Objectives:

•  Understand that natural does not equal safe!

•  Understand the ways in which pets can be exposed to herbal preparations.

•  Be familiar with documented cases of herbal intoxication in pets.

•  Know where to find information on herbal toxicity.

Broadly defined, herbs are plants used for medicinal purposes or for their olfactory or flavoring properties. There is increasing interest in and use of herbs and other "natural" products by both veterinarians and animal owners to treat medical problems (herbal medicine). Many of these plant-derived chemicals are biologically active and, if exposure is of sufficient magnitude, potentially toxic. There are numerous case reports in the medical literature documenting serious and potentially life-threatening adverse effects following human and animal exposure to herbal preparations. However, it is important to point out that, considered as a group, herbal products do not appear to be associated with a higher incidence of adverse effects or intoxication than from ingestion of prescription or OTC pharmaceuticals. The goal of this presentation is to alert veterinarians to the risk to animals associated with the use of herbal preparations.

Another alternative medicine that employs plant and other natural products is homeopathy. Homeopathic medicines are extremely dilute formulations of plant extracts that contain no significant pharmacologic action. Because of the nature of homeopathic medicines, they present no poisoning hazard even though the label may indicate that they were derived from a potentially toxic plant or other substance. Given the lack of toxicity of homeopathic preparations, they will not be discussed further.

Herbal product formulations can be classified into Chinese patent medicines, raw herbs, herb decoctions and herbal teas.¹ Chinese patent medicines are concentrated liquids such as tinctures (alcohol used as a vehicle), pills, and tablets. Raw herbs can be consumed directly or dried and ground into powders for consumption. Decoctions are concentrated herb extracts prepared by boiling the herb in water which, with continued boiling, is reduced to a small volume. Herbal teas are prepared by steeping the raw herbs in warm or hot water. In general, concentrations of active constituents are greatest in patent medicines and decoctions and less in raw herbs and herbal teas. It is important to note that concentrations of active constituents may vary between lots of the same formulation unless manufacturers standardize their products based upon analysis of biologically important constituents. Raw herbs may contain highly variable concentrations of biologically active chemicals. It is also important to point out that the FDA does not regulate the quality, consistency or authenticity of herbal products. Herbal products are considered dietary supplements. Labels may use a number of colloquial herb names making identification difficult.

There are various ways in which poisoning of an animal might occur. Use of a remedy that contains a know toxin is one possibility. For example, chronic use of a herbal remedy containing hepatotoxic pyrrolizidine alkaloids may result in liver failure. Alternatively, administration of a misidentified plant may result in poisoning. Contamination of commercially prepared herbal remedies with toxic plants has been documented in the medical literature.² Seeds of poison hemlock (Conium maculatum) have been found in anise seed. Recently, plantain sold as a dietary supplement was found to contain cardiac glycosides from Digitalis.

Just as with traditional prescription medications, pet intoxication following accidental ingestion of an improperly stored remedy may occur. This is particularly true with dogs due to their indiscriminant eating habits. Some herbal remedies, particularly Chinese patent medicines, may contain inorganic contaminants such as arsenic, lead or mercury or intentionally added pharmaceuticals such as non-steroidal anti-inflammatories, corticosteroids, caffeine or sedatives.

Herbal preparations may contain numerous biologically active compounds. When these remedies are used in conjunction with other traditional pharmaceuticals, the potential exists for adverse drug interactions. In addition, several naturally-occurring chemicals found in herbal remedies cause liver enzyme induction.² This may result in altered metabolism of other drugs or chemicals resulting in either enhanced or diminished drug efficacy or toxicity. Coexisting disease may alter the metabolism of herbal constituents thus predisposing to adverse reactions.

Of particular concern to veterinarians is the possibility of species differences in susceptibility to the toxic effects of herbal constituents. Unfortunately, little information exists for informed judgements to be made. For example, cat hemoglobin is quite susceptible to oxidative damage. The volatile oil in garlic contains oxidants such as allicin.⁴ Thus, one can hypothesize that oxidant-induced Heinz body anemia would be more likely to occur in cats given garlic than in other species. However, there is no information to substantiate or refute such a hypothesis.

