Toxicologic Pathology

The morphology of alveologenic tumor, hemangiosarcoma, lymphangioma, intrabronchial papilloma and adenomatosis observed in the lung of guinea pigs is described. Electron micrographs revealed alveologenic tumor to consist of Type II pneumocytes and the lesion of adenomatosis to consist of distended alveoli lined with ciliated bronchial type epithelial cells.

A relationship between the dose of gamma or X-ray irradiation received and the frequency of guinea pigs with lung tumors could not be established. In guinea pigs, which survived over 20 months, the frequency of alveologenic tumors in the inbred strains was 23/107 in irradiated and 11/79 in untreated guinea pigs; this difference was statistically not significant. The frequency of tumor bearing inbred males (11/60) was significantly lower than of tumor bearing noninbred males (23/65). In the irradiated guinea pigs alveologenic tumors occurred earlier and tumor nodules in the lung were more numerous than in the untreated guinea pigs.

Primary hemangiosarcoma involved the lung of one untreated and one irradiated strain 2 guinea pig. A single lymphangioma was found in an untreated inbred guinea pig. Intrabronchial papillomas were observed twice in irradiated and once in untreated guinea pigs.

Adenomatosis was present in the lung of 2 untreated inbred and 5 irradiated noninbred guinea pigs.

A histologic study was done on the spontaneously occuring precursor and neoplastic lesions of mammary gland in inbred and hybrid female mice.

Hyperplastic alveolar nodules (HAN) are small groups of non-encapsulated mammary acini lined by a single layer of low cubodial epithelial cells. The stroma of HAN often contain macrophages laden with ceroid pigment, which imparts to them a yellow color. Microfoci of carcinoma may be found within HAN, and adenoacanthomas may arise within acini in which there is chronic inflammation. Plaques are pregnancy-dependent lesions which occur in three albino mouse strains: DD, GRS, and RIII. These plaques are disc-shaped, are circumscribed or unencapsulated, have a central myxomatous core, and have acini which exhibit radial symmetry. Plaques can give rise to adenocarcinomas type P, type B (papillary and cystic) and also to the unusual and distinctive pale cell carcinoma. The spontaneous tumors described in this paper are mammary gland adenocarcinomas with sebaceous cell nests, tumors which are papillomas and contain basal epithelial elements and acini derived from mammary, sebaceous glands, or hair follicles.

Tabulations of the results of the initial approximately 200 NCI carcinogenesis bioassays conducted in mice and rats were published recently. However, no analysis of the results were provided. Such an analysis is the subject of this report.

Ninety eight NCI bioassays were positive for carcinogenicity. Only three bioassays (<2%) were negative in both species and the ratio of positive to negative bioassays was 33:1. The remaining 47% of the bioassays were considered to be suggestive or inconclusive and it is inappropriate to refer to the total positive rate as 50%. The liver was the predominant tumor site and the only tumors produced in either rodent species in 19% of the positive bioassays were in the livers of mice. The high ratio of positive to negative results and the use of the mouse liver as a discriminating target organ raise serious concerns about the carcinogenesis protocol and in the methods of evaluating the results. Several recommendations are offered which may be useful in the current reexamination of bioassay procedures.

Thickening of the endocardium is sometimes observed in rats and other animals as a spontaneous or experimentally induced lesion. However, its nature, pathogenesis, and significance are not well understood.

In this study, 480 Sprague-Dawley CD outbred albino rats between the ages of 6 and 25 months were examined grossly and microscopically. Endocardial thickening was observed in six cases. It was diffuse and was caused by proliforation of fibroblast-like cells, most frequently involving the left ventricle.

Endocardial thickening in Sprague-Dawley rats appears to be primarily due to endomyocardial fibrosis. It may represent repair of damage to subendocardial myocardium occurring spontaneously or as a consequence of exposure to chemicals or other agents.

In order to develop an optimal method for measuring male gonad weight, one that is both statistically dependable (i.e. not subject to wide fluctuations within similarly treated groups) and appropriate with respect to end uses of data, testis, epididymis, and epididymal fat pad weights were obtained from normal adult male rats and subjected to statistical analyses. The results underscore the necessity for omitting the epididymal fat pad from “gonad” weight measurements since there appeared to be no relationship between its weight and the weight of either the testis or epididymis. Furthermore, the inclusion of epididymal fat resulted in large variation in total unit weight. An interdependent relationship was shown for testis and epididymis weights, indicating it may be appropriate to report a combined value for these entities, though this decision should be based on the intent of the study. A significant saving in time was effected by obtaining the weight of the testis alone. In studies which require male gonad weight assessment, therefore, the testis, excluding epididymis and epididymal fat, should be weighed to maximize the combined factors of time/cost effectiveness and scientific validity.

Examining rats and mice for small numbers of external parasites can be accomplished by washing the anesthetized animal in a detergent-disinfectant bath. The sediment is concentrated by centrifugation and examined microscopically for parasites, their parts or eggs. This method was successfully used to demonstrate mites of the genus Radfordia on six of seven rodents for which skin scrapings had failed to contain evidence of mite infestation.

Two naturally occurring cases of chemodectoma, one in a 10-week-old albino male rat and another in a 2-year-old albino female rat, are reported. They appear to be the first reported cases of chemodectoma in rats although one case of aortic body tumor was reported previously in an albino rat.

The effect of uniform exsanguination on absolute and relative organ weights was assessed. The data demonstrate that the simple, rapid, and uniform procedure described for exsanguination of rats prior to necropsy significantly (P < .05) reduces both absolute and relative liver and kidney weights with respect to weights from animals that are not exsanguinated. In addition, liver weight standard deviation relative to controls is significantly (P < .05) reduced, increasing sensitivity of the measurement. Exsanguination also decreases agonal change related variation in macroscopic tissue appearance, enhancing the gross examination.