Perna canaliculus - scientific name of Green Lipped Mussel Green Lipped Mussel is a popular…
This includes a lot of reference articles for any of you research gurus out there. I am also attaching a question/ answer session from another veterinarian who has been using DoTerra essential oils for years here:
The Science Behind Cats and Essential Oils
By: Melissa Sheldon, DVM
Owner and Founder of AnimalEO
As a veterinarian practicing Veterinary Aromatic Medicine as my specialty, I find it incredibly frustrating when others make claims about feline physiology and metabolism, without any true understanding or references to their concerns. Certified Animal Aromatherapists, Certified Human Aromatherapists, other veterinarians, veterinary technicians, those who practice Applied Zoopharmacognosy, and many more have failed to provide me with the research and evidence to prove their claims on what is or isn’t safe with animals (especially cats) and aromatherapy. So, I set out to do it for them.
Recently, a post on Facebook went “viral” – stating that they unknowingly poisoned their cat by diffusing essential oils in their home. Over 500,000 shares have been made of this post, and to say that I have been contacted by many concerned people, would be an understatement. So let’s tackle the claims and research behind both sides of the story head on – and with no bias.
I apologize for not linking each research article to its source online, however, when you see the number of items, you’ll understand how I opted out of this time consuming project for the moment.
There is a lot of confusion regarding the metabolism of essential oils, especially in regards to cats. It is not uncommon that someone who is using essential oils with a certain species, will be ridiculed and ostracized. However, those who carry the biggest stick in the complaint, rarely have any animal physiology or pharmacology training. It is not that being safe is wrong, I value those who would like to take the cautionary path and avoid all use of essential oils with species of concern. However, to say that no one can do it, is just like saying that cats cannot have Morphine in veterinary medicine. It is just out of date information, and although you are welcome to practice the safest of safe protocols, we need to change the informational tide of what we truly know to be accurate in the animal field.
Where does this controversy come from? Let’s take cats as our example. They are commonly reported as being “deficient” in their liver enzymes. That they just cannot metabolize essential oils, and that they will build up over time, creating horrible side effects and potential death. I would like to think that cats are not deficient, they are just cats. Just like saying that we are deficient in fur, or that Australians drive on the “wrong” side of the road from Americans, it is a point of view type of statement. We are comparing a completely different animal species, with a completely different metabolism set up, to completely unrelated species such as dogs and humans. Let’s let cats be cats. And just enjoy them for the unique creatures they are.
Where did our misconception about cats come from? One main research article that is used to support that phenols are toxic to cats is from 1972. This is very, very old in the medical field. And if one reads further into the research, it has nothing to do with natural essential oils, and everything to do with benzyl alcohol being injected, added to meat products as a preservative, or used as a bacteriostatic in drug or biological products. Sure, if you only read the headline of “Toxicosis in cats from the use of benzyl alcohol in lactated Ringer’s solution” in the Journal of American Veterinary Medical Association in 1983, you may worry also about the use of any phenol. However, we really need to evaluate apples to apples. If you knew nothing of veterinary medicine, feline physiology, or the vast difference between a chemical benzene ring and a natural substance containing a benzene ring, you would err on the side of caution. Which seems to be the case for most of the aromatherapy world at this time.
And sadly, more current information is out there. Even in the November 1984 edition of Veterinary Clinics of North America: Small Animal Practice – Vol. 14, No. 6; titled Symposium on Advances in Feline Medicine II, there is an incredibly profound statement by Jeff R. Wilcke DVM, MS. “Even drugs known for toxicity in cats can be used safely if we are aware of and compensate for certain peculiarities.” That basically says it all. And that is 1984! Here we are – some 33 years later, still questioning if essential oils are killing cats, and reporting all over the place that it is a huge area of concern.
Cats would be dropping over dead all over the world, if essential oils were truly as toxic as those reports imply. With the amazing amount of essential oil use in households containing all sorts of animals, I am impressed at the level of safety actually witnessed. Just like with the phenol research, it will matter what quality of essential oil is used. I do not think that synthetics or altered essential oils should be in the same category at all with true and natural essential oils.
Certainly, any essential oil that would be more towards a “fragrance-grade” oil – will have the potential to cause long term problems. Just as we documented cases of liver value elevation in homes with a lot of air freshener and artificial fragrance use, these lesser essential oils are akin to spraying perfume on your cat and wondering why that didn’t bode well. And it is just unfortunate in the current market of essential oils that there are so many poor grade essential oils being sold as high quality. If you are purchasing an essential oil based on cost, or because it is easily available at the health food or grocery store – you have likely already selected some of the poorer grade oils on the market. But hype does not also guarantee quality. Marketing is just marketing, no matter how convincing it may sound. It is best to consider if your essential oil source is truly “on the line” at the end of the day for the results and quality that you obtain. If they say you can use an oil with your cat, and you experience an adverse event, is that person or product truly held accountable? If not, proceed with caution.
Can cats metabolize essential oils? Yes, they can. And no, they will not build up over time, although cats can have what we refer to as a different half-life for a chemical, or elimination time. In a study of plasma half-lives for sodium salicylate it was discovered that ponies, swine, goats, dogs, and cats had drastically different elimination times. Ponies had a 1.0 hour half-life, while the others displayed 5.9, 0.78, 8.6, and 37.6 hours respectively. A cat actually took almost 38 hours to eliminate the drug, while a dog took just under 9. Does this mean the cat is deficient? No, it means the cat is not a dog, and the cat is not a goat, and the cat is not a pony! And look at how fast a goat eliminated the drug – we do not call the other species deficient in the goats shadow – we just accept that there are species differences. And that my friend, is how drug doses are created.
