"The first written account of rhododendrons goes back to the 4th Century B. C. in Greece. It relates to the poisoning of ten thousand soldiers by honey of Rhododendron luteum (Azalea pontica). Rhododendron poisoning has since been confirmed repeatedly. A poisonous compound is found in rhododendron nectar, producing low blood pressure, shock and even death."
from the Ozark ARS Chapter Newsletter, September 1998
|Plant||Azalea and Rhododendron|
|Toxic Agents||Grayanotoxin (formerly known as andromedotoxin, acetylandromedol, and rhodotoxin), arbutin glucoside|
|Type of Poisoning||Internal poisoning|
|Poisonous Part||All parts|
|Symptoms||Nausea, salivation, vomiting, weakness, dizziness, difficulty in breathing, loss of balance. 100 to 225 grams of azalea (Rhododendron occidentale) leaves must be eaten to seriously poison a 55 lb child.|
|Plant||Azalea and Rhododendron|
|Toxic Principle||Andromedotoxins (grayanotoxins) are water-soluble diterpenoid compounds. Leaves and flower nectar (including honey made from plant nectar) are sources of the toxin.|
|Toxicity||As little as 3 ml nectar/kg body weight or 0.2% of the body weight as leaves may be toxic or lethal.|
|Mechanism||Andromedotoxins bind to and modify the sodium channels of cell membranes, leading to prolonged depolarization and excitation. Modification of the sodium channels favors calcium movement into cells and results in a positive inotropic effect similar to that of digitalis.|
|Clinical signs||Salivation and a burning sensation in the mouth are followed by emesis, diarrhea, muscular weakness and impaired vision. Bradycardia, hypotension (caused by vasodilation) and atrioventricular block are serious cardiovascular effects that may be lethal. Dyspnea, depression, and prostration develop, and death may occur within 1-2 days. Ruminants often bloat. Aspiration pneumonia can develop secondary to emesis.|
|Treatment||Detoxification: Emesis is used where appropriate. Activated charcoal should be administered repeatedly the first day.
Supportive therapy: Fluid replacement therapy and respiratory support may be necessary. Atropine is recommended for severe bradycardia. Isoproterenol or sodium channel blockers (e.g., quinidine) may be used to treat heart block.
|Precautions||Honey made from the plants has been reported to cause cardiac arrhythmias, emesis, mild paralysis and convulsions in humans and is known as “mad honey”.|
|Plant||Azalea and Rhododendron|
|Toxicity Rating||Moderate. These plants grow wild in the East and cause significant problems there, the danger from these plants in Indiana is much less.|
|Poisonous Part||All parts, especially leaves.|
|Symptoms||Stomach irritation, abdominal pain, abnormal heart rate and rhythm, convulsions, coma, death.|
|Mechanism||These plants, as well as mountain laurel (Kalmia spp.) contain grayanotoxins (glycosides) which affect the gastroenteric (stomach and intestines) and cardiovascular systems. The older name for this toxin was andromedotoxin.
In order for toxic signs to manifest, 0.2% by weight of green leaves needs to be ingested. Gastroenteric signs develop first, generally within 6 hours of ingestion, including salivating, vomiting (in capable species), diarrhea, abdominal pain, and tremors. Disturbances in cardiac rate and rhythm may then be noted. If sufficient quantites were consumed, convulsions may occur, followed by coma and death. Not all affected animals will die, and livestock may recover without treatment, depending upon amount ingested.
|First Aid||Prevent further ingestion and provide supportive care. Veterinary attention is needed if ingestion was recent, or if clinical signs are present.|
From U S Food & Drug Administration Center for Food Safety & Applied Nutrition Food borne Pathogenic Microorganisms and Natural Toxins 1992 (Bad Bug Book)
1. Name of Toxin: Grayanotoxin (formerly known as andromedotoxin, acetylandromedol, and rhodotoxin)
2. Name of Acute Disease: Honey Intoxication
Honey intoxication is caused by the consumption of honey produced from the nectar of rhododendrons. The grayanotoxins cause the intoxication. The specific grayanotoxins vary with the plant species. These compounds are diterpenes, polyhydroxylated cyclic hydrocarbons that do not contain nitrogen. Other names associated with the disease is rhododendron poisoning, mad honey intoxication or grayanotoxin poisoning.
