Location: Poisonous Plant Research2015 Annual Report
Objective 1: Develop and implement novel management protocols for establishing improved forage species on sites infested with known poisonous plants to reduce the risk of livestock mortality and morbidity, improve livestock performance, and improve rangeland resiliency and diversity. Specifically, develop science-based guidelines for grazing livestock on rangelands infested with Lupinus, Senecio, Delphinium and swainsonine and selenium-containing plants. Objective 2: Reduce the risks of livestock losses due to variations in quantitative and qualitative differences in toxin accumulation over time and plant species by quantifying the influence of endophytes, climate changes, and genotype on plant toxin accumulation (particularly swainsonine-containing plants and Delphinium and Lupinus species). Objective 3: Enhance feed and food safety by improving risk assessment and diagnosis of plant-induced poisoning to livestock by improving analytical methods for analyzing plant and animal tissues for toxins; measuring toxicokinetics, assessing carcinogenic and genotoxic potential, and identifying toxin metabolites and biomarkers of toxicoses. Objective 4: Develop improved procedures with guidelines for diagnostic and prognostic evaluation to reduce negative impacts of poisonous plants on livestock reproduction and embryo/fetal growth by improving early identification of poisoned animals, predicting poisoning outcomes, and management and treatment options through improved understanding of clinical, morphological and molecular alterations of plant-induced toxicosis. Objective 5: Develop guidelines to aid producers and land managers in making genetic-based herd management decisions to improve livestock performance and safety on grazed rangelands infested with poisonous plants through the use of identified animal genes, physiological pathways, and molecular mechanisms of action that underlie Conium, Cicuta, Delphinium, Lupinus, and Nicotiana, and other neurotoxic plant effects.
Livestock poisoning by plants results in over $503,000,000 lost to the livestock industry annually in the 17 western United States from death losses and abortions alone (Holechek, 2002). Plant poisonings extend worldwide to include 333 million poisonous plant-infested hectares in China and 60 million hectares in the central western region of Brazil, to name a few. There are over 6,000 species of pyrrolizidine alkaloid (PA)-containing plants, and over 350 individual PAs causing diseases in animals and humans have been identified. Economic losses are much larger as significant amounts of nutritious forage are wasted and management costs are increased due to the threat of toxic plant-related livestock losses. The Poisonous Plant Research Laboratory (PPRL) has provided worldwide leadership in poisonous plant research to the livestock industry and consumers including numerous solutions to toxic plant problems using an integrated, interdisciplinary approach (see Figure below). The research team investigates plant poisonings in a systematic matter by identifying the plant, describing the effects in animals, determining the toxin(s) and evaluating the mechanisms of action. The ultimate goal is to develop research-based solutions to reduce livestock losses from toxic plants. There are five coordinated objectives in this project plan providing guidelines for potential genetic-based management. This research will reduce livestock losses from plants and enhance the economic well-being of rural communities, improve rangeland health by combating invasive plant species, and help to provide safe animal products free from potential plant toxins for consumers.
Poisonous plants continue to cause significant economic loss to the livestock industry and negatively impact the nearby rural communities and regions. Losses include direct death losses, birth defects in offspring, reduced reproductive performance, lost production capacity, increased management costs, lost forage value and lost opportunities. Toxins from poisonous plants may contaminate food supplies resulting in health risks to the human population. ARS researchers at the Poisonous Plant Research Lab (PPRL) in Logan, Utah, continue to perform interdisciplinary research through a concerted team approach to provide new information and tools for livestock producers and land managers to mitigate poisonous plant losses. Five objectives have been defined in the project plan beginning with plant identification, progressing through chemical analysis and characterization of secondary compounds, to toxicology and pharmacology of toxins, description of the etiology of plant poisoning, diagnosis and prognosis of poisoning and finally to develop strategies and management approaches for livestock producers to reduce losses. Evaluation of improved rangeland grass species and forage Kochia varieties seeded and established into research, demonstration and ranch scale plots on the channeled scablands of east central Washington State continues. The most successful species include Vavilov II (an improved Siberian wheat grass), Hycrest (an improved crested wheat grass), Sherman Big Blue (a native grass) and two forage Kochia varieties (Immigrant and Sahro). After 4 years these species show the most promise to establish and persist, providing the potential to improve forage quality while successfully competing with cheat grass, medusahead rye and poisonous plants. Plots were recently grazed by cattle and data suggest these selected species and varieties have great potential to improve the rangelands in this harsh environment. Last year two ranchers initiated larger scale plantings on their respective ranches