Essential oils need to be regarded similarly to how we use drugs. There are species considerations, dosing considerations, and interval considerations. This is normal.
What really is the case with cat metabolism? The actual science behind the specific differences in cat metabolism is as follows. When cats are compared to other species, it appears that they have less ability to conjugate xenobiotics with glucuronic acid. There appears to be a lack of UDP-glucuronyltransferase activity towards certain substrates. However UDP-glucose dyhydrogenase and glucouronic acid are present in amounts consistent with normal activity in other species. Glucuronides of endogenous body compounds such as bilirubin, are formed in normal rates in cats. However, when glucuronides are formed for phenols, it may be a smaller percentage of the total drug eliminated. There is a variation in some of the enzyme affinity for different “drug molecules”, and so we need to allow this to influence our therapeutic protocols for everything we expose a cat to.
The nature of the chemical the cat is exposed to, and the presence of alternative pathways for metabolism, need to be considered in feline pharmacokinetics of essential oils. How efficient the alternative pathways are, and what metabolite they might produce in the process, also must be considered. Some metabolites can indeed be viewed as toxic in their own right, but in some instances the metabolite is the more biologically active or beneficial molecule to the body. To quote Dr. Wilcke, “Alternative metabolic pathways may produce compounds that are as toxic, if not more so, than the parent compound, and in greater quantities than expected for other species. This situation is very difficult to predict until the drug is actually used in cats.”
So we need to be careful about our extrapolation of generalities to cats and other animals of concern, such as ferrets. The wealth of information present to show that cats are tolerating proper use of essential oils is far more current, and overwhelming in amount. When we consider that there are several essential oil distribution companies with several million people each within them. And all of those members are using essential oils almost daily in their home, and that 63% of all homes contain animals…I think we need a check and balance of how toxic this situation really is. The simple evidence is that in the absence of gross mis-use and overdose of essential oils, they really are quite safe.
Just the Science
The following research articles appear to be much of the basis for our concern with cats, but also what is ignored in terms of continuing advancement of our education and knowledge base. I will start with the oldest first. And this is not even close to all relevant material.
1963. Larson, EJ: Toxicity of low doses of aspirin in the cat. J. Am. Vet. Med. Assoc., 143:837-840.
1965. Jones, LM (ed): Veterinary Pharmacology and Therapeutics. Edition 3. Ames, Iowa State University Press.
1965. Roe FJ, Field WE. Chronic toxicity of essential oils and certain other products of natural origin. Food Cosmet. Toxicol. 3(2):311-23.
1966. Dutton, GJ (ed): Glucouronic Acid: Free and Combined Chemistry, Biochemistry, Pharmacology, and Medicine. New York, Academic Press.
1967. Herrgesell, JD.: Aspirin poisoning in the cat. J. Am. Vet. Med. Assoc., 151:452-455.
1968. Davis LE, Donnelly EJ: Analgesic drugs in the cat. J. Am. Vet. Med. Assoc., 153:1161-1167.
1969. Zontine, WJ, Uno, T: Acute aspirin toxicity in a cat. Vet. Med. Small Anim. Clin., 64:680-682.
1971. Yeh SY, Chernov HI, Woods LA. Metabolism of morphine by cats. J. Pharm. Sci. 60(3):469-471.
1972. Davis LE, Westfall BA: Species differences in biotransformation and excretion of salicylate. Am. J. Vet. Res., 33:1253-1262.
1972. Jansen PL, Henderson PT. Influence of phenobarbital treatment on p-nitrophenol and bilirubin glucuronidation in Wistar rat, Gunn rat and cat. Biochem. Pharmacol. 15;21(18):2457-62.
1972. Bedford, PGC, and Clarke, EGC: Experimental benzoic acid poisoning in the cat. Vet. Rec., 90:53-58.
1973. Yeary, RA, and Swanson, W: Aspirin dosages for the cat. J. Am. Vet. Med. Assoc., 163:1177-1178.
1973. Hietanen E, Vainio H. Interspecies variations in small intestinal and hepatic drug hydroxylation and glucuronidation. Acta. Pharmacol. Toxicol. (Copenh). 33(1):57-64.
1974. Fertziger AP, Stein EA, Lynch JJ. Letter: Suppression of morphine-induced mania in cats. Psychopharmacologia. 8;36(2):185-7.
1974. Capel ID, Millburn P, Williams RT. The Conjugation of 1- and 2-Naphthols and other Phenols in the Cat and Pig. Xenobiotica. 4(10):601-615.
1975. Finco, DR, Duncan JR, Schall, WD, et. al.: Acetaminophen toxicosis in the cat. J. Am. Vet. Med. Assoc., 166:469-472.
1975. Schillings RT, Sisenwine SF, Schwartz MH, Ruelius HW. Lorazepam: glucuronide formation in the cat. Drug Metab. Dispos. 3(2):85-8.