3. Nature of Disease: The intoxication is rarely fatal and generally lasts for no more than 24 hours. Generally the disease induces dizziness, weakness, excessive perspiration, nausea, and vomiting shortly after the toxic honey is ingested. Other symptoms that can occur are low blood pressure or shock, bradyarrhythima (slowness of the heart beat associated with an irregularity in the heart rhythm), sinus bradycardia (a slow sinus rhythm, with a heart rate less than 60), nodal rhythm (pertaining to a node, particularly the atrioventricular node), Wolff-Parkinson-White syndrome (anomalous atrioventricular excitation) and complete atrioventricular block.
4. Normal Course of the Disease: The grayanotoxins bind to sodium channels in cell membranes. The binding unit is the group II receptor site, localized on a region of the sodium channel that is involved in the voltage-dependent activation and inactivation. These compounds prevent inactivation; thus, excitable cells (nerve and muscle) are maintained in a state of depolarization, during which entry of calcium into the cells may be facilitated. This action is similar to that exerted by the alkaloids of veratrum and aconite. All of the observed responses of skeletal and heart muscles, nerves, and the central nervous system are related to the membrane effects.
Because the intoxication is rarely fatal and recovery generally occurs within 24 hours, intervention may not be required. Severe low blood pressure usually responds to the administration of fluids and correction of bradycardia; therapy with vasopressors (agents that stimulate contraction of the muscular tissue of the capillaries and arteries) is only rarely required. Sinus bradycardia and conduction defects usually respond to atropine therapy; however, in at least one instance the use of a temporary pacemaker was required.
5. Diagnosis of Human Illness: In humans, symptoms of poisoning occur after a dose-dependent latent period of a few minutes to two or more hours and include salivation, vomiting, and both circumoral (around or near the mouth) and extremity paresthesia (abnormal sensations). Pronounced low blood pressure and sinus bradycardia develop. In severe intoxication, loss of coordination and progressive muscular weakness result. Extrasystoles (a premature contraction of the heart that is independent of the normal rhythm and arises in response to an impulse in some part of the heart other than the sinoatrial node; called also premature beat) and ventricular tachycardia (an abnormally rapid ventricular rhythm with aberrant ventricular excitation, usually in excess of 150 per minute) with both atrioventricular and intraventricular conduction disturbances also may occur. Convulsions are reported occasionally.
6. Associated Foods: Grayanotoxin poisoning most commonly results from the ingestion of grayanotoxin-contaminated honey, although it may result from the ingestion of the leaves, flowers, and nectar of rhododendrons. Not all rhododendrons produce grayanotoxins. Rhododendron ponticum grows extensively on the mountains of the eastern Black Sea area of Turkey. This species has been associated with honey poisoning since 401 BC. A number of toxic species are native to the United States. Of particular importance are the western azalea (Rhododendron occidentale) found from Oregon to southern California, the California rosebay (Rhododendron macrophyllum) found from British Columbia to central California, and Rhododendron albiflorum found from British Columbia to Oregon and in Colorado. In the eastern half of the United States grayanotoxin-contaminated honey may be derived from other members of the botanical family Ericaceae, to which rhododendrons belong. Mountain laurel (Kalmia latifolia) and sheep laurel (Kalmia angustifolia) are probably the most important sources of the toxin.
7. Relative Frequency of Disease: Grayanotoxin poisoning in humans is rare. However, cases of honey intoxication should be anticipated everywhere. Some may be ascribed to a increase consumption of imported honey. Others may result from the ingestion of unprocessed honey with the increased desire of natural foods in the American diet.
