Characterization of oligosaccharides from the urine of loco-intoxicated sheep.

Two major oligosaccharides were isolated by preparative HPLC from the urine of a locoweed-fed sheep. Analysis by gas-liquid chromatography and mass-spectrometry indicated compositions of (Man)4(GlcNAc)2 and (Man)5(GlcNAc)2, respectively. Structures were determined by digestion with alpha-D-mannosidase and endo-beta-N-acetylglucosaminidases D and H, and comparison of the products by HPLC with synthetic standards, and oligosaccharides isolated from human mannosidosis urine. Incubation with an exo-beta-N-acetylglucosaminidase was without effect.

Induced mannosidosis-excretion of oligosaccharides by locoweed-intoxicated sheep.

Daily urine samples were collected from a locoweed-fed sheep, and the oligosaccharide content examined by thin-layer and liquid chromatography. An unusual pattern of urine oligosaccharides was observed, which appears to be characteristic of loco intoxication. Changes in the pattern could be correlated with the onset of visible disease, which occurred approximately 5 weeks after the typical urine sugars were first detected. HPLC showed that these sugars consisted of two homologous series of oligosaccharides containing one and two residues of 2-acetamido-2-deoxy-D-glucose, respectively.

Locoweed-induced neuronal storage disease characterized by meganeurite formation.

Golgi staining was performed on cerebral cortex and thalamus of adult animals chronically intoxicated with an alpha-mannosidase inhibitor found in locoweed (Astragalus lentiginosus). The widespread occurrence of large, aspiny meganeurites was discovered on cortical pyramidal and thalamic principal neurons but aberrant spines and neurite growth were not observed. Ectopic neurite growth is known to be characteristic of alpha-mannosidosis of early onset in inherited and induced feline models. The absence of neuritogenesis in a storage disease known to be so characterized when induced in younger animals suggests that this unusual phenomenon is in some way linked to normal developmental processes associated with brain maturation.

Pine needle abortion in cattle: metabolism of isocupressic acid.

The rumen and hepatic metabolism of the cattle abortifacient compound isocupressic acid (ICA) was examined in vitro and in vivo. ICA was incubated for 56 h in bovine rumen inoculum and was found to be converted to three compounds identified as imbricatoloic acid, a structurally uncharacterized isomer of imbricatoloic acid, and dihydroagathic acid. In preparations of liver homogenates, ICA was found to be oxidized to agathic acid. No differences in ICA metabolites were detected in comparing the cow, sheep, pig, goat, guinea pig, and rat livers; however, guinea pig and rat liver homogenates were less efficient in converting ICA to agathic acid. ICA had been administered to cows orally and by intravenous infusion and induced abortions after either method of treatment. After intravenous infusion, agathic acid was identified as the major metabolite together with minor amounts of dihydroagathic acid. After oral administration, dihydroagathic acid was identified as the major metabolite with minor amounts of agathic acid, imbricatoloic acid, and a structurally uncharacterized metabolite tentatively identified as tetrahydroagathic acid.

Serum alpha-mannosidase activity and the clinicopathologic alterations of locoweed (Astragalus mollissimus) intoxication in range cattle.

Subclinical intoxication of livestock with Astragalus and Oxytropis species (locoweeds) results in decreased animal feed conversion, reduced weight gains, and reproductive failure. Sensitive diagnostic methods to definitively diagnose and monitor intoxication are needed to minimize these losses and better manage locoweed-infested pastures and rangelands. Sera from cattle grazing locoweed were evaluated for alpha-mannosidase activity, serum biochemical values, electrolytes, and thyroid hormone concentrations. As the cows began to ingest locoweed, the mean serum alpha-mannosidase activities dropped significantly (400.0 microM to 72.5 microM). Changes in other serum chemistry values were less specific; however, individual animals (generally those ingesting more locoweed) had elevated levels of alkaline phosphatase (ALP), aspartate aminotransferase, and lactate dehydrogenase, with decreased serum total protein (5.8 +/- 0.8 g/dl) and albumin (2.3 +/- 0.3 g/dl). Mean serum thyroid concentrations (both T4 and T3) were lower in animals that were ingesting locoweed. The calculated swainsonine dose correlated statistically with serum alpha-mannosidase activity, ALP, albumin, Cl, CO2, and thyroid hormone T3. This correlation suggests that serum alpha-mannosidase activity along with potential changes in ALP, albumin, and thyroid hormone concentrations is a sensitive indicator of locoweed exposure and intoxication. These parameters may also be useful for monitoring intoxication and allowing subclinically affected cattle to be removed from infested areas before irreversible damage occurs.