1978. Erichsen, DF, Harris SG, and Upson DW: Plasma levels of digoxin in the cat: Some clinical applications. J. Am. Anim. Hosp. Assoc., 14:734-737.
1980. Erichsen, DF, Harris, SG, and Upson DW: Therapeutic and toxic plasma concentrations of digoxin in the cat. Am. J. Vet. Res., 41:2049-2058.
1980. Davis, LE: Clinical pharmacology of salicylates. J. Am. Vet. Med. Assoc., 176:65-66.
1982. Federal Drug Administration Bureau of Veterinary Medicine: Benzyl alcohol hazardous as a parenteral preservative. J. Am. Vet. Med. Assoc., 181:641.
1982. Schleifer, JH and Carson TL: Toxicity of benzyl alcohol preservative. Letter. J. Am. Vet. Med Assoc., 181:853.
1982. Bolton, G. R., and Powell, W.: Plasma kinetics of digoxin in the cat. Am. J. Vet. Res., 43:1994-1999.
1982. Akesson, C. E. and Linero, P.E.: Effect of chloramphenicol on serum salicylate concentrations in cats and dogs. Am. J. Vet. Res., 43:1471-1472.
1982. Gaunt, SD, Baker DC, and Green RA.: Clinicopathologic evaluation of N-acetylcysteine therapy in acetaminophen toxicosis in the cat. Am. J. Vet. Res., 42-1981.
1982. Schmoldt A, von der Eldern-Dellbrügge U, Benthe HF. On the glucuronidation of digitalis compounds in different species. Arch. Int. Pharmacodyn. Ther. 255(2):180-90.
1983. Cullison, R. F., Menard, P.D., and Buck W.B.: Toxicosis in cats from the use of benzyl alcohol in lactated Ringer’s solution. J. Am. Vet. Med. Assoc., 182:61.
1983. Prasuhn, LW: Tylenol poisoning in the cat. Letter. J. Am. Vet. Med. Assoc., 182:4.
1984. Wilcke, JR: Idiosyncracies of Drug Metabolism in Cats: Effects on Pharmacotherapeutics in Feline Practice. Symposium on Advances in Feline Medicine II. Vet. Clin. North Am. Small Anim. Pract., 14(6):1345-1354.
1984. Hassell TM, Maguire JH, Cooper CG, Johnson PT. Phenytoin metabolism in the cat after long-term oral administration. Epilepsia. 25(5):556-63.
1984. Savides MC, Oehme FW, Nash SL, Leipold HW. The toxicity and biotransformation of single doses of acetaminophen in dogs and cats. Toxicol. Appl. Pharmacol. 5;74(1):26-34.
1984. Smith GS, Watkins JB, Thompson TN, Rozman K, Klaassen CD. Oxidative and conjugative metabolism of xenobiotics by livers of cattle, sheep, swine and rats. J. Anim. Sci. 58(2):386-95.
1985. Vollmer KO, von Hodenberg A. Metabolism of thymoxamine. III. Structure elucidation of the metabolites and interspecies comparison. Eur. J. Drug Metab. Pharmacokinet. 10(2):139-45.
1986. Watkins JB 3rd, Klaassen CD. Xenobiotic biotransformation in livestock: comparison to other species commonly used in toxicity testing. J. Anim. Sci. 63(3):933-42.
1986. Rousseaux CG, Smith RA, Nicholson S. Acute Pinesol toxicity in a domestic cat. Vet. Hum. Toxicol. 28(4):316-7.
1986. Elegbede JA, Maltzman TH, Verma AK, Tanner MA, Elson CE, Gould MN. Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re-evaluation. Carcinogenesis. 7(12):2047-9.
1986. Hink WF, Fee BJ. Toxicity of D-limonene, the major component of citrus peel oil, to all life stages of the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae). J. Med. Entomol. Jul 28;23(4):400-4.
1986. Hooser SB, Beasley VR, Everitt JI. Effects of an insecticidal dip containing d-limonene in the cat. J. Am. Vet. Med. Assoc. Oct 15;189(8):905-8.
1988. Powers KA, Hooser SB, Sundberg JP, Beasley VR. An evaluation of the acute toxicity of an insecticidal spray containing linalool, d-limonene, and piperonyl butoxide applied topically to domestic cats. Vet Hum Toxicol. Jun;30(3):206-10.
1988. Hink WF, Liberati TA, Collart MG. Toxicity of linalool to life stages of the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae), and its efficacy in carpet and on animals. J. Med. Entomol. Jan;25(1):1-4.
1990. Magdalou J, Chajes V, Lafaurie C, Siest G. Glucuronidation of 2-arylpropionic acids pirprofen, flurbiprofen, and ibuprofen by liver microsomes. Drug Metab. Dispos. 18(5):692-7.
1990. Webb DR, Kanerva RL, Hysell DK, Alden CL, Lehman-McKeeman LD. Assessment of the subchronic oral toxicity of d-limonene in dogs. Food Chem Toxicol. Oct;28(10):669-75.
1990. Hooser SB. Toxicology of selected pesticides, drugs, and chemicals. D-limonene, linalool, and crude citrus oil extracts. Vet. Clin North Am Small Anim. Pract. Mar;20(2):383-5. Review.
1992. Frank AA, Ross JL, Sawvell BK. Toxic epidermal necrolysis associated with flea dips. Vet. Hum. Toxicol. Feb;34(1):57-61.