using the technology provided by ARS researchers. One rancher seeded a quarter section of rangeland and has put into place a 5 year plan to reseed his entire ranch using this information and technology. Locoweed seedlings were treated with different fungicides to evaluate the effects on swainsonine production by the endophyte and to determine if swainsonine levels could be reduced to lower the risk of locoweed poisoning from these otherwise nutritious plants. Data analysis was completed on the effects of elevated CO2 levels on locoweed growth and swainsonine concentrations. Additional progress has been made on elucidating the biosynthetic pathway of swainsonine. This research is in collaboration with scientists at the University of Kentucky and New Mexico State University. Genome sequencing of two swainsonine producing fungal endophytes continues and ARS scientists in collaboration with researchers at Indiana University have identified several Convolvulaceae taxa species that contain swainsonine. Recent cattle and sheep losses have been reported after grazing forages growing on seleniferous soils. Pen studies were conducted to determine the effects of high selenium in the diet on reproductive performance. Feeding trials to compare the effects of high selenium in the diet on feed preferences in sheep, cattle and elk and to determine the rate of absorption and elimination of different chemical forms of selenium were completed and published. Tremetone was reported to be the toxin in rayless goldenrod in the Southwest and white snakeroot in the Midwest since the 1900's. Chemical studies have isolated and characterized numerous benzofuran ketones (BFK) including tremetone from these plants. Subsequent animal studies suggest that tremetone is not the primary toxin. It is likely that other benzofuran ketones act together with tremetone to cause toxicity. ARS scientists at PPRL are using different animal models and chemical extraction techniques to determine the active principle in these plants. Numerous plant populations from different geographical locations with variable BFK concentrations are being evaluated to determine why poisoning in animals occurs in some locations while the same or similar plant species in another location may not cause poisoning. Larkspur specific primers have been developed and validated for diagnostic purposes to assist veterinarians in identifying the cause of plant associated death losses in cattle. Initial research using PCR-based methods to detect larkspur in rumen cultures and in the rumens of live cannulated cows shows promise. Analytical methods developed by ARS scientists at Logan, Utah, were used to detect pyrrolizidine alkaloids (PAs) in contaminated food and feed supplies. We determined that a traditional Peruvian herbal tea that is available internationally contains toxic levels of the dehydropyrrolizidine alkaloids (DHPAs) and is a risk to cause liver disease in people. An aquatic plant (Senegal tea) that produces toxic DHPAs suggests a potential risk of water contamination for humans and animals. We continue to monitor subsistence grain supplies from the Tigray region of Ethiopia, honey and pollen samples from the islands of Hawaii and contaminated chicken feed from Colombia. The analytical methods for detection of DHPA metabolites in liver and blood from diagnostic samples were significantly improved and are being used to investigate the relative toxicity of individual alkaloids in cell culture and small animal models. Further progress has been made on the National Institute of Health (NIH) funded DHPA research including large scale isolation and purification of epimeric lycopsamine and intermedine and synthesis and purification of their N-oxides. Analytical methods to screen herbal products for PAs have been completed. Echimidine was isolated from Echium vulgare and purified and the N-oxide synthesized. Three separate commercial samples of butterbur root powder (Petasites spp.), an herbal remedy, were screened for PAs and one contained two DHPAs. Collaborative research with a scientist funded through the Department of Defense was completed and research results published, including histologic evaluation of DHPA carcinogenicity studies in P53 heterozygous mice. Both acute exposures and chronic low dose exposure to riddelliine caused increased incidence of PA-induced neoplasms. The neoplasm type differed by exposure, i.e. chronic low dose exposures produced hepatic vascular neoplasms while acute high dose exposures produced neoplasms outside the hepatic vasculature. This suggests that any PA exposure can increase the incidence of PA-related carcinogenesis. Research using cell cultures and chick models to better document PA toxicity and correlate that toxicity to their carcinogenicity continues, and specific PAs have been ranked according to their toxicity to cells. Four PAs—lasiocarpine, seneciphylline, senecionine and heliotrine—are more toxic than riddelliine. Twenty purified DHPAs from different plant sources have been evaluated and ranked relative to their toxicity using cell culture models and highly sensitive chick models. Studies to evaluate the carcinogenic potential of most toxic alkaloids in a mouse P-53 model have begun. Analyses to detect DHPA metabolites or adducts in tissues have been refined. We found that riddelliine consistently produces nearly 10 times more adducts than the other alkaloids in our chick model. How these adducts are involved in riddelliine-induced carcinogenesis remains to be determined. Locoweed poisoning was studied in numerous animal models and ARS scientists found that huge differences in sensitivity, disease progression, lesions and lesion distribution exist