Pyrrole detection and the pathologic progression of Cynoglossum officinale (houndstongue) poisoning in horses.

Houndstongue (Cynoglossum officinale), a noxious weed that contains pyrrolizidine alkaloids (PAs), infests pastures and fields in the western United States and Europe. The purpose of this study was to develop techniques to better diagnose PA poisoning and describe the progression of gross and microscopic lesions caused by houndstongue intoxication. Six horses were gavaged daily with a suspension of houndstongue containing 5 or 15 mg/kg total PA for 14 days. Two horses were treated similarly with ground alfalfa as controls. Liver biopsy samples and serum biochemical and hematologic values were evaluated biweekly. Within 7 days after dosing, horses treated with 15 mg/kg PA developed severe liver disease characterized by altered bile acid metabolism, elevated serum enzymes, and extensive hepatocellular necrosis with minimal periportal fibrosis and biliary hyperplasia. The condition of these animals continued to deteriorate, and they were euthanized. For several weeks after dosing, horses treated with 5 mg/kg PA were depressed, had transient elevations of serum enzymes and bile acids, and developed minimal periportal hepatocellular necrosis with fibrosis. The biochemical changes resolved by 6-8 weeks; however, the histologic disease persisted with extensive megalocytosis by week 14. Throughout the study, the rate of hepatocellular proliferation remained constant. Biliary cells had an increase in mitotic rate that correlated with the histologic changes. Hepatic tissue-bound pyrroles (PA metabolites) were identified in necropsy samples of treated animals using gas chromatography/mass spectrometry and photometrically with Ehrlich's reagent. These findings suggest that pyrrole extraction and identification are useful in documenting PA exposure and that houndstongue is extremely toxic to horses.

Dose response of sheep poisoned with locoweed (Oxytropis sericea).

Locoweed poisoning occurs when livestock consume swainsonine-containing Astragalus and Oxytropis species over several weeks. Although the clinical and histologic changes of poisoning have been described, the dose or duration of swainsonine ingestion that results in significant or irreversible damage is not known. The purpose of this research was to document the swainsonine doses that produce clinical intoxication and histologic lesions. Twenty-one mixed-breed wethers were dosed by gavage with ground Oxytropis sericea to obtain swainsonine doses of 0.0, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.0 mg/kg/day for 30 days. Sheep receiving > or = 0.2 mg/kg gained less weight than controls. After 16 days, animals receiving > or = 0.4 mg/kg were depressed, reluctant to move, and did not eat their feed rations. All treatment groups had serum biochemical changes, including depressed alpha-mannosidase, increased aspartate aminotransferase and alkaline phosphatase, as well as sporadic changes in lactate dehydrogenase, sodium, chloride, magnesium, albumin, and osmolarity. Typical locoweed-induced cellular vacuolation was seen in the following tissues and swainsonine doses: exocrine pancreas at > or = 0.05 mg/kg; proximal convoluted renal and thyroid follicular epithelium at > or = 0.1 mg/kg; Purkinje's cells, Kupffer's cells, splenic and lymph node macrophages, and transitional epithelium of the urinary bladder at > or = 0.2 mg/kg; neurons of the basal ganglia, mesencephalon, and metencephalon at > or = 0.4 mg/kg; and cerebellar neurons and glia at > or = 0.8 mg/kg. Histologic lesions were generally found when tissue swainsonine concentrations were approximately 150 ng/g. Both the clinical and histologic lesions, especially cerebellar lesions are suggestive of neurologic dysfunction even at low daily swainsonine doses of 0.2 mg/kg, suggesting that prolonged locoweed exposure, even at low doses, results in significant production losses as well as histologic and functional damage.

The fetal cleft palate: II. Scarless healing after in utero repair of a congenital model.

