Tissue from 10-11 weeks old Sprague Dawley Rats

SIGNALMENT: (age, breed, sex, species, and scientific name) 

Sprague Dawley rats, females

Groups of female rats, 10-11 weeks old, were exposed to a toxic vapor 6 hrs/day, 5 days/week for 6 weeks. The rats were then observed for 18 months after the end of exposure.

Not Applicable

No hematologic changes at end of exposure.

1. Squamous metaplasia of the nasal mucosa
2. Keratinizing squamous cell carcinoma of the nasopharyngeal duct

1,2,3,4 Diepoxybutane (butadiene diepoxide) exposure, 2.5ppm

Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA

Reports in the literature suggest that one reason for the greater sensitivity of mice to the carcinogenicity of 1,3 butadiene (BD) is that exposed mice metabolize much more of the BD to 1,2,3,4, diepoxybutane (BDO2) than do exposed rats. The purpose of this study was to determine the tumorgenicity of BDO2 in rats and mice exposed to the same concentration of the agent.

At the end of the six-week exposure, significant lesions were present in the nose of both species, concentrated around the main airflow pathway. Necrosis, inflammation and squamous metaplasia of the nasal mucosa, as well as atrophy of the turbinate bones were present. At six months after exposure, the squamous metaplasia was quiescent in the mice, but was more florid in the rats. Later, keratinizing squamous cell carcinomas developed from the metaplastic foci in the rats, but not the mice.

These findings indicate that the metabolite of BD, BDO2, is carcinogenic in the respiratory tract of rats. An increase in respiratory tract tumors was not observed in similarly exposed mice despite the fact that metabolic studies indicated mice should have received twice the dose to respiratory tissues compared with the rats. High cytosolic activity of detoxification enzymes in mice may account, in part, for the difference in response.

1. Henderson RF, Barr EB, Belinsky SA, Benson JM, Hahn FF, and Menache MG. "1,3-Butadiene: Cancer, Mutations, and Adducts Part I: Carcinogenicity of 1,2,3,4,-Diepoxybutane". Health Effects Institute Research Report Number 92, pp11-43; 2000.

2. Henderson RF, Hahn FF, Barr EB, Belinsky SA, Menace MG, Benson JM. "Carcinogenicity of Inhaled Butadiene Diepoxide in Female B6C3F1 Mice and Sprague-Dawley Rats". Toxicol Sci 52:33-44, 1999.



2x objective, H&E stain. Overview of the nasal cavity of a rat near the caudal end of the level of the nasopharyngeal duct. The nasopharyngeal duct is nearly occluded by a keratinized protrusion from the wall of the duct.


10x objective, H&E stain. Details of the base of the keratinizing squamous cell carcinoma showing destruction of the basement membrane.


10x objective, H&E stain. Details of the periphery of the keratinizing squamous cell carcinoma showing invasion.


2x objective, H&E stain. Overview of the nasal cavity of a rat at the level of the vomeronasal organ. Marked squamous cell metaplasia of the nasal mucosa.


10x objective, H&E stain. Details of the marked squamous cell metaplasia showing marked keratinization and intact basement membrane.


1 Comment

Interesting case but not sure carcinoma is correct diagnosis

June 6, 2019 07:36 AM by John R. Foster, BSc,PhD,FRCPath, FIATP, HonFBTS

I'm only going on the photographs that you show, but the clear presence of considerable submucosal inflammation and the clear chronic irritation that the compound has, led me to at least consider a non-neoplastic proliferative lesion analagous to the adenomyosis that occurs in the GI tract under conditions of chronic irritation.  Despite evidence of apparent penetration of the basement membrane the morphology of the mucosa is still well differentiated and hyperplastic, and the bulk of the lesion is within the lumen.  I suspect I would still plum for squamous metaplasia albeit marked.   

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