1994. Villar D, Knight MJ, Hansen SR, Buck WB. Toxicity of melaleuca oil and related essential oils applied topically on dogs and cats. Vet. Hum. Toxicol. 36(2):139-42.
1994. Grosjean, Nelly. Veterinary Aromatherapy: Natural remedies for cats, dogs, horses, birds & for the rearing of farm animals. St. Edmundsbury Press, England.
1995. Rosenbaum MR, Kerlin RL. Erythema multiforme major and disseminated intravascular coagulation in a dog following application of a d-limonene-based insecticidal dip. J. Am. Vet. Med. Assoc. Nov 15;207(10):1315-9.
1995. Nicholson SS. Toxicity of Insecticides and Skin Care Products of Botanical Origin. Veterinary Dermatology 6(3).
1997. Court MH and Greenblatt, DJ: Biochemical Basis for Deficient Paracetamol Glucuronidation in Cats: an Interspecies Comparison of Enzyme Constraint in Liver Microsomes. J. Pharm. Pharmacol., 49:466-449.
1997. Court MH, Greenblatt DJ. Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes. Biochem. Pharmacol. 53(7):1041-7.
1997. Chauret N, Gauthier A, Martin J, Nicoll-Griffith DA. In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse. Drug Metab. Dispos. 25(10):1130-6.
1998. Bischoff K, Guale FJ. Australian tea tree (Melaleuca alternifolia) oil poisoning in three purebred cats. Vet. Diagn. Invest. 10(2):208-10.
1999. Guitart R, Manosa S, Guerrero X, Mateo R. Animal poisonings: the 10-year experience of a veterinary analytical toxicology laboratory. Vet. Hum. Toxicol. 41(5):331-5.
2000. Castro E, Soraci A, Fogel F, Tapia O. Chiral inversion of R(-) fenoprofen and ketoprofen enantiomers in cats. J. Vet. Pharmacol. Ther. 23(5):265-71.
2000. Court MH, Greenblatt DJ. Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics. 10(4):355-69.
2001. Castro EF, Soraci AL, Franci R, Fogel FA, Tapia MO. Disposition of suprofen enantiomers in the cat. Vet. J. 162(1):38-43.
2002. Lee JA, Budgin JB, Mauldin EA. Acute necrotizing dermatitis and septicemia after application of a d-limonene-based insecticidal shampoo in a cat. J Am Vet Med Assoc. Jul 15;221(2):258-62, 239-40.
2002. Leigh Bell, Kristen. Holistic Aromatherapy for Animals: A Comprehensive Guide to the Use of Essential Oils & Hydrosols with Animals. Findhorn Press, Scotland, UK.
2003. Wynn, SG and Marsden, S. Manual of Natural Veterinary Medicine: Science and Tradition. Mosby/Elsevier.
2004. Krishnaswamy S, Hao Q, Von Moltke LL, Greenblatt DJ, Court MH. Evaluation of 5-hydroxytryptophol and other endogenous serotonin (5-hydroxytryptamine) analogs as substrates for UDP-glucuronosyltransferase 1A6. Drug Metab. Dispos. 32(8):862-9.
2005. Robertson, SA. Managing pain in feline patients. Vet. Clin. North Am. Small Anim. Pract. 35(1):129-146.
2006. Tanaka N, Miyasho T, Shinkyo R, Sakaki T, Yokota H. cDNA cloning and characterization of feline CYP1A1 and CYP1A2. Life Sci. 25;79(26):2463-73.
2007. Lascelles BD, Court MH, Hardie EM, Robertson SA. Nonsteroidal anti-inflammatory drugs in cats: a review. Vet. Anaesth. Analg. 34(4):228-50.
2007. Sun J. D-Limonene: safety and clinical applications. Altern. Med. Rev. 12(3):259-64.
2008. Hovda LR. Toxin exposures in small animals. in: Bonagura Jd and Twedt dC (eds). Kirk’s current veterinary therapy XIV. Philadelphia: Elsevier Saunders, 2008, pp 92–94
2010. Grave TW, Boag AK. Feline toxicological emergencies: when to suspect and what to do. J. Feline Med. Surg. Nov;12(11):849-60.
2010. Poppenga R. Toxicological Emergencies In: Drobatz KJaC, Merilee F, ed. Feline Emergency and Critical Care Medicine. Aimes, Iowa: Blackwell Publishing, Ltd, 2010.
2011. Rishniw M, Wynn SG. Azodyl, a synbiotic, fails to alter azotemia in cats with chronic kidney disease when sprinkled onto food. J. Fel. Med. Surg. 13(6): 405-409.
2011. Shrestha B1, Reed JM, Starks PT, Kaufman GE, Goldstone JV, Roelke ME, O’Brien SJ, Koepfli KP, Frank LG, Court MH. Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory. PLoS One. Mar 28;6(3):e18046.
2012. Norrgran J, Jones B, Lindquist NG, Bergman A. Decabromobiphenyl, polybrominated diphenyl ethers, and brominated phenolic compounds in serum of cats diagnosed with the endocrine disease feline hyperthyroidism. Arch. Environ. Contam. Toxicol. 63(1):161-8.
2012. Genovese AG, McLean MK, Khan SA. Adverse reactions from essential oil-containing natural flea products exempted from Environmental Protection Agency regulations in dogs and cats. J. Vet. Emerg. Crit. Care (San Antonio). 22(4):470-5.
