- Email: [email protected]
Propylene Glycol
CHAPTER
Propylene Glycol Karyn Bischoff, DVM, MS, DABVT
72
• P ropylene glycol (PG) is used as automotive antifreeze, in hydraulic fluid, industrial and pharmaceutical solvent, cosmetics, and as an additive in processed foods. • Clinical signs following oral exposure are related to propylene glycol’s narcotic effects and lactic acidosis: depression, ataxia, muscle twitching, and seizures. • Increased numbers of Heinz bodies, reticulocytes, and lower packed cell volumes occur in animals, particularly felines, exposed to propylene glycol.
S
mall animals occasionally have access to automotive solvents. Dogs and cats sometimes obtain access to a garage where there are open containers, or solvents can be found in an outdoor setting when automobile radiators are drained or fluids leak. The most toxic radiator fluid is ethylene glycol (see Chapter 47 on Ethylene Glycol), which animals frequently have access to, and it presents a significant problem to the small animal practitioner. Propylene glycol is commonly used as a relatively “safe” alternative to ethylene glycol as antifreeze. Propylene glycol has other uses ranging from industrial solvent to food additive. It was once used in semimoist cat foods, some of which contained more than 10% propylene glycol. However, propylene glycol is no longer used in cat foods because cats are particularly susceptible to its adverse effects. Toxicosis from large doses of propylene glycol has been reported in people and various other species.
Sources Propylene glycol, or 1,2-propanediol, is a stable, colorless, odorless, viscous liquid with a specific gravity of 1.036. It is an excellent solvent because it is freely miscible with water yet dissolves hydrophobic substances. Among the glycols, propylene glycol has the lowest toxicity.1 Unlike ethylene glycol, propylene glycol does not cause oxalate nephrosis. Propylene glycol is classified by the Food and Drug Administration (FDA) as “generally recognized as safe” except for use in cat foods. Because of these properties, it is used not only as automotive antifreeze, hydraulic fluid, and an industrial solvent, but also as a pharmaceutical solvent for oral, topical, and injectable preparations; an ingredient in cosmetics; and an additive in processed foods for human and animal consumption.
Toxic Dose The oral median lethal dose (LD50) for propylene glycol in dogs is reported to be as low as 9 mL/kg, although for most laboratory animal species it is approximately 20 mL/kg.2-5 The toxic concentration in blood in humans is estimated at 100 mg/dL, although metabolic 763
764 SECTION 4 Specific Toxicants changes have been reported at blood concentrations as low as 12 mg/dL.6,7 Patients with hepatic or renal disease are at increased risk for propylene glycol toxicosis.6,7
Toxicokinetics Acute propylene glycol toxicosis has occurred in humans, horses, and cattle because of ingestion, parenteral administration, and topical treatment for burns.2,3,8-16 The condition has also been experimentally produced in cats, dogs, laboratory animals, goats, and chickens.1,3-5,17-21 Propylene glycol is palatable to dogs.22 It is absorbed rapidly in the digestive system.8 Toxic doses can also be absorbed through damaged skin, and toxicosis has been reported in burn patients.1,16,23,24 Experimental inhalation exposures of 5 mg/dL and greater were associated with adverse effects in dogs.25 Oral and pulmonary absorption of propylene glycol are rapid and the volume of distribution is 0.5 L/kg in humans.25,26 Between 12% and 55% of propylene glycol is excreted in the urine as the parent compound or a glucuronide conjugate in humans, and renal clearance decreases as dose increases.7,26-30 Remaining propylene glycol is oxidized by two saturable enzymes, hepatic alcohol dehydrogenase and aldehyde dehydrogenase, to D and L isomers of lactic acid.8 L-lactic acid enters the citric acid cycle and is metabolized rapidly.10 However, D-lactic acid is not readily metabolized, accumulates in plasma, and produces lactic acidosis.10,30 Propylene glycol concentrates in the central nervous system in humans.15 Propylene glycol has narcotic effects similar to those of ethanol, although it is only about one third as potent.1,2,10,16,23 Dogs eliminate propylene glycol almost completely within 24 hours.18 The elimination half-life in mature humans is 1.4 to 5 hours, and 10 to 31 hours in infants.26,29 Heinz body formation occurs through the interaction of propylene glycol or its metabolite with the sulfhydryl groups on the hemoglobin molecule.1,31,32 The hemoglobin molecule becomes denatured and adheres to the cell membrane. Cats are particularly sensitive, possibly because their hemoglobin contains eight sulfhydryl groups and because they have less ability to conjugate propylene glycol with glucuronide than other domestic species. Heinz body numbers decrease to reference ranges within 8 weeks of cessation of exposure.33,34
