Page 1019 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Yew (Taxus spp.) Alkaloids Chapter | 66 951

VetBooks.ir TABLE 66.2 Oral Lethal Doses of Yew Leaves in Animals

Estimated Average
Animal
b,c,d
Body Weight (kg) a LD min of Yew LD min (g Yew Leaves/kg Estimated LD min of Taxines
(mg/kg Body Weight)
Body Weight)
Leaves (g)
Chicken 1.82 30 16.5 82.5
Cow 250 500 2.0 10.0
Dog 13 30 2.3 11.5
Goat 40 480 12.0 60.0
Horse 500 100 200 0.2 0.4 1.0 2.0
Pig 102 75 0.7 3.5
Sheep 40 100 2.5 12.5
Mouse 0.025 Not reported Not reported 0.5 (s.c.) e
Rat 0.25 Not reported Not reported 5.0 (s.c.) e
Human 80 50 100 0.6 1.3 3.0 6.5
Rabbit 2.5 1.75 0.7 3.5
a
Estimated average body weights of adult animals in this table referenced in Spector (1956).
b
Clarke and Clarke (1988).
c
Tekol (1991), Tekol and Go¨gu ¨sten (1999).
d
Watt and Breyer-Brandwijk (1962).
e
Mose and rat LD min s are based on subcutaneous (s.c.) dose.
visible only by microscopic examination) are found in the abnormalities (with the exception of large pieces of yew
mouth, stomach content, rumen content, and/or small intes- leaves and stems, if they are present in the gastrointestinal
tine (Frommherz et al., 2006; Lacasse et al., 2007; tract) are observed (Kingsbury, 1964; Alden et al., 1977;
Handeland, 2008; Panzeri et al., 2010). Occasionally, expo- Ogden, 1988; Rooks, 1994). An exception to this is one
sure may be indicated in the history but gross identification case of yew poisoning in a horse in which ecchymotic
of intact plant material is not observed. This can be espe- hemorrhages were visible grossly along the endocardial
cially true in species, such as horses, that masticate their surfaces of the ventricles, and microscopically, mild mul-
food more thoroughly. In these cases, diagnosis of taxine tifocal necrosis of the myocardium was identified in the
poisoning often requires a more detailed microscopic and/or ventricular wall and papillary muscles of the heart
chemical evaluation of the gastrointestinal contents (Karns, (Tiwary et al., 2005). In subacute poisonings, gastroenter-
1983; Tiwary et al., 2005). itis may be evident; however, the inflammation is proba-
Chemical analysis of biological samples using gas bly due to irritant oils present in the yew and not due to
chromatography/mass spectroscopy (GC/MS) or liquid taxine alkaloids (Watt and Breyer-Brandwijk, 1962;
chromatography/mass spectroscopy (LC/MS) has been Kingsbury, 1964; Evans and Cook, 1991). Rarely, other
successful in diagnosing some cases of yew poisoning in gross changes have been reported at necropsy, including
mammals (Stahr et al., 1977; Kite et al., 2000; Tiwary moderate to severe rumenitis, superficial hemorrhages in
et al., 2005). LC/MS has been used to detect taxine B and the right ventricular myocardium and right atrium, and
isotaxine B in blood (Beike et al., 2003; Frommherz mild focal interstitial myocarditis (Ogden, 1988; Panter
et al., 2006) and taxines A and B from yew plant frag- et al., 1993). There have been two reports of presumptive,
ments (Hough et al., 2010). GC/MS and LC/MS detection chronic toxicity in cattle in which, histologically, areas of
of 3,5-dimethoxyphenol, an aglycone metabolite of taxi- the myocardium were observed to be replaced with
catine, has been used as a unique marker for yew expo- fibrous connective tissue consistent with myocardial
sure in mammals. 3,5-Dimethoxyphenol has been necrosis (Burcham et al., 2013; Sula et al., 2013).
detected in blood, serum, urine, bile, and gastric contents In cases of yew poisoning in humans, the gross ana-
from mammals exposed to yew plants (Froldi et al., 2010; tomic observations documented include acute congestion
Panzeri et al., 2010; Kobusiak-Prokopowicz et al., 2016). of internal organs, cerebral edema, and hemorrhagic pul-
At postmortem examination, there are no lesions that monary edema (Beike et al., 2003; Wehner and Gawatz,
are pathognomonic in animals that have died due to yew 2003). In these cases, histology of the myocardium
toxicosis. Indeed, neither gross nor microscopic revealed interstitial edema, positive staining for troponin C