2012. McLean MK, Hansen SR. An overview of trends in animal poisoning cases in the United States: 2002–2010. Vet. Clin. North Am. Small Anim. Pract. 42: 219–228.
2012. Caloni F, Cortinovis C, Rivolta M, Davanzo F. Animal poisoning in Italy: 10 years of epidemiological data from the Poison Control Centre of Milan. Vet. Rec. 21;170(16):415.
2013. Moraes TM, Rozza AL, Kushima H, Pellizzon CH, Rocha LR, Hiruma-Lima CA. Healing actions of essential oils from Citrus aurantium and d-limonene in the gastric mucosa: the roles of VEGF, PCNA, and COX-2 in cell proliferation. J. Med. Food. 16(12):1162-7.
2013. Court, MH: Feline drug metabolism and disposition: pharmacokinetic
evidence for species differences and molecular mechanisms. Vet. Clin. North Am. Small Anim. Pract., 43(5):1039-1054.
2013. Ebner T, Schänzle G, Weber W, Sent U, Elliott J. In vitro glucuronidation of the angiotensin II receptor antagonist telmisartan in the cat: a comparison with other species. J. Vet. Pharmacol. Ther. 36(2):154-60.
2013. Kim YW, Kim MJ, Chung BY, Bang du Y, Lim SK, Choi SM, Lim DS, Cho MC, Yoon K, Kim HS, Kim KB, Kim YS, Kwack SJ, Lee BM. Safety evaluation and risk assessment of d-Limonene. J. Toxicol. Environ. Health B Crit Rev. 16(1):17-38.
2014. Khan SA, McLean MK, Slater MR. Concentrated tea tree oil toxicosis in dogs and cats: 443 cases (2002-2012). J. Am. Vet. Med. Assoc. 1;244(1):95-99.
2014. Saengtienchai A, Ikenaka Y, Nakayama SM, Mizukawa H, Kakehi M, Bortey-Sam N, Darwish WS, Tsubota T, Terasaki M, Poapolathep A, Ishizuka M. Identification of interspecific differences in phase II reactions: determination of metabolites in the urine of 16 mammalian species exposed to environmental pyrene. Environ. Toxicol. Chem. 33(9):2062-2069.
2014. Van Beusekom CD, Fink-Gremmels J, Schrickx JA. Comparing the glucuronidation capacity of the feline liver with substrate-specific glucuronidation in dogs. J. Vet. Pharmacol. Ther. 37(1):18-24.
2014. Dhibi S, Mbarki S, Elfeki A, Hfaiedh N. Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat. Bosn J Basic Med Sci. May;14(2):99-104.
2014. McDonnel SJ, Tell LA, Murphy BG. Pharmacokinetics and pharmacodynamics of suberoylanilide hydroxamic acid in cats. J. Vet. Pharmacol. Ther. 37(2):196-200.
2014. Caloni F, Cortinovis C, Pizzo F, Rivolta M, Davanzo F. Epidemiological study (2006-2012) on the poisoning of small animals by human and veterinary drugs. Vet Rec. 1;174(9):222.
2014. Audrain H, Kenward C, Lovell CR, Green C, Ormerod AD, Sansom J, Chowdhury MM, Cooper SM, Johnston GA, Wilkinson M, King C, Stone N, Horne HL, Holden CR, Wakelin S, Buckley DA. Allergy to oxidized limonene and linalool is frequent in the U.K. Br J Dermatol. Aug;171(2):292-7.
2015. Van Beusekom CD, van den Heuvel JJ, Koenderink JB, Russel FG, Schrickx JA. Feline hepatic biotransformation of diazepam: Differences between cats and dogs. Res. Vet. Sci. 103:119-25.
2015. Kakehi M, Ikenaka Y, Nakayama SM, Kawai YK, Watanabe KP, Mizukawa H, Nomiyama K, Tanabe S, Ishizuka M. Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species. Toxicol. Sci. 147(2):360-9.
2015. Addie DD, Boucraut-Baralon C, Egberink H, Frymus T, Gruffydd-Jones T, Hartmann K, Horzinek MC, Hosie MJ, Lloret A, Lutz H, Marsilio F, Pennisi MG, Radford AD, Thiry E, Truyen U, Möstl K. European Advisory Board on Cat Diseases. Disinfectant choices in veterinary practices, shelters and households: ABCD guidelines on safe and effective disinfection for feline environments. J. Fel. Med. Surg. 17(7):594-605.
2015. Ramos CAF, Sá RCDS, Alves MF, Benedito RB, de Sousa DP, Diniz MFFM, Araújo MST, de Almeida RN. Histopathological and biochemical assessment of d-limonene-induced liver injury in rats. Toxicol. Rep. 9;2:482-488.
2016. Redmon JM, Shrestha B, Cerundolo R, Court MH. Soy isoflavone metabolism in cats compared with other species: urinary metabolite concentrations and glucuronidation by liver microsomes. Xenobiotica. 46(5):406-15.
2017. Slovak JE, Mealey K, Court MH: Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes. J. Vet. Pharmacol. Ther. 40(2):123-129.
2017. Mizukawa H, Ikenaka Y, Kakehi M, Nakayama S, Ishizuka M. Characterization of Species Differences in Xenobiotic Metabolism in Non-experimental Animals. Yakugaku Zasshi. 137(3):257-263.
