Fenbendazole is a widely used anthelmintic drug in veterinary medicine that has a wide range of activity, high degree of efficacy and generally, a wide margin of safety in most species.6,8,9 However, fenbendazole and albendazole have been associated with toxicoses in some species. Toxic changes include radiomimetic lesions in the bone marrow and small intestine in birds,7,9,11 elevated liver enzymes in quail,3 bone marrow suppression in dogs, cats and birds,7,13 teratogenic effects in rodents and sea urchins,1,4 and tumor promoter effects in rats10. Fenbendazole is widely prescribed as an anthelminthic in reptiles, and to date, no toxic effects have been documented in reptiles in regard to this drug. This report describes clinical presentation and pathology associated with fenbendazole overdose in four Fea’s vipers (Azemiops feae).
Two adult male and two adult female Fea’s vipers entered quarantine at the Dallas Zoo within 2–3 wk of collection in Asia. Fea’s vipers have historically been difficult to maintain in captivity and previous mortalities have shown moderate to severe intestinal nematodiasis. The broker that shipped these animals administered a single oral dose of 25 mg fenbendazole (Panacur, 100 mg/ml, Hoechst Roussel Vet, Warren, NJ, USA) prior to shipment. On entry to quarantine, the two males weighed 37 g and 48 g and the two females weighed 24 g and 58 g, respectively. Snakes were assist-fed, but largely inappetent on their own. All, but the largest female, lost weight during the time period. The minimal fecal material available for analysis was negative for parasitic ova. Males died 31 days and 32 days post-entry to quarantine and the females died 40 days and 71 days post-entry.
Necropsy of all snakes revealed good body condition and segmental thickening and reddening of the entire small intestine. No parasites were found. The most significant histopathologic changes were in segments of the small intestine of all snakes. The affected intestine had moderate to severe necrosis of mucosal epithelium, generally along the entire length of the villus, and particularly severe at the base of the villus. Complete ulceration and stromal collapse occurred in some areas. Mildly increased numbers of lymphocytes, plasma cells, histiocytes, and eosinophilic granulocytes were in the lamina propria, accompanied by extensive congestion and edema. Few areas of mucosal epithelial regeneration were detected. The lesions were associated with bacterial overgrowth. All snakes also had mild to moderate fibrinous rhinitis with intralesional bacteria. Changes consistent with sepsis were seen in all snakes. Electron microscopy performed on formalin-preserved gut mucosa from the first snake that died revealed degeneration and necrosis of enterocytes. No viral particles were seen.
Reptiles and amphibians have intestinal mucosal morphologic features that differ from those of mammals and birds. The latter have crypts of rapidly dividing cells that replace the sloughed enterocytes of the villi. Reptiles do not have crypts, but have long villi and villous folds,5 and appear to replace sloughed enterocytes directly from underlying basal cells of the villi. The radiomimetic intestinal lesions seen in birds with fenbendazole toxicosis manifest predominantly in the crypts, where cell turnover is highest. A radiomimetic insult to enterocytes in a reptile would be expected to have a more generalized distribution in the villous enterocytes, as seen in these cases. Secondary intestinal changes are similar to those of affected birds.
The recommended dose for fenbendazole in reptiles is 50–100 mg/kg PO once, repeated in 2 wk2,12 or 50 mg/kg PO q 24 h for 3–5 days.2 The estimated oral dose of fenbendazole administered to these vipers was 25 mg. The calculated dosage was 685 mg/kg and 526 mg/kg for the two males and 1064 mg/kg and 428 mg/kg for the two females.
Little is known about this snake species and they have proven to be a challenge to maintain in captivity. The estimated dose of fenbendazole administered to these snakes was considerably higher than the recommended dose. The size and nature of these snakes precluded extensive diagnostic testing. Fenbendazole is regarded as a safe anthelmintic, which can affect how it is administered to individual animals. These findings document the effects seen with a fenbendazole overdose in Fea’s vipers.
1. Barron, S., B.J. Baseheart, T.M. Segar, T. Deveraux, and J.A. Willford. 2000. The behavioral and teratogenic potential of fenbendazole: a medication for pinworm infestation. Neurotoxicol. Teratol. 22:871–877.
2. Carpenter, J.W., T.Y. Mashima, and D.J. Rupiper. 2001. In: Exotic Animal Formulary. W.B. Saunders Co., Philadelphia, Pennsylvania. P. 51.
3. Dalvi, RR. 1989. Comparative studies on the effect of fenbendazole on the liver and liver microsomal enzymes in goats, quail and rats. Vet. Res. Commun. 13:135–139.
4. Deiana, L., A.M. Congiu, C. Carru, G.M. Pes, and G. Arru. 1990. Embryotoxicity of fenbendazole in Paracentrotus lividus. Bull. Soc. Ital. Biol. Sper. 66:1137–1144.
5. Ferri, S., L.C. Junqueira, L. F. Medeiros, and L.O. Mederios. 1976. Gross, microscopic and ultrastructural study of the intestinal tube of Xenodon merremii Wagler, 1824 (Ophidia). J. Anat. 121:291–301.
6. Hayes, R.H., F.W. Oehme, and H. Leipold. 1983. Toxicity investigation of fenbendazole, an anthelmintic of swine. Am. J. Vet. Res. 44:1108–1111.
7. Howard, L.L., R. Papendick, I.H. Stalis, J.L. Allen, M. Sutherland-Smith, J.R. Zuba, D. Ward, and B.A. Rideout. 1999. Benzimidazole toxicity in birds. Proc. Annu. Conf. Am. Assoc. Zoo Vet. Pp. 36.
8. Muser, R.K., and J.W. Paul. 1984. Safety of fenbendazole use in cattle. Mod. Vet. Pract. 65:371–374.
9. Papendick, R. I. Stalis, C. Harvey, B. Rideout, J. Zuba, J. Allen, and M. Sutherland-Smith. 1998. Suspected fenbendazole toxicity in birds. Proc. Annu. Conf. Am. Assoc. Zoo Vet. and Am. Assoc. Wildl. Vet. Pp 144–146.
10. Shoda. T., H. Onodera, M. Takeda, C. Uneyama, T. Imazawa, K. Takegawa, K. Yasuhara, T. Watanabe, M. Hirose, and K. Mitsumori. 1999. Liver tumor promoting effects of fenbendazole in rats. Toxicol. Pathol. 27:553–562.
11. Stalis, I.H., B.A. Rideout, J.L. Allen, and M. Sutherland-Smith. 1995. Possible albendazole toxicity in birds. Proc. Annu. Conf. Am. Assoc. Zoo Vet., Wildl. Dis. Assoc., and Am. Assoc. Wildl. Vet. Pp. 216–217.
12. Stein, G. 1996. Reptile and amphibian formulary. In: Mader, D.R. (ed.). Reptile Medicine and Surgery. W.B. Saunders Co., Philadelphia, Pennsylvania. Pp. 467.
13. Stokol, T., J.F. Randolph, S. Nachbar, C. Rodi, and S.C. Barr. 1997. Development of bone marrow toxicosis after albendazole administration in a dog and a cat. J. Am. Vet. Med. Assoc. 210:1753–1756.