In vitro assessment of the dermal penetration potential of sodium fluoroacetate using a formulated product.

This paper presents experimental data on the skin absorption of sodium fluoroacetate from a formulated product using an in vitro approach and human skin. Sodium fluoroacetate is a pesticide, typically applied in formulation (1080) for the control of unwanted vertebrate invasive species. It has been assigned a Skin Notation by the ACGIH, and other international workplace health regulatory bodies, due to its predicted ability to permeate intact and abraded human skin. However, there is a distinct lack of experimental data on the skin absorption of sodium fluoroacetate to support this assignment. This study found that sodium fluoroacetate, as a formulated product, permeated the human epidermis when in direct contact for greater than 10 hr. A steady-state flux (Jss) of 1.31 ± 0.043 µg/cm2/hr and a lag time of 6.1 hr was calculated from cumulative skin permeation data. This study provides important empirical evidence in support of the assignment of a Skin Notation.

Mass spectrometry characterization of anticoagulant rodenticides and hydroxyl metabolites.

RATIONALE: Anticoagulant rodenticides (ARs) are used worldwide for rodent population control to protect human health and biodiversity, and to prevent agricultural and economic losses. Rodents may develop a metabolic resistance to ARs. In order to help understand such metabolic resistance, mass spectrometry was used to position the hydroxylated group of hydroxyl metabolites of second-generation ARs (SGARs). METHODS: Most AR pesticides are derived from the 4-hydroxycoumarin/thiocoumarin family. We used low-resolution and high-resolution mass spectrometry to understand the fragmentation pathways of the ARs and their respective metabolites, and to better define the structure of their tandem mass spectrometry product ions. RESULTS: Seven specific product ions were evidenced for five ARs, with their respective chemical structures. Those ions were obtained as well from the mass spectra of the hydroxyl metabolites of four SGARs, difenacoum (DFM), brodifacoum (BFM), difethialone (DFTL) and flocoumafen (FLO), with different positions of the hydroxyl group. CONCLUSIONS: The differences in chemical structure between DFM on the one hand and BFM, FLO and DFTL on the other could explain the differences in bioavailability between these two groups of molecules. The defined product ions will be used to investigate the part played by the metabolic issue in the field resistance of SGARs.

Evaluating a Rapid Field Assessment System for Anticoagulant Rodenticide Exposure of Raptors.

Anticoagulant rodenticides (ARs) are commonly used to control rodent pests. However, worldwide, their use is associated with secondary and tertiary poisoning of nontarget species, especially predatory and scavenging birds. No medical device can rapidly test for AR exposure of avian wildlife. Prothrombin time (PT) is a useful biomarker for AR exposure, and multiple commercially available point-of-care (POC) devices measure PT of humans, and domestic and companion mammals. We evaluated the potential of one commercially available POC device, the Coag-Sense® PT/INR Monitoring System, to rapidly detect AR exposure of living birds of prey. The Coag-Sense device delivered repeatable PT measurements on avian blood samples collected from four species of raptors trapped during migration (Intraclass Correlation Coefficient > 0.9; overall intra-sample variation CV: 5.7%). However, PT measurements reported by the Coag-Sense system from 81 ferruginous hawk (Buteo regalis) nestlings were not correlated to those measured by a one-stage laboratory avian PT assay (r = - 0.017, p = 0.88). Although precise, the lack of agreement in PT estimates from the Coag-Sense device and the laboratory assay indicates that this device is not suitable for detecting potential AR exposure of birds of prey. The lack of suitability may be related to the use of a mammalian reagent in the clotting reaction, suggesting that the device may perform better in testing mammalian wildlife.

GABAA receptor subtype selectivity of the proconvulsant rodenticide TETS.

The rodenticide tetramethylenedisulfotetramine (TETS) is a potent convulsant (lethal dose in humans 7-10 mg) that is listed as a possible threat agent by the United States Department of Homeland Security. TETS has previously been studied in vivo for toxicity and in vitro in binding assays, with the latter demonstrating it to be a non-competitive antagonist on GABAA receptors. To determine whether TETS exhibits subtype selectivity for a particular GABAA receptor combination, we used whole-cell patch-clamp to determine the potency of TETS on the major synaptic and extrasynaptic GABAA receptors associated with convulsant activity. The active component of picrotoxin, picrotoxinin, was used as a control. While picrotoxinin did not differentiate well between 13 GABAA receptors, TETS exhibited the highest activity on α2ß3γ2 (IC50 480 nM, 95% CI 320-640 nM) and α6ß3γ2 (IC50 400 nM, 95% CI 290-510 nM). Introducing ß1 or ß2 subunits into these receptor combinations reduced or abolished TETS sensitivity, suggesting that TETS preferentially affects receptors with α2/ß3 or α6/ß3 composition. Since α2ß3γ2 receptors make up 15-20% of the GABAA receptors in the mammalian CNS, we suggest that α2ß3γ2 is probably the most important GABAA receptor for the seizure-inducing activity of TETS.

