424 Veterinary Technician August 2001

======TOXICOLOGY BRIEF Onion Breath

Denise M. Simmons, LVT

normally active poodle arrives for its appointment appearing weak and listless. On examination, the animal’s heart and respiration rates are elevated, a fresh urine sample is tinged dark red, hematocrit is low, and mucous membranes are pale. The client is sure that the poodle has not had access to anything harmful (e.g., garbage, houseplants, mousetraps). In fact, the owner explains that she has Ataken special steps to enhance both her health and that of her pet. After reading about the numerous benefits of onions, she added grilled Bermuda onions to both of their diets about a week ago. Now, her dog has become depressed and weak. What could be wrong?

Onion Toxicity dogs with G6PD deficiency (a genetic Heinz-body hemolytic anemia is disorder), lower G6PD levels cause what could be wrong. Onions— lower GSH levels, resulting in a whether cooked, raw, or dehydrated— greater risk of oxidative injury. 4 contain sulfur compounds (Box 1) Yamamoto and Maede reported that that, when chewed, are hydrolyzed to dogs may also be more susceptible to thiosulfinates. Thiosulfinates decom- onion-induced oxidation if they have pose to a number of disulfides, includ- innately high concentrations (five to ing dipropenyl disulfide (or n-propyl seven times normal) of erythrocyte 4 disulfide), which appears to be the GSH. In this study, dogs with this trait most toxic disulfide.1 These disulfides had increased oxidative injury from the are oxidizing agents that can cause he- compound 4-aminophenyl disulfide, molysis of erythrocytes. suggesting that perhaps onions contain Glutathione, a ubiquitous tripep- the reducing power that converts oxi- a similar oxidant. These dogs also had tide, plays an important protective role dized glutathione to reduced glu- high potassium and low sodium con- against oxidative damage. Glutathione tathione (GSH; Figure 1). Without centrations, which are attributable to participates in various biologic GSH, hydrogen peroxide accumulates the function of sodium-potassiumÐAT- processes, including protein and DNA and causes oxidation of the sulfhydryl Pase. Normal canine erythrocytes lack synthesis, transcellular amino acid groups of the globin chains, leading to this enzyme and have high sodium and transport, metabolic enzyme activity, denaturation of hemoglobin and for- low potassium concentrations. This and protection of cells against free mation of precipitates (i.e., Heinz bod- trait is common in many dogs, espe- radicals and carcinogens. The liver, ies; Figure 2). The erythrocyte cell Onions are of the genus Allium, in kidneys, intestinal mucosa, and ery- membrane may be damaged, resulting the family Liliaceae. The true onion throcytes contain the highest amounts in the erythrocyte being removed from is classified as Allium cepa; the of glutathione, perhaps due to their in- circulation or possibly lysing within nodding wild onion is classified as creased risk of exposure to free radi- circulation, causing hemoglobinemia Allium cernuum; the shallot as cals and/or their susceptibility to auto- and hemoglobinuria.3 Allium ascalonicum; and the green oxidation after free radical injury.2 onion, or common leek, as Allium ampeloprasm. Through the hexose monophosphate Species Susceptibility Garlic, which is also of the family cycle (also known as the pentose Dogs Liliaceae, is related to onions and phosphate pathway), glucose-6-phos- All dogs that eat onions are suscep- has similar chemical characteristics. phate dehydrogenase (G6PD) provides tible to their toxic effects. However, in

Toxicology Brief is contributed by veterinary technicians at the American Society for the Prevention of Cruelty to Animals–Animal Poison Control Center, 1717 S. Philo Rd., Suite 36, Urbana, IL 61802; hotline: 888-4ANI-HELP (888-426-4435) or 900-680-0000 (a $45 consultation fee is charged to the caller’s telephone bill); email: [email protected] (for nonemergency information only); web site: www.napcc.aspca.org.

