Foothill death camas [Zigadenus paniculatus; or Toxicoscordion paniculatum] is one of about 15 death camas species in North America that is poisonous to grazing livestock. The major toxins in death camas are zygadenine and zygacine, the 3-acetyl ester of zygadenine. However, during plant flower to seed pod growth stages, 3-angeloylzygadenine and 3-veratroylzygadenine become major alkaloids in these reproductive tissues. We hypothesized that 3-angeloylzygadenine, and 3-veratroylzygadenine would be metabolized by esterases in liver, plasma, and rumen to zygadenine. Three death camas alkaloids, zygacine (as a positive control), 3-angeloylzygadenine, and 3-veratroylzygadenine were evaluated with in vitro rumen, plasma and liver S9 incubations. Results from these experiments indicated that 3-veratroylzygadenine was metabolized but not 3-angeloylzygadenine. To confirm the in vitro metabolism results, sheep were orally dosed death camas plant material containing only the reproductive parts of the plants, blood was collected by venipuncture, and alkaloid concentrations measured. The metabolism of 3-veratroylzygadenine but not 3-angeloylzygadenine was confirmed with the in vivo sheep dosing experiments, and we accepted our esterase metabolism hypothesis for 3-veratroylzygadenine.

The alkaloids swainsonine and calystegines are found in some Ipomoea species. Swainsonine is a potent cellular glycosidase inhibitor that often poisons livestock while the calystegines inhibit cellular glycosides and can cause cellular glycoside dysfunction. The role of the calystegines in a livestock model is lacking as no studies to date have experimentally dosed calystegines alone in livestock. The objective of this study was to directly compare goats dosed with Ipomoea carnea containing both swainsonine and calystegines and I. carnea containing only the calystegines. Three groups of four goats were treated with ground alfalfa (control), I. carnea containing both swainsonine and calystegines or I. carnea containing only the calystegines, for 45 days. Animals were observed daily; body weights, serum biochemistries, and serum swainsonine concentrations were determined weekly. On day 45, all animals were euthanized and necropsied. Goats treated with I. carnea containing only the calystegines showed no changes in clinical disease, serum biochemistries, and histologic lesions while goats treated with swainsonine and the calystegines developed clinical disease and showed changes in serum biochemistries and histologic lesions characteristic of animals poisoned by other plants containing swainsonine. The data suggests that the calystegines play no role in field cases or experimental studies for plants containing swainsonine and the calystegines. Swainsonine is the principal driver of toxicity in plants containing both these toxins.

Larkspurs (Delphinium spp.) are one of the most problematic plants for cattle producers in North America. Previous research has shown that there is a difference in the alkaloid composition between different species of larkspurs, and between different populations of the same species. Differences in the chemical profiles of the various larkspurs and their associated toxicities in rodent models and in cattle have been documented. However, different methods were used to analyze the plant material and to characterize its toxicity. In this study, plant material from 20 larkspur collections was extracted using the same method and analyzed using the same liquid chromatography-mass spectrometry method, and the acute toxicity of each extract was tested using a mouse median lethal dose assay with the same strain of mice purchased from one vendor. The results from this study demonstrate the large variations in alkaloid composition and concentrations between the various species and populations of larkspurs in the western USA. The data also demonstrate a strong correlation between the N-(methylsuccinimido) anthranoyllycoctonine alkaloid content of the plant and its toxicity in a mouse model. The results from this study provide a standardized comparison of the risk of some of the more common and problematic larkspurs in the western USA.

Prepared and stored feeds, fodder, silage, and hay may be contaminated by toxic plants resulting in the loss of livestock. Several poisonous plants have played significant roles in livestock deaths from forage consumption in recent years in the Western United States including Salvia reflexa. Metagenomic data, genome skims and metabarcodes, have been used for identification and characterization of plants in complex botanical matrices including diet composition of animals, mixed forages, and herbal products. Here, chemistry, genome skims, and metabarcoding were used to retrospectively describe the composition of contaminated alfalfa hay from a case of Salvia reflexa (lanceleaf sage) poisoning that killed 165 cattle. Genome skims and metabarcoding provided similar estimates of the relative abundance of the Salvia in the hay samples when compared to chemical methods. Additionally, genome skims and metabarcoding provided similar estimates of species composition in the contaminated hay and rumen contents of poisoned animals. The data demonstrate that genome skims and DNA metabarcoding may provide useful tools for plant poisoning investigations.