Anticoagulant rodenticide exposure and toxicosis in four species of birds of prey in Massachusetts, USA, 2012-2016, in relation to use of rodenticides by pest management professionals.

Restrictions on second-generation anticoagulant rodenticides (SGARs) in the United States, which were partially implemented in 2011, prohibit the sale of SGAR products through general consumer outlets to minimize use by non-professional or non-agricultural applicators. This study analyzed liver tissue from four species of birds of prey admitted to a wildlife clinic in Massachusetts, USA, from 2012-2016 for residues of anticoagulant rodenticides (ARs). Ninety-four birds were analyzed; 16 were symptomatic for AR toxicosis, and 78 asymptomatic. Ninety-six percent of all birds tested were positive for SGARs: 100% of those diagnosed with AR toxicosis ante-mortem and/or post-mortem and 95% of subclinically exposed birds. Brodifacoum was found in 95% of all birds. Sixty-six percent of all birds contained residues of two or more SGARs. A significant increase in exposures to multiple SGARs occurred in later years in the study. Pesticide use reports (PURs) filed with the Massachusetts Department of Agricultural Resources were reviewed to determine the frequency of use of different ARs by pest management professionals (PMPs) across five years. This study finds that the three SGARs favored by PMPs-bromadiolone, difethialone, brodifacoum-were present in combination in the majority of birds, with increases in multiple exposures driven by increased detections of bromadiolone and difethialone. Continued monitoring of AR residues in nontarget species following full implementation of sales and packaging restrictions in the US is needed in order to elucidate the role of PMP use of SGARs in wildlife exposures and to evaluate the effectiveness of current mitigation measures.

Plant Secondary Metabolites as Rodent Repellents: a Systematic Review.

The vast number of plant secondary metabolites (PSMs) produced by higher plants has generated many efforts to exploit their potential for pest control. We performed a systematic literature search to retrieve relevant publications, and we evaluated these according to PSM groups to derive information about the potential for developing plant-derived rodent repellents. We screened a total of 54 publications where different compounds or plants were tested regarding rodent behavior/metabolism. In the search for widely applicable products, we recommend multi-species systematic screening of PSMs, especially from the essential oil and terpenoid group, as laboratory experiments have uniformly shown the strongest effects across species. Other groups of compounds might be more suitable for the management of species-specific or sex-specific issues, as the effects of some compounds on particular rodent target species or sex might not be present in non-target species or in both sexes. Although plant metabolites have potential as a tool for ecologically-based rodent management, this review demonstrates inconsistent success across laboratory, enclosure, and field studies, which ultimately has lead to a small number of currently registered PSM-based rodent repellents.

Exposure pathways of anticoagulant rodenticides to nontarget wildlife.

Second-generation anticoagulant rodenticides are widely reported to contaminate and poison nontarget wildlife, primarily predatory birds and mammals. Exposure pathways, however, have not been well defined. Here, we examined potential movement of rodenticides from deployment of bait to exposure of small mammals and other biota. At two adjacent working farms, we placed baits containing either brodifacoum or bromadiolone. We monitored movement of those compounds to the surrounding environment by collecting small mammals, birds, and invertebrates. Similar collections were made at a third agricultural setting without active bait deployment, but located among intensive livestock production and regular rodenticide use by farmers. Livers and whole invertebrate samples were analyzed for rodenticides using a sensitive LC-MSMS method. Norway rats (Rattus norvegicus) from both baited and non-baited farms had residues of brodifacoum or bromadiolone, implicating rats as an important exposure pathway to wildlife. Among 35 analyzed nontarget small mammals, a single vole had high hepatic residues (18.6 µ/g), providing some indication of a small mammal pathway. One song sparrow (Melospiza melodia) sample from a baited farm contained 0.073 µg/g of brodifacoum in liver, while 0.39 µg/g of diphacinone was measured in a pool of carrion beetles (Dermestes spp.) from the non-baited farm area, implicating avian and invertebrate components in exposure pathways. Regurgitated pellets of barn owl (Tyto alba) selected randomly from baited farms contained no detectable rodenticide residues, while 90% of owl pellets collected from a variety of farms, and selected for the presence of rat fur, contained detectable anticoagulant residues. We recorded behavior of a captive sample of a representative songbird, the house sparrow (Passer domesticus); they readily entered bait stations and fed on (unloaded) bait.