Clinical Signs Clinical signs of acute propylene glycol poisoning in small animals are related to its narcotic effects and to lactic acidosis. Most patients present with central nervous system depression and ataxia after they have ingested large quantities of propylene glycol.8,26,27,35-39 Seizures have also been reported in human cases.2,6,8-10 Muscle twitching is sometimes evident in cats.21 The author is familiar with a case of malicious poisoning with propylene glycol where three dogs were found dead. Parenteral overdosing with propylene glycol has been associated with hypotension in cats and circulatory collapse in dogs and other species.8,10,18,20,28 Renal failure due to acute tubular injury is reported in people.6,7 Intravenous infusion of undiluted propylene glycol is associated with hemolysis because of the hyperosmolarity of the compound.8 Osmotic diuresis and dehydration are also commonly seen with oral and parenteral exposure to propylene glycol.1,4,19,22 Topical exposure to propylene glycol has been associated with contact dermatitis due to hypersensitivity in humans.14 Mucosal irritation has been reported with chronic respiratory exposure in laboratory rodents.25
Minimum Database Clinical pathologic findings in animals with propylene glycol toxicosis are consistent with metabolic acidosis and hyperosmolarity. Animals have an increase in the ion gap, which correlates with blood lactic acid concentrations.3,8-11,40 Carbon dioxide and carbonic acid concentrations are low.10 Hypoglycemia has been reported in some animals.1 Urine has a low specific gravity because of osmotic diuresis and casts are sometimes observed.11,15 Blood
Chapter 72 | Propylene Glycol 765
urea nitrogen and creatinine are elevated in people due to proximal convoluted tubular injury.9 The serum is hyperosmolar after intravenous administration, and the increase in osmolarity correlates with the circulating propylene glycol concentration.6,8 Hemoglobinuria has been reported in dogs and other species secondary to hemolysis after high intravenous doses of propylene glycol.3,20,27 Heinz body formation has been reported in cats and horses secondary to ingestion of propylene glycol.1,17,31-33,38 Heinz bodies were present in up to 18% of erythrocytes in adult cats and 36% in kittens as a result of dietary exposure.4,17,31,32 There have been no reports of clinical anemia or methemoglobinemia in cats because of chronic dietary exposure to propylene glycol, although PCVs are mildly reduced.31,36,41 However, such exposure could predispose feline red cells to more severe oxidative damage by other agents, such as acetaminophen.17 Experimental dogs fed diets containing 20% propylene glycol had decreased PCVs, increased reticulocyte counts, increased nucleated erythrocyte counts, and evidence of hemolysis.1,42 Similar changes were seen in experimental dogs with chronic respiratory exposure to propylene glycol.25
Confirmatory Tests Diagnosis of propylene glycol toxicosis is usually based on a history of exposure. Propylene glycol can be detected in urine and serum by gas chromatography.9,12,23 Poisoning was confirmed using gas chromatography to detect residue in a container found near the three dogs in the terminal case mentioned previously. Importantly, propylene glycol will produce a false positive for ethylene glycol on some commercially available ethylene glycol test kits (refer to Chapter 47, “Ethylene Glycol”).
Treatment Treatment of acute propylene glycol toxicosis is supportive. Intravenous fluids containing sodium bicarbonate should be administered as needed to correct dehydration and acidosis, and any electrolyte abnormalities should be corrective. A horse with propylene glycol toxicosis was treated by gastric lavage to remove remaining material in the stomach, activated charcoal to adsorb propylene glycol, and given isotonic sodium bicarbonate and dexamethasone IV. Blood gas was monitored on an hourly basis.38 Because of rapid gastrointestinal absorption, gastrointestinal decontamination is unlikely to be beneficial in most cases. Vitamin C was administered to diminish oxidative damage to erythrocytes in an intoxicated horse.38 However, experimental administration of vitamin C and vitamin E failed to significantly decrease Heinz body formation in cats fed a diet containing propylene glycol, and N-acetylcysteine was only slightly beneficial.41 Fomepizole was used in a human patient given excessive doses of propylene glycol intravenously to decrease the rate of metabolism (via alcohol dehydrogenase) and production of lactic acid.40 Although of possible use in veterinary medicine, fomepizole treatment of propylene glycol toxicosis in cats should be pursued with caution, because it is possible that the parent compound is responsible for the erythrocyte damage seen in this species.
