Page 685 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

650 SECTION | IX Gases, Solvents and Other Industrial Toxicants

VetBooks.ir acetone, and 4-methylpyrazole will prevent the metabo- conjugated with glucuronic acid and eliminated in the
urine (Fig. 49.2). The CNS depression resulting from
lism of isopropanol to acetone.
large, single doses of propylene glycol is probably due to
GLYCOL TOXICOSES the excessive presence of propylene glycol and not to its
metabolic products (Cavender and Sowinski, 1994).
Propylene Glycol Toxicosis
Diagnosis and Treatment
Propylene glycol (1,2-propanediol, CH 3 CH(OH)CH 2 OH)
is one of the least toxic of the glycols. It is used as auto- Clinical signs depend on the quantity ingested and may
motive antifreeze, an industrial and pharmaceutical sol- include depression, ataxia, muscle fasciculations, hypo-
vent, in cosmetics, and as an additive in processed food tension, osmotic diuresis, respiratory arrest, and circula-
for human and animal consumption. Although it is consid- tory collapse. Clinical signs in ruminants are similar to
ered nontoxic compared to EG, it causes CNS depression those seen in other species and include ataxia, depression,
and lactic acidosis when ingested in large quantities. and recumbency (Pintchuck et al., 1993). Laboratory find-
When used as an additive in semimoist cat food, it caused ings include metabolic acidosis, increased anion gap,
Heinz body formation in erythrocytes (inclusions within hyper osmolality of the plasma, and the presence of Heinz
red blood cells composed of denatured hemoglobin) but bodies in cats and horses. Diagnosis is usually based on
did not cause anemia when ingested in small quantities history of exposure and can be confirmed by measuring
(Christopher et al., 1989a,b; Weiss et al., 1990; Bauer propylene glycol concentrations in urine and serum by
et al., 1992a,b). However, cats eating such diets were gas chromatography. Treatment for all species is support-
more susceptible to other additional causes of oxidative ive and includes correction of hydration and acid-base
injury, and although overt anemia may not occur, red cells abnormalities. Most animals recover within 24 27 h with
with Heinz bodies have a reduced life span. supportive care. To slow the production of toxic metabo-
Consequently, the use of propylene glycol in cat foods is lites 4-methylpyrazole may be given. Dialysis may be
prohibited in the United States. used after significant exposure in dogs.
The oral median lethal dose for propylene glycol
in dogs has been reported to be as low as 9 mL/kg Butylene Glycol Toxicosis
( 8.7 g/kg) (Bischoff, 2006b). Fatal cases of malicious
propylene glycol toxicosis have been reported in Butylene glycol (1,2-, 1,3-, and 1,4-butanediol,C 4 H 10 O 2 )
dogs (Bischoff, 2006b). It is considered relatively is used as antifreeze, as an industrial cleaner, and in cos-
unpalatable to dogs (Marshall and Doty, 1990). Fatal pro- metics. Although no published reports of butylene glycol
pylene glycol toxicosis was reported in a horse that was toxicosis in domestic animals were found in the literature,
inadvertently given 7.6 mL/kg ( 7.3 g/kg) propylene there are numerous reports of human intoxications from
glycol orally instead of mineral oil for potential grain butylene glycol or the metabolite gamma-hydroxybutyrate
overload (Dorman and Hascheck, 1991). Cause of death (Dyer, 1991; Mack, 1993). Butylene glycol and the
was presumed to be from respiratory arrest. Propylene metabolite gamma-hydroxybutyrate are used as “recrea-
glycol toxicosis has been reported in at least two other tional” drugs and were once marketed by health food
horses with colic in which propylene glycol was mistak- stores as a food additive for bodybuilders and to treat
enly administered instead of mineral oil (Myers and depression and insomnia.
Usenik, 1969; McClanahan et al., 1998); both horses sur- 1,3-Butanediol has been used as an antidote for experi-
vived: they were both given approximately 6 mL/kg mental EG toxicosis in dogs because it is a competitive
( 5.8 g/kg) body weight via nasogastric tube. Heinz substrate for ADH (Thrall et al., 1982; Murphy et al.,
body formation also occurs in horses ingesting propylene 1984; Cox et al., 1992). Although it was found to be a
glycol (McClanahan et al., 1998). Propylene glycol may more effective antidote than ethanol, in that more unmetab-
be used to treat and prevent bovine ketosis, which may olized EG was excreted in the urine in patients treated with
partially explain the availability and apparent ease with 1,3-butanediol, CNS depression was as severe or more
which it is confused with mineral oil. severe than that induced by ethanol therapy, and plasma
hyperosmolality and metabolic acidosis were more severe
Toxicokinetics than with ethanol therapy (Thrall et al., 1982).
In mammals, part of the propylene glycol dose is elimi-
nated unchanged by the kidney and part is metabolized by Toxicokinetics
the liver to lactic acid (responsible for metabolic acidosis) Butylene glycol is metabolized by ADH to acetoacetate
by ADH and further metabolized to pyruvic acid; in mam- and gamma-hydroxybutyrate, the so-called “date
mals, with the exception of cats, the remainder is rape” drug.