Anticoagulant rodenticides in red-tailed hawks, Buteo jamaicensis, and great horned owls, Bubo virginianus, from New Jersey, USA, 2008-2010.

Liver samples from red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus) were analyzed for anticoagulant rodenticides. Residues of one or more second generation anticoagulant rodenticides (SGARs) were detected in 81 % of red-tailed hawks and 82 % of great horned owls. The most frequently detected SGAR was brodifacoum, which was detected in 76 % of red-tailed hawks and 73 % of great horned owls. Bromadiolone was detected in 20 % of red-tailed hawks and 27 % of great horned owls. Difenacoum was detected in one great horned owl. No other ARs were detected. There were no significant differences between species in the frequency of detection or concentration of brodifacoum or bromadiolone. There was a marginally significant difference (p = 0.0497) between total SGAR residues in red-tailed hawks (0.117 mg/kg) and great horned owls (0.070 mg/kg). There were no seasonal differences in the frequency of detection or concentration of brodifacoum in red-tailed hawks. The data suggest that SGARs pose a significant risk of poisoning to predatory birds in New Jersey.

Widespread exposure to anticoagulant rodenticides among common urban mesopredators in Chicago.

Anticoagulant rodenticides (ARs) are currently the most common method to control rats in cities, but these compounds also cause morbidity and mortality in non-target wildlife. Little attention has been focused on AR exposure among mesopredators despite their ecological role as scavengers and prey for larger carnivores, thus serving as an important bridge in the biomagnification of rodenticides in food webs. In this study, we sampled liver tissue from raccoons (Procyon lotor; n = 37), skunks (Mephitis mephitis; n = 15), and Virginia opossums (Didelphis virginiana; n = 45) euthanized by pest professionals and brown rats (Rattus norvegicus; n = 101) trapped in alleys in Chicago, USA to evaluate how often these species are exposed to ARs. We tested whether mesopredators had a higher prevalence of ARs and to more AR compounds compared to rats and calculated biomagnification factors (mean concentration in mesopredators/rats) as indicators of biomagnification. Of 93 sampled mesopredators, 100 % were exposed to at least one AR compound, mainly brodifacoum (≥80 %), and 79 % were exposed to multiple AR compounds. We also documented teal stomach contents consistent with the consumption of rat bait and altricial young tested positive to the same AR as their mother, suggesting mammary transfer. Of the 101 rats, 74 % tested positive to at least one AR compound and 32 % were exposed to multiple AR compounds. All mesopredator species had biomagnification factors exceeding 1.00 for brodifacoum (6.57-29.07) and bromadiolone (1.08-4.31). Our results suggest widespread exposure to ARs among urban mesopredators and biomagnification of ARs in mesopredators compared to rats. Policies that limit AR availability to non-target species, such as restricting the sale and use of ARs to licensed professionals in indoor settings, education on alternatives, and more emphasis on waste management may reduce health risks for urban wildlife and people in cities around the world.

Widespread use of anticoagulant rodenticides in agricultural and urban environments. A menace to the viability of the endangered Bonelli's eagle (Aquila fasciata) populations.

Anticoagulant rodenticides (ARs) are one of the most toxic groups of compounds currently used worldwide for rodent pest control. Toxic baits are often, directly or indirectly, ingested by non-target animals, resulting in secondary poisoning and frequently affecting apex predators. Their presence in many species of raptors is quite common, particularly scavenger species, with some of these acting as sentinels for the presence of these substances in the environment. However, there is less data on the presence of ARs in Bonelli's eagle, one of the most endangered eagle species in Spain and which is experiencing a negative population trend in Europe. This medium-sized eagle feeds predominantly on live species, and rarely consumes carrion. In this study, 17 carcasses of Bonelli's eagles from the Eastern Spain were necropsied. Both first and second generation ARs in their livers were analyzed by HPLC-MS-TOF revealing that all the eagles studied had been exposed to at least 5 ARs, out of a total of 10 ARs analyzed, with 7 being the highest number of ARs detected in a sample. Second generation ARs were the most prevalent, particularly bromadiolone and brodifacoum, with the highest concentrations in 94% of the cases. More than a third of the eagles presented a liver concentration of greater than 200 ng/g ARs, suggesting AR poisoning. The elevated presence of these compounds in Bonelli's eagles could be a new cause of mortality for this species or could explain other causes of death, such as the increased mortality in power lines, and should be taken into account for their conservation. At the same time, the presence of these compounds in the environment also represents a risk to public health, as the most frequent species in the diet of Bonelli's eagle (rabbits and partridges) are also hunted and consumed by hunters and their families.