Prognosis The prognosis is highly variable depending on the exposure dose and time interval between exposure and initiation of treatment. In general, it would be considered guarded to fair.
Gross and Histologic Lesions There are sometimes no gross or microscopic lesions in animals poisoned with propylene glycol.18 A foul or garlic-like odor to gastrointestinal contents has been reported in horses and a llama.38,39 Reported kidney lesions include congestion and tubular necrosis.5,12,35 Liver lesions have been reported in horses.35
766 SECTION 4 Specific Toxicants
Differential Diagnoses Some toxicants that could mimic this clinical presentation include ivermectin and other macrolide antiparasitic agents, ethylene glycol, methanol, diethylene glycol, 2-butoxyethanol, sedatives and tranquilizers, isopropanol, ethanol, xylitol, and amitraz. Other causes of a hemolytic anemia are zinc, naphthalene-containing mothballs, onions, acetaminophen, copper, and pit viper snakebites.
References 1. Christopher MM, Perman V, Eaton JW: Contribution of propylene glycol-induced Heinz body formation to anemia in cats, J Am Vet MedAssoc 194(8):1045–1056, 1989. 2. Yu DK, Elmquist WF, Sawchuck RJ: Pharmacokinetics of propylene glycol in humans during multiple dosing regimens, J Pharmacol Sci 74(8):876–879, 1985. 3. Dorman DC, Hascheck WM: Fatal propylene glycol toxicosis in a horse, J Am Vet Med Assoc 198(9): 1643–1644, 1991. 4. Ruddick JA: Toxicology, metabolism, and biochemistry of 1,2-propanediol, Toxicol Appl Pharmacol 21(1):102–111, 1972. 5. Gaunt IF, Carpanini FMB: Long-term toxicity of propylene glycol in rats, Food Cosmet Toxicol 10(5): 151–162, 1972. 6. Kraut JA, Kurtz I: Toxic alcohol ingestions: clinical features, diagnosis, and management, Clin J Am Soc Neprhol 3(1):208–225, 2008. 7. Zar T, Graeber C, Perazella MA: Recognition, treatment, and prevention of propylene glycol toxicity, Semin Dialysis 20(3):217–219, 2007. 8. Pastemak G: Ethylene/propylene glycol toxicity. In Goldfrank L, editor: Case studies in environmental medicine 30, San Rafael, CA, 1993, DeLima Associates. 9. Cate JC, Hedrick R: Propylene glycol intoxication and lactic acidosis, N Engl JMed 303(21):1237, 1980. 10. Christopher MM, Eckfeldt H, Eaton JW: Propylene glycol ingestion causes D-lactic acidosis, Lab Invest 60(1):114, 1990. 11. Van de Wiele B, Rubinstein E, et al: Propylene glycol toxicity caused by prolonged infusion of etomidate, J Neurosurg Anesthesiol 7(4):259–262, 1995. 12. McConnel JR, McAllister JL, Gross GG: Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema, Neurosurgery 38(1):232–233, 1996. 13. Levy ML, Aranda M, Zelman V, et al: Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema, Neurosurgery 37(2):363–371, 1995. 14. Angelini G, Meneghini CL: Contact allergy from propylene glycol, Contact Dermatitis 7(4):197–198, 1981. 15. Fligner CL, Jack R, Twiggs GA, et al: Hyperosmolality induced by propylene glycol, JAMA 253(11):1606– 1609, 1985. 16. MacDonald MG, Getson PR, Glasgow AM, et al: Propylene glycol: increased incidence of seizures in low birth weight infants, Pediatrics 79(4):622–625, 1987. 17. Bauer MC, Weiss DJ, Perman V: Hematological alterations in kittens induced by 6% and 12% dietary propylene glycol, Vet Hum Toxicol 34(2):127–131, 1992. 18. Hanzlik PH, Newman HW, Van Winkle W Jr, et al: Toxicity, fate and excretion of propylene glycol and some other glycols, J Pharmacol Exp Ther 67(12):101–113, 1939. 