The oxidative metabolism of fenbendazole (FBZ) was studied in hepatic fractions prepared from livers of cattle, sheep, goats, chickens, ducks, turkeys, rats, rabbits and catfish. All species produced the sulfoxide metabolite (oxfendazole; FBZ-SO), and p-hydroxyfenbendazole (FBZ-OH) was produced by all species except sheep. The product of demethoxycarbonylation, fenbendazole amine (FBZ-NH2), was not produced by liver preparations of any species. A fourth metabolite, resulting from the further oxidation of oxfendazole, fenbendazole sulfone (FBZ-SO2), was formed in all species but at highly varying rates. The chicken exhibited the highest overall rate of FBZ metabolism, followed by the duck, goat, sheep, steer, catfish, rat, rabbit, and turkey. Considerable variation was evident among avian species, the duck and turkey produced substantially less of the FBZ-OH and FBZ-SO2 metabolites than the chicken. Catfish liver preparations formed equivalent amounts of metabolite at 25 degrees C and 37 degrees C incubation temperatures. The formation of the sulfone metabolite (FBZ-SO2), however, was practically nonexistent in catfish.

Abstract. 3-Methylindole (3MI) damages nasal olfactory epithelium in mice. Lesions were studied histologically from 30 minutes to 28 days after intraperitoneal injection of 400 mg 3MI/kg. Cellular swelling was apparent in olfactory epithelium by 6 hours after injection of 3M1, while respiratory epithelium was normal. Necrosis of olfactory epithelium and subepithelial glands was diffuse by 48 hours. Subsequent ulceration resulted in epithelial hyperplasia, squamous metaplasia, fibroplasia, and ossification. Partially occlusive intranasal fibrous and osseous tissue persisted through 28 days after 3MI injection.3-Methylindole (3MI), a ruminal metabolite of tryptophan, is a cause of acute bovine pulmonary edema and interstitial emphysema (ABPE).8 Experimentally, 3MI also induces pulmonary edema in ~h e e p ,~.~ rats,21 and mice.Io In small ruminant^,^ mice,10,24 and 3MI selectively damages nonciliated bronchiolar epithelial (Clara) cells. Olfactory epithelium in the nasal mucosa of mice is also selectively injured by 3MI.25 3-Methylindole is thought to be metabolized by mixed function oxidases (MFO).6J3J7-20 In the nasal cavity, olfactory epithelium is the major site of MFO activity in rats, mice, hamsters, guinea pigs, rabbits, and dogs.I2 In the present study, C57BL mice were chosen as an inbred strain with inducible MFO l 6 to facilitate further study of 3MI toxicosis. This paper describes 3MI-induced nasal mucosal damage in mice. Materials and MethodsA total of 65 C57BW6N 35-day-old male mice (Hilltop Lab Animals, Inc.) were divided into 13 groups. The mice were housed five per cage, with 12 hour light : dark cycle, and maintained on Purina Rat Chow and water ad libitum from 1 week before treatment to the end of the experiment. A 4% solution of 3MI in corn oil was injected intraperitoneally in four mice per group at a dose of 400 mg 3MI/kg. The fifth mouse in each group received a comparable volume of corn oil by the same route and served as a control.Mice were killed by cervical dislocation %, 1, 6, 12, and 24 hours, and 2,3,5,7, 10, 14,2 1, and 28 days after injection of 3MI. Tissues were fixed by perfusion of 5 to 6 ml of cacodylate-buffered 2% formaldehyde1 Yo glutaraldehyde via the right cardiac ventricle. The head was removed and the nasal cavity flushed with the same fixative through a 20-gauge cannula inserted 2-3 mm into the nasopharynx. The skin and mandibles were removed, and the head was immersed in fixative for at least 48 hours. To decalcify bone, the head was immersed in equal volumes of 20% sodium citrate and 50% formic acid for approximately 24 hours, then transferred to a saturated solution of sodium bicarbonate and washed in running tap water overnight to return pH to neutral. Frontal sections of the head through the plane of the first molar tooth were embedded in methacrylate. Sections cut at 2-3 bm were stained with hematoxlyin and eosin (HE) for light microscopy. ResultsWithin 30 minutes of 3MI injection, mice were lethargic with slowed respiratory rate. By 24 hours, mice were huddled and c...

The excretion of total urinary proteins (TUP) of rats beginning at weaning and extending to 12 months of age was correlated with the output of the sex-dependent α2u-globulin and albumin. At puberty, 40 days of age, the excretion of TUP corresponded to the output of α2u-globulin. At this age, α2u represented 30% of the total while albumin less than 10%. From 100 to 200 days of age, TUP remained constant while the excretion of albumin steadily increased. After 150–180 days of age, the concentrations of α2u and albumin in TUP were approximately equal. Thereafter, the excretion of albumin and TUP increased markedly whereas α2u excretion remained constant. At 373 days of age, albumin represented over 50–60% of the TUP while α2u was only 6–7%. Female rats which excrete little or no α2u exhibited a much lower level of proteinuria than the male during the first year. We suggest the existence of two phases of proteinuria in the male rat, namely, an early physiologic or α2u-globulinuric phase and a later albuminuric phase during which increasing quantities of plasma proteins, especially albumin, are lost.

Brunfelsia calcyina var. floribunda is an ornamental evergreen shrub found in the United States. A diagnosis of the fatal intoxication of a canine due to consumption of plant material (primarily berries) was made. The significant features of the clinical constellation were similar to those seen with substances interfering with the neurotransmission process, such as lathyrus or strychnine. Necropsy findings on the canine were unrevealing. Toxicologic studies performed on mice and rats with ground shrub material demonstrated that all parts of this plant are toxic, but unequally so. All plant preparations produced signs similar to those of a spinal convulsant. There were no distinguishing gross pathologic or histopathologic findings associated with the toxicoses induced in the laboratory animals with preparations from this plant. The toxic principles from this shrub are water soluble and very stable. The ability of aqueous extracts stored at 4 C to produce the clinical syndrome and subsequent lethality remained unchanged over a period of 4 months. Exposures are not always fatal. They most often occur in the canine and there is a significant hazard for small children.