8. Target Population: All people are believed to be susceptible to honey intoxication. The increased desire of the American public for natural (unprocessed) foods, may result in more cases of grayanotoxin poisoning. Individuals who obtain honey from farmers who may have only a few hives are at increased risk. The pooling of massive quantities of honey during commercial processing generally dilutes any toxic substance.
9. Analysis in Foods: The grayanotoxins can be isolated from the suspect commodity by typical extraction procedures for naturally occurring terpenes. The toxins are identified by thin layer chromatography.
10. Selected Outbreaks: Several cases of grayanotoxin poisonings in humans have been documented in the 1980s. These reports come from Turkey and Austria. The Austrian case resulted from the consumption of honey that was brought back from a visit to Turkey. From 1984 to 1986, 16 patients were treated for honey intoxication in Turkey. The symptoms started approximately 1 h after 50 g of honey was consumed. In an average of 24 h, all of the patients recovered. The case in Austria resulted in cardiac arrhythmia, which required a temporal pacemaker to prevent further decrease in heart rate. After a few hours, pacemaker simulation was no longer needed. The Austrian case shows that with increased travel throughout the world, the risk of grayanotoxin poisoning is possible outside the areas of Ericaceae-dominated vegetation, namely, Turkey, Japan, Brazil, United States, Nepal, and British Columbia. In 1983 several British veterinarians reported a incident of grayanotoxin poisoning in goats. One of the four animals died. Post-mortem examination showed grayanotoxin in the rumen contents.
Department of Cardiology, Division of Pacing and Electrophysiology, Institute of Cardiology, Istanbul University, Haseki-Fatih, Istanbul, Turkey and Department of Cardiology, Cerrahpasa School of Medicine, Istanbul University, Fatih, Istanbul, Turkey
In this study, two hospitals in Turkey evaluated the history of non-commercial honey intake in all patients referred to our institution for investigation of slow heart rate or atrioventricular (AV) conduction abnormalities. Between April 2008 and December 2008, 173 patients were referred to our institution for assessment of sinus bradycardia and various degrees of AV block and/or permanent pacemaker implantation. All patients were questioned about history of honey intake. Detailed evaluation revealed a history of daily honey intake for a long period of time in five of the patients (2.8%). This non-commercial honey was made by different amateur beekeepers in eastern Back Sea region of Turkey. Discontinuation of honey intake resulted in prompt normalization of conduction and significant symptomatic improvement. None of the patients were admitted to hospital and all were asymptomatic during 3 months follow-up. Holter monitoring for 24-h revealed no abnormality at first and third month.
Hungry Children in Daehongdan Die from Eating Azalea Flowers
Children in North Korea died after eating azalea flowers in Daehongdan County. In Sambong Middle School, 9 students were dead from azalea poisoning. Adults know what to eat and what not, but young children can’t tell and just put anything in their mouths because they are hungry. After eating three or four potatoes, they are still hungry and they run up to the mountains and pluck anything to eat. This spring, they ate fistful of azalea petals several times and they died of poisoning. Chang Mi-oak says, ‘They pick basketful of azalea petals and eat them, but if they eat too much at one time, it causes gastrospasms. If they eat them when their stomach is empty, they will die foaming in their mouth. I suffered gastrospasms when I ate azalea. Adults like me cannot control hunger; it is needless to say in case of children.’
Lee Sung-ja says, ‘I warn my older child everyday. The older one would not do, but my younger one may eat flowers while I am not around. So whenever they go out together I admonish the older one, ‘don’t let your brother eat flowers’ several times. My older one tells me that many of his classmates die and asks me, ‘Mother, what can I do?’ It pains me greatly. Children who have no parents die so easily.’Return to Top
RHODODENDRON POISONING IN RUMINANTS
From Cornell Veterinary Medicine
RHODODENDRON SIMSII POISONING IN BIRDS
From Cornell Veterinary Medicine
Visit Henning's Home Page