19. Moon PF: Acute toxicosis in two dogs associated with etomidate-propylene glycol infusion, Lab An Sci 44(6):590–594, 1994. 20. Seidenfeld MA, Hanzlik PJ: The general properties, actions and toxicity of propylene glycol, J Pharmacol Exp Ther 44:109–121, 1932. 21. Marshall DA, Doty RL: Taste responses of dogs to ethylene glycol, propylene glycol, and ethylene glycolbased antifreeze, J Am Vet Med Assoc 197(12):1599–1602, 1990. 22. Glasgow AM, Boeckx RL, Miller MK, et al: Hyperosmolality in small infants due to propylene glycol, Pediatrics 72(3):353–355, 1983. 23. Kelner MJ, Bailey DN: Propylene glycol as a cause of lactic acidosis, J Anal Toxicol 9(1):40–42, 1985. 24. Lehman AJ, Newman HW: Propylene glycol: rate of metabolism, absorption, and excretion with a method for estimation in body fluids, J Pharmacol Exp Ther 60:312–322, 1937. 25. Werley MS, McDonald P, Lilly P, et al: Non-clinical safety and pharmacokinetic evaulations of propylene glycol aerosol in Sprague-Dawley rats and Beagle dogs, Toxicol 287(1-3):76–90, 2011. 26. Brooks DE, Wallace KL: Acute propylene glycol ingestion, Clin Toxicol 40(4):513–516, 2002. 27. Arulanantham K, Genel M: Central nervous system toxicity associated with ingestion of propylene glycol, J Pediatr 93(3):515–516, 1978.
Chapter 72 | Propylene Glycol 767 28. Yu DK, Sawchuk RJ: Pharmacokinetics of propylene glycol in the rabbit, J Pharmacokinet Biopharm 15(5):453–471, 1987. 29. Allegaert K, Vanhaesenbrouck S, Kulo A, et al: Prospective assessment of short-term propylene glycol tolerance in neonates, Arch Dis Child 95(12):1054–1058, 2010. 30. Pintchuk PA, Galey FD, George LW: Propylene glycol toxicity in adult dairy cows, J Vet Intern Med 7(3):150, 1993. 31. Weiss D, McClay CB, Christopher MM, et al: Effects of propylene glycol containing diets on acetaminophen-induced methemoglobinemia in cats, J Am Vet Med Assoc 196(11):1816–1819, 1990. 32. Bauer MC, Weiss DJ, Perman V: Hematologic alterations in adult cats fed 6% or 12% propylene glycol, Am J Vet Res 53(1):69–72, 1992. 33. Dzanis DA: Propylene glycol unsafe for use in cat foods, FDA Vet 9(1):1–3, 1994. 34. Hickman MA, Rodgers QR, Morris JG: Effects of diet on Heinz body formation in kittens, Am J Vet Res 50(3):475–478, 1990. 35. Myers VS, Usenik EA: Propylene glycol intoxication of horses, J Am Vet Med Assoc 155(12):1969, 1841. 36. Gross DR, Kitzman JV, Adams HR: Cardiovascular effects of intravenous administration of propylene glycol and oxytetracycline and propylene glycol in calves, Am J Vet Res 40(6):783–791, 1979. 37. Martin G, Finberg L: Propylene glycol: a potentially toxic vehicle in liquid dosage form, J Pediatr 77(5):877–878, 1970. 38. McLanahan S, Hunter J, Murphy M, et al: Propylene glycol toxicosis in a mare, Vet Hum Toxicol 40(5):294–296, 1998. 39. Ivany JM, Anderson DE: Propylene glycol toxicosis in a llama, J Am Vet Med Assoc 218(2):243–244, 2001. 40. Zosel A, Egelhoff E, Heard K: Severe lactic acidosis from iatrogenic propylene glycol overdose, Pharmacother 30(2):219, 2011. 41. Hill AS, O’Niell S, Rogers QR, et al: Antioxidant prevention of Heinz body formation and oxidative injury in cats, Am J Vet Res 62(3):370–374, 2001. 42. Weil CS, Woodside MD, Smyth HF Jr, et al: Results of feeding propylene glycol in the diet to dogs for two years, Food Cosmet Toxicol 9(4):479–490, 1971.