2017. Burnett K, Puschner B, Ramsey JJ, Lin Y, Wei A, Fascetti AJ. Lack of glucuronidation products of trans-resveratrol in plasma and urine of cats. J. Anim. Physiol. Anim. Nutr. (Berl). 101(2):284-292.
Interpretation of the Data
Science shows – cats do possess less of the enzymes required for the metabolism of many items. Why do we state specific oils as cautionary for cats? Let’s tackle a few.
Citrus oils. These are often listed as toxic to cats for a variety of reasons. A Google search reveals many of these theories, however very little link to any actual data or research. Among claims I found the following statements.
Citrus oils contain monoterpene hydrocarbons (limonene) which can be toxic to cats.
d-Limonene and linalool are citrus oils with insecticidal properties. These are metabolized in the liver resulting in liver damage or failure.
Cats are uniquely sensitive to phenolics and other compounds containing benzene rings. Compounds preserved in benzyl alcohol are toxic to cats.
My cat had to be euthanized last January with the symptoms of Essential Oil poisoning, because I had no idea that the Citrus and Pine Oils I was diffusing near her litter box were causing her harm. Until I purchased this book recently, I had no idea that these seemingly harmless oils could be fatal to cats.
Limonene is a terpene that leads to the citrus scent of lemons. D-limonene has been used in dog shampoos and fragrances. The small amount present in dog products is safe for most sizes of dogs. For cats, it can prove lethal. Limonene is also used in flavoring compounds, cosmetic products, and cleaning products. Keep all of these away from your feline.
Citrus Oils: d-limonene and linalool are common citrus oils that be found in a variety of household products, including household and personal fragrances, cleansers, insect repellants, and even pet dips. These oils acts as irritants to the skin and gastric mucosa and commonly cause skin lesions and gastrointestinal upset. Exposure via the dermal or oral route can cause toxicity.
In actuality – it was pretty difficult to find cases of citrus toxicity in cats. The main toxicity report regarding felines was for d-limonene. With a search PubMed for “limonene toxicity feline” – only three articles were found. One of these articles focused on the toxicity of d-limonene against the cat flea, and not actually as toxic to a cat. The other two articles (from 1986 and 1988) related to an insecticidal spray or dip containing d-limonene being applied to cats in high concentrations.
From “Effects of an insecticidal dip containing d-limonene in the cat” Journal of the American Veterinary Medical Association, 1986 – the following abstract is quoted:
“A study was undertaken to determine the effects of a single dermal application of a commercial insecticidal dip containing 78.2% d-limonene in cats. At the manufacturer’s recommended concentration of 1.5 oz/gal of water, no clinical signs or lesions of toxicosis were seen. At 5 times the recommended concentration, clinical signs were mild and consisted of hypersalivation of short duration, ataxia, and muscle tremors resembling shivering. At 15 times the recommended concentration, clinical signs included hypersalivation lasting 15 to 30 minutes, moderate-to-severe ataxia lasting 1 to 5 hours, muscle tremors resembling shivering lasting 1 to 4 hours, and severe hypothermia beginning soon after treatment and lasting 5 hours. Gross lesions were confined to excoriation of the scrotal and perineal areas of the treated male cats at the 15 X concentration. No deaths or other lasting effects were seen at any dosage.”
In general, all cases reported of citrus oil toxicity in cats also maintained that there was dermal exposure to the cats, at 5-10 times the normal concentrations. These were mainly within the dip and spray formulations.
Not related to the metabolism of d-limonene were articles on necrotizing dermatitis and severe skin reactions to the application of products (mainly for fleas) containing d-limonene. This was certainly not the only ingredient within the product, and certainly not obtained directly as an essential oil.
Please see the article from 2007 “D-Limonene: safety and clinical applications”for more complete information on safety data regarding d-limonene.
Linalool. In a search for “linalool toxicity feline” only two articles were found. Only one article (shared in the 1988 article An evaluation of the acute toxicity of an insecticidal spray containing linalool, d-limonene, and piperonyl butoxide applied topically to domestic cats.) referenced toxicity to cats. While the other article was in regards to linalool having toxic effects against the cat flea again, and not the cat itself.
It would appear, that based on research that linalool and limonene were effective against cat fleas, that someone created a product which did not possibly bode well for the feline population experiencing it. However, it would seem that these articles were taken as a blanket statement to say “no citrus oil, ever” for cats.
Eucalyptus. This oil is often reported as toxic to cats. While the essential oil and eucalyptol (1,8-cineole) is reported as toxic on the ASPCA Toxic and Non-Toxic Plants list, it does not give any further references or information as to why this might be. A search on PubMed, does not reveal any associations directly with eucalyptus and animals. It is likely that gross misuse with topical applications or ingestion of the plant has resulted in this listing. Also, no information on species of eucalyptus is provided. While some may show concern for the high 1,8-cineole content of most eucalyptus oil, without gross and toxic misuse of the oil, it does not appear to have extreme toxicity concerns. Research even indicates it being protective against hepatotoxicity (2014 Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat.) Research would appear to support that while topical and oral administrations of this oil should be done with care, diffusion is likely to hold no harm. More information can be found on eucalyptus safety within Tisserand and Young’s Essential Oil Safety second edition.
