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The purpose of this study was to determine if 60 Hz magnetic fields can alter the clinical progression of leukemia in an animal model. Large granular lymphocytic (LGL) leukemia cells from spleens of leukemic rats were transplanted into young male Fischer 344 rats, producing signs of leukemia in approximately 2-3 months. The animals were randomly assigned to 4 treatment groups (108/group) as follows: 1) 10 G (1.0 mT) linearly polarized 60 Hz magnetic fields, 2) sham exposed [null energized unit with residual 20 mG (2 microT) fields], 3) ambient controls [

Pulmonary carcinogenesis in the rat from a variety of agents may not represent a clear stochastic effect but a threshold response. Both weakly genotoxic quartz and highly genotoxic, α-emitting 239PuO2 induce carcinomas in the lungs of rats. The pathogenesis of pulmonary carcinoma was similar for quartz and plutonium. In both cases, pulmonary carcinogenesis may be explained on the basis of type I alveolar epithelial cell cytotoxicity and type II alveolar epithelial cell proliferative repair. Pulmonary carcinomas are derived from focal regions of particle aggregation in the lung parenchyma, with a gradual evolution of focal inflammation, fibrosis, type II cell hyperplasia, alveolar bronchiolarization, cuboidal and squamous metaplasia, and finally, carcinoma formation. Small doses of particles are insufficient to cause proliferative repair and therefore do not induce carcinomas. Twelve of 53 rats (22.6%) exposed to quartz dust developed pulmonary carcinomas (10 squamous carcinomas and 2 adenocarcino...

Clinical and pathologic data were reviewed for 72 owl monkeys that died between January 1987 and May 1990 at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru. Tissue samples from 39 animals were examined. Hypertrophic cardiac disease (51% of animals examined), dilative cardiomyopathy (26%), and nephropathy (87%) were the most common diagnoses. The incidence of all three diseases appeared to increase with time in captivity. Nephropathy was less severe in colony-born animals.

An adult male owl monkey (Aotus nancymai) had hypercalcemia associated with a disseminated case of histoplasmosis (Histoplasma capsulatum var. capsulatum). Histopathologic examination of tissues at necropsy showed moderate to marked numbers of small granulomas involving multiple organs. The granulomas contained numerous round, basophilic, intracellular structures, 1-2 microns in diameter, that stained positive in Periodic acid-Schiff and Gomori's methenamine silver tests. The hypercalcemia in this case was attributed to enhance conversion of dietary vitamin D to 1,25-dihydroxycholecalciferol by the granulomas.

A wild-caught male Aotus vociferans died spontaneously during quarantine. Histologic examination of the heart showed several small myocardial arteries replaced with fibrinoid necrosis and adjacent inflammation that included lymphocytes and large histiocytic cells. Less often, similar inflammatory foci were observed in the myocardium interstitium. The lesions observed in the heart of the owl monkey resembled Aschoff bodies.

Monitoring mule deer (Odocoileus hemionus) on a former plutonium production site along the Columbia River at the Hanford Site, Washington (USA) revealed 27 (23%) of 116 adult males had unusually shaped, velvet-covered antlers and abnormally developed testicles. We captured 32 males to examine age-class differences and the ratio of affected to unaffected deer and determine whether affected testicles were atrophic or hypoplastic. We found testicular atrophy in most deer with velvet-covered antlers, primarily in animals older than 5 yr. Deer had marked to extreme stages of testicular atrophy, indicating permanent sterility. Decreased serum levels of testosterone and compensatory increased levels of luteininzing hormone and follicle stimulating hormone were detected in all affected males; thus, the gondopituitary hormonal pathway may have responded to abnormally low levels of testosterone in the affected animals. Brucella spp. antibodies in sera were not detected and 9 (90%) of 10 affected animals were seropositive for epizootic hemorrhagic disease virus (EHDV-2) and bluetongue virus (BTV-11) as compared to 12 (63%) of 19 unaffected animals; however, signs of other infectious diseases were not observed. Testicular degeneration generally exceeded that observed with nutritional disorders and poisons in domestic species. Also, severity of the atrophy and apparent lack of other affected tissues suggested that radiation may not be responsible. Testicular atrophy in mule deer has been reported elsewhere; however, neither prevalence has been as high nor or occurrence as well confined to a specific geographical area, as that observed at the Hanford Site. Furthermore, no physiological or age-related influences were described. Documenting the status of such variables and examining their relationships to this phenomenon is a crucial step in understanding the reproductive capacity of a wild deer population.

Of the 232 tamarins (133 Saguinus mystax and 99 Saguinus labiatus) that died at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru from January 1987 to December 1990, 23 monkeys (9.9%) were diagnosed as having chronic colitis. Typically, the cecal and colonic mucosa was greyish and small yellowish cysts, measuring 1-4 mm, were found randomly distributed bulging the mucosa. Microscopically, colitis cystica profunda was diagnosed additionally in six more animals, giving a total of 29 cases (12.5%). This is the first report to our knowledge that describes colitis cystica profunda in a nonhuman primate.