Propylene Glycol Karyn Bischoff, DVM, MS, DABVT
72
• P ropylene glycol (PG) is used as automotive antifreeze, in hydraulic fluid, industrial and pharmaceutical solvent, cosmetics, and as an additive in processed foods. • Clinical signs following oral exposure are related to propylene glycol’s narcotic effects and lactic acidosis: depression, ataxia, muscle twitching, and seizures. • Increased numbers of Heinz bodies, reticulocytes, and lower packed cell volumes occur in animals, particularly felines, exposed to propylene glycol.
S
mall animals occasionally have access to automotive solvents. Dogs and cats sometimes obtain access to a garage where there are open containers, or solvents can be found in an outdoor setting when automobile radiators are drained or fluids leak. The most toxic radiator fluid is ethylene glycol (see Chapter 47 on Ethylene Glycol), which animals frequently have access to, and it presents a significant problem to the small animal practitioner. Propylene glycol is commonly used as a relatively “safe” alternative to ethylene glycol as antifreeze. Propylene glycol has other uses ranging from industrial solvent to food additive. It was once used in semimoist cat foods, some of which contained more than 10% propylene glycol. However, propylene glycol is no longer used in cat foods because cats are particularly susceptible to its adverse effects. Toxicosis from large doses of propylene glycol has been reported in people and various other species.
Sources Propylene glycol, or 1,2-propanediol, is a stable, colorless, odorless, viscous liquid with a specific gravity of 1.036. It is an excellent solvent because it is freely miscible with water yet dissolves hydrophobic substances. Among the glycols, propylene glycol has the lowest toxicity.1 Unlike ethylene glycol, propylene glycol does not cause oxalate nephrosis. Propylene glycol is classified by the Food and Drug Administration (FDA) as “generally recognized as safe” except for use in cat foods. Because of these properties, it is used not only as automotive antifreeze, hydraulic fluid, and an industrial solvent, but also as a pharmaceutical solvent for oral, topical, and injectable preparations; an ingredient in cosmetics; and an additive in processed foods for human and animal consumption.
Toxic Dose The oral median lethal dose (LD50) for propylene glycol in dogs is reported to be as low as 9 mL/kg, although for most laboratory animal species it is approximately 20 mL/kg.2-5 The toxic concentration in blood in humans is estimated at 100 mg/dL, although metabolic 763
764 SECTION 4 Specific Toxicants changes have been reported at blood concentrations as low as 12 mg/dL.6,7 Patients with hepatic or renal disease are at increased risk for propylene glycol toxicosis.6,7
Toxicokinetics Acute propylene glycol toxicosis has occurred in humans, horses, and cattle because of ingestion, parenteral administration, and topical treatment for burns.2,3,8-16 The condition has also been experimentally produced in cats, dogs, laboratory animals, goats, and chickens.1,3-5,17-21 Propylene glycol is palatable to dogs.22 It is absorbed rapidly in the digestive system.8 Toxic doses can also be absorbed through damaged skin, and toxicosis has been reported in burn patients.1,16,23,24 Experimental inhalation exposures of 5 mg/dL and greater were associated with adverse effects in dogs.25 Oral and pulmonary absorption of propylene glycol are rapid and the volume of distribution is 0.5 L/kg in humans.25,26 Between 12% and 55% of propylene glycol is excreted in the urine as the parent compound or a glucuronide conjugate in humans, and renal clearance decreases as dose increases.7,26-30 Remaining propylene glycol is oxidized by two saturable enzymes, hepatic alcohol dehydrogenase and aldehyde dehydrogenase, to D and L isomers of lactic acid.8 L-lactic acid enters the citric acid cycle and is metabolized rapidly.10 However, D-lactic acid is not readily metabolized, accumulates in plasma, and produces lactic acidosis.10,30 Propylene glycol concentrates in the central nervous system in humans.15 Propylene glycol has narcotic effects similar to those of ethanol, although it is only about one third as potent.1,2,10,16,23 Dogs eliminate propylene glycol almost completely within 24 hours.18 The elimination half-life in mature humans is 1.4 to 5 hours, and 10 to 31 hours in infants.26,29 Heinz body formation occurs through the interaction of propylene glycol or its metabolite with the sulfhydryl groups on the hemoglobin molecule.1,31,32 The hemoglobin molecule becomes denatured and adheres to the cell membrane. Cats are particularly sensitive, possibly because their hemoglobin contains eight sulfhydryl groups and because they have less ability to conjugate propylene glycol with glucuronide than other domestic species. Heinz body numbers decrease to reference ranges within 8 weeks of cessation of exposure.33,34
