title: Assessment of toxicity and coagulopathy of brodifacoum in Japanese quail and testing in wild owls.
abstract: Based on detection of hepatic residues, scavenging and predatory non-target raptors are widely exposed to second generation anticoagulant rodenticides (SGARs). A small proportion, generally <10%, of tested birds are diagnosed as acutely poisoned. Little is known, however, of sub-lethal effects of SGARs, such as interaction of clotting capacity with traumatic injury. Assessment of coagulation function of birds submitted live to wildlife rehabilitators or veterinarians may provide a means of establishing the proportion of animals suffering sub-lethal coagulopathies, as well as identifying individuals requiring treatment. As a first step in exploring the potential of this approach, we dosed Japanese quail (Coturnix japonica) with the SGAR, brodifacoum, at 0, 0.8, 1.4, 1.9, and 2.5 mg/kg and sampled birds at 1, 3, 5 and 7 days post-dosing. Prothrombin time (PT), which measures the extrinsic coagulation pathway, was significantly prolonged in 98% of brodifacoum-exposed quail in a dose- and time-dependent manner. 50-fold prolongation of PT occurred at higher brodifacoum dosages and correlated to hemorrhage found at necropsy. Activated clotting time (ACT), a measure of the intrinsic pathway also increased with dose and time. Hemoglobin (Hb) and hematocrit (Hct) decreased dose- and time-dependently at doses ≥1.4 mg/kg with no significant change at 0.8 mg/kg. Reference intervals for PT (10.0-16.2 s), ACT (30-180 s), Hb (9.6-18.4 g/dl), and Hct (34-55%) were established in Japanese quail. Species-specific reference intervals are required as barn owl PT (17-29 s) and quail PT were different. The proportion of brodifacoum-exposed quail with hemorrhage was not correlated with liver residues, but was correlated with PT, suggesting that this assay is a useful indicator of avian anticoagulant rodenticide exposure. PTs measured in free-living barn owls sampled between April 2009 and August 2010 in the lower Fraser Valley of BC do not suggest significant exposure to SGARs.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, BC, V5A 1S6, USA.
authors.forename: Kirstin H
authors.initials: KH
authors.lastname: Webster
authors.forename: Kendal E
authors.initials: KE
authors.lastname: Harr
authors.forename: Darin C
authors.initials: DC
authors.lastname: Bennett
authors.forename: Tony D
authors.initials: TD
authors.lastname: Williams
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Cheng
authors.forename: France
authors.initials: F
authors.lastname: Maisonneuve
authors.forename: John E
authors.initials: JE
authors.lastname: Elliott
mesh_terms: D015110:4-Hydroxycoumarins / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects; D003370:Coturnix / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D008099:Liver / Q000378:metabolism; D011517:Prothrombin Time; D012378:Rodenticides / Q000008:administration & dosage / Q000633:toxicity*; D020305:Strigiformes / Q000378:metabolism; D013997:Time Factors
chemical_list: D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D012378:Rodenticides; C013418:bromfenacoum
references.citation: Environ Int. 2011 Jul;37(5):914-20
references.pmid: 21481471
references.citation: Environ Toxicol Chem. 2011 May;30(5):1213-22
references.pmid: 21337606
references.citation: Environ Toxicol Chem. 2008 Feb;27(2):452-60
references.pmid: 18348626
references.citation: J Wildl Dis. 1999 Apr;35(2):187-93
references.pmid: 10231745
references.citation: Pharmacology. 1983;27(5):281-8
references.pmid: 6657737
references.citation: Blood. 1990 Jul 1;76(1):1-16
references.pmid: 2194585
references.citation: Sci Total Environ. 2008 Mar 15;392(1):93-8
references.pmid: 18082246
references.citation: Ecotoxicology. 2002 Feb;11(1):35-48
references.pmid: 11898799
references.citation: J Zoo Wildl Med. 2011 Mar;42(1):88-97
references.pmid: 22946375
references.citation: Environ Pollut. 1990;68(1-2):101-17
references.pmid: 15092196
references.citation: Arch Environ Contam Toxicol. 1994 Feb;26(2):227-33
references.pmid: 8311513
references.citation: Br J Pharmacol. 1991 Oct;104(2):531-5
references.pmid: 1797316
references.citation: Vet Clin Pathol. 2011 Mar;40(1):107-12
references.pmid: 21366659
references.citation: J Comp Pathol. 1977 Jul;87(3):451-7
references.pmid: 908771
references.citation: Comp Biochem Physiol C Toxicol Pharmacol. 2010 Jun;152(1):114-9
references.pmid: 20346414
references.citation: J Comp Pathol. 1970 Oct;80(4):525-33
references.pmid: 5492282
references.citation: Am J Vet Res. 2001 Sep;62(9):1455-60
references.pmid: 11560277
references.citation: J Thromb Haemost. 2008 Nov;6(11):1876-83
references.pmid: 18761718
references.citation: Vet Clin North Am Exot Anim Pract. 2000 Jan;3(1):1-17, v
references.pmid: 11228822
references.citation: Nature. 1975 Jan 24;253(5489):275-7
references.pmid: 1113846
references.citation: Arch Environ Contam Toxicol. 2010 Feb;58(2):451-9
references.pmid: 19826750
references.citation: Poult Sci. 1975 Jul;54(4):969-80
references.pmid: 1161726
references.citation: Arch Environ Contam Toxicol. 2012 Oct;63(3):437-44
references.pmid: 22588365
references.citation: J Avian Med Surg. 2008 Mar;22(1):41-6
references.pmid: 18543601
references.citation: J Nutr. 2000 Aug;130(8):1877-80
references.pmid: 10917896
references.citation: Clin Appl Thromb Hemost. 2001 Oct;7(4):269-75
references.pmid: 11697707
references.citation: Vet J. 2012 Dec;194(3):278-9
references.pmid: 22831990
references.citation: J Small Anim Pract. 1978 Jul;19(7):417-22
references.pmid: 692084
references.citation: PLoS One. 2012;7(7):e40163
references.pmid: 22808110
references.citation: Toxicol Rev. 2005;24(4):259-69
references.pmid: 16499407
references.citation: Pharmacogenomics J. 2007 Apr;7(2):99-111
references.pmid: 16983400
references.citation: J Zoo Wildl Med. 1998 Sep;29(3):324-7
references.pmid: 9809607
references.citation: Am Heart J. 1998 Sep;136(3):477-9
references.pmid: 9736140
references.citation: Bull Environ Contam Toxicol. 2003 Jan;70(1):34-40
references.pmid: 12478421
references.citation: Environ Toxicol Chem. 2014 Jan;33(1):74-81
references.pmid: 24014246
references.citation: Br J Pharmacol. 1985 Jan;84(1):81-91
references.pmid: 3978316
references.citation: Vet Clin Pathol. 2012 Dec;41(4):441-53
references.pmid: 23240820
references.citation: Environ Monit Assess. 2014 Feb;186(2):895-906
references.pmid: 24048882
references.citation: Toxicol Appl Pharmacol. 1976 Mar;35(3):437-46
references.pmid: 1265758
references.citation: Ecotoxicology. 2012 Apr;21(3):832-46
references.pmid: 22227859