Cannabis sativa (varieties for industrial use or animal feed are termed hemp), and its extracted byproducts are being considered for animal feed due to their high protein content. However, if hemp disrupts fertility and reproduction in livestock, it should not be used as a feed source. We hypothesized that the phytocannabinoids in hemp would disrupt fertility and reproduction, cause craniofacial defects (cyclops, cleft palate, misshapen head), and low birth weight in lambs. To test this hypothesis, 22 timed pregnant ewes were dosed with hemp in the form of dried ground hemp plant material at 150 mg/kg body weight per day total cannabinoids, and from gestational days 10 to 20 and a separate 22 timed pregnant ewes were dosed similarly with dried ground grass hay as a control. The most prevalent cannabinoids in the plant material were cannabidiolic acid (CBDA) at a concentration of 23.2 mg/g, and cannabidiol (CBD) at a concentration of 5.8 mg/g. Delta 9-tetrahydrocannabidiol was present in the plant material at a concentration of 0.3 mg/g. The hemp used in this study had crude protein concentrations of 15.6%, neutral detergent fiber concentrations of 42.2%, and in vitro true digestibility concentrations of 83.6%. After 10 d of dosing with hemp, a serum sample was obtained from each of the ewes, CBDA was measured at a concentration of 652 ± 38 ng/mL and CBD was measured at 16 ± 0.9 ng/mL. THC was not detected in the serum. The average gestation length for lambs from the hemp treated ewes was 148 ± 0.38 d, and the average gestation length for lambs from the grass hay treated ewes was 149 ± 0.38 d (P = 0.23). The numbers of male and female lambs did not significantly vary from expected (50:50) (P = 0.32). There were no significant fetal deformities (P > 0.05) or weight differences between the treatment groups (P > 0.05), and as expected, the lamb weights significantly increased over time (P < 0.05). These results suggest that Cannabis sativa may have the potential with further research to be a suitable protein source for gestating sheep.

Geyer larkspur is a native perennial forb that is toxic to cattle. Herbicide control of Geyer larkspur is variable and depends on the growth stage of the plant when the herbicide is applied. The objectives of this study were to 1) evaluate aminopyralid, aminopyralid + florpyrauxifen-benzyl, aminopyralid + 2,4-D, aminopyralid + metsulfuron-methyl, metsulfuron-methyl, triclopyr, and triclopyr + 2,4-D for efficacy in controlling Geyer larkspur; 2) determine whether plant growth stage (vegetative or flowering) at the time of herbicide application influences herbicide effectiveness; and 3) determine whether herbicide treatment alters the norditerpenoid alkaloid content of Geyer larkspur. Plots were established in eastern Wyoming in 2021 and northern Colorado in 2022. Herbicide application at the different phenological stages did not affect Geyer larkspur density at the Wyoming site (P = 0.1065; data not shown). Geyer larkspur density at the Wyoming site was reduced by all herbicide treatments 1 yr after treatment (YAT) at the vegetative stage and by all herbicides except triclopyr 2 YAT (P = 0.0249). Geyer larkspur density at the flowering stage was reduced by all herbicides except metsulfuron-methyl, triclopyr, and triclopyr + 2,4-D at 1 YAT and by triclopyr and triclopyr + 2,4-D at 2 YAT. In contrast, there were no differences in Geyer larkspur density across treatments at the Colorado site (P = 0.9621). Precipitation was below average several months prior to herbicide application, which may have affected herbicide effectiveness. The metsulfuron-methyl treatment resulted in the highest total alkaloid concentrations of Geyer larkspur at the vegetative stage and the lowest concentrations at the flowering stage at the Wyoming site. Efforts to control Geyer larkspur in semiarid rangelands can be effectively accomplished by applying aminopyralid herbicides at either the vegetative or flowering growth stage provided environmental conditions prior to herbicide application are sufficient for plant growth and uptake of the herbicide.