The role of fetal surgery in the treatment of non-life-threatening congenital anomalies remains a source of much debate. Before such undertakings can be justified, models must be established that closely resemble the respective human anomalies, and the feasibility and safety of these in utero procedures must be demonstrated. The authors recently described and characterized a congenital model of cleft palate in the goat. The present work demonstrates the methodology they developed to successfully repair these congenital cleft palates in utero, and it shows palatal healing and development after repair. A surgically created cleft model was developed for comparative purposes. Palatal shelf closure normally occurs at approximately day 38 of gestation in the caprine species. Six pregnant goats were gavaged twice daily during gestational days 32 to 41 (term, 145 days) with a plant slurry of Nicotiana glauca containing the piperidine alkaloid anabasine; the 12 fetuses had complete congenital clefts of the secondary palate. Repair of the congenital clefts was performed at 85 days of gestation using a modified von Langenbeck technique employing lateral relaxing incisions with elevation and midline approximation of full-thickness, bilateral, mucoperiosteal palatal flaps followed by single-layer closure. Six congenitally clefted fetuses underwent in utero repair, six remained as unrepaired controls. Twelve normal fetuses underwent surgical cleft creation by excision of a 20 x 3 mm full-thickness midline section of the secondary palate extending from the alveolus to the uvula, at 85 days of gestation. Six surgically clefted fetuses underwent concurrent repair of the cleft at that time; six clefted fetuses remained as unrepaired controls. At 2 weeks of age, no congenitally or surgically created clefts repaired in utero demonstrated gross or histologic evidence of scar formation. A slight indentation at the site of repair was the only remaining evidence of a cleft. At 6 months of age, normal palatal architecture, including that of mucosal, muscular, and glandular elements, was seen grossly and histologically. Cross-section through the mid-portion of the repaired congenitally clefted palates demonstrated reconstitution of a bilaminar palate, with distinct oral and nasal mucosal layers, after single-layer repair. In utero cleft palate repair is technically feasible and results in scarless healing of the mucoperiosteum and velum. The present work represents the first in utero repair of a congenital cleft palate model in any species. The use of a congenital cleft palate model that can be consistently reproduced with high predictability and little variation represents the ideal experimental situation. It provides an opportunity to manipulate specific variables, assess the influence of each change on the outcome and, subsequently, extrapolate such findings to the clinical arena with a greater degree of relevance.

Natural plant toxicants in milk: a review.

Elimination of plant toxicants via milk by lactating animals is considered a minor route of excretion; however, it may be important when the health of the neonate or food safety in humans is considered. Among plant toxicants excreted in milk is tremetol or tremetone, the toxin in white snakeroot (Eupatorium rugosum) and rayless goldenrod (Haplopappus heterophyllus). These plants have been responsible for intoxication of cows and their suckling calves and for many human poisonings. Other plant toxins excreted through the milk that pose a toxicity hazard include pyrrolizidine alkaloids in Senecio, Crotalaria, Heliotropium, Echium, Amsinckia, Symphytum (comfrey), Cynoglossum (hounds tongue) and Festuca (tall fescue); piperidine alkaloids in Conium, tobacco and others; quinolizidine alkaloids in Lupinus; sesquiterpene lactones of bitterweed and rubber weed; and glucosinolates in Amoracia (horseradish), Brassica (cabbage, broccoli, etc.), Limnanthes (meadowfoam), Nasturtium (watercress), Raphanus (radish) and Thlaspi (stinkweed). Many plants such as Astragalus, Oonopsis, Stanleya, Xylorrhiza, Aster, Atriplex, Sideranthus and Machaeranthera accumulate selenium and may cause intoxication when grazed. Selenium is found in the milk at concentrations relative to the amounts ingested by the lactating animal. Excretion of selenium via the milk is important in the deficiency state, but when in excess it may cause toxicity to offspring.

Feed preferences and habituation of sheep poisoned by locoweed.

Livestock addiction to locoweed is commonly cited as a clinical sign of locoweed poisoning. However, there have been no physiological or pathological explanations for the reported addiction. Four hypotheses were tested to evaluate locoweed's (Astragalus lentiginosus) addictive nature: 1) animals become psychologically addicted to locoweed; 2) animals have an innate preference for locoweed; 3) animals become habituated to locoweed in the sense of acquiring an acceptance or liking for it; and 4) intoxicated animals lose the ability to discriminate between feeds and eat whatever is present. Two feeding trials were conducted to evaluate these hypotheses. In 1987, 20 ewes were fed a pelleted basal feed consisting of alfalfa with 20% locoweed to induce locoweed poisoning. Five control ewes were fed pelleted alfalfa. In 1988, seven ewes were fed a basal feed consisting of alfalfa and 15% locoweed, and five control ewes were fed pelleted alfalfa. At 2- to 3-wk intervals, ewes from both trials were placed on cafeteria trials and offered a choice of four feeds (100% locoweed pellets, 15% or 20% locoweed pellets, mixed grain pellets and alfalfa pellets) to evaluate their preferences at increasing levels of intoxication. Sheep did not seek out locoweed, which would have indicated a psychological addiction. Locoweed was not innately palatable to sheep. One ewe habituated to 100% locoweed and two ewes habituated to the 15% locoweed diet. The rest of the ewes rejected the 100% locoweed pellets and the 15% or 20% locoweed basal feed when the choice of feeds was offered, even though they were severely intoxicated. Sheep show neither initial preference nor addiction to locoweed but may acquire preference (habituation).