An aerosol exposure system and procedures for delivering asbestos cement (AC) dust to the lungs of hamsters are described. Groups of hamsters were exposed to AC aerosol concentrations of 1 and 10 μg/liter, respectively, 3 hr/day, 5 days/week, for 3 and 6 months and were sacrificed for histopathologic examination. One subgroup from both the 1- and the 10-μg/liter exposure group was withdrawn from exposure after 3 months and sacrificed after a 3-month recovery period to determine whether or not some of the histologic changes might be reversible. There was an apparent dose — response relationship between AC exposure and the number of asbestos bodies and small randomly distributed foci of alveolar macrophages. No other treatment-related lesions were observed. The 3-month recovery period had no apparent effect.

Two groups of 96 male Syrian golden hamsters were exposed to respirable asbestos cement aerosol at concentrations of approximately 1 and approximately 10 micrograms/liter, respectively, 3 hours/day, 5 days/week. Average fiber counts ranged from 5 to about 120 fibers/cm3. Each group was randomly divided into six subgroups of 16 animals. The first subgroup was sacrificed after 3 months of exposure, the second after 6 months, and the third after 15 months. The fourth subgroup was withdrawn from exposure after 3 months, observed for an additional 3 months, and then sacrificed. The fifth and sixth subgroups were withdrawn after 3 and 6 months of exposure, respectively, and maintained for observation up to the 15-month exposure point of the third subgroup at which time all surviving animals were sacrificed. All other experimental procedures were similar to those delineated in a previous publication describing the development of an animal model, techniques, and an exposure system for asbestos cement dust inhalation (A. P. Wehner, G. E. Dagle, and W. C. Cannon, 1978, Environ. Res. 16, 393-407). The asbestos cement exposures had no significant effect on body weight and mortality of the animals. Higher aerosol concentration and longer exposure times increased the number of macrophages and ferruginous bodies found in the lungs of the exposed animals. Recovery periods had no effect on the incidence of macrophages and ferruginous bodies. The incidence of very slight to slight fibrosis in the animals sacrificed after 15 months of exposure shows a significant (P less than 0.01) trend when the untreated control group and the 1 and 10 microgram/liter dose level groups are compared, indicating a dose-response relationship. Development of minimal fibrosis continued in animals withdrawn from exposure. No primary carcinomas of the lung and respiratory tract and no mesotheliomas were found.

The release properties of three compounds, representative of three different subfractions of cigarette smoke condensate (CSC), were characterized from a beeswax-tricaprylin matrix. These compounds were nicotine (weak base fraction), 3-methylcholanthrene (a polycyclic hydrocarbon similar to compounds in the neutral fraction), and phenol (weak acid fraction). The release profiles for the three materials vary greatly, indicating that the beeswax-tricaprylin vehicle does not provide a uniform administration of whole CSC or multicomponent fractions of CSC to the implant site. The pellets will produce a varying exposure of the CSC components to the tissue, based on the chemical nature of the individual component. The release of nicotine from the beeswax-tricaprylin vehicle was found to be rapid and dependent on the geometry of the pellet and concentration. The in vitro release data for nicotine correlated well both with the single component in vivo data and with in vivo data where nicotine was part of whole CSC in the implant pellet. The release of 3-methylcholanthrene was slow and had approximately zero-order kinetics. The phenol release profile was between nicotine and 3-methylcholanthrene, which correlates with the relative polarity of the three materials. Modeling the release characteristics of a component of CSC by testing its individual release properties in vitro was found to be a promising method (i) to establish the dose and dose rate of various components of CSC from implant vehicles, and (ii) to evaluate in vivo exposure data in terms of the exposure rate of the various components of CSC.

A single large po or sc dose of indomethacin, 80 times the antiinflammatory dose, produced a high incidence of intestinal perforations 72 hr after administration to fed rats; the perforations were confined to the mid-portion of the small intestine. When food was withheld from indomethacin-treated rats, the lesion incidence after a dose of 16 mg/kg po was reduced from 100% to zero. In a 72-hr study, it was found that food deprivation only on the day of drug administration prevented the intestinal perforations, while feeding the rats on the day of drug administration produced 100% ulcer incidence. Lesions produced by sc drug administration could also be prevented by starvation. The incidence of intestinal perforation was altered by the duration of food deprivation and the amount of food consumed. Intestinal ulcers could also be prevented, after either po or sc administration, by ligation of the bile duct. It appeared possible that there was a relationship between food intake, bile flow, and intestinal ulcers. Bile duct ligation reduced the incidence of intestinal perforation after indomethacin from 100% to zero. A time response curve indicated that bile duct ligation up to 8 hours after drug administration reduced the incidence of perforation; however, a 60% incidence of intestinal lesions was found when the bile duct was ligated 3 hours after indomethacin was given. When segments of the small intestine were isolated as Thiry loops, ulceration was prevented in the loops but occurred in the anastomosed intestine.