Evidence-based therapies to manage the clinical signs of intoxication caused by toxic plants in livestock are lacking. For that reason, the aim of this work was to develop a drug-based intervention for the management of clinical signs of piperidine alkaloid intoxication in livestock. The actions of anabasine, coniine, gamma-coniceine, and two total alkaloid extracts from Lupinus sulphureus were compared in the presence and absence of the nicotinic acetylcholine receptor partial agonist varenicline in RD cells, mice and goats. Pretreatment of RD cells with 10.0 mu M varenicline significantly shifted the anabasine fifty percent effective concentration (EC50) value to a greater concentration and blocked the response of the cells to coniine. gamma-coniceine did not have any effect on RD cells as measured by membrane potential sensing dye. Swiss Webster mice median lethal dose (LD50) values for anabasine, coniine, gamma-coniceine were 1.5, 5.5, and 3.7 mg/kg respectively, and pretreatment with 10.0 mg/kg i. p. dosed varenicline shifted the LD50 values to 4.2, 9.1, and 4.3 mg/kg respectively. The rodent LD50 value of the Pendelton, WA L. sulphureus quinolizidine alkaloid extract was shifted to a lesser concentration by varenicline while the Ritzville, WA L. sulphureus piperidine alkaloid extract was shifted to a greater concentration by varenicline. The clinical signs of intoxication in goats orally dosed with Conium maculatum were exacerbated by 0.5, 1.0 and 10.0 mg/kg i. v. dosed varenicline. These results suggest that varenicline was effective at shifting piperidine alkaloid EC50 values in RD cells and increasing piperidine but not quinolizidine alkaloid LD50 values in mice and was not useful at managing the clinical signs of poison hemlock intoxication in goats.

Death Camas (Zigadenus spp.) are common poisonous plants distributed throughout North America. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. Both cattle and sheep can be poisoned by grazing death camas, however, sheep consume death camas more readily and are most often poisoned. We hypothesized that the presence of enzymes, including esterases present in the rumen, liver, and blood of livestock would metabolize zygacine. The objective of this study was to investigate the metabolism of zygacine in sheep and cattle using in-vitro and in-vivo systems. Results from experiments where zygacine was incubated in rumen culture, plasma, liver S9 fractions, and liver microsomes and from the analysis of rumen and sera from sheep and cattle dosed death camas plant material demonstrated that zygacine is metabolized to zygadenine in the rumen, liver and blood of sheep and cattle. The results from this study indicate that diagnosticians should analyze for zygadenine, and not zygacine, in the rumen and sera for the diagnosis of livestock suspected to have been poisoned by foothill death camas.

Foothill death camas (Zigadenus paniculatus) is a common poisonous plant found throughout western North America. The toxic alkaloids in foothill death camas are zygadenine, esters of zygadenine, with zygacine, the 3-acetyl ester of zygadenine, often being the most abundant. Two additional esters of zygadenine that are found primarily in the floral parts of foothill death camas are 3-angeloylzygadenine and 3-veratroylzygadeine. Recent research has shown that very little zygacine is detected in the blood of animals dosed with zygacine. A recent investigation into the metabolism of zygacine demonstrated that zygacine is rapidly metabolized to zygadenine, demonstrating a clear first pass effect. The objective of this study was to determine if there is a difference in the acute toxicity of zygacine and zygadenine to mice and sheep. Additionally, two other esters of zygadenine, 3-angeloylzygadenine and 3-veratroylzygadenine, were evaluated for their acute toxicity in a mouse IV LD50 assay. All three esters of zygadenine tested were more toxic than zygadenine, with the following rank order of toxicity in the mouse IV LD50 assay: zygadenine-HCl (59.5 mg/kg) < zygacine-HCl (1.6 mg/kg) < angeloylzygadenine-HCl (1.0 mg/kg) < veratroylzygadenine-HCl (0.5 mg/kg). Similar to the results of the mouse experiments, zygacine-HCl was significantly more toxic than zygadenine-HCl in sheep dosed IV with pure compounds. Sheep dosed with 1.25 mg/kg zygacine-HCl showed severe clinical signs of poisoning. Whereas a dose of 12.5 mg/kg zygadenine-HCl was required to elicit a similar onset and severity of clinical signs. Overall, these data indicate that zygacine is more toxic than zygadenine when administered IV, when first pass metabolism is bypassed.

Lupines are responsible for a condition in cattle referred to as "crooked calf syndrome" (CCS) that occurs when pregnant cattle graze teratogenic lupines. A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to determine if an intermittent schedule of ten continuous days of lupine treatment followed by 5 d off treatment would be sufficient to decrease, or prevent, the incidence of lupine-induced malformations. Continuous dosing of the teratogenic lupine (Lupinus leucophyllus) to pregnant cows for 30 d during the most susceptible stage of pregnancy (gestation days 40 to 70) resulted in severe skeletal birth defects in their calves. However, intermittent dosing of the teratogenic lupine demonstrated that interrupted intake of lupine reduced the severity, or eliminated, permanent skeletal malformations in calves born to cows dosed lupine. Toxicokinetic and ultrasound data demonstrated a clear inverse correlation between serum anagyrine (the primary teratogenic alkaloid in some lupines) concentrations in the dam and fetal movement. In the intermittent group, fetal movement quickly returned to normal after lupine feeding stopped and remained normal until lupine treatment resumed. Therefore, interrupting lupine intake for at least 5 d through an intermittent grazing program could reduce the severity of the CCS. Furthermore, this method would allow ranchers to move cattle back into lupine pastures after a brief interruption, which would allow for more efficient utilization of forage resources. An intermittent lupine dosing regimen in pregnant cattle of 10 d on, 5 d off, significantly prevents skeletal malformations from occurring. Therefore, a grazing rotation that results in intermittent exposure to teratogenic lupines can reduce the occurrence of crooked calf syndrome. Lupines are responsible for a condition in cattle referred to as "crooked calf syndrome" (CCS) that occurs when pregnant cattle graze teratogenic lupines. A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to determine if an intermittent schedule of ten continuous days on lupine treatment followed by 5 d off treatment would be sufficient to decrease, or prevent, the incidence of lupine-induced malformations. The data reported in this study demonstrate that interrupting lupine intake for at least 5 d through an intermittent grazing program could reduce the severity of the CCS. Furthermore, this method would allow ranchers to move cattle back into lupine pastures after a brief interruption, which would allow for more efficient utilization of forage resources.

Lupines (Lupinus spp.) are a common plant species on western U.S. rangelands with several lupine species containing alkaloids that can be toxic and/or teratogenic to livestock. In North America, more than 150 lupine species are recognized with some ranches or grazing allotments containing multiple species. One or more of these lupine species may contain alkaloids that are teratogenic to cattle. Previous work has shown that lupine alkaloids can be detected in earwax of cattle grazing lupine infested rangelands. Our hypothesis is that earwax can be used to determine if cattle have been exposed to teratogenic alkaloids from multiple lupine species. Two lupine species, L. sericeus and L. polyphyllus, were present on a rangeland in east-central Idaho. The teratogen, anagyrine, was detected in L. sericeus and the teratogen, ammodendrine, was detected in L. polyphyllus plants collected on this rangeland. In this study, earwax was collected from 69 pregnant cows that had previously grazed a rangeland containing two different lupine species containing alkaloids that cause crooked calf syndrome (CCS). Anagyrine was detected in the earwax of all 69 cows sampled. Ammodendrine, was detected in the earwax of 28 of the 69 cows sampled. Earwax is a good non-invasive sample to aid in the diagnosis of cattle that have consumed lupine and does appear, in this case, to be a good diagnostic tool to differentiate between more than one lupine species that may be the cause of CCS. Concentrations of anagyrine or ammodendrine did not correlate with the incidence of CCS.

Foothill death camas (Z. paniculatus) grows on the foothill ranges of western North America and is acutely toxic to livestock grazing these ranges. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. In this study, earwax was evaluated as a specimen to determine livestock exposure to foothill death camas. Death camas alkaloids were detected in the earwax of sheep administered oral doses of foothill death camas alkaloids. In addition, death camas alkaloids were detected in the earwax of sheep that grazed rangeland with abundant death camas. This study demonstrates the potential of earwax as a noninvasive specimen for chemical analyses to aid in the diagnosis of livestock that may have been exposed to and poisoned by death camas. The results from this study indicate that diagnosticians should analyze for zygacine and zygadenine in the earwax of livestock suspected to have been poisoned by foothill death camas.