Clinical Signs Clinical signs of acute propylene glycol poisoning in small animals are related to its narcotic effects and to lactic acidosis. Most patients present with central nervous system depression and ataxia after they have ingested large quantities of propylene glycol.8,26,27,35-39 Seizures have also been reported in human cases.2,6,8-10 Muscle twitching is sometimes evident in cats.21 The author is familiar with a case of malicious poisoning with propylene glycol where three dogs were found dead. Parenteral overdosing with propylene glycol has been associated with hypotension in cats and circulatory collapse in dogs and other species.8,10,18,20,28 Renal failure due to acute tubular injury is reported in people.6,7 Intravenous infusion of undiluted propylene glycol is associated with hemolysis because of the hyperosmolarity of the compound.8 Osmotic diuresis and dehydration are also commonly seen with oral and parenteral exposure to propylene glycol.1,4,19,22 Topical exposure to propylene glycol has been associated with contact dermatitis due to hypersensitivity in humans.14 Mucosal irritation has been reported with chronic respiratory exposure in laboratory rodents.25
Minimum Database Clinical pathologic findings in animals with propylene glycol toxicosis are consistent with metabolic acidosis and hyperosmolarity. Animals have an increase in the ion gap, which correlates with blood lactic acid concentrations.3,8-11,40 Carbon dioxide and carbonic acid concentrations are low.10 Hypoglycemia has been reported in some animals.1 Urine has a low specific gravity because of osmotic diuresis and casts are sometimes observed.11,15 Blood
Chapter 72 | Propylene Glycol 765
urea nitrogen and creatinine are elevated in people due to proximal convoluted tubular injury.9 The serum is hyperosmolar after intravenous administration, and the increase in osmolarity correlates with the circulating propylene glycol concentration.6,8 Hemoglobinuria has been reported in dogs and other species secondary to hemolysis after high intravenous doses of propylene glycol.3,20,27 Heinz body formation has been reported in cats and horses secondary to ingestion of propylene glycol.1,17,31-33,38 Heinz bodies were present in up to 18% of erythrocytes in adult cats and 36% in kittens as a result of dietary exposure.4,17,31,32 There have been no reports of clinical anemia or methemoglobinemia in cats because of chronic dietary exposure to propylene glycol, although PCVs are mildly reduced.31,36,41 However, such exposure could predispose feline red cells to more severe oxidative damage by other agents, such as acetaminophen.17 Experimental dogs fed diets containing 20% propylene glycol had decreased PCVs, increased reticulocyte counts, increased nucleated erythrocyte counts, and evidence of hemolysis.1,42 Similar changes were seen in experimental dogs with chronic respiratory exposure to propylene glycol.25
Confirmatory Tests Diagnosis of propylene glycol toxicosis is usually based on a history of exposure. Propylene glycol can be detected in urine and serum by gas chromatography.9,12,23 Poisoning was confirmed using gas chromatography to detect residue in a container found near the three dogs in the terminal case mentioned previously. Importantly, propylene glycol will produce a false positive for ethylene glycol on some commercially available ethylene glycol test kits (refer to Chapter 47, “Ethylene Glycol”).
Treatment Treatment of acute propylene glycol toxicosis is supportive. Intravenous fluids containing sodium bicarbonate should be administered as needed to correct dehydration and acidosis, and any electrolyte abnormalities should be corrective. A horse with propylene glycol toxicosis was treated by gastric lavage to remove remaining material in the stomach, activated charcoal to adsorb propylene glycol, and given isotonic sodium bicarbonate and dexamethasone IV. Blood gas was monitored on an hourly basis.38 Because of rapid gastrointestinal absorption, gastrointestinal decontamination is unlikely to be beneficial in most cases. Vitamin C was administered to diminish oxidative damage to erythrocytes in an intoxicated horse.38 However, experimental administration of vitamin C and vitamin E failed to significantly decrease Heinz body formation in cats fed a diet containing propylene glycol, and N-acetylcysteine was only slightly beneficial.41 Fomepizole was used in a human patient given excessive doses of propylene glycol intravenously to decrease the rate of metabolism (via alcohol dehydrogenase) and production of lactic acid.40 Although of possible use in veterinary medicine, fomepizole treatment of propylene glycol toxicosis in cats should be pursued with caution, because it is possible that the parent compound is responsible for the erythrocyte damage seen in this species.