Rat poison's long reach.

Supertoxic rodenticides are building up inside unintended targets, including birds, mammals, and insects. Scientists want to understand the damage-and limit it.

Evaluation of anticoagulant rodenticide sensitivity by examining in vivo and in vitro responses in avian species, focusing on raptors.

Anticoagulant rodenticides (ARs) are used to control pest rodent species but can result in secondary poisoning of non-target animals, especially raptors. In the present study, differences in AR sensitivity among avian species were evaluated by comparing in vivo warfarin pharmacokinetics and effects, measuring cytochrome P450s (CYPs) expression involved in AR metabolism, and conducting in vitro inhibition assays of the AR target enzyme Vitamin K 2,3-epoxide reductase (VKOR). Oral administration of warfarin at 4 mg/kg body weight did not prolong prothrombin time in chickens (Gallus gallus), rock pigeons (Columba livia), or Eastern buzzards (Buteo japonicus). Rock pigeons and buzzards exhibited shorter plasma half-life of warfarin compared to chickens. For the metabolite analysis, 4'-hydroxywarfarin was predominantly detected in all birds, while 10-hydroxywarfarin was only found in pigeons and raptors, indicating interspecific differences in AR metabolism among birds likely due to differential expression of CYP enzymes involved in the metabolism of ARs and variation of VKOR activities among these avian species. The present findings, and results of our earlier investigations, demonstrate pronounced differences in AR sensitivity and pharmacokinetics among bird species, and in particular raptors. While ecological risk assessment and mitigation efforts for ARs have been extensive, AR exposure and adverse effects in predatory and scavenging wildlife continues. Toxicokinetic and toxicodynamic data will assist in such risk assessments and mitigation efforts.

Active metabolite of the neurotoxic rodenticide bromethalin along with anticoagulant rodenticides detected in birds of prey in the northeastern United States.

Little is known about the ecologic fate of the neurotoxic rodenticide bromethalin, which is currently registered for use in the United States, Canada, and other countries including Australia. There is minimal research on bromethalin's potential to cause secondary toxicosis in nontarget wildlife. The aim of this study was to evaluate adipose tissue in four species of birds of prey presented to a wildlife clinic in Massachusetts, USA, for desmethylbromethalin (DMB), the active metabolite of bromethalin. Birds were also screened for anticoagulant rodenticides (ARs) in liver tissue to present a more complete picture of rodenticide exposures in this geographic area and to evaluate the impact of current mitigation measures in place during the time of sampling, 2021-2022. A total of 44 hawks and owls were included; DMB was found in 29.5% of birds and ARs were present in 95.5%. All birds with DMB detections also had residues of ARs. Among birds positive for ARs, 81% had two or more compounds. To the authors' knowledge the data presented here represent the first published monitoring study to document bromethalin/DMB bioaccumulation in obligate carnivores. As DMB is a more potent neurotoxicant than its parent compound, these results are cause for concern and an indication that further monitoring and study of the potential risk of bromethalin to wildlife species is needed. These findings have global implications as increasing concern regarding exposure to and toxicosis from ARs in nontarget wildlife worldwide leads to a search for alternatives and effective mitigation approaches.

Anticoagulant rodenticides are associated with increased stress and reduced body condition of avian scavengers in the Pacific Northwest.