According to annual surveys of herbs sold in the U.S., the most commonly used herbs include coneflower (Echinacea spp.), garlic (Allium sativa), ginseng (Panax spp.), gingko (Ginkgo biloba) St. John's wort (Hypericum perforatum), saw palmetto (Serenoa repens), goldenseal (Hydrastis canadensis), aloe (Aloe spp.), astragalus (Astragalus spp.), cayenne (Capsicum spp.), bilberry (Vaccinium myrtillus) and cat's claw (Uncaria tomentosa). Presumably, these herbs would be those to which pets are most likely to be exposed. According to the recently published Botanic Safety Handbook, coneflower, saw palmetto, aloe (gel used internally), astragalus and cayenne (used internally) should be considered safe when used appropriately. Garlic, ginseng, gingko, St. John's wort, goldenseal, aloe (gel used externally, dried juice used externally), and cayenne (used externally) have some restrictions for use.³ For example, in humans, garlic should not be used by nursing mothers and cayenne should not be applied to injured skin or near eyes. Both gingko and St. John's wort are contraindicated in individuals taking monamine oxidase inhibitors. There is insufficient data available for bilberry and cat's claw to make a determination regarding their safety.

Other herbal preparations that may be associated with significant adverse effects include:

Pennyroyal oil

Pennyroyal oil is a volatile oil derived from Mentha pulegium and Hedeoma pulegiodes. Pennyroyal oil has a long history of use as a flea repellant and has been used to induce menstruation and abortions in humans. There is one case report of pennyroyal oil toxicosis in the veterinary literature in which a dog was dermally exposed to pennyroyal oil at ~ 2 g per kg.⁴ Within 1 hr of application, the dog became listless and within 2 hr began vomiting. Thirty hr after exposure, the dog exhibited diarrhea, hemoptysis and epistaxis. Soon thereafter, the dog developed seizures and died. Histopathologic examination of liver tissue showed massive hepatocellular necrosis. The toxin in pennyroyal oil is thought to be pulegone which is bioactivated to a hepatotoxic metabolite called menthofuran.

Oil of Wintergreen:

Oil of wintergreen is derived from Gaultheria procumbens. The oil contains a glycoside that, when hydrolyzed, releases methyl salicylate. The oil is readily absorbed through skin and is used to treat muscle aches and pains. Salicylates are toxic to dogs and cats. Since cats metabolize salicylates much more slowly than other species they are more likely to be overdosed. Intoxicated cats may present with depression, anorexia, emesis, gastric hemorrhage, toxic hepatitis, anemia, bone marrow hypoplasia, hypernea and hyperpyrexia.

Melaleuca Oil

Melaleuca oil is derived from the leaves of the Australia tea tree (Melaleuca alternifolia); often referred to as tea tree oil. The oil contains terpenes, sesquiterpenes, and hydrocarbons. A variety of commercially available products contain the oil and shampoos and the pure oil have been sold for use on dogs, cats, ferrets and horses. Tea tree oil toxicosis has been reported in dogs and cats.^5,6 A recent case report describes the illness of three cats exposed dermally to pure melaleuca oil for flea control.⁵ Clinical signs in one or more of the cats included hypothermia, ataxia, dehydration, nervousness, trembling and coma. There were moderate increases in serum ALT and AST concentrations. Two cats recovered within 48 hours following decontamination and supportive care. However, one cat died ~ 3 days following exposure. The primary constituent of the oil, terpinen-4-ol, was detected in the urine of the cats.

Citrus Oil

Citrus oil and citrus oil constituents such as D-limonene and linalool have been shown to have insecticidal activity. While D-limonene has been used safely as an insecticide on dogs and cats, some citrus oil formulations or use of pure citrus oil may pose a poisoning hazard. Fatal adverse reactions have been reported in cats following the use of an "organic" citrus oil dip.⁷ Hypersalivation, muscle tremors, ataxia, lateral recumbency, coma and death were noted experimentally in three cats following use of the dip according to label directions.