between animal species. Recent research indicates this is largely due to swainsonine's affinity to a species' mannosidase enzymes. Additional comparisons of mannosidase expression in tissues and correlation of that expression with lesion development continue. Dose response studies of swainsonine poisoning have been completed in goats and initial results suggest goat susceptibility is similar to that of cows and sheep. Comparative studies of species specific locoweed-induced ophthalmic lesions have been completed and are being prepared for publication. We found that locoweed related changes in vision are due to neurological lesions in the brain and not lesions in the eye. Additional progress and new information to aid livestock producers and land managers in making genetic-based grazing decisions to improve livestock performance and safety on grazed rangelands infested with poisonous plants has been completed. Results from genome sequencing experiments have calculated that cattle susceptibility to larkspur is 90% heritable and one-third of the heritability can be attributed to a single candidate gene. Animal genes, physiological pathways, and molecular mechanisms of action that underlie the effects of neurotoxic plants such as lupine, larkspurs, and poison hemlock have been identified. Five cattle breeds have been tested and resistant and sensitive animals identified in all 5 breeds. The current focus is to identify individuals in the Angus breed from multiple ranches, test these animals for sensitivity to the neurotoxins and associate responses with the gene marker(s). Studies were completed and published regarding the co-exposure of cattle to death camas and low larkspur. Evaluation of the chemistry of juniper bark and needles from young and mature trees determined that there are no differences in the concentration of the abortifacient compounds between young and mature western juniper trees. Samples of bark and needles have been collected bi-monthly for two years to evaluate seasonal variations in the abortifacient compounds in western juniper trees. Recent studies determined that consumption of western juniper bark does not affect the estrous cycle in beef cattle.
1. A biomarker to identify cattle resistant to poisoning by neurotoxic plants. ARS scientists from Logan, Utah, and Clay Center, Nebraska, used a large DNA assay to identify genes for resistance to larkspur poisoning from five breeds of cattle. The ARS scientists identified a gene region that is associated with larkspur resistance. The research team then tested DNA from 32 Angus cattle to identify further genetic variation associated with larkspur resistance. Results from these experiments suggest that cattle resistance to larkspur is highly heritable and can be attributed to one or two gene regions. These experiments will allow us to work towards development of commercially available DNA markers for larkspur tolerance in cattle. This information will benefit ranchers in regions where larkspur and other neurotoxic plants infest the rangelands and will allow producers to make genetic-based grazing decisions to select replacement heifers and bulls for resistance and reduce cattle losses.
2. Rangeland improvements on the channeled scablands. ARS scientists at Logan, Utah, seeded research plots, demonstration plots and ranch scale plots on the channeled scablands of east central Washington to determine if improved perennial grasses and selected forbs could be established on this harsh landscape and if these improvements would out-compete annual grasses and ultimately reduce the utilization of lupine to mitigate the impact of lupine-induced "crooked calf syndrome" in this region. Over the last 4 years, ARS scientists demonstrated that improved perennial grasses and forage Kochia could be established and they have persisted in the research plots and demonstration plots. These improved species have also prevented the reinvasion of annual grasses in these plots. The improved grasses include Hycrest II, Vavilov II, Bozoisky II, and Sherman Big bluegrass (a native) and immigrant forage Kochia. This technology has now been expanded to ranch scale plots and two ranchers have put into place long range plans to improve their entire ranches using this information. This research has the potential to transform the severely degraded rangelands in east central Washington to a sustainable and productive ecosystem for livestock and wildlife.
3. Relative risk of Ipomoea carnea to grazing livestock on an annual basis. Ipomoea carnea is known to cause a neurologic disease in grazing livestock in Brazil and other parts of the world. To better understand the relative toxicity and nutritional content of I. carnea, ARS researchers in Logan, Utah, and their Brazilian colleagues investigated the toxins swainsonine and calystegine and crude protein amounts in leaves of I. carnea on a monthly basis for a year in northern and northeastern Brazil. Swainsonine concentrations were detected at amounts that could potentially poison an animal throughout the year although there was some variation between months. Swainsonine concentrations were generally the highest during the rainy season or the months immediately following the rainy season at one location. Total calystegine amounts were similar to those reported previously while crude protein amounts are similar to those found in other Ipomoea species and are such that they may explain why I. carnea becomes desirable to grazing livestock as forage becomes limited during the dry season. Understanding swainsonine, calystegine, and protein concentrations in Ipomoea carnea on an annual basis may help make better management decisions to mitigate livestock losses.