Anticoagulant rodenticides (AR) have been used globally to manage commensal rodents for decades. However their application has also resulted in primary, secondary, and tertiary poisoning in wildlife. Widespread exposure to ARs (primarily second generation ARs; SGARs) in raptors and avian scavengers has triggered considerable conservation concern over their potential effects on populations. To identify risk to extant raptor and avian scavenger populations in Oregon and potential future risk to the California condor (Gymnogyps californianus) flock recently established in northern California, we assessed AR exposure and physiological responses in two avian scavenger species (common ravens [Corvus corax] and turkey vultures [Cathartes aura]) throughout Oregon between 2013 and 2019. AR exposure was widespread with 51% (35/68) of common ravens and 86% (63/73) of turkey vultures containing AR residues. The more acutely toxic SGAR brodifacoum was present in 83% and 90% of AR exposed common ravens and turkey vultures. The odds of AR exposure in common ravens were 4.7-fold higher along the coastal region compared to interior Oregon. For common ravens and turkey vultures that were exposed to ARs, respectively, 54% and 56% had concentrations that exceeded the 5% probability of toxicosis (>20 ng/g ww; Thomas et al., 2011), and 20% and 5% exceeded the 20% probability of toxicosis (>80 ng/g ww; Thomas et al., 2011). Common ravens exhibited a physiological response to AR exposure with fecal corticosterone metabolites increasing with sum ARs (ΣAR) concentrations. Both female common raven and turkey vultures' body condition was negatively correlated with increasing ΣAR concentrations. Our results suggest avian scavengers in Oregon are experiencing extensive AR exposure and the newly established population of California condors in northern California may experience similar AR exposure if they feed in southern Oregon. Understanding the sources of ARs across the landscape is an important first step in reducing or eliminating AR exposure in avian scavengers.

Design and synthesis of prodrugs of the rat selective toxicant norbormide.

Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, one major drawback of NRB as a viable rodenticide relates to an evolutionary aversion developed by the rat leading to sub-lethal dosing due to either its unpleasant 'taste' or rapid onset of effects. A series of NRB prodrugs were prepared in an effort to 'mask' this acute response. Their synthesis and biological evaluation (in vitro vasoconstrictory activity, in vitro hydrolytic and enzymatic stability and lethality/palatability in vivo) is described. Compound 19 displayed the most promising profile with respect to a delay in the onset of symptoms and was subsequently demonstrated to be significantly more palatable to rats.

High exposure rates of anticoagulant rodenticides in predatory bird species in intensively managed landscapes in Denmark.

The extensive use of anticoagulant rodenticides (ARs) for rodent control has led to widespread secondary exposure in nontarget predatory wildlife species. We investigated exposure rates and concentrations of five ARs in liver samples from five raptors and six owls from Denmark. A total of 430 birds were analysed. ARs were detected in 84-100 % of individual birds within each species. Multiple AR exposure was detected in 73 % of all birds. Average number of substances detected in individual birds was 2.2 with no differences between owls and raptors. Difenacoum, bromadiolone, and brodifacoum were the most prevalent substances and occurred in the highest concentrations. Second-generation ARs made up 96 % of the summed AR burden. Among the six core species (sample size >30), summed AR concentrations were lower in rough-legged buzzard (Buteo lagopus) and long-eared owl (Asio otus) than in barn owl (Tyto alba), buzzard (B. buteo), kestrel (Falco tinnunculus), and tawny owl (Strix aluco). There was a strong tendency for seasonal variations in the summed AR concentration with levels being lowest during autumn, which is probably related to an influx of less-exposed migrating birds from northern Scandinavia during autumn. High hepatic AR residue concentrations (>100 ng/g wet weight), which have been associated with symptoms of rodenticide poisoning and increased mortality, were recorded high frequencies (12.9-37.4 %) in five of the six core species. The results suggest that the present use of ARs in Denmark, at least locally, may have adverse effects on reproduction and, ultimately, population status in some raptors and owls.

Accidental discharge of brodifacoum baits into a freshwater lake: a case study.

Approximately 700 kg of cereal bait containing 20 ppm of the anticoagulant rodenticide brodifacoum was spilled into a southern New Zealand lake in 2010 from a helicopter being used to transport containers of brodifacoum bait for an aerial baiting operation. In the month after the spill no residual brodifacoum was detected in samples of lake water, sediment, benthic invertebrates, eels, and two birds.

New insights on in vitro biotransformation of anticoagulant rodenticides in fish.

The assessment of the bioaccumulation potential of chemicals is an essential and mandatory part of their regulatory environmental risk and hazard assessment. So far, in vitro data on fish metabolism is rarely available for biocidal active substances such as anticoagulant rodenticides. In this case study we present in vitro biotransformation rates of eight biocidal and one pharmaceutical anticoagulants in rainbow trout (Oncorhynchus mykiss) liver subcellular S9 fraction (RT-S9) determined following the Organisation for Economic Co-operation and Development test guideline 319B method at two different incubