Alfred P. Wehner

Chronic inhalation of cobalt oxide and cigarette smoke by hamsters

Exposure of hamsters to CoO aerosol (10 g/L, 7 hrs./day, 5 days/week) caused pneumoconiosis but affected neither the life span nor the incidence of other than pneumoconiotic lesions. No carcinogenic effects of CoO were observed. While cigarette smoke exposures significantly increased the incidence of certain types of other than pneumoconiotic lesions including tumors, they also increased the life span of the smoke-exposed animals significantly. The latter phenomenon may account for the higher tumor incidence in the smoke-exposed animals. No effect of the smoke exposures on incidence and degree of pneumoconiosis was observed. The mean body weights of the smoke-exposed groups were significantly reduced.

Chronic inhalation of nickel oxide and cigarette smoke by hamsters

Chronic inhalation of NiO and cigarette smoke (CS) by hamsters eventually caused pneumoconiosis whose development was unaffected by CS. No carcinogenic or cocarcinogenic effect of NiO and CS was observed, CS exposure increased laryngeal lesions, reduced body weight, and increased lifespan.

Lung changes in rats following inhalation exposure to volcanic ash for two years

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.

Inhalation bioassay of cigarette smoke in rats

Abstract 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.

Acute and subchronic inhalation exposures of hamsters to nickel-enriched fly ash

Abstract 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.

Chronic inhalation of absestos and cigarette smoke by hamsters

Abstract One hundred and two male Syrian golden hamsters received chronic exposures to a respirable aerosol of Canadian chrysotile asbestos (mean aerosol concentration = 23 μg/l) 7 hours per day, 5 days per week. Half of the animals were also exposed for 10 minutes to cigarette smoke in modified Hamburg II smoking machines, three times per day, 5 days per week, for the duration of their life span. The other half of the animals received sham-smoke exposures. Another group of 102 hamsters served as controls. Half of the controls received smoke exposures, the other half received sham exposures. Asbestos exposure resulted in earlier and more severe lung lesions than in identical groups of concurrent experiments, which had received life span exposures to aerosols of NiO (53 μg/l) and CoO (10 μg/l), or which were treated with diethylnitrosamine (12 × 0.25 mg by s.c. injection). Asbestosis developed in all animals and forced discontinuation of the asbestos exposures after 11 months. Of 12 lung adenomas found in 510 hamsters, ten occurred among the 102 animals of the asbestosexposed groups, indicating an early neoplastic response. However, perhaps on account of their significantly shorter life span due to asbestosis, the incidence of laryngeal lesions and of malignant tumors wassignificantly lower in the asbestos + smoke-exposed group than in the control group having received smoke exposures. Neither a carcinogenic effect of asbestos nor a cocarcinogenic effect of cigarette smoke was observed. Cigarette smoke inhalation resulted in significantly lower mean body weights of the smoke-exposed groups.

Dosimetry and cardiopulmonary function in rats chronically exposed to cigarette smoke

Abstract Groups of 80 female F-344 rats were exposed, in Maddox-ORNL smoking machines, to smoke from three types of research cigarettes: high tar, low nicotine (HT-LN, code 13 as provided by the National Cancer Institute); low tar, high nicotine (LT-HN, code 27); and high tar, high nicotine (HT-HN, code 32). Rats were exposed to approximately 10 puffs of cigarette smoke during each of eight daily exposure sessions, 7 days/week for 24 months. Additional groups were sham-exposed on the same schedule, or served as untreated “shelf” controls. Heart rate and breathing pattern (tidal volume, respiration rate, and minute volume) were measured both during exposure and while the animals were not exposed to smoke. During exposure, smoke-exposed rats inhaled 75% less air and had 40% lower heart rates than sham-exposed rats. Results were similar for all smoke-exposed groups, and differences between sham- and smoke-exposed groups persisted throughout the 24-month exposure. When not being exposed, heart rate and breathing pattern were also different between smoke- and sham-exposed groups; tidal volumes were higher and respiration and heart rates were lower in smoke-exposed than in sham-exposed animals. In general, these differences between smoke- and sham-exposed groups developed during the first 12 months of exposure and diminished thereafter. Of the smoke-exposed groups, rats exposed to LT-HN cigarettes showed the greatest changes, and rats exposed to HT-LN cigarettes showed the least changes, in heart rate and breathing patterns. Arterial blood pressure was consistently higher in smoke-exposed than in sham-exposed animals following 18 and 24 months of exposure. This study showed that cardiopulmonary function in rats was significantly affected by chronic cigarette-smoke exposure.

Toxicology of Inhaled NiO and CoO in Syrian Golden Hamsters

Syrian golden hamsters exposed in several manners to the inhalation of nickelous oxide (NiO) and cobaltous oxide (CoO) showed completely different behavior in response to these two compounds. Exposures ranged from 3 to 7 hours per day for up to 60 days. The NiO concentrations were from 10 to 190 µg/liter, and CoO concentrations were from 2 to 160 µg/liter. Nearly 20% of the inhaled NiO was retained in the lungs after initial clearance, and 45% of this was still present after 45 days. Comparable figures for CoO were less than 1% after initial clearance and none after 6 days. No hamster exposed to NiO at any concentration died before scheduled sacrifice within 6 months postexposure. All the hamsters exposed to CoO at 106 µg/liter died by the fourth of the 3-hour exposures.

Chronic inhalation exposure of hamsters to nickel-enriched fly ash

Abstract 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.

Lung clearance of neutron-activated Mount St. Helens volcanic ash in the rat

To determine pulmonary deposition and clearance of inhaled volcanic ash, rats received a single 60-min, nose-only exposure to neutron-activated ash. Over a period of 128 days after exposure, the rats were sacrificed in groups of five animals. Lungs were analyzed for the radionuclide tracers 46Sc, 59Fe, and 60Co by gamma-ray spectrometry. The alveolar ash burdens, determined by the radionuclides 46Sc and 59Fe, are in good agreement for the majority of samples analyzed, indicating ash particulate levels in the lungs, rather than leached radionuclides. The ash deposition estimates based on 60Co were appreciably lower for the lungs, indicating that 60Co leached from the ash. Approximately 110 micrograms ash, or 6% of the inhaled ash, was initially retained in the deep lung. The biological half-time of the alveolar ash burden was 39 days. After 90 days, the mean lung burden had decreased to about 20% of its initial value; 128 days after exposure, about 10% remained.