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Box 1. Sulfur Compounds Found in Onions ingest onion peels by raiding the garbage or stealing onion pieces from The toxicity of onions is based on their disulfide concentration, which is increased when the table or off the floor. Pets can also they are grown in soil that is high in sulfur. Sulfur is a widely distributed element found ingest onions in table scraps or home- in abundance (ranked as the 16th element) in both free and combined states. Huge made diets provided by owners who subterranean deposits are found in many parts of Louisiana and Texas as well as in are unaware of the toxic effects. Colorado, Nevada, Wyoming, and California. In addition, sulfur dioxide is an air pollutant released into the atmosphere during combustion of fossil fuel (e.g., gas, Toxic Doses petroleum, coal). Plants can take up this sulfur, thereby increasing their sulfur content. An early study5 revealed onion toxi- city in dogs when the amount of creased numbers of Heinz bod- onions fed was more than 0.5% of the Oxidized animal’s weight. To induce hemolytic GSH ies as a result of other diseases 6 glutathione Glucose-6-phosphate such as diabetes mellitus, hy- anemia, dogs in one study were fed dehydrogenase perthyroidism, and lymphoma. 30 g of onions/kg of body weight A cat that has ingested oxidant- (which is 3% of body weight) once daily for 3 days. In another study,4 Figure 1—Conversion of oxidized glutathione to re- containing foods such as dogs ranging in weight from 9.9 to 12 duced glutathione (GSH). onions, however, may develop severe, life-threatening anemia kg were fed 200 g one time (1.6% to in conjunction with Heinz-body 2% of body weight). Depending on the formation. Therefore, cat own- size and type, an onion’s weight can ers should be cautioned to check range from 0.5 to 16 oz (14 to 455 g). labels on foods or herbal reme- A review of the ASPCA Animal Poi- dies to ensure that onions are son Control Center case record data- not among the ingredients. base for Allium cepa exposure over a 2-year period revealed 23 cases (20 Large Animals dogs, 3 cats). Six of the affected dogs Of large animals, cattle are the and one cat showed clinical signs. The most susceptible to onion toxici- data revealed that it takes a fairly large ty. Horses are not as susceptible, amount of ingested onions before signs and sheep and goats are some- are observed but that the dose in the re- what resistant. In areas where ported cases was consistently over 0.5% of the animal’s body weight. Figure 2—Heinz bodies (arrows). (New methylene onions are grown commercially, blue stain, original magnification ×100) sheep may be fed cull onions (deemed unfit for human con- Clinical Picture cially Japanese breeds (e.g., Akitas, sumption) free choice without experi- Adverse effects from onion ingestion Shiba Inus).4 encing toxicity; for cattle, ingestion of are dependent on species sensitivity more than 25% of their diet as onions and amount ingested (Boxes 2 and 3). Cats may be hazardous.1 While it does not In chronic exposures at low doses, the Feline erythrocytes are extremely explain the relative resistance of sheep anemic effect is lessened because ery- susceptible to oxidative damage, par- and goats, the oxidative threat to cattle throcytes are being regenerated simul- ticularly hemoglobin denaturation. Be- is greater because onions also contain taneously. The hematocrit may not reach its lowest point until several days cause of its molecular configuration, S-methylcysteine sulfoxide (SMCO). 5 feline hemoglobin is approximately SMCO is metabolized in the rumen, after onion exposure. In the study in which dogs were fed 30 g of onion/kg two to three times more prone to ox- producing dimethyl disulfide, another 6 idative damage than is that of other oxidant. Because SMCO is absorbed in of body weight once daily for 3 days, animals.2 Other enzymatic factors in- the intestine and not converted to di- the hematocrit was 40% of preexpo- crease feline dependence on glu- methyl disulfide, it does not affect non- sure value on day 5 of the study and tathione for oxidative protection com- ruminants, including hindgut fermen- returned to normal within 10 to 14 pared with other mammals.2 Because a tors (e.g., rabbits, guinea pigs, horses).1 days postexposure. A high level of Heinz bodies appeared suddenly on small number of Heinz bodies are of- 7 ten found in feline erythrocytes, it is Exposure day 2 and continued for 4 days. important to interpret the number of In cool, early spring, wild onions, Heinz bodies in conjunction with the which can be found in pastures when Treatment history and severity of anemia. Cats there is little else growing, will tempt Severe onion toxicosis can be with only mild anemia may have in- grazing animals. Dogs and cats may lethal.8 As with any toxicosis, the first 426 Veterinary Technician August 2001 Toxicology Brief

