The fetotoxic effects of AR in pregnant fishers and their fetuses are unknown

Complete centroids were generated for 42 monitored fishers, 12 fishers from the northwestern California population and 30 from the southern Sierra Nevada population . Of these fishers, 3-month MCP centroids were generated for 39 fishers, and 6-month centroids for 27 . Spatial analysis for 6-month centroids from the KRFP could not be conducted because all fishers in the data set were AR exposed. Sixteen fishers were excluded from the analysis due to lack of monitoring data. No spatial clustering of AR exposure was detected for any of the temporal periods, specific AR compounds, generation class of AR, or distribution of numbers of ARs per fisher in any of the study areas .Cause-specific mortality factors for all 58 fishers sampled ranged widely and included predation, infectious and non-infectious disease processes and vehicular strikes . The cause of death for four of these fishers was attributed to lethal toxicosis, indicated by AR exposure with simultaneous coagulopathy and bleeding into tissues or cavities and ruling out any concurrent processes that might cause hemorrhaging. Two of the four fishers killed by ARs were from the southern Sierra Nevada population, and two were from northern California and the case details are described below.An adult male fisher was recovered on 15 April 2009, grow racks with lights in the southern Sierra Nevada at the SNAMP project area. The fisher showed no signs of predation or scavenging . Gross necropsy determined that the fisher was in good nutritional and fair postmortem condition.

Frank blood was observed in both the thoracic and abdominal cavities , and in the pericardial sac . The stomach and lower gastrointestinal tract contained some blood but no prey or formed feces, and no mucosal changes were noted. There were no other findings on gross examination. Histopathologically, no significant changes were observed in any tissues. Brodifacoum and BRM were detected and quantified in the liver sample at 0.38 ppm and 0.11 ppm, respectively, and CHL at trace levels . The second fisher mortality was a lactating adult female recovered on 2 May 2010 in the center of a paved rural highway in the SNAMP project area approximately 3.7 km from Yosemite National Park. Vehicular strike was initially suspected as the cause of mortality due to the location of the carcass but lacerations, abrasions and visual evidence of trauma were not seen on gross examination of the intact carcass. The post-mortem state of the carcass was good and the nutritional state was poor . Shallow subcutaneous hemorrhage was noted over the hindquarters and spinal column with no associated fractures, punctures or abrasions. There was approximately 20 ml of frank blood within the thoracic cavity. There was no evidence of pneumothorax, vessel ruptures, or visceral tearing. No blood or visceral damage was seen in the abdominal cavity. Stomach contents contained various rodent parts with formed feces in the descending colon. Histopathologically, no significant changes were observed in any tissues. Brodifacoum and BRM were detected and quantified at 0.60 ppm and 0.17 ppm, while one first generation AR, DIP was detected at a trace level within the liver tissue .

No evidence was present to suggest that this fisher died due to vehicular trauma, despite its location on the highway.A sub-adult male fisher was recovered on 4 May 2010 at the base of several riparian shrubs near a watercourse in northwestern California at the HVRFP. Severe ectoparasitism on the carcass was noted in the field with ticks in both replete and non-replete stages. Predation was not suspected due to absence of external wounds. The gross necropsy determined that this fisher was in poor nutritional condition with no subcutaneous or visceral fat. Frank blood was present in the right external ear canal, nasal and oral cavities, within the lumen of the trachea and within the periorbital tissue with no associated skull fractures or punctures.The stomach was devoid of prey. The colon only contained semiformed feces. Ectoparisitism was severe with approximately 48 female and 10 male American dog ticks and 8 female and 2 male western black-legged ticks removed from various regions of the fisher. The liver sample from this fisher had quantifiable levels of BRD at 0.04 ppm as well as a trace level of CHL . The second northern California fisher AR death, was an adult male recovered on 26 May 2010 at the HVRFP. Field observations included no evidence of predation or scavenging. The nutritional state as well as the postmortem condition were poor. Gross necropsy determined that the fisher had no body fat present in any of the tissues. Frank blood was present in both thoracic and abdominal cavities. The stomach contained red and black fluid but no prey. Ectoparasitism was severe with 204 female and 27 male adult American dog ticks in both replete and non-replete stages on areas of the muzzle, chest, tops of fore-and hind-limbs as well as inguinal sections. Severe nematodiasis was seen in skeletal muscle throughout the body . Pulmonary nematodiasis was also noted in the marginal portions of the lungs. Histopathologically, no notable disease processes were seen but severe parasitism was noted. The liver sample for this fisher had quantifiable levels of BRD at 0.61 ppm and trace levels of BRM .Necropsies and AR testing was performed on four kits who were all still dependent on mother’s milk when they died following maternal abandonment from their mothers death. One kit, a female fisher from KRFP tested positive for AR exposure.