4. Determination of the relative toxicity of different rayless goldenrod (Isocoma) species. Rayless goldenrod is toxic to livestock; similar species are also suspected to be toxic but their toxicity has never been scientifically demonstrated. ARS researchers in Logan, Utah, tested the relative toxicity of four Isocoma species in a recently developed goat model and determined that Isocoma pluriflora and Isocoma tenuisecta were toxic. Isocoma acradenia and Isocoma rusbyii were not toxic even though they contained significantly more of the benzofuran ketone compounds than Isocoma pluriflora. These results demonstrate that there is an additional compound(s) that contributes to, or is responsible for, the toxicity of the Isocoma spp.
5. Pyrrolizidine alkaloid (PA) carcinogenesis. Pyrrolizidine alkaloids (PAs) often contaminate feed, food, and medicinal or herbal products and can poison livestock, wildlife and humans. ARS scientists at Logan Utah, used cell culture and a sensitive chick model to determine the toxicity of four PAs. Research was published showing that riddelliine-induced tumors occurred most often in high-dose, short exposures and chronic, low-dose exposures. The type of tumor differed by exposure. This work indicates that any PA exposure may increase the incidence of PA-related liver cancer.
6. Evaluation of dehydropyrrolizidine alkaloids (DHPAs) in an herbal tea. ARS scientists at Logan, Utah, chemically evaluated "asmachilca", a Peruvian traditional herbal tea mixture. This herbal tea is commercially available throughout the world. Two previously undescribed major alkaloids in this herbal preparation were isolated and their structures identified. This research has significant health implications for people using herbal products.
7. Late term abortions in cattle ingesting juniper. Pinus and Juniperus spp. have been shown to cause late term abortions in cattle. ARS scientists at Logan, Utah, recently characterized the abortifacient effects of western juniper trees in cattle, demonstrating that bark and needles will cause late term abortions. Additionally, the effects of western juniper consumption on the estrous cycle in beef cattle were studied, with no adverse impact. ARS scientists also evaluated the variation in abortifacient compounds in western juniper trees across the state of Oregon as well as seasonal differences over multiple years. These results indicate that western juniper trees throughout their geographical distribution are a risk to cause late term abortions in cattle, however, there does not seem to be any adverse effect on the estrous cycle. This information is important to cattle producers who graze their cattle on rangelands where western juniper trees grow.
8. Transfer of rayless goldenrod (RGR) toxins into milk. Rayless goldenrod (Isocoma pluriflora) poisons livestock in the southwestern United States. The toxin has historically been thought to be tremetone. ARS scientists at Logan, Utah, have shown that tremetone is only one of several toxins in rayless goldenrod. These toxins are transferred through the milk of lactating goats and poison the nursing baby goats. This research is significant to cattle, horse, and goat breeders in the southwest where RGR grows and has implications for animal and human health.
9. Certain lupines reduce fetal movement in pregnant cattle. ARS scientists at Logan, Utah, determined that lupines contain toxins that will reduce fetal movement in pregnant heifers and there appears to be a breed difference in sensitivity. Pregnant Angus and Holstein heifers were fed the same amount of dried ground lupine. There were significant differences between the two breeds when fetal movement was monitored with ultrasound and there were differences in toxin levels in the blood that paralleled the lack of fetal activity. This information is helpful to cow calf producers, suggesting that there is the potential to make breed-based grazing decisions to select animals that are more resistant to lupines for grazing on pastures infested with toxic lupine species.
10. Detection of toxic plants in poisoned animals. Toxic plants are a significant cause of livestock losses worldwide. Correctly determining the causative agent responsible for the death of an animal whether by disease, poisonous plant, or other means is critical in developing strategies to prevent future losses. ARS researchers at Logan, Utah, are developing an alternative diagnostic tool to detect the genetic material from a specific plant within a complex matrix such as rumen (stomach) contents. A pair of primers specific to larkspur was developed; using these primers, a Polymerase Chain Reaction (PCR) product was detected in samples from in vivo, in vitro, and in vivo/in vitro coupled digestions of larkspur. Lastly, larkspur was detected in a matrix of ruminal material where the amount of larkspur was far less than what one would expect to find in the rumen contents of a poisoned animal. The PCR-based technique holds promise to diagnose larkspur and perhaps other toxic plant-caused losses.
