Inhalation of tetranitromethane causes nasal passage irritation and pulmonary carcinogenesis in rodents.

Fischer 344 rats and B6C3F1 mice were exposed for 2 years to vapors of tetranitromethane at concentrations below (0.5 ppm) and slightly above (2 or 5 ppm) the current U.S. recommended occupational exposure limit. Under the conditions of exposure of 6 h/day, 5 days/week, tetranitromethane was found to cause mild irritation and hyperplastic lesions in the nasal passages, but not nasal cavity neoplasms were observed. In contrast, nearly all animals exposed to the higher TNM concentrations, and the majority of animals exposed to the lower concentrations developed alveolar/bronchiolar adenoma or carcinoma; squamous cell neoplasms of the lung also occurred in exposed rats. The extent of the lung tumor response, and the low concentrations of tetranitromethane required for this response, are unprecedented in National Toxicology Program (NTP) studies.

Long-term, low-level exposure of mice prone to mammary tumors to 435 MHz radiofrequency radiation.

The purpose of this study was to determine if chronic, low-level exposure of mice prone to mammary tumors to 435 MHz radiofrequency (RF) radiation promotes an earlier onset, a faster growth rate or a greater total incidence of mammary tumors than in sham-exposed controls. Two hundred female C3H/HeJ mice were exposed for 21 months (22 h/day, 7 days/week) to a horizontally polarized 435 MHz pulse-wave (1.0 micros pulse width, 1.0 kHz pulse rate) RF radiation environment with an incident power density of 1.0 mW/cm2 (SAR = 0.32 W/kg). An additional 200 mice were sham-exposed. Animals that died spontaneously, became moribund or were euthanized after 21 months of exposure were completely necropsied; tissues were subjected to histopathological examinations. Concerning mammary carcinomas, there were no significant differences between the two groups with respect to latency to tumor onset, tumor growth rate and overall tumor incidence. Histopathological examination revealed no significant differences in numbers of malignant, metastatic or benign neoplasms between groups. Survival probability was estimated by the Kaplan-Meier method; no significant difference between groups was noted (Cox's test). Under the conditions of this long-term study, low-level exposure of mice prone to mammary tumors to 435 MHz RF radiation did not affect the incidence of mammary tumors, tumor growth rate, latency to tumor onset or animal longevity when compared to sham-exposed controls.

Chronic, low-level (1.0 W/kg) exposure of mice prone to mammary cancer to 2450 MHz microwaves.

In a previous study (Frei et al., Bioelectromagnetics 19, 20-31, 1998), we showed that low-level (0.3 W/kg), long-term exposure of mice prone to mammary tumors to 2450 MHz radiofrequency (RF) radiation did not affect the incidence of mammary tumors, latency to tumor onset, tumor growth rate or animal survival when compared to sham-irradiated animals. In the current study, the specific absorption rate (SAR) was increased from 0.3 W/kg to 1.0 W/kg. The same biological end points were used. One hundred C3H/HeJ mice were exposed in circularly polarized waveguides for 78 weeks (20 h/day, 7 days/week) to continuous-wave, 2450 MHz RF radiation; 100 mice were sham-exposed. There was no significant difference between exposed and sham-exposed groups with respect to the incidence of palpated mammary tumors (sham-exposed = 30%; irradiated = 38%), latency to tumor onset (sham-exposed = 62.0 +/- 2.3 weeks; irradiated = 62.5 +/- 2.2 weeks) and rate of tumor growth. Histopathological evaluations revealed no significant difference in numbers of malignant, metastatic or benign neoplasms between the two groups. Thus long-term exposures of mice prone to mammary tumors to 2450 MHz RF radiation at SARs of 0.3 and 1.0 W/kg had no significant effects when compared to sham-irradiated animals.

Myocarditis of probable viral origin in chickens.

Severe nonsuppurative myocarditis with Feulgen-positive intranuclear inclusions in six adult White Leghorn chickens is described. Livers of three birds had mild to moderate centrilobular coagulative necrosis, with no inclusions. The myocardial intranuclear inclusions contained a large number of 18-to-20-nm particles; these are compared with members of the family Parvoviridae.

Glossitis of military working dogs in south Vietnam; histopathologic observations.

Glossitis, known clinically as "redtongue," was studied in tissues from 34 military working dogs (MWD) in the Republic of Vietnam. This condition was manifested grossly by loss of lingual papillae on the dorsal margins of the rostral third of the tongue. Microscopically, the principal lesions consisted of loss of filiform papillae, hemorrhage and edema in the lamina propria, acanthosis, and cellular infiltration. The cause of glossitis remains unknown at this time.

Lymphosarcoma in an infant northern fur seal (Callorhinus ursinus).

An infant northern fur seal (Callhorinus ursinus) died in a rookery on St. Paul Island, Pribilof Islands, Alaska. Grossly, slight enlargement of the mesenteric lymph nodes was seen. Microscopically, a lymphosarcoma composed of sheets of monomorphic lymphoid cells in sections of lymph node and tonsil was seen. Electron microscopy of formalin-fixed tissues revealed several structures that were possible of viral origin in the cytoplasm of the neoplastic cells.

Orbital chondroma rodens in a dog.

A chondroma rodens involving the superficial medial aspect of the right orbit was diagnosed in a 9-year-old dog referred because of chronic unilateral epiphora. Examination revealed several ophthalmic abnormalities attributable to a space-occupying mass in the superficial medial aspect of the orbit. The mass was excised; however, regrowths at the primary site necessitated additional surgical interventions. The dog was given radiation therapy, which provided encouraging results. Subtle histologic differences as well as differing epidemiologic features suggest that chondroma rodens is not analogous to the human entity of juvenile aponeurotic fibroma, to which it has been compared in the past.