Prognosis The prognosis is highly variable depending on the exposure dose and time interval between exposure and initiation of treatment. In general, it would be considered guarded to fair.
Gross and Histologic Lesions There are sometimes no gross or microscopic lesions in animals poisoned with propylene glycol.18 A foul or garlic-like odor to gastrointestinal contents has been reported in horses and a llama.38,39 Reported kidney lesions include congestion and tubular necrosis.5,12,35 Liver lesions have been reported in horses.35
766 SECTION 4 Specific Toxicants
Differential Diagnoses Some toxicants that could mimic this clinical presentation include ivermectin and other macrolide antiparasitic agents, ethylene glycol, methanol, diethylene glycol, 2-butoxyethanol, sedatives and tranquilizers, isopropanol, ethanol, xylitol, and amitraz. Other causes of a hemolytic anemia are zinc, naphthalene-containing mothballs, onions, acetaminophen, copper, and pit viper snakebites.
References 1. Christopher MM, Perman V, Eaton JW: Contribution of propylene glycol-induced Heinz body formation to anemia in cats, J Am Vet MedAssoc 194(8):1045–1056, 1989. 2. Yu DK, Elmquist WF, Sawchuck RJ: Pharmacokinetics of propylene glycol in humans during multiple dosing regimens, J Pharmacol Sci 74(8):876–879, 1985. 3. Dorman DC, Hascheck WM: Fatal propylene glycol toxicosis in a horse, J Am Vet Med Assoc 198(9): 1643–1644, 1991. 4. Ruddick JA: Toxicology, metabolism, and biochemistry of 1,2-propanediol, Toxicol Appl Pharmacol 21(1):102–111, 1972. 5. Gaunt IF, Carpanini FMB: Long-term toxicity of propylene glycol in rats, Food Cosmet Toxicol 10(5): 151–162, 1972. 6. Kraut JA, Kurtz I: Toxic alcohol ingestions: clinical features, diagnosis, and management, Clin J Am Soc Neprhol 3(1):208–225, 2008. 7. Zar T, Graeber C, Perazella MA: Recognition, treatment, and prevention of propylene glycol toxicity, Semin Dialysis 20(3):217–219, 2007. 8. Pastemak G: Ethylene/propylene glycol toxicity. In Goldfrank L, editor: Case studies in environmental medicine 30, San Rafael, CA, 1993, DeLima Associates. 9. Cate JC, Hedrick R: Propylene glycol intoxication and lactic acidosis, N Engl JMed 303(21):1237, 1980. 10. Christopher MM, Eckfeldt H, Eaton JW: Propylene glycol ingestion causes D-lactic acidosis, Lab Invest 60(1):114, 1990. 11. Van de Wiele B, Rubinstein E, et al: Propylene glycol toxicity caused by prolonged infusion of etomidate, J Neurosurg Anesthesiol 7(4):259–262, 1995. 12. McConnel JR, McAllister JL, Gross GG: Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema, Neurosurgery 38(1):232–233, 1996. 13. Levy ML, Aranda M, Zelman V, et al: Propylene glycol toxicity following continuous etomidate infusion for the control of refractory cerebral edema, Neurosurgery 37(2):363–371, 1995. 14. Angelini G, Meneghini CL: Contact allergy from propylene glycol, Contact Dermatitis 7(4):197–198, 1981. 15. Fligner CL, Jack R, Twiggs GA, et al: Hyperosmolality induced by propylene glycol, JAMA 253(11):1606– 1609, 1985. 16. MacDonald MG, Getson PR, Glasgow AM, et al: Propylene glycol: increased incidence of seizures in low birth weight infants, Pediatrics 79(4):622–625, 1987. 17. Bauer MC, Weiss DJ, Perman V: Hematological alterations in kittens induced by 6% and 12% dietary propylene glycol, Vet Hum Toxicol 34(2):127–131, 1992. 