Ponderosa pine needle-induced parturition in cattle.

Needles of the Ponderosa pine (Pinus ponderosa) induce premature parturition in cattle when ingested during late pregnancy, especially during the third trimester. The closer to term, the more likely that pine needles will induce parturition. Experiments were designed to describe the clinical signs and behavior associated with ingestion of pine needles. Pine needles adversely affected only pregnant cows and did not seem to affect nonpregnant, cycling cows, sheep, goats, or rabbits. Premature parturition was more likely if cows ingested the needles after the 8th mo of pregnancy, if they ingested pine needles over a period of 3 d or more, and if cows ate a relatively large amount of pine needles (about 2.2 to 2.7 kg/d). A synthetic progesterone, melangesterol acetate, and a prostaglandin inhibitor (ketoprofen) seemed to be of some prophylactic benefit; however, further research is required to assess the practicality of the approach and the magnitude of the benefit. Ponderosa pine bark and new-growth branch tips, which seem to be more potent inducers of premature parturition, may be useful in the extraction and identification of the parturifacient component(s).

Ultrasound studies of the effects of certain poisonous plants on uterine function and fetal development in livestock.

Ingestion of locoweed (Astragalus spp. and Oxytropis spp.) by pregnant livestock may result in fetal malformations, delayed placentation, reduced placental and uterine vascular development, hydrops amnii, hydrops allantois, abnormal cotyledonary development, interruption of fetal fluid balance, and abortion. Ultrasonography of pregnant sheep fed locoweed demonstrated that abortion was first preceded by changes in fetal heart rate and strength of contraction and structural changes of the cotyledons, followed by increased accumulation of fetal fluid within the placental membranes and death of the fetus. During pregnancy the toxic agent in locoweed (swainsonine) apparently passes through the placental barrier to the fetus and during lactation through the milk to the neonate. Poison-hemlock (Conium maculatum), wild tree tobacco (Nicotiana glauca), and lunara lupine (Lupinus formosus) all contain piperidine alkaloids and induce fetal malformations, including multiple congenital contractures and cleft palate in livestock. Ultrasonography studies of pregnant sheep and goats gavaged with these plants during 30 to 60 d of gestation suggests that the primary cause of multiple congenital contractures and cleft palate is the degree and the duration of the alkaloid-induced fetal immobilization.

Cattle grazing Wahweap milkvetch in southeastern Utah.

Cattle's grazing of the locoweed Wahweap milkvetch (Astragalus lentiginosus var. wahweapensis) was evaluated on desert and foothill winter range during the winter of 1986 to 1987. Dry, dead stalks of Wahweap milkvetch that had grown in 1985 and 1986 made up 15% of cattle diets overall, and 24% of diets when cattle grazed gravelly benches where it was abundant. Nutritional quality of Wahweap milkvetch was higher than of most associated forage, but its alkaloid concentration varied among the senescent stages. One cow aborted and two cows developed clinical signs of locoweed poisoning, including water belly (hydrops amnii). Microscopic lesions consisting of cytoplasmic foamy vacuolation were evident in both the dam and fetus. Because senescent stalks of Wahweap milkvetch are palatable and readily grazed by cattle, ranchers should not permit cattle to graze infested sites until other green forage is available in the spring.

Grazing of spotted locoweed (Astragalus lentiginosus) by cattle and horses in Arizona.