Adenocarcinoma of the frontal sinus with extension to the brain in a horse.

A space-occupying intracranial mass was diagnosed in a horse. The clinical findings included blindness, circling to the right, apprehension, anorexia, weight loss, and leaning against the stall. On ophthalmoscopic examination, the most striking observation was complete bilateral devascularization of the retinas. The horse was euthanatized and necropsied. Necroscopy revealed the mass to occupy the olfactory and frontal areas of the left hemisphere of the brain and part of the left frontal sinus. Microscopically, the mass was an adenocarcinoma and probably arose from the lining epithelium of the sinus or from the subepithelial glands.

Modified Pagano Levin medium to isolate Candida species.

The use of Pagano Levin medium for primary isolation of Candida species from highly contaminated specimens proved unsatisfactory owing to overgrowth by bacteria and fungi. Addition of cycloheximide and chloramphenicol to the medium greatly improved results by inhibiting overgrowth. The additional inhibitors also altered rate of growth and degree of pigmentation reported for some of the Candida species.

A lifetime oncogenicity study in rats with acrylamide.

A lifetime oncogenicity study in Fischer 344 rats was conducted to accurately characterize the carcinogenic potency of acrylamide. Acrylamide was administered in drinking water throughout the 106-week study at concentrations required to provide a dose of 0, 0.1, 0.5, or 2.0 mg/kg/day to males or 0, 1.0, or 3.0 mg/kg/day to females. Complete necropsy and gross pathology examinations were performed on all study animals. Histopathology examinations were conducted on selected tissues of all high-dose and control animals. Selected tissues from intermediate and low-dose groups were subjected to histopathological examinations as required to clarify high- and control-dose group observations. There was no visual observation of neurotoxicity in any study animal but sciatic nerve degeneration was observed in the male and female high-dose groups. Increased mortality related to acrylamide was observed in the high-dose male group from Month 17 to the end of the study and in the high-dose females during Month 24. Mesotheliomas of the testicular tunic were significantly increased in the high-dose male group. The combined incidence of mammary gland adenocarcinomas and fibroadenomas was significantly increased in both acrylamide-dosed female groups. Males and females in the high-dose groups as well as females of the low-dose group had significantly (p < 0.001) increased thyroid follicular cell adenomas and adenocarcinomas. A variety of other tumor types observed with increased incidence in a previous acrylamide oncogenicity study (i.e., combined CNS glial neoplasms, papillomas of the oral cavity, adenomas of the clitoral gland, and uterine adenocarcinomas) were not observed to be present at increased incidence in this study. This study confirms previously described acrylamide induction of benign tumors of the thyroid and mammary glands as well as mesotheliomas of the testis. By using a larger number of animals with an unbalanced study design, this study showed that acrylamide did not induce glial tumors and demonstrated that the no-observable-effect level for scrotal mesotheliomas is 0.5 mg/kg. It also demonstrated that the increased incidence of mammary tumors was again within historical control ranges.

Three variations of hairlessness associated with albinism in the laboratory rat.

The relationship of three variants of hairlessness, or hypotrichosis, in laboratory rats were examined morphologically, genetically and histologically. The results indicated that the recessive gene causing the fuzzy characteristic in Wistar Furth rats and genes responsible for two other hypotrichotic coat variants in albino rats were the same gene or closely linked genes. The genes were in Linkage Group I of the Norway rat and were closely associated with the albino gene (c), with a recombination percentage of approximately 18%. The hypotrichotic animals had fewer and smaller hair follicles, smaller hair shafts, and a reduction of medullated hair shafts.

Preclinical toxicology studies of 4-ipomeanol: a novel candidate for clinical evaluation in lung cancer.

4-Ipomeanol (ipomeanol) is being developed as a potential antitumor agent to treat lung cancer. Ipomeanol produced a dose-related toxicity in CD2F1 mice, Fischer 344 rats, and beagle dogs. The LD50 in mice after a single iv dose of ipomeanol was 35 mg/kg in males and 26 mg/kg in females. Minimal cumulative toxicity occurred in mice after seven doses; LD50 was 30 mg/kg/day in males and 21 mg/kg/day in females. In rats, iv doses greater than or equal to 15 mg/kg were lethal. Labored respiration, terminal bronchiolar epithelial necrosis, interstitial inflammation, and alveolar edema were present in rats dosed with ipomeanol at greater than or equal to 9 mg/kg. In addition to pulmonary lesions, splenic and thymic lymphocyte depletion and/or necrosis was present. Ipomeanol had little cumulative toxicity in rats given seven daily doses. In dogs, iv doses greater than 12 mg/kg were lethal. Dogs treated with lethal doses of ipomeanol showed rapid, shallow respiration and pulmonary edema prior to death; diffuse pulmonary congestion or hemorrhage and diffuse renal congestion were present at necropsy. Pulmonary microscopic changes caused by nonlethal doses of ipomeanol included subacute interstitial inflammation and necrosis of respiratory bronchiolar and alveolar duct epithelium. In contrast to rodents, seven daily doses of ipomeanol were cumulatively toxic in dogs. The nonlethal pulmonary effects of ipomeanol were reversible in all three species. Tolerance to lethal doses of ipomeanol occurred in animals of all three species pretreated with multiple nontoxic doses of the drug. The LD50 of ipomeanol in male and female mice increased 2.4- and 4.5-fold, respectively, in tolerant mice. In rats and dogs, previously lethal doses of 48 and 24 mg/kg were nonlethal after tolerance was induced by pretreatment with seven daily doses of ipomeanol.