This kit was approximately six weeks of age and was recovered within a monitored maternal den tree shortly after maternal abandonment. Cause of death was determined to be acute starvation and dehydration. The liver tissue contained trace level of BRD but there was no associated hemorrhaging in any tissues, body cavities or lumina, suggesting that this finding was not clinically significant.Our findings demonstrate that anticoagulant rodenticides, which were not previously investigated in fishers or other remote forest carnivores, are a cause of mortality and may represent a conservation threat to these isolated California populations. This isthe first documentation of exposure to ARs and of direct mortality from ARs in fishers anywhere in their geographic range. Earlier studies suggest ARs posed little or no additive mortality effects on non-target populations. The shortfall of many of these studies was the utilization of common cosmopolitan species so they did not take in consideration that AR mortality may be additive in otherwise compromised populations. The spatially ubiquitous exposure observed within all post-weaning age classes and across the project areas in their contemporary range in California is of significant concern especially considering the recent work of Spencer et al. , who demonstrated that even a small increase in human-caused mortality of 10–20% in the isolated Southern Sierra Nevada fisher population would be enough to prevent population expansion if other restrictive habitat elements were removed. The high rate of exposure to second generation AR compounds in these populations is surprising and cause for concern. This generation of ARs are not only more acutely toxic, but have long retention through biphasic elimination in mammal tissues. Second-generation ARs are more toxic because death can occur from a single primary ingestion by a rodent. However, rolling benches for growing rodents can receive a lethal dose of second-generation ARs in one feeding bout and it can take up to 7 days before clinical signs manifest. Therefore, prey that have consumed a ‘‘super-lethal’’ dose of AR can pose a substantial risk to predators for several days prior to death. In one study, a group of Norway rats was given a choice between BRD bait and untreated food and another group had access only to the BRD bait. Both groups consumed 10 and 20 median lethal doses on the first day and 40 to 80 LD50 doses by day 6.5, respectively. If sources for these toxicants are maintained for even short periods, exposed rodents, the main prey source for fishers in these populations can pose significant threats to their predators. Many manufactures use ‘‘flavorizers’’ since the AR compound may be bitter and unpalatable to rodent pests. Emulsions used to increase palatability include sucrose, bacon, cheese, peanut butter, and apple flavors , and thus could be palatable to generalist carnivores like fishers. Although we did not visually detect AR bait in the stomach or GI tracts of any fishers that died, primary poisoning cannot be completely ruled out.In addition to the risk from lethal toxicosis, sub-lethal AR exposure may compromise fishers through a reduction in the function of normal clotting. The occurrence of AR -exposed wildlife dying from minor wounds that otherwise might have easily resolved themselves if ARs were not present suggests contributory lethal effects. Several cases describe raptors receiving minor defensive lacerations or trauma from prey that lead to the raptor’s death by exsanguination or hemorrhaging.

Fishers actively pursue a wide array of terrestrial and arboreal prey. Hence, it is conceivable that a fisher could receive similar wounds or trauma from prey, or during the pursuit of prey. Consequently, if clotting mechanisms were compromised due to ARs, benign injuries could lead to serious complications. The leading causes of mortality within the USFWS DPS is intraguild predation . It is possible that some of these cases, AR exposure could have compromised clotting mechanisms at the predation attempt and this deserves further study. High levels of tick infestations were noted in two of the AR mortalities when compared to other sympatric species within the same project area. In addition, locations of of these replete ticks were in infrequent regions in other captures, most likely due to a lack of regular grooming. Whether ARs played a role by allowing more ticks to obtain a blood meal due to immobilization due to compromised clotting factors is unknown. Furthermore, sublethal AR exposure may decrease an animal’s resilience to environmental stressors. In a study on rabbits and rats subjected to stressors such as severe decreases in ambient temperature , approximately 10% of test animals died; however when animals were exposed to low non-lethal doses of anticoagulants and subjected to the same stressors, mortality rates increased to 40–70%. It is unknown if stressors or injuries from environmental, physiological or even pathogenic factors could predispose fishers to elevated mortality rates when coupled with AR exposure.The documentation of neonatal or lactational transfer of AR to a dependent fisher kit was unexpected, and the effects of AR exposure to a kit during fetal development or shortly after birth are unstudied. AR exposure in pregnant or whelping domestic canids varied, causing no clinical signs in some cases but death due to coagulopathy immediately after delivery in other cases. The female fisher who gave birth to this kit did not exhibit clinical signs at pre- or postpartum captures and monitoring of her maternal den site verified that one kit survived from that litter . Nevertheless, clinical signs including hemorrhaging, inappetence and lethargy have been seen in domestic canid puppies of AR-exposed mothers. Mild to severe manifestations such as low birth weight, stillbirth or eventually neonatal death has been documented in several cases. In one human study where pregnant women received low doses of warfarin due to severe risk of thromboembolic events, 33% of them had stillbirths, 28% had abortions, and 11% of the neonates died shortly after birth. The range for congenital anomalies and miscarriages in pregnant females for prescribed doses of warfarin varied from 15 to 56% and long-term neurological symptoms have been reported in children that were exposed in-utero. In addition, because fishers exhibit delayed implantation of the blastocyst, whether ARs may cause pregnant females to abort or reabsorb the fetus merits further research. The transfer of first generation ARs from mother to offspring in milk is not well-understood and there are no data on lactational transfer of second-generation ARs.The quantity of AR we observed in fisher liver tissues varied and overlapped extensively in both sublethal and lethal cases with no clear indication of a numeric threshold that might indicate an amount leading to morbidity or mortality. This lack of predictive ability has been shown in numerous wildlife cases. For example, Brodifacoum, the most prominent AR compound detected in fishers in this study ranged considerably in lethal cases among individual mustelid species, with 0.32– 1.72 ppm in stoats, 0.7 ppm in least weasels, 1.47–1.97 in ferrets and 9.2 ppm in American mink.