is not successful). For large animals, study9 reported the use of corticoster- Box 2. Common Signs of Onion activated charcoal can be given at 0.5 oids, which, in retrospect, were deemed Poisoning in Dogs and Cats to 1 g/kg PO with a stomach tube. unnecessary for treatment. The animal’s hematocrit should be Treatment should also include nutri- Pale or icteric mucous membranes Weakness, depression monitored over a period of time (fre- tional intervention. Dietary protein Rapid heart and respiration rates quency depends on the overall condi- and amino acid quantity and composi- (caused by hypoxia) tion of the animal) to ascertain the tion have a significant influence on Vomiting, anorexia, and/or diarrhea severity of anemia and whether it is glutathione synthesis. Studies in rats Onion odor on breath degenerative or regenerative. It may demonstrated that prolonged fasting or take several days after onion ingestion a low-protein diet results in a signifi- step is to remove the source of the tox- for the hematocrit to reach its lowest cant reduction in hepatic glutathione icity. For cases in which a significant point. Heinz-body hemolytic anemia is levels, potentiating hepatic injury amount of onions have been ingested usually regenerative; therefore, the an- caused by oxidative stress. within the past 2 hours and there are imal’s prognosis is good if it has no Although nutritional therapy is im- no contraindications to emesis (i.e., other preexisting hematologic disor- portant for all species, it is critical for hypoxic, comatose, dyspneic, lacking ders. Whole-blood transfusions may cats. Dietary imbalance (specifically normal pharyngeal and/or gag reflex- be necessary for critically ill animals. insufficient taurine) or anorexia has a es), vomiting should be induced by Another possibility for dogs is the use more rapid and/or more adverse effect giving the animal 3% hydrogen perox- of Oxyglobin¨ (Biopure Corp., Cam- on glutathione metabolism in cats than ide orally (1 ml/lb of body weight, not bridge, MA; see product literature for in other species.2 to exceed 45 ml), followed by the ad- effects on serum chemistry, hematol- ministration of activated charcoal. ogy, urinalysis, and clinical signs). Conclusion Within the clinic, apomorphine can Other supportive therapies depend on Onions can cause potentially seri- also be used to induce vomiting. Other the animal’s overall condition. If vom- ous, life-threatening toxicity when suf- emesis methods are not recommended iting, diarrhea, renal injury, or shock is ficient quantities are ingested. Cats are (e.g., syrup of ipecac is unreliable and present, intravenous fluid therapy and extremely susceptible because of the may cause protracted vomiting, and correction of electrolyte and acidÐbase differences in their hemoglobin struc- salt can cause a salt toxicosis if emesis disturbances is warranted. One case ture and protective enzymes. The Toxicology Brief Veterinary Technician August 2001 427

Box 3. Common Laboratory Findings in Onion Toxicity 5. Kay JM: Onion toxicity in a dog. Mod Vet Pract 64(6):477Ð478, 1983. Low hematocrit (e.g., dogs <37%, cats <24%, cattle <26%, sheep <24%, goats <20%, 6. Ogawa E, Shinoki T, Akahori F, horses <32%) Masaoka T: Effect of onion ingestion Hemoglobinuria (dark-colored urine ranging from red wine to almost black) on anti-oxidizing agents in dog erythro- cytes. Jpn J Vet Sci 48(4): 685Ð690, Hemoglobinemia 1986. Methemoglobinemia7 7. Coles EH: Veterinary Clinical Patholo- Abnormal erythrocyte morphology gy, ed 4. Philadelphia, WB Saunders —Heinz bodies (refer to a laboratory reference for staining requirements) Co, 1986, p 40. —Eccentrocytes (hemoglobin concentrated to one side of the cell) 8. Beasley VR: A Systems Affected Ap- —Leukocytosis with a left shift, increased total leukocyte count as cells move from proach to Veterinary Toxicology. Chica- the marginal granulocyte pool to the circulating granulocyte pool, and go, University of Illinois, 1999, p 886. thrombocytosis due to increased bone marrow activity7 9. Solter P, Scott R: Onion ingestion and subsequent Heinz body anemia in a dog: A case report. JAAHA 23(5):544Ð heredity of some dogs, specifically Danville, IL, Interstate Publishers, 546, 1987. Japanese breeds, can significantly in- 1998. crease the severity of the toxicosis. Of 2. Fettman MJ: Comparative aspects of About the Author glutathione metabolism affecting indi- Ms. Simmons works at the ASPCA the domestic grazing animals, cattle vidual susceptibility to oxidant injury. are the most susceptible to onion toxic- Compend Contin Educ Pract Vet 13(7): and the Animal Emergency Clin- ity. The Heinz-body hemolytic anemia 1079Ð1087, 1991. ic in Champaign, Illinois. She caused by onions is usually regenera- 3. Robbins SL, Kumar V: Pathologic Ba- lives in a log home with three tive; therefore, prognosis is good with sis of Disease, ed 5. Philadelphia, WB horses, six dogs, four cats, and Saunders Co, 1994, p 591. supportive care and recovery usually seven birds. She has a strong in- 4. Yamamoto O, Maede Y: Susceptibility terest in community involvement occurs in 10 to 14 days. to onion-induced hemolysis in dogs with hereditary high erythrocyte re- with animals and animal welfare References duced glutathione and potassium con- and plans eventually to move her 1. Cheeke PR: Natural Toxicants in Feeds, centrations. Am J Vet Res 53(1):134Ð career in that direction. Forages, and Poisonous Plants, ed 2. 136, 1992.