Pyrrolizidine alkaloids (PA)

Pyrrolizidine alkaloids (PA): over 60 plants used medicinally contain PAs. The more widely used PA-containing herbs in the U.S. include comfrey (Symphytum spp.), coltsfoot (Tussilago farfara), borage (Borago officinale) and several species of Eupatorium. PAs constitute a large class of compounds with individual PAs varying in toxicity. Chronic consumption of toxic PAs has been associated with fatal liver disease in humans and livestock. Hepatotoxicity is thought to be due to toxic PA metabolites which act as alkylating agents and impair hepatocyte cell division and cause cellular necrosis.

Ephedra (Ma Huang)

Ephedra (Ma Huang) contains the alkaloid, ephedrine. Ephedra has been used to treat bronchial asthma, nasal congestion and allergic disorders. More recently, it has been promoted for weight loss, although its efficacy for this purpose is questionable. Clinical signs associated with intoxication with ephedra are related to its sympathomimetic effect and include hypertension, restlessness, hyperexciteability, and cardiac rhythm disturbances such as tachycardia.

5-Hydroxytryptophan:

There are a number of well known toxic plants which are not found in herbal trade but which may be used by individuals ignorant of their toxicity. These include (along with primary target organ systems) Aconitum spp. (nervous, cardiac), Adonis vernalis (GI, heart), Claviceps purpurea (vascular), Cantharanthus roseus (CNS), Chondrodendron tomentosum (skeletal muscle), Colchium autumnale (GI, cardiovascular, renal), Conium maculatum (nervous), Croton tiglium (GI), Datura spp. (nervous), Gelsemium sempervirens (GI, nervous), Hyoscyamus niger (nervous, heart), Nicotiana spp. (nervous), Rauwolfia spp. (vascular), Strophanthus kombe, (cardiac) and Strychnos nux-vomica (nervous).

Lay publications promoting the use of herbal remedies may confuse clients regarding the hazards associated with plant use. One publication entitled Natural Healing for Dogs and Cats written by Diane Stein states that "various herbs like lobelia (for chest and lung congestion, coughs and pneumonia) have been claimed to be "toxic" and removed from the market, to return by popular demand sometime later. The latest claims of toxicity are for comfrey and sassafras......but the claims are totally unfounded, usually based on one case of misuse with no other validation." She goes on to state that "any herb with negative properties has been dropped from the pharmacopia long ago. There are no negative side effects from healing herbs." Reader beware!

Without a history of exposure to a herbal remedy, the diagnosis of intoxication is difficult. Clinical signs are often non-specific and the animal may have concurrent signs due to an underlying disease condition. In some instances, a constituent of a herbal remedy may be detected in a biologic specimen. For example, pulegone was found in liver tissue from a dog intoxicated by pennyroyal oil. However, many veterinary diagnostic laboratories do not have such broad capabilities to detect natural products and laboratory confirmation of exposure or intoxication is often impossible. In suspected herbal poisonings, a veterinary toxicologist should be consulted about available laboratory procedures and appropriate tissue samples for submission.

Treatment is directed toward undertaking appropriate decontamination procedures such as inducing emesis and administering activated charcoal with or without a cathartic. Indications and contraindications for decontamination procedures should be followed. In general, other treatment is symptomatic and supportive. The adage "treat the symptoms and not the patient" is appropriate in most suspected poisonings due to herbal preparations.

References

1.  Ko, RJ (1998) Herbal products information. In: Poisoning and Toxicology Compendium with Symptoms Index. Leikin, JB and Paloucek, FP (eds.), pp. 833-839, Lexi-Comp Inc., Cleveland, OH.

2.  DeSmet, PAGM (1991): Adverse Effects of Herbal Drugs. Springer-Verlag, New York, NY.

3.  McGuffin, M, Hobbs, C, Upton, R and Goldberg (1997): Botanic Safety Handbook. CRC Press, Boca Raton, FL.

4.  Sudekum, M, Poppenga, RH, Raju, N and Braselton, WE (1992): Pennyroyal oil toxicosis in a dog. JAVMA 200: 817-818.

5.  Bischoff, K and Guale, F (1998): Australian tea tree (Melaleuca alternafolia) oil poisoning in three purebred cats. J Vet Diagn Invest 10:208-210.

6.  Villar, D, Knight, MJ, Hanson, SR and Buck, WB (1994): Toxicity of Melaleuca oil and related essential oils applied topically on dogs and cats. Vet Hum Toxicol 36:139-142.