Proquazone is a chemically distinctive non-steroidal anti-inflammatory drug (NSAID) and is orally effective as an anti-inflammatory, analgesic and anti-pyretic in animals. As with other NSAID's the main toxic effect was gastrointestinal irritation with sequellae. Comparative relative potency of proquazone with other NSAID's with regard to gastrointestinal effects was: rat-indomethacin greater than naproxen = proquazone greater than phenylbutazone; dog-indomethacin greater than naproxen greater than proquazone greater than phenylbutazone. In addition to gastrointestinal effects in minipigs, inflammatory renal changes occurred; renal changes also occurred in pigs treated with phenylbutazone. No evidence of carcinogenicity was seen in rodent oncogenicity studies. Evidence of teratogenicity was not seen in rat and rabbit teratological studies. In reproduction/perinatal studies in rats dose levels that induced intestinal lesions in the dams resulted in decreased survival of young to weaning. A major human metabolite of proquazone, the m-hydroxy derivative, was shown to be less toxic than the parent compound.

No abstract

Calcitonin, the serum calcium-lowering hormone, has been used in the treatment of hypercalcemia of malignancy and postmenopausal osteoporosis in humans for several years without any adverse erects. Recent studies in rats have indicated that calcitonin may be associated with morphologic effects on the pituitary. A large study was performed on 2 strains of rats, Sprague-Dawley (SD) and , with 2 types of calcitonin, salmon-derived ( s o ) and porcine-derived (pCT) calcitonin to evaluate possible effects on the pituitary. Sixteen groups of 42 male and 42 female SD or F-344 rats were given 0 (vehicle control), 1.25, 5.0, or 80.0 IU/kg/day of s C T or pCT, once daily, subcutaneously, for 1 yr.An increased incidence of adenomas of the adenohypophysis was observed in male SD rats at all dose levels of sCT, female SD rats given 80 IU/kg/day of sCT, male SD rats at the high dose level of pCT, and male F-344 rats at the high dose level of s C T . Also, an increased incidence of total proliferative lesions, due mostly to an increased incidence of focal hyperplasia of the pars distalis, occurred in female F-344 rats given the high dose of sCT. These pituitary proliferations were histologically similar to those that occur spontaneously, and the incidences observed were comparable to those that could occur in rats on 2-yr or lifetime studies, indicating that the injection of calcitonin had decreased the latency period.

No abstract

No abstract