Information about rhodotoxin

U S Food & Drug Administration Center for Food Safety & Applied Nutrition
Foodborne Pathogenic Microorganisms and Natural Toxins 1992 (Bad Bug Book)
html://vm.cfsan.fda.gov/%nov/chap44.html

    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 hone 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 toxin 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.History of Recent 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.

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10. AZALEA, RHODODENDRON 

(Rhododendron spp.) 

(heath family)

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. 

ANIMALS AFFECTED: All animals may be affected.

DANGEROUS PARTS OF PLANT: all parts, especially leaves.

CLASS OF SIGNS: Stomach irritation, abdominal pain, abnormal heart rate and rhythm,
convulsions, coma, death.

PLANT DESCRIPTION: These perennial shrubs have tough, glossy, smooth-margined
evergreen leaves. The large, showy flowers are in terminal clusters and have five white, pink,
or red petals (fig. 10). Some horticultural varieties have yellow or orange petals. Common and
local names for these plants include "lambkill" and "calfkill". These plants have been used by
people to commit suicide.

SIGNS: 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. 

SAFETY IN PREPARED FEEDS: These plants are not safe in hay nor in any other prepared
feed.

PREVENTION: Animals should not be allowed to graze these plants. Keep hungry livestock
away from areas where these plants grow. Pets may nibble or taste the leaves out of
curiosity or boredom, and this is not advised, but seldom leads to clinical toxicosis. Honey
made from the nectar of these flowers is also toxic and should not be consumed, so exercise
caution when placing beehives.