 0 | 2 | 0 | 1 |
| Oral mucosa | ||||
| Atypical hyperplasia | 0 | 16 | 0 | 9 |
| Squamous cell papilloma | 0 | 11 | 1 | 8 |
| Squamous cell carcinoma | 0 | 1 | 0 | 0 |
| Soft palate | ||||
| Atypical hyperplasia | 0 | 13 | 0 | 4 |
| Squamous cell papilloma | 0 | 10 | 4 | 3 |
| Squamous cell carcinomac | 0 | 1 | 0 | 0 |
| Epiglottis | ||||
| Atypical hyperplasia | 0 | 16 | 1 | 9 |
| Squamous cell papilloma | 0 | 11 | 0 | 6 |
| Squamous cell carcinoma | 0 | 1 | 0 | 2 |
| Pharynx | ||||
| Atypical hyperplasia | 0 | 18 | 0 | 12 |
| Squamous cell papilloma | 0 | 11 | 0 | 9 |
| Squamous cell carcinoma | 0 | 1 | 0 | 3 |
| Number of rats with papilloma or carcinoma of the oral cavity | 0 | 20 | 7 | 12 |
| Esophagus | ||||
| Atypical hyperplasia | 0 | 18 | 0 | 12 |
| Squamous cell papilloma | 0 | 19 | 1 | 12 |
| Squamous cell carcinoma | 0 | 2 | 0 | 4 |
aBecause of autolysis, a limited set of tissues (i.e. tongue, pharynx and esophagus) was evaluated from a 12th animal.
bAtypical hyperplasia refers to hyperplastic lesions involving the epithelium that are characterized by downward irregular, often finger-like, projections of the basal layers of the epithelium into the underlying tissue; increased mitoses and dysplasia reminiscent of squamous cell carcinoma in situ may also be observed in the most florid representation.
cSoft palate was secondarily involved in two control animals and one (R)-NNN-treated animal due to extension from squamous cell carcinoma involving the hard palate and/or nasal cavity.