Dogs exposed by inhalation to an aerosol of fused aluminosilicate particles containing the radionuclide yttrium 90 developed radiation pneumonitis. The aerosol had a mean aerodynamic diameter of 0.8 to 1.2 mu with a sigma(g) of 1.6 to 1.9. The 36 dogs included in this report received initial lung burdens of 590 to 5200 muCi (90)Y/kg body weight and died at 7.5 to 237 days after exposure with total cumulative radiation doses to lung of 9300 to 70,000 rads. Vascular lesions in the lungs were marked. Early changes included edema of vessel walls with leukocytic infiltration, dilation of perivascular lymphatic channels, and occasional periarterial lymphangiectasia. Splitting and reduplication of the elastica were occasionally visible. The most striking inflammatory vascular changes were vasculitis and fibrinoid necrosis, which involved bronchial and pulmonary vessels at some-what different times. Such lesions were often segmental and included fibrinoid necrosis and a variable leukocytic infiltrate in and around the actively involved lesions. Vasculitis was most commonly seen in small muscular arterioles, but veins and venules also occasionally exhibited similar inflammatory lesions. Progressive vascular inflammation led to extensive intimal proliferative lesions and fibromuscular hypertrophy with eventual fibrous accumulation around blood vessels, obliterative intimal and medial thickening, and luminal narrowing. Such changes eventually formed the morphologic basis for increased pulmonary vascular resistance and the development of cardiac dilation and hypertrophy reflecting pulmonary hypertension.

The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis, focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury.

To determine the effects of inhaled 144Ce, 126 Beagle dogs (including 15 controls) were exposed to aerosols of either 144Ce in fused clay or stable cerium in fused clay. To date, 15 dogs have died 143–410 days after inhalation exposure from radiation pneumonitis and pulmonary fibrosis. Primary pulmonary neoplasms caused the deaths of 5 dogs 750–1318 days after inhalation exposure. Calculated pulmonary radiation doses until death ranged from 23,000–48,000 rads. Pulmonary hemangiosarcomas were found in all 5 dogs and metastasis in 4. In addition, 1 dog had a pulmonary fibrosarcoma and another had a bronchiolo-alveolar carcinoma, both of which metastasized to the tracheobronchial lymph nodes. Only 3 dogs with similar initial lung burdens of 144Ce died without pulmonary neoplasms, at 186, 193, and 410 days after inhalation exposure. The 91 dogs exposed to 144Ce-fused clay and all controls have survived 239–1565 days after inhalation exposure including 44 surviving >750 days, with pulmonary radiation doses from 2–36,000 rads.

MUGGENBURG, B. A.; MAUDERLY, J. L.; PICKRELL, J. A.; CHIFFELLE, T. L.; JONES, R. K.; LUFT, U. C.; MCCLELLAN, R. O.; PFLEGER, R. C. Author Information

Five Beagle dogs were exposed by inhalation to an aerosol farmed by passing liquid droplets containing 241Am through a heating column at 600°C. The resulting particles, presumed to be relatively insoluble, formed a distribution with an activity median aerodynamic diameter of about 0.9 μm and a geometric standard deviation of about 1.5. One dog was frozen shortly post-inhalation and used as a counting standard; the remaining four were held for urine and feces collections for up to 138 days; these four were sacrificed at 127, 256, 512 and 1022 days post-exposure. Initial body burdens ranged from 4.4 to 4.9 μCi/kg. Tissue analyses indicated the greatest long-term doses to be received by the tracheobronchial lymph nodes, liver, lung, bone and thyroid in descending order. Respiratory measurements showed increased frequency and decreased tidal volumes in the two early sacrifice dogs only. Hematologic findings included reduced total white cells, platelets, lymphocytes and neutrophils, but little change in hematocrit. Pathologic findings centered around fibrotic changes in lung and lymph nodes, fatty deposits and cellular degeneration in liver, bone marrow depletion, glomerulosclerosis and severely damaged thyroid.

The toxicity of ${}^{90}{\rm Y}$ in the beagle is being investigated as part of a program to evaluate the biological effects of inhaled radionuclides. Thirtythree beagles were exposed to aerosols of ${}^{90}{\rm Y}$ in fused clay resulting in initial lung burdens (ILB) of 80-5200 μCi ${}^{90}{\rm Y}/{\rm kg}$ body weight. Cumulative beta radiation dose to the lungs to infinity or death ranged from 990 to 55,000 rads. Twenty-one dogs with ILBs from 670 to 5200 μCi/kg and beta radiation doses to lung ranging from 8400 to 55,000 rads died between 7.5 and 163 days postexposure. Clinical signs included progressive increase of respiratory rates, abnormal lung sounds on auscultation, progressive weight loss, lymphopenia, and eventual cyanosis. Principal pathological findings were pulmonary and pleural fibrosis, occlusive pulmonary vascular lesions, metaplasia and/or hyperplasia of terminal bronchiole and alveolar epithelium, right-heart dilatation an...

To aid in assessing the hazard associated with airborne radio-cerium, two groups of rats were exposed by inhalation to heat-treated ${}^{144}{\rm Ce}$ hydroxide aerosols resulting in body burdens of ∼3.0 (0.85-6.6) or ∼170 (79-300) μCi ${}^{144}{\rm Ce}/{\rm kg}$ body weight. Following initial rapid clearance, the ${}^{144}{\rm Ce}$ had an effective half-time of 130 days in lung. Based on average kinetics of whole-body and lung retention, estimated cumulative β-radiation doses to lungs of the high-level rats were 620 rads at 100 days, 1000 rads at 300 days and 1150 rads at 600 days postinhalation exposure, per μCi initial lung burden. Estimated cumulative doses to lungs to time of death averaged 5100 rads and ranged from 2400 to 8800 rads. Other organs of interest, for which β-radiation doses were calculated, are skeleton, liver and tracheobronchial lymph nodes. ${}^{144}{\rm Ce}$ also concentrated significantly in kidneys. Median survival times were 135 and 393 days postexposure for the high-level and lo...

The toxicity of ${}^{137}{\rm CsCl}$ , because of a relatively uniform whole-body exposure, has been investigated as part of a program to evaluate the biological effects of internally deposited radionuclides. Sixty-six beagles (12-14 months of age) were given ${}^{137}{\rm CsCl}$ in saline iv to provide one group of six dogs with mean initial body burdens of 3800 μCi ${}^{137}{\rm Cs}/{\rm kg}$ and five groups of 12 dogs each with mean initial body burdens of 2800, 1900, 1400, 970, and 0 μCi ${}^{137}{\rm CsCl}$ . Eleven dogs have died at less than 1 year postinjection: the six at the highest level between 19 and 33 days with cumulative whole-body doses of 950-1400 rads; four in the 2800 μCi/kg group between 24 and 81 days with cumulative whole-body doses of 860-1400 rads; and one at 77 days in the 1900 μCi/kg group with a cumulative whole-body dose of 1300 rads. Prior to death, all dogs became febrile, anorexic, hemorrhagic...