Spotted locoweed (Astragalus lentiginosus var. diphysus) is a toxic, perennial plant that may, if sufficient precipitation occurs, dominate the herbaceous vegetation of pinyon-juniper woodlands on the Colorado Plateau. Six cow/calf pairs and four horses grazed a 20-ha pasture with dense patches of locoweed in eastern Arizona during spring 1998. Locoweed density was 0.7 plants/m2 in the pasture. Locoweed averaged 30.4% NDF and 18.4% CP. Concentrations of the locoweed toxin, swainsonine, fluctuated from 1.25 to 2 mg/g in locoweed. Horses ate more (P < 0.01) bites of locoweed than did cows (15.4 and 5.1% of bites, respectively). Horses generally increased locoweed consumption over time since they ate approximately 5% of bites in the preflower stage compared with 25% of bites in the pod stage. Cattle consumed almost no locoweed (< 1% of bites) until the pod stage, when they increased consumption to 15% of bites. Horses were very avid (approximately 65 to 95% of bites) in selecting the small quantities (approximately 40 to 150 kg/ha) of available green grass, and it appeared that their propensity to eat scarce green forage influenced their locoweed consumption as well. Horses ate relatively little dry grass, even when it was abundant, whereas cattle ate large amounts of dry grass until green grasses became more abundant. Calves began eating locoweed on the same day as their dams and ate approximately 20% of their bites as locoweed. Serum concentrations of swainsonine were higher (P < 0.05) in horses than in cattle (433 vs. 170 ng/mL, respectively). Baseline swainsonine was zero in all animals, but swainsonine was rapidly increased to above 800 ng/mL in serum of horses as they ate locoweed. Horses exhibited depression after eating locoweed for about 2 wk; after 5 wk of exposure, horses became anorectic and behaviorally unstable. Although limited in scope, this study indicates that horses should not be exposed to spotted locoweed.

The effect of natural toxins on reproduction in livestock.

Reproductive efficiency is the most important economic factor in livestock production. Thus, the hypothalamo-pituitary-gonadal regulatory axis, accessory sexual organ functionality, and the complex events involved in fertilization, implantation, and embryonic and fetal development may be sensitive to therapeutic agents, environmental pollutants, and natural toxicants. There are many factors that adversely affect reproduction, one of which is toxic substances in the diets of animals. Toxic materials can affect reproductive success by causing abortions, interfering with libido, estrus, oogenesis, or spermatogenesis, causing emaciation and subsequent abnormal mating behavior, birth defects, and increasing the time between parturition and rebreeding. Examples of natural toxicants in poisonous plants interfering with reproduction are numerous. Abortion in livestock from locoweeds, ponderosa pine needles, broom snakeweeds, fescue, and others are reported in studies. Selenium and seleniferous forage inhibit estrus in cattle and swine. Emaciation and temporary illness from sneezeweeds, bitterweed, locoweed, larkspur, lupines, and others may interfere with mating. Embryonic loss and birth defects from Veratrum, lupines, locoweeds, poison hemlock, and so on, may occur. As suggested, toxins have many diverse and economically adverse effects on reproductive performance in livestock.

Operant analysis of chronic locoweed intoxication in sheep.

Five sheep were fed a 10% locoweed (Oxytropis sericea) pellet or alfalfa pellets for 3- to 5-wk periods to determine the effects of intermittent locoweed ingestion on operant responding; three controls were fed alfalfa pellets for 22 wk. Sheep were trained to respond to a multiple schedule with a fixed ratio (FR) 5 and fixed interval (FI) 50 s as major elements; performance was reinforced with rolled barley. Locoweed-treated sheep decreased (P < .05) FR response rate after 4 wk of locoweed feeding, but this decrease first appeared during the first recovery period (wk 6). The FR response rate of intoxicated sheep did not return to baseline during the remainder of the study and differed from controls during most of the study. Controls did not deviate (P > .05) from their FR baseline except during wk 2. Sheep did not stabilize on the FI component. As locoweed-treated sheep became progressively more intoxicated, they altered their pattern of FR responses, with longer post-reinforcement pauses, and a slower overall FR rate. Intoxicated sheep ingested an average of .21 mg swainsonine.kg-1.d-1. Overt signs of intoxication were noted when two sheep were stressed on wk 17. These two sheep had neuroviseral vacuolation typical of locoweed poisoning, whereas the three remaining locoweed-treated sheep that were euthanatized 5 wk later showed little histologic evidence of intoxication. Our findings indicate that "on-off" or cyclic grazing of locoweed ranges should be approached cautiously. Such a grazing program may be feasible because of the rapid resolution of histologic pathology; however, an initial toxic insult of 4 wk seems to be excessive, even at low doses, because sheep may exhibit persistent behavioral abnormalities that require > 6 wk to resolve.