One 6-hr inhalation exposure of hamsters to Ni-enriched fly ash (NEFA) aerosol (respirable aerosol concentration ∼200 μg/liter) deposited about 80 μg in the deep lung, of which 75 μg was still present 30 days postexposure. The animals tolerated the exposure well during the 30-day postexposure observation period. Two-month exposures of hamsters to NEFA or fly ash (FA) aerosols (∼185 μg/liter) resulted in a deep lung burden of about 5.7 mg, dark discoloration of lungs, heavily dustladen macrophages, and significantly higher lung weights than in controls, but only minimal inflammatory reaction and no deaths. There was no difference between NEFA and FA effects. The NEFA contained 9% Ni; FA contained 0.03% NI. The results of this study indicate low acute and subchronic toxicity and slow lung clearance of NEFA and FA.

Hamsters were chronically exposed to ∼70 μg/liter respirable nickel-enriched fly ash (NEFA) aerosol, ∼17 μg/liter NEFA, or ∼70 μg/liter fly ash (FA) for up to 20 months. A control group received sham exposures. The NEFA particles of respirable size contained approximately 6% nickel, compared to about 0.3% for FA. Five hamsters/group were sacrificed after 4, 8, 12, or 16 months of exposure. An additional five hamsters/group were withdrawn from exposure at the same intervals for lifelong observations. Exposures to NEFA had no significant effect on body weight and life span of the animals although heavy deposits of NEFA in the lungs were demonstrated. However, lung weights of the high NEFA- and of the FA-exposed animals were significantly higher than those of the low-NEFA group and the controls, and mean lung volumes were significantly larger for the high-NEFA group and the FA group than for the low-NEFA group and the controls. Dust was deposited (anthracosis) in the lungs of all exposed hamsters. Incidence and severity of interstitial reaction and bronchiolization were significantly higher in the dust-exposed groups than in the sham-exposed controls. The severity of anthracosis, interstitial reaction, and bronchiolization was significantly lower in the low-NEFA group than in the high-NEFA and FA groups. While two malignant primary thorax tumors were found in two hamsters of the high-NEFA group, no statistically significant carcinogenesis was observed. Of the exposure-related changes, only anthracosis decreased after withdrawal from exposure. Pulmonary nickel burdens after 20 months of exposure suggest that the pulmonary clearance rate was slower in the high-NEFA group than in the low-NEFA group.

The lungs are diffusely tan to gray, with black foci, typically 1-2 mm in diameter, that tend to be distributed in subpleural areas (Fig. 222). Lung weights and volumes are increased after prolonged exposure.

Rats were exposed by inhalation to 5 or 50 mg/m3 Mount St. Helens volcanic ash, to 50 mg/m3 quartz (positive controls), or to filtered room air (sham-exposed controls), for 6 hr/day, 5 days/week, for up to 24 months to investigate biological effects of chronic inhalation exposure to volcanic ash under controlled laboratory conditions. Exposure-related lung changes comprised accelerated respiratory frequency; alveolar macrophage accumulation; interstitial reaction; lymphoreticular reaction in peribronchiolar regions and in mediastinal lymph nodes; alveolar proteinosis in the 50- mg/m3 ash- or quartz-exposed groups; increase in fresh lung weights; decreased body weight and increased mortality in the quartz-exposed group; and epidermoid carcinomas especially in the quartz-exposed females and, to a lesser extent, in the 50-mg/m3 ash-exposed females. The observed changes reflect significant dose-response and agent-response relationships.

Groups of 80 female rats were exposed to cigarette smoke from three types (code 13 = high tar, low nicotine; code 27 = low tar, medium nicotine; code 32 = high tar, high nicotine) of cigarettes in Maddox-ORNL smoking machines, eight cigarettes per day, 7 days per week, for up to 24 months. An additional group received sham exposures and a fifth group served as untreated controls. The sham-exposed animals had significantly lower body weights than the untreated controls. The smoke-exposed animals had significantly lower weights than the sham-exposed controls; the weights were lower for the code 27 and code 32 animals than for the code 13 animals during the second year of exposure. The survival of the code 13 animals was similar to that for the sham-exposed and untreated control group; survival times of the code 27 and code 32 animals were shorter. Body weight and survival reflected the high- and low-nicotine dose groups indicated by in vivo dosimetry measurements. Smoke-induced histopathologic lesions consisted primarily of pulmonary smoke granulomas; the smoke granulomas were less severe in the code 27 exposure group than in the groups exposed to smoke from code 13 or code 32 cigarettes. Additional changes included pulmonary alveolar epithelial hyperplasia, and squamous metaplasia and basal cell hyperplasia of laryngeal and tracheal epithelium. One primary epidermoid carcinoma was found in the lung of a code 27 rat. The rats tolerated the chronic exposures relatively well and certain of the smoke-induced lesions allowed differentiation between the different types of cigarettes.

A wild-caught adult female Saguinus mystax died after 54 months in captivity. At necropsy, a small reddish zone in the renal cortex of one kidney was shown histologically to be a hemangiosarcoma.