11. Presence of toxic dehydropyrrolizidine alkaloids (DHPAs) in Senegal tea and comfrey. ARS scientists at Logan, Utah, determined that the aquatic plant Senegal tea produces potentially toxic DHPAs. This information on Senegal tea suggests there is a potential environmental threat and that it could be a health risk to humans and livestock from contaminated water sources. Four additional DHPAs and their N-oxides were identified in comfrey. This research provides valuable information and resources for other researchers and has significant implications for the division of dietary supplements at NIH and the herbal industry.
12. Consumption of larkspur pellets by cattle that are resistant or sensitive to toxicity. Consumption of larkspur alkaloids causes muscle weakness and collapse in cattle and may result in death. ARS scientists at Logan, Utah, conducted a study to quantify consumption of larkspur alkaloids and relate plant intake and clinical effects to blood alkaloid levels and beef cattle genetics. A 25% larkspur pellet was offered to all the cattle and while they readily ate the pellets the first day, they refused to eat any more pellets on subsequent days. The genetically sensitive cattle showed clinical signs while the genetically resistant cattle did not. Blood levels of the major larkspur alkaloid, methyllycaconitine (MLA), were measured and in the genetically susceptible animals was approximately 250 ng/mL, lower than the previously determined toxic threshold. This is the first in a series of studies using larkspur resistant and sensitive cattle that will provide important information for livestock producers and veterinarians regarding larkspur toxicosis and provide further information for genetic-based grazing decisions.
13. Evaluation of the N-oxide form of the locoweed toxin swainsonine. The N-oxide form of the locoweed toxin swainsonine has been reported to be present in locoweeds by previous qualitative analyses. ARS scientists in Logan, Utah, developed a new method for quantitative analysis of swainsonine N-oxide. This method uses a simple one step extraction process followed by a derivatization step and then analysis by liquid chromatography-mass spectrometry. This allows rapid screening of plants containing the locoweed toxin swainsonine in plant species found worldwide. This research is important for other scientists quantifying the toxins in plants containing N-oxides of swainsonine and will improve the screening of plants for poisoning potential.
14. Effect of larkspur ingestion in cattle over multiple days. Larkspurs are a major cause of cattle losses on western ranges in the U.S., especially on foothill and mountain rangelands. To simulate natural grazing conditions on the range, ARS scientists at Logan, Utah, performed multiple dose experiments over a period of days in order to determine the effect of repeated doses of larkspur in a controlled pen setting. The no adverse effect level was determined, which provides an approximation of how much plant can be safely consumed without adverse effects. Additionally, several dosing scenarios were modeled using computer software. These data provide a more detailed understanding of the amount of larkspur cattle can safely consume without becoming severely poisoned. This will be helpful for livestock owners to effectively manage their cattle in larkspur infested rangelands.
15. Relative toxicity of different larkspur species. Larkspurs (Delphinium spp.) are poisonous plants on rangelands throughout the western United States and Canada. ARS scientists at Logan, Utah, determined the alkaloid (toxin) composition of spiked larkspur and compared its toxicity in cattle to two tall larkspur species. The results indicate that predictions of larkspur toxicity can't be accurately made based on the ratio of one alkaloid type to another. Understanding the relative risk of each larkspur species is important to developing management strategies to mitigate livestock losses.
16. Carbon application to the soil reduces competition from medusahead. Medusahead is an invasive annual grass that decreases biological diversity, reduces livestock forage production, degrades ecological function of native plant communities, increases the frequency of wildfires on rangelands, and predisposes animals to ingest poisonous plants. ARS scientists at Logan, Utah established plots on two ranches located in Adams County in eastern Washington. Additional carbon (C) or nitrogen (N) was added to the soil to determine the effects of carbon nitrogen balance on suppression of medusahead populations to improve establishment and persistence of perennial grasses and forbs. Vegetation and soil will be monitored over two growing seasons. This technology will add another tool for the rancher to fight the invasion of annual grasses and improve rangeland conditions to enhance the economic viability of rural communities.
17. Comparative toxicity of water hemlock in animals. Water hemlock is considered one of the most toxic plants in North America. ARS scientists at Logan, Utah, demonstrated that tubers and green seed of water hemlock are very toxic whereas stalks, stems, leaves, flowers, and mature seeds are of low risk for poisoning. Chemical analysis demonstrated a direct correlation between the water hemlock toxins in the various plant parts and their toxicity. Furthermore, recent cell culture studies were performed to characterize the mechanism of action of the water hemlock toxins as well as to identify potential treatments, or antidotes. This information is useful for livestock producers and veterinarians as well as medical personnel who treat humans.