Effects of feeding ponderosa pine needles during pregnancy: comparative studies with bison, cattle, goats, and sheep.

Four experiments were conducted to determine the effect of feeding dried pine needles (Pinus ponderosa; PN) on the abortion rate of ruminants. In Exp. 1, cattle were fed 5.4 kg of PN daily for 21 d starting at 116, 167, 215, or 254 d of pregnancy. The PN did not cause abortions when started at 116 d; thereafter, the percentage of cows that aborted increased linearly, and the interval to abortion decreased linearly (both P < .01); all cows fed PN beginning at 254 d aborted. In Exp. 2, cattle were fed .7, 1.4, or 2.7 kg of PN for 21 d or 2.7 kg for 1 or 3 d. Sheep and goats were fed .8 and .5 kg of PN, respectively, starting at 121 d of pregnancy. The PN induced some abortions in cattle when fed for 1 (11%) or 3 (30%) d, but the abortion rate was greater (P < .01) when the PN were fed for longer periods of time (80, 90, and 100% aborted in 19, 17, and 10 d for .7-, 1.4-, and 2.7-kg doses, respectively). No goats or sheep aborted in response to PN feeding. Pregnancy rates during the next breeding season for cows that aborted in response to the PN were slightly higher than rates for control cows (94 vs 87%). In Exp. 3, buffalo (Bison bison) and cattle were fed 2.25 kg of PN from the same collection. Abortions were induced in all buffalo and cattle that were fed PN.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of vaccination against methyllycaconitine toxicity in mice.

The purpose of this study was to determine whether larkspur toxins conjugated to protein carriers would promote active immunity in mice. Mice were injected with several larkspur toxin-protein conjugates or adjuvant alone to determine whether the resulting immunological response altered animal susceptibility to methyllycaconitine, the major toxic larkspur alkaloid. Although vaccinations increased the calculated lethal dose 50% (LD50) for intravenous methyllycaconitine toxicity, overlapping confidence intervals did not provide evidence of differences between the vaccinated and control groups. In the lycoctonine conjugate (LYC)-vaccinated group, mouse survival was related (P = 0.001) to serum titers for methyllycaconitine doses up to 4.5 mg/kg of body weight. When mice withlow antibody titers were removed from the vaccinated groups in which titer was related to survival, the recalculated LD50 estimates were 20% greater than the LD50 of the control group. However, the 95% confidence intervals of the recalculated LD50 groups overlapped with the control groups. Overall, these results suggest that vaccination altered methyllycaconitine toxicity in mice and that vaccination may be useful in decreasing the effects of larkspur toxins in animals. Additional studies are warranted to continue development of potential larkspur vaccines for livestock.

Tissue swainsonine clearance in sheep chronically poisoned with locoweed (Oxytropis sericea).

Locoweed poisoning is seen throughout the world and annually costs the livestock industry millions of dollars. Swainsonine inhibits lysosomal alpha-mannosidase and Golgi mannosidase II. Poisoned animals are lethargic, anorexic, emaciated, and have neurologic signs that range from subtle apprehension to seizures. Swainsonine is water-soluble, rapidly absorbed, and likely to be widely distributed in the tissues of poisoned animals. The purpose of this study was to quantify swainsonine in tissues of locoweed-poisoned sheep and determine the rate of swainsonine clearance from animal tissues. Twenty-four crossbred wethers were gavaged with ground Oxytropis sericea to obtain swainsonine doses of 1 mg swainsonine x kg(-1) BW x d(-1) for 30 d. After dosing, the sheep were killed on d 0, 1, 2, 3, 4, 6, 14, 30, 60, and 160. Animal weights and feed consumption were monitored. Serum was collected during dosing and withdrawal periods, and tissues were collected at necropsy. Serum swainsonine concentrations were determined using an alpha-mannosidase inhibition assay. Swainsonine concentrations in skeletal muscle, heart, brain, and serum were similar at approximately 250 ng/g. Clearance from these tissues was also similar, with half-lives (T(1/2)) of less than 20 h. Swainsonine at more than 2,000 ng/g, was detected in the liver, spleen, kidney, and pancreas. Clearance from liver, kidney, and pancreas was about T(1/2) 60 h. These findings imply that poisoned sheep have significant tissue swainsonine concentrations and animals exposed to locoweed should be withheld from slaughter for at least 25 d (10 T(1/2)) to ensure that the locoweed toxin has cleared from animal tissues and products.