PATULIN MYCOTOXICOSIS IN THE SYRIAN HAMSTER, MOUSE AND RAT

EDMUND RALPH MCKINLEY, Purdue University

Abstract

These studies were conducted to define the toxicity of patulin for various routes of administration of single and multiple doses in the Syrian hamsters, mouse and rat. The single-dose 72 hour LD(,50) values for male Syrian hamsters when administered by various routes were oral 31.5, sc 23.0 and ip 10.0 mg/kg body weight. The single-dose 72 hour LD(,50) values for patulin when administered to weanling male Swiss ICR mice were oral 48.0, sc 10.0 and ip 7.5 mg/kg body weight. Patulin administered to Sprague-Dawley rats by the oral, sc and ip routes resulted in 72 hour LD(,50) values of 55.0, 11.0 and 10.0 mg/kg body weight respectively. Mortality was greatest in all species at 0-24 hours post-administration when patulin was administered by the oral and sc routes but was delayed in all species when administered by the ip route. Patulin administered orally either daily or every other day for two weeks at 50 or 75% of the oral LD(,50) resulted in greatest mortality at 3-7 days post-administration in the rat and mouse and at 1-2 days post-administration in the hamster. No evidence of cumulative toxicity was found in any tested species. Mortality was dose dependent in the mouse but not in the hamster or rat. In the multiple dose study, weight gain of all treated groups was less than controls. Most test groups exhibited an initial loss in body weight but began gaining weight by day four. This weight loss was attributed to dehydration. The principal gross and microscopic alterations in mice, hamsters and rats were in the gastrointestinal tract. Hyperemia, distention, ulceration and inflammatory changes were present in the stomach and small intestine of mice, rats and hamsters and in the cecum of hamsters. Patulin was administered to 200g rats at 50 and 75% of the oral LD(,50) and clinicopathologic alterations determined. Principal changes were a metabolic alkalosis with respiratory compensation characterized by an elevated pH and bicarbonate with a delayed increase in pCO(,2). Urine volume and plasma protein were decreased in patulin-treated rats. Total white blood cell counts were elevated and were attributed to the inflammatory changes in the gastrointestinal tract. Serum sodium levels decreased significantly with time. Serum potassium and chloride were not significantly altered; however, potassium levels exhibited a tendency to increase in patulin-treated animals.

Degree

Ph.D.

Subject Area

Animal diseases

COinS