Phenols. While research shows that cats have a decreased ability to metabolize phenols, this does not mean that they are completely unable. In the November 1984 edition of Veterinary Clinics of North America: Small Animal Practice – Vol. 14, No. 6; titled Symposium on Advances in Feline Medicine II, Jeff R. Wilcke DVM, MS states, “Even drugs known for toxicity in cats can be used safely if we are aware of and compensate for certain peculiarities.”
In the 2011 article Azodyl, a synbiotic, fails to alter azotemia in cats with chronic kidney disease when sprinkled onto food.; Doctors Rishniw and Wynn state the following: “Recently, investigators have examined the ability of probiotic-prebiotic combination (known as ‘synbiotic’) therapy to aid in reducing azotemia – a process called ‘enteric dialysis’. Specific bacteria capable of metabolizing urea, creatinine, indoles, phenol and nitrosamine into non-toxic metabolites, have been selected for this purpose.” The statement would indicate that there are alternative methods for phenol metabolism, than simply the liver enzyme pathways that cats possess.
With logical and appropriate use of essential oils containing natural phenol compounds, cats clearly compensate for any reduction in metabolism speed. It again, is all dependent on the dose and frequency of administration. While it may seem logical that cats have lost their ability to metabolize plant related chemicals due to their “hypercarnivory”(2011 Shrestha et.al.) – it is interested to consider these statements from 2017 Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes.
“However, given the major role for glucuronidation…metabolism in humans, there are concerns that the known deficiencies of UGT1A9 (and other UGTs) in cats could also cause deficient MPA glucuronidation, potentially delaying MPA clearance and leading to MPA accumulation and toxicity. Without a good understanding of MPA clearance in cats, it is not possible to determine the dose required to achieve an effective and safe blood concentration in the feline species….we did find significantly slower formation of the MPA phenol glucuronide in cats vs. dogs and humans. However, we also found a much smaller difference in overall metabolism…by conjugation when comparing cat liver microsomes with dog and human liver microsomes despite significantly reduced MPA pheno glucuronide formation in cats. This occurred in large part because of the substantially higher relative contribution of glucosidation to total MPA conjugation in cat liver microsomes (60%) when compared to the dog (34%) and especially the human (2%) liver microsomes.”
“Although glucosidation is the major pathway for conjugative metabolism of xenobiotics in nonvertebrate species (including insects and plants), glucuronidation is the dominant conjugative clearance mechanism in all vertebrates studied to date.”
“In future studies, one should consider the potential for glucosidation (vs. glucuronidation) as a major alternate clearance pathway for drugs used in cats.”
“Our results indicate that cats may express a UGT that has a higher catalytic efficiency for glucosidation of MPA than those expressed by humans and dogs.”
These statements would seem to indicate, that while cats are “deficient” in one respect, they excel in others. And the fact that they perform glucosidation so much more efficiently when compared to humans or dogs, shows that they have other pathways of metabolism – even those that are normally more prevalent in insects and plants.
Benzene Rings, Benzyl Alcohol. These are also often listed as toxic to cats, and often are linked with phenol toxicity explanations. The main research that supports this claim is from 1982, when the FDA issued a statement finally claiming Benzyl alcohol hazardous as a parenteral preservative. While this substance is related to other chemicals found within essential oils, it is noteworthy that this is a synthetic compound, which was being used as a preservative in intravenous fluids. A much different situation than the proper use within aromatherapy applications. Benzyl alcohol is mainly found in “essential oils” that are not recommended for use with animals – these include Benzoin and other absolutes such as hyacinth, narcissus, violet leaf, champaca, bakul, and jasmine.
Pinene. An alkene hydrocarbon, this constituent is found in over 400 essential oils (Tisserand and Young 2014). While there is a report on Pine-sol toxicity (1986 Acute Pinesol toxicity in a domestic cat) it does appear that possibly this listing is more related to the increased potential of α-pinene containing oils to oxidize and cause increased rates of sensitization and reaction. While again, we should be careful to use fresh, non-damaged essential oils, and use them with proper dilutions and protocols, there did not appear to be an overt reason to avoid the chemical pinene in cats specifically.
Terpineol. Also found listed as contraindicated for cats, it is also “found in a great many essential oils” according to Tisserand and Young. Terpineol does not appear to have basis to avoid in cats specifically.
Single essential oils are also included on lists to avoid with cats. I urge you to find further reading within the reference book Essential Oil Safety, second edition by Robert Tisserand and Rodney Young. This book will help you the most when deciphering toxicity concerns and cautions.
Lemon, lime, orange, grapefruit, bergamot, mandarin, tangerine, petitgrain, and neroli all are included on lists as they are in the Citrus class of oils.
Cinnamon, clove, thyme, oregano, savory, and cassia are all higher in Phenols.
Cajuput is high in 1,8-cineole and also contains terpineol.
Camphor is an essential oil, and a chemical constituent found in many essential oils. There is a lot of data contained within Tisserand and Young’s Essential Oil Safety on camphor which I encourage you to read. Listings cautioning against the use of camphor, never qualify if it is the constituent or the essential oil they are referring to. In high concentrations, it can pose health risks, and is listed as toxic in regards to humans. Camphor (many species) essential oil is not recommended for use within Veterinary Aromatic Medicine. Camphor as a chemical constituent can be found in small percentages within many essential oils known to be safe for use with animals, however oils high in camphor content, are often not used (Spike Lavender).
