[M-ZZ51] Environmental Pollution, Environmental Toxicology and Humans/Animals Health

[MZZ51-P03] Evaluation of anticoagulant rodenticides (ARs) sensitivity in sea turtles

*Shouta MM NAKAYAMA^1,2, Yoshiya Yamamura^1,3, Satomi Kondo⁴, Chiyo Kitayama⁴, Takahiro Ichise¹, Yoshinori Ikenaka^1,5,6,7, Mayumi Ishizuka¹ (1.Faculty of Veterinary Medicine, Hokkaido University, 2.School of Veterinary Medicine, The University of Zambia, 3.The Institute of Environmental Toxicology, 4.Everlasting Nature of Asia (ELNA), 5.Water Research Group, School of Environmental Sciences and Development, North-West University, Private Bag X6001, Potchefstroom 2531, South Africa, 6.Translational Research Unit, Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan, 7.One Health Research Center, Hokkaido University, Sapporo 060-0818, Japan)

Keywords:anticoagulant rodenticides (ARs), chemical sensitivity, species differences

Rodents such as black rats (Rattus rattus) and Norway rats (Rattus norvegicus) have been artificially introduced to islands many times, where they have generally caused severe damage to native ecosystems. Although anticoagulant rodenticides (ARs) are effectively used for the elimination of invasive rodents, nontarget species are also frequently exposed to ARs and secondary poisonings occur widely. However, little data is available on the effects of ARs, especially on marine organisms. To evaluate the effects of ARs on aquatic ecosystems, we chose green sea turtles (Chelonia mydas), which are one of the most common marine organisms around the Ogasawara islands, japan as our primary study species. The sensitivity of these turtles to ARs was assessed using both in vivo and in vitro approaches. We administered 4 mg/kg of warfarin sodium either orally or intravenously to juvenile green sea turtles. The turtles exhibited slow pharmacokinetics, and extension of prothrombin time (PT) was observed only with intravenous warfarin administration. This result indicates that in the green sea turtles, most of the warfarin administered orally was not absorbed, or it took a long time to be distributed throughout the body. We also conducted an in vitro investigation using liver microsomes from two other turtle species (softshell turtle and red-eared slider) and rats, as well as green sea turtles. The cytochrome P450 metabolic activity in the liver was lower than in rats. Additionally, vitamin K epoxide reductase (VKOR), which is the target enzyme of ARs, was inhibited by warfarin in the turtles at lower or similar concentration levels as in rats. These data indicate that turtles may be more sensitive to ARs than rats. In addition, we observed interspecific differences in warfarin metabolism among the three turtle species we studied. Vmax/Km values were higher in the red-eared sliders than in the Chinese softshell turtles or green sea turtles. This result indicates that red-eared sliders have a greater detoxification capacity when warfarin is present in concentrations that are physiologically tolerated. In conclusion, we expect that these findings will be helpful for sea turtle conservation following accidental AR-broadcast incidents.