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Spontaneously occurring diseases of the kidneys are very common in laboratory rats. These diseases include chronic progressive nephrosis, nephrocalcinosis, renal tubular epithelial hyaline droplets, renal tubular hypertrophy, and renal tubular basophilia. As increasing numbers of rats are used in long-term toxicity and carcinogenicity studies, recognizing spontaneously occurring renal lesions and understanding their etiology and pathogenesis are important in making an assessment of the safety of drugs and chemicals that are being tested. The purpose of this paper is to review the incidence, morphology, and pathogenesis of these spontaneous diseases. Some of the factors that alter the incidence and/or severity of these spontaneous diseases will also be discussed.

Absrracr. Spontaneous paresis and paralysis associated with degenerative spinal cord and spinal nerve root lesions occurred in three strains of rats used in studies of aging. Focal or segmental spinal cord lesions had mild to severe dernyelination, loss of nerve axons, and lipid-filled gitter cells. The lesions were limited to the white matter and were most severe in the lateral and ventral funiculi. The nerve roots had cholesterol clefts, focal hemorrhage, and demyelination. Atrophy of the skeletal muscle probably was secondary to the cord lesions. Vertebral lesions that involved the spinal canal and vascular blood flow were found, which may explain pathogenesis.Spontaneous posterior paralysis with associated spinal cord and spinal nerve root lesions occurs in several rat strains [3, 5, 131. The syndrome is usually associated with aging since the paralysis has been seen only in rats more than 2 years old. Along with paralysis, severe atrophy of skeletal muscle in the posterior part of the body also has been seen. The condition is progressive and eventually results in death. The cause and pathogenesis are unknown. Some rats had tumors in the spinal cord or canal that could have caused paralysis whilst others had large pituitary tumors. However, in most rats, no specific cause could be found.Three different strains of rats were kept for aging studies at the Institute for Experimental Gerontology. Sporadic cases of paralysis occurred in two strains, but the incidence was very low. We have noticed that the third strain (F, hybrid of the other two strains) has a much higher incidence of posterior paresis and paralysis. Preliminary studies on these rats are presented and the pathologic features are compared to those in other reports [3, 5, 9, 131.

The occurrence of tumors in 236 female and 74 male BN/Bi rats that were allowed to live out their normal lifespans was described. For most neoplasms, the risk of a rat dying with a specific tumor increased with age. Some tumors, however, had a peak incidence; therefore, animals surviving these periods were at less risk than were their younger cohorts. The number dying with metastatic cancers was greatest in females over 30 months of age. Unexpectedly, males had a peak risk period at 25-30 months, so that males that died in older age groups had less risk of dying with a metastatic tumor. Lesions were often multiple, even in rats dying at a young age. Surprisingly, the percent dead with multiple tumors did not increase significantly with age. Some animals in every age group died without a tumor, and the percentage without neoplasms did not decrease, even in the older age groups.

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A long-term study was conducted to determine the possible chronic toxicity and oncogenicity of methylene chloride. Rats and hamsters were exposed by inhalation to 0, 500, 1500, or 3500 ppm of methylene chloride for 6 hr per day, 5 days a week, for 2 years. No exposure-related cytogenetic effects were present in male or female rats exposed to 500, 1500, or 3500 ppm. Females rats exposed to 3500 ppm had an increased mortality rate while female hamsters exposed to 1500 or 3500 ppm had decreased mortality rates. Carboxyhemoglobin values were elevated in rats and hamsters exposed to 500, 1500, or 3500 ppm with the percentage increase in hamsters greater than in rats. Minimal histopathologic effects were present in the livers of rats exposed to 500, 1500, or 3500 ppm. Decreased amyloidosis was observed in the liver and other organs in hamsters exposed to 500, 1500 or 3500 ppm. While the number of female rats with a benign tumor was not increased, the total number of benign mammary tumors was increased in female rats in an exposure-related manner. This effect was also evident in male rats in the 1500- and 3500-ppm exposure groups. Finally, male rats exposed to 1500 or 3500 ppm had an increased number of sarcomas in the ventral neck region located in or around the salivary glands. Therefore, in this 2-year study, some effects were observed in male and female rats exposed to 500, 1500, or 3500 ppm of methylene chloride. In contrast, hamsters exposed to the same exposure concentrations had less extensive spontaneous geriatric changes, decreased mortality (females), and lacked evidence of definite target organ toxicity.

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