Due to climate change and increasing summer temperatures, tropical cattle may graze where temperate cattle have grazed, exposing tropical cattle to toxic plants they may be unfamiliar with. This work compared the toxicity of Lupinus leucophyllus (velvet lupine) in temperate and tropical cattle. Orally dosed velvet lupine in tropical cattle caused death. If producers opt to graze tropical cattle, additional care must be taken on rangelands where toxic lupines like velvet lupine grow.

Salvia reflexa is an annual forb that has recently (2021) been reported to contaminate hay and cause fatal hepatotoxicity in cattle. It is possible that prior poisoning cases may have gone unrecognized due to the lack of information on fatal hepatotoxicity caused by S. reflexa. Two cases are reported. Case 1 occurred in December 2001 in Montana, in which 30 cows died out of 105. Case 2 occurred in 2023 in Wyoming, in which 111 cows out of 155 died. Poisoned cows in both cases had elevated aspartate aminotransferase and alkaline phosphatase activities with microscopic severe acute centrilobular necrosis with hemorrhage. These lesions were similar to those described previously in clinical and experimental S. reflexa trials. Hepatotoxic diterpenes of S. reflexa, salviarin and rhyacophiline, were detected in hay samples in both cases and in rumen contents from animals in Case 2. Plant specimens of S. reflexa were collected from 2 herbaria, representing collections from 12 states, and screened for salviarin and rhyacophiline. The S. reflexa toxins were found in herbarium samples suggesting if S. reflexa is present, it is potentially toxic to cattle.

The United States National Cancer Institute defines a biomarker as: "A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease." In Veterinary Medicine, biomarkers associated with plant poisonings of livestock have great utility. Since grazing livestock poisoned by toxic plants are often found dead, biomarkers of plant poisoning allow for a more rapid postmortem diagnosis and response to prevent further deaths. The presence and concentration of toxins in poisonous plants are biomarkers of risk for livestock poisoning that can be measured by the chemical analysis of plant material. More difficult is, the detection of plant toxins or biomarkers in biological samples from intoxicated or deceased animals. The purpose of this article is to review potential biomarkers of plant poisoning in grazing livestock in the Western North America including recently investigated non-invasive sampling techniques. Plants discussed include larkspur, lupine, water hemlock, swainsonine-containing plants, selenium-containing plants, and pyrrolizidine alkaloid containing plants. Other factors such as animal age and sex that affect plant biomarker concentrations in vivo are also discussed.

Objective: The objectives of this study were to evaluate (1) whether a reduction in basal diet intake occurs due to larkspur consumption, (2) how long it takes for animals to resume, to baseline, intake levels, and (3) whether there is a dose-dependent reduction of dietary intake by animals given an oral bolus dose of larkspur. Materials and Methods: Sixteen Angus heifers were housed in individual pens. Four animals were assigned to 1 of 4 treatment groups in a replicated 4 x 4 Latin square experimental design with 14-d periods consisting of a 6-d baseline period to measure feed intake and 8 d of sample and data collection. Heifers were fed once daily starting at 2.5% of BW and each subsequent day at 5% above previous day intake. On d 7, cattle were given an oral dose of a standardized amount of N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids in the form of dried ground larkspur (Delphinium barbeyi) at 1 of 3 doses: high, medium, or low, at 8, 6, and 4 mg of MSAL-type alkaloids/kg of BW, respectively, or a control of ground alfalfa hay. Results and Discussion: There was a dose-dependent reduction of intake, with the medium treatment intake of basal diet reduced for 1 d after dosing. Animals on the high treatment reduced basal diet intake for 2 d after dosing. Implications and Applications: These results indibasal diet intakes, and it can take 2 to 3 d for animals to return to normal intake.