Colegate, S.M., Gardner, D.R., Betz, J.M., Panter, K.E. 2014. Semi-automated separation of the epimeric dehydropyrrolizidine alkaloids lycopsamine and intermedine: Preparation of their N-oxides and NMR comparison with diastereoisomeric rinderine and echinatine. Phytochemical Analysis. 25(5):429-38.
Goodman, L.E., Cibils, A.F., Lopez, S.C., Steiner, R.L., Graham, J.D., Mcdaniel, K.C., Abbott, L.B., Stegelmeier, B.L., Hallford, D.M. 2014. Targeted grazing of white locoweed: Short-term effects of herbivory regime on vegetation and sheep. Rangeland Ecology and Management. 67(6):680-92.
Field, R.A., Stegelmeier, B.L., Colegate, S.M., Brown, A.W., Green, B.T. 2015. An in vitro comparison of the cytotoxic potential of selected dehydropyrrolizidine alkaloids and some N-oxides. Toxicon. 97:36-45.
Cook, D., Pfister, J.A., Constantino, J., Roper, J.M., Gardner, D.R., Welch, K.D., Hammond, Z.J., Green, B.T. 2015. Development of a PCR-based method for detection of Delphinium species in poisoned cattle. Journal of Agricultural and Food Chemistry. 63:1120-1125.
Cook, D., Welch, K.D., Green, B.T., Gardner, D.R., Pfister, J.A., Constantino, J., Stonecipher, C.A. 2015. The relative toxicity of Delphinium stachydeum in mice and cattle. Toxicon. 99:36-43.
Welch, K.D., Panter, K.E., Lee, S.T., Gardner, D.R. 2015. The effect of intermittent dosing of Nicotiana glauca on teratogenesis in goats. Toxicon. 93:119-124.
Edgar, J.A., Molyneux, R.J., Colegate, S.M. 2014. Pyrrolizidine alkaloids: Potential role in the etiology of cancers, pulmonary hypertension, congenital anomalies, and liver disease. Chemical Research in Toxicology. 28(1):4-20.
Welch, K.D., Stonecipher, C.A., Gardner, D.R., Panter, K.E., Parsons, C., Deboodt, T., Johnson, B. 2015. The effect of western juniper on the estrous cycle in beef cattle. Research in Veterinary Science. 98:16-18.
Boppre, M., Colegate, S.M. 2015. Recognition of pyrrolizidine alkaloid esters in the invasive aquatic plant Gymnocoronis spilanthoides (Asteraceae). Phytochemical Analysis. 26(3):215-225.
Cook, D., Oliveira, C.A., Gardner, D.R., Pfister, J.A., Riet-Correa, G.A., Riet-Correa, F. 2015. Changes in swainsonine, calystegine, and nitrogen concentrations on an annual basis in Ipomoea carnea. Toxicon. 95:62-66.
Snider, D.B., Gardner, D.R., Janke, B.H., Ensley, S.M. 2014. Pine needle abortion biomarker detected in bovine fetal fluids. Journal of Veterinary Diagnostic Investigation. 27(1):74-79.
Pfister, J.A., Davis, T.Z., Hall, J.O., Stegelmeier, B.L., Panter, K.E. 2015. Elk (Cervus elaphus canadensis) preference for feeds varying in selenium concentration. Journal of Animal Science. doi: 10.2527/jas2015-9008.
Stegelmeier, B.L., Brown, A., Welch, K.D. 2015. Safety concerns of herbal products and traditional Chinese herbal medicines: Dehydopyrrolizidine alkaloids and aristolochic acid. Journal of Applied Toxicology. doi: 10.1002/jat.3192.
Lee, S.T., Cook, D., Davis, T.Z., Gardner, D.R., Johnson, R.L., Stonecipher, C.A. 2015. A survey of tremetone, dehydrotremetone and structurally related compounds in Isocoma spp. (Goldenbush) in the southwestern United States. Journal of Agricultural and Food Chemistry. 63(3):872-879.
Davis, T.Z., Lee, S.T., Collett, M.G., Stegelmeier, B.L., Green, B.T., Buck, S.R., Pfister, J.A. 2015. Toxicity of White Snakeroot (Ageratina altissima) and chemical extracts of White Snakeroot in goats. Journal of Agricultural and Food Chemistry. 63(7):2092-2097.