Regulatory process for drugs used by the poultry industry.

The availability of safe and effective drugs to treat and control poultry diseases and to enhance the efficiency of poultry production depends on the rate at which new drugs are approved by the Food and Drug Administration. This paper briefly describes the components of the regulatory approval process for a new animal drug for use in food-producing animals, with specific reference to some problems encountered in the approval process for poultry drugs.

Estrogenic potencies of resorcylic acid lactones and 17 beta-estradiol in female rats.

Uterotrophic response in sexually immature female rats has been used to rank the relative estrogenic potencies of six resorcylic acid lactones (RALs) and to compare their activities with that of 17 beta-estradiol. On oral administration, the estrogenic potency relative to 17 beta-estradiol is as follows: 7 alpha-zearalenol, 10 times less; zeranol, 150 times less; taleranol, 350 times less; zearalanone, 400 times less; zearalenone, 650 times less; 7 beta-zearalenol, 3500 times less. On subcutaneous administration, zeranol is 500 times less estrogenic than 17 beta-estradiol.

Observations on anaplasmosis following field exposure to heavy and light infestations with Boophilus microplus.

Two groups of Normandy calves were exposed to heavy (mean half body count = greater than 300) or light (mean half body count = 9) natural infestations with Boophilus microplus. All of the calves became infected with Anaplasma marginale. Despite the difference in tick challenge level, there was no significant difference in the incubation period, increase in body temperature, level or duration of Anaplasma parasitemia, decrease in packed cell volume, or complement-fixing antibody response, between the heavily and lightly infected calves. Neither the incubation period nor the clinical severity of anaplasmosis was significantly influenced by the number of infested tick vectors.

Biotransformation of zeranol: disposition and metabolism in the female rat, rabbit, dog, monkey and man.

The disposition of [3H]zeranol has been studied in the female Wistar rat, New Zealand rabbit, beagle dog, rhesus monkey and man. The blood elimination half-life of total radioactivity in rabbit was 26 h, monkey 18 h and man 22 h. In all species studied the drug was absorbed, oxidized and/or conjugated, and was extensively excreted via the bile in all species except rabbit and man, in which urinary excretion predominated. Blood total radioactivity in man probably consisted entirely of conjugates of zeranol and/or its metabolites. Urinary metabolites in all species included conjugates (beta-glucuronides and/or sulphates) of zeranol and the major metabolite zearalanone. A more polar minor metabolite was isolated from human urine and was shown to be hydroxy-zeranol. Taleranol (7 beta-zearalanol, the lower-melting diastereoisomer), a probable metabolite of zeranol (7 alpha-zearalanol, the higher-melting diastereoisomer) in animals and in man, was shown to be a urinary metabolite in a female New Zealand white rabbit which had received [3H]zeranol (8 mg/kg per day) for seven days. A reverse isotope dilution method was developed for the quantification of both diastereoisomers of zearalanol, and also zearalanone, in urine.

Zeranol: a review of the metabolism, toxicology, and analytical methods for detection of tissue residues.

Zeranol, an anabolic agent produced commercially for use in cattle and sheep intended for human consumption, is noncarcinogenic, nonteratogenic, and nonmutagenic. Toxicity testing (acute, subacute, and chronic) in several species by various routes of administration reveals an extremely low toxicity, the oral rat LD50 exceeding 40 g/kg. Postmortem abnormalities of high-dose animals are attributed to the effects of the compound on the endocrine system. Both zeranol itself and zearalanone, the major Phase I metabolite in the seven species studied, are excreted in the feces and in the urine, either free or as sulfates/glucuronides. A minor urinary metabolite has been identified as taleranol, an epimer of zeranol. Both metabolites exhibit a very low order of toxicity (oral rat LD50 exceeding 10 g/kg in both cases), and both exhibit less biological activity than the parent compound. The four types of analytical methods which have been employed for the specific detection and quantitation of residues of zeranol in edible tissues are: (1) gas chromatography (detection limit = 20 ppb), (2) high-performance liquid chromatography (detection limit = 5 ppb), (3) thin-layer chromatography (detection limit = 1-3 ppb), and (4) radioimmunoassay methods (detection limit to be published). The following residue levels were determined radiometrically in tissue samples taken 45 days after implantation of cattle with 36 mg tritiated zeranol: less than or equal to 2 ppb in liver, less than or equal to 1 ppb in kidney and fat, and less than or equal to 0.2 ppb in muscle and plasma. A no-effect level (NEL) of 0.225 mg/kg was determined as the highest oral dosage of zeranol which produced no estrogenic effects in female monkeys. Based on the NEL, a tolerance level for tissue residues of zeranol was calculated as 315 ppb.

Toxicity of Cassia occidentalis in the horse.

Three Shetland ponies were given a single oral dose of ground Cassia occidentalis seeds in aqueous suspension. The clinical signs observed resembled those seen in naturally occurring and experimental cases in cattle. The syndrome was characterized by an afebrile course, incoordination, recumbency and death. Elevations of blood alkaline phosphatase, CPK, LDH, and SGOT were observed. Although muscle lesions were not seen grossly, microscopic lesions included segmental necrosis of skeletal muscle fibers. The findings were regarded as sufficiently characteristic of C. occidentalis poisoning to be useful in differential diagnosis. When Cassia poisoning is suspected, access of the affected horses to the plant should be demonstrated.

The acute oral toxicity of hymenoxon in sheep.

The acute oral toxicity of hymenoxon is dose-dependent, and the clinical signs and pathologic lesions are qualitatively identical to those of animals fed whole bitterweed. There was no synergistic effect when sheep were fed hymenoxon with hymenolane.

Comparison of three methods of immunization against bovine anaplasmosis: evaluation of protection afforded against field challenge exposure.

The efficacy of three immunization methods for bovine anaplasmosis was tested on 88 yearling Normandy cattle which were challenge-exposed under field conditions in an enzootic zone in Colombia, South American. A total of 30 cattle were immunized (premunized) with a presumed mild Colombian isolate of Anaplasma marginale; 29 calves were vaccinated with an attenuated A marginale of ovine origin; and 29 were exposed to a virulent A marginale stabilate of Colombian origin. Twenty-nine nonvaccinated cattle served as controls. Parasitemia, packed cell volume, body weight, and complement-fixation antibody response were monitored to determine host response to challenge exposure. The calves experienced a Babesia challenge exposure following arrival in the enzootic zone, after which a transient increase in Anaplasma parasitemia, accompanied by a decrease in packed cell volume, occurred in most of the vaccinated calves. However, neither clinical anaplasmosis nor mortality due to the disease occurred in the immunized cattle. Twenty-seven of the nonvaccinated calves had signs of clinical anaplasmosis and five (17%) died of the disease.