18. Hanzlik PH, Newman HW, Van Winkle W Jr, et al: Toxicity, fate and excretion of propylene glycol and some other glycols, J Pharmacol Exp Ther 67(12):101–113, 1939. 19. Moon PF: Acute toxicosis in two dogs associated with etomidate-propylene glycol infusion, Lab An Sci 44(6):590–594, 1994. 20. Seidenfeld MA, Hanzlik PJ: The general properties, actions and toxicity of propylene glycol, J Pharmacol Exp Ther 44:109–121, 1932. 21. Marshall DA, Doty RL: Taste responses of dogs to ethylene glycol, propylene glycol, and ethylene glycolbased antifreeze, J Am Vet Med Assoc 197(12):1599–1602, 1990. 22. Glasgow AM, Boeckx RL, Miller MK, et al: Hyperosmolality in small infants due to propylene glycol, Pediatrics 72(3):353–355, 1983. 23. Kelner MJ, Bailey DN: Propylene glycol as a cause of lactic acidosis, J Anal Toxicol 9(1):40–42, 1985. 24. Lehman AJ, Newman HW: Propylene glycol: rate of metabolism, absorption, and excretion with a method for estimation in body fluids, J Pharmacol Exp Ther 60:312–322, 1937. 25. Werley MS, McDonald P, Lilly P, et al: Non-clinical safety and pharmacokinetic evaulations of propylene glycol aerosol in Sprague-Dawley rats and Beagle dogs, Toxicol 287(1-3):76–90, 2011. 26. Brooks DE, Wallace KL: Acute propylene glycol ingestion, Clin Toxicol 40(4):513–516, 2002. 27. Arulanantham K, Genel M: Central nervous system toxicity associated with ingestion of propylene glycol, J Pediatr 93(3):515–516, 1978.
Chapter 72 | Propylene Glycol 767 28. Yu DK, Sawchuk RJ: Pharmacokinetics of propylene glycol in the rabbit, J Pharmacokinet Biopharm 15(5):453–471, 1987. 29. Allegaert K, Vanhaesenbrouck S, Kulo A, et al: Prospective assessment of short-term propylene glycol tolerance in neonates, Arch Dis Child 95(12):1054–1058, 2010. 30. Pintchuk PA, Galey FD, George LW: Propylene glycol toxicity in adult dairy cows, J Vet Intern Med 7(3):150, 1993. 31. Weiss D, McClay CB, Christopher MM, et al: Effects of propylene glycol containing diets on acetaminophen-induced methemoglobinemia in cats, J Am Vet Med Assoc 196(11):1816–1819, 1990. 32. Bauer MC, Weiss DJ, Perman V: Hematologic alterations in adult cats fed 6% or 12% propylene glycol, Am J Vet Res 53(1):69–72, 1992. 33. Dzanis DA: Propylene glycol unsafe for use in cat foods, FDA Vet 9(1):1–3, 1994. 34. Hickman MA, Rodgers QR, Morris JG: Effects of diet on Heinz body formation in kittens, Am J Vet Res 50(3):475–478, 1990. 35. Myers VS, Usenik EA: Propylene glycol intoxication of horses, J Am Vet Med Assoc 155(12):1969, 1841. 36. Gross DR, Kitzman JV, Adams HR: Cardiovascular effects of intravenous administration of propylene glycol and oxytetracycline and propylene glycol in calves, Am J Vet Res 40(6):783–791, 1979. 37. Martin G, Finberg L: Propylene glycol: a potentially toxic vehicle in liquid dosage form, J Pediatr 77(5):877–878, 1970. 38. McLanahan S, Hunter J, Murphy M, et al: Propylene glycol toxicosis in a mare, Vet Hum Toxicol 40(5):294–296, 1998. 39. Ivany JM, Anderson DE: Propylene glycol toxicosis in a llama, J Am Vet Med Assoc 218(2):243–244, 2001. 40. Zosel A, Egelhoff E, Heard K: Severe lactic acidosis from iatrogenic propylene glycol overdose, Pharmacother 30(2):219, 2011. 41. Hill AS, O’Niell S, Rogers QR, et al: Antioxidant prevention of Heinz body formation and oxidative injury in cats, Am J Vet Res 62(3):370–374, 2001. 42. Weil CS, Woodside MD, Smyth HF Jr, et al: Results of feeding propylene glycol in the diet to dogs for two years, Food Cosmet Toxicol 9(4):479–490, 1971.