Pine (while no species is ever mentioned) contains pinene and terpineol, but is also prone to oxidation issues that can cause increase of dermatitis issues. Fir, Cypress, Juniper, and Spruce are likely included in most of the tree oil or “pine-type” categories to avoid.
Peppermint is often included in lists of oils to be avoided with cats. But research reviews, and even the most respected conservative animal references, rarely list it. Most toxicity or adverse events are from gross misuse and overdosage situations (full undiluted applications).
Tansy is often included in lists to be avoided with cats, again with no apparent justification. While certain species may have shown signs of adverse reactions with gross overuse, Tisserand and Young, Essential Oil Safety list Tansy (Tanacetum vulgare) as “Slightly toxic (oral), non-toxic (dermal)” for animals. The β-Thujone presence in this oil is likely what earns its concern, and listing – which is regarded as moderately toxic. In general, this is an oil that is not recommended for use within Veterinary Aromatic Medicine.
Tea Tree (or Melaleuca alternifolia) is almost always found on cautionary lists, however almost every report of toxicity is gross misuse.
Birch and Wintergreen should be avoided for use with animals due to methyl salicylate content.
Rue often makes the list of oils to avoid, but in actuality it is considered safe by the FDA for human consumption according to Tisserand and Young. While this oil is not commonly used with animals, it has been within reasonable guidelines. It actually has available safety data with animals, and shows quite safe levels in terms of LD50 measurements. Aromatherapy literature carries much caution for this ketone rich oil, which has been thought to be neurotoxic or cause seizures. However, according to Tisserand and Young “A convulsant effect for rue oil seems unlikely.”
There are a few oils that make the list as contraindicated for cats – but truly remain listed as contraindicated for almost all of the aromatherapy world. Bitter Almond, Boldo, Calamus, Garlic, Horseradish, Mustard, Sassafras, Wormseed (Chemopodium), and Pennyroyal are likely to be found on anyone’s list of oils that are not commonly used or recommended for use, even with humans.
Summary and Conclusion
Clearly, essential oils are not benign substances. They must be respected and used with care. However, when reports of toxicity occur, it is greatly important that further information is provided regarding the case. In veterinary medicine, and with pet poison control centers everywhere, it would be irresponsible and unheard of to not ask further questions about a potential poisoning. However, the questions regarding essential oils and their evaluation are usually not collected in a clinical case. If you called the poison control center about potential rodenticide ingestion, you will immediately be asked for the active ingredients, brand, amount consumed, etc…to help with the evaluation and treatment options.
With essential oil toxicity cases I rarely find that information on the species of oil used, brand, lot number, purchase date, dosage and route to have been collected. This is vastly important to accurate and truthful documentation of valid concerns for every animal lover. Complete blood work and a minimum data base, is also rarely collected, nor compared to earlier values. If someone reports a case of essential oil toxicity to you – please do ask for the medical information. At a minimum I would ask for the species and source of the essential oil, purchase date, how it was used, how long it was used for, prior health concerns for the animal, weight and species of the animal, prior blood work results and status, and current laboratory and physical exam findings. So often, essential oils are the obvious thing to blame when an animal all of a sudden appears ill. And the internet is an easy way to find support of this theory. However, in true clinical evaluation, I often find very poor cause and effect relationships. With the vast number of people using essential oils in their home, we can be quick to get into a trap of blaming any illness upon the presence of essential oils. And this, we need to be careful to avoid. I have consulted with many veterinarians who missed the true diagnosis for weeks, due to the assumption that the essential oils were at the root cause. While I will never say essential oils cannot hurt an animal, we also need to be realistic that when a Facebook post is shared over half a million times, all to animal loving people – the statistics are in the favor of someone also having an animal that falls sick at the time of reading it.
We should be required to obtain more information to prove cause and effect relationships. And I urge you to always look at each research article, Facebook post, reference book, blog, or what-have-you with a critical eye. I often say I need to know more than “My cat was dying, so I applied essential oils and my cat died!” – as proof to a toxicity concern. I greatly sympathize with all of those who are concerned that they have unknowingly injured their animal with the use of essential oils. However, let’s not forget that there are many more animal guardians who have compromised the health of their animal with poor diet (causing crystals and stones in urine) or with chronic use of fabric softeners, air fresheners, or second hand smoke. I merely urge a stance of critical evaluation, instead of fear-based and poorly documented reports and concerns.
Melissa Shelton DVM
More on the author: Melissa Shelton DVM attained her degree from The University of Minnesota College of Veterinary Medicine in 1999. She is the owner of Crow River Animal Hospital in Howard Lake, MN – where her work with the medical use of essential oils for animals began in 2008. In 2011, she dedicated her practice solely to the research and advancement of veterinary aromatic medicine. Dr. Shelton is devoted to providing accurate, honest, and documented information regarding essential oil use in the animal kingdom – and is a popular speaker at veterinary conferences. In 2014, Dr. Shelton introduced animalEO, a line of veterinary essential oil products for animals. She has presented on the use of essential oils throughout the United States, Japan, Australia, and Canada and has also authored several books and journal articles regarding the use of essential oils in animals.
More information can be found on our website www.animalEO.info
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