Toxicity and tissue residues from diphenylhydantoin fed to chickens

Within three experiments with broiler-type crossbred chickens, diphenlyhydantoin (DPH) was administered via the diet at levels ranging from 10 to 2500 mg./kg. Feed intake and body weight gain were adversely affected by levels of 100 mg./kg. or higher. A hemorrhagic syndrome occurred in 16 percent of the chickens fed 100-1000 mg./kg. and 33 percent of those fed 2500 mg./kg. Twenty percent of the chickens fed 1000 mg./kg. were anemic; none of those receiving 250 mg./kg. were anemic. Other toxic manifestations included neurological side effects of a lethargic stupor, excitability to a disturbance, or a characteristic condition referred to as "head under." Pair-feeding experiments revealed thatlowered feed intake was not responsible for any of the clinical signs. All of the toxicity signs were reversible in 3 to 4 weeks following withdrawal of DPH. Muscle samples contained 2.5 to 11.4 mcg. DPH/g. at drug levels of 1000 and 2500 mg. DPH/kg. diet. Dose-response curves revealed that plasma, adipose, kidney and liver had levels which were, respectively, 1.05, 1.51, 2.19, and 2.85 times those of muscle.