A novel process is described for the synthesis of di- and trisubstituted cyclohexenes from an arene. These compounds are prepared from three independent nucleophilic addition reactions to a phenyl sulfone (PhSO2R; R = Me, Ph, and NC4H8) dihapto-coordinated to the tungsten complex {WTp(NO)(PMe3)}(Tp = trispyrazolylborate). Such a coordination renders the dearomatized aryl ring susceptible to protonation at a carbon ortho to the sulfone group. The resulting arenium species readily reacts with the first nucleophile to form a dihapto-coordinated sulfonylated diene complex. This complex can again be protonated, and the subsequent nucleophilic addition forms a trisubstituted cyclohexene species bearing a sulfonyl group at an allylic position. Loss of the sulfinate anion forms a π-allyl species, to which a third nucleophile can be added. The trisubstituted cyclohexene can then be oxidatively decomplexed, either before or after substitution of the sulfonyl group. Nucleophiles employed include masked enolates, cyanide, amines, amides, and hydride, with all three additions occurring to the same face of the ring, anti to the metal. Of the 12 novel functionalized cyclohexenes prepared as examples of this methodology, nine compounds meet five independent criteria for evaluating drug likeliness. Structural assignments are supported with nine crystal structures, density functional theory studies, and full 2D NMR analysis.

A critical mediator of evolution is natural selection, which operates by the divergent reproductive success of individuals and results in conformity of an organism with its environment. Reproductive function has evolved to support germline transmission. In mammalian ovaries, this requires healthy, active gonad function, and follicle development. However, healthy follicles do not contribute to germline transmission in a dead animal. Therefore, support of the health and survival of the organism, in addition to fertility, must be considered as an integral part of reproductive function. Reproductive and chronological aging both impose a burden on health and increase disease rates. Tremors are a common movement disorder and are often correlated with increasing age. Muscle quality is diminished with age and these declines are gender-specific and are influenced by menopause. In the current experiments, we evaluated aging-associated and reproduction-influenced changes in motor function, utilizing changes in tremor amplitude and grip strength. Tremor amplitude was increased with aging in normal female mice. This increase in tremor amplitude was prevented in aged female mice that received ovarian tissue transplants, both in mice that received germ cell-containing or germ cell-depleted ovarian tissue. Grip strength was decreased with aging in normal female mice. This decrease in grip strength was prevented in aged female mice that received either germ cell-containing or germ cell-depleted tissue transplants. As expected, estradiol levels decreased with aging in normal female mice. Estradiol levels did not change with exposure to young ovarian tissues/cells. Surprisingly, estradiol levels were not increased in aged females that received ovaries from actively cycling, young donors. Overall, tremor amplitude and grip strength were negatively influenced by aging and positively influenced by exposure to young ovarian tissues/cells in aged female mice, and this positive influence was independent of ovarian germ cells and estradiol levels. These findings provide a strong incentive for further investigation of the influence of ovarian somatic tissue on health. In addition, changes in tremor amplitude may serve as an additional marker of biological age.

Larkspurs (Delphinium spp.) are native forbs that are poisonous to cattle and cost livestock producers millions of dollars in losses each year. Macro and micro minerals are required for normal functioning of essentially all metabolic processes in ruminants. The role that mineral status may play in larkspur poisoning in cattle is not clear. In this study, we seek to determine the effects a mineral-salt supplement, commonly used by cattle producers, to potentially reduce cattle losses to larkspur. The ability of mineral-salt supplementation to alter susceptibility to larkspur toxicosis was evaluated in a pen study. Animals supplemented with mineral-salt were found to be less susceptible to larkspur poisoning than the non-supplemented animals. A separate group of animals were then grazed on larkspur infested rangelands. One group was supplemented with a mineral-salt mix and the other group did not receive any mineral-salt. Supplementing cattle with the mineral-salt mix did not alter larkspur consumption (P > 0.05). However, overall larkspur consumption was low and averaged 3 ± 1.0% and 2 ± 1.1% for cattle supplemented with mineral and non-supplemented, respectively. Serum was collected from animals once a week during the grazing study. Average and maximum serum concentrations of toxic larkspur alkaloids were numerically higher in mineral-salt supplemented cattle compared with the non-supplemented animals. Results from the pen study suggest that a good mineral supplementation program will provide a protective effect for animals grazing in larkspur-infested ranges. The mineral-salt supplemented steers, in the grazing study, were not observed to consume less larkspur than the non-supplemented animals; however, the mineral-salt supplemented animals had higher concentrations of larkspur alkaloids in their serum indicating they may be able to tolerate higher larkspur consumption. The data also indicate that mineral-salt supplementation must be continuous throughout the time the animals are grazing these rangelands as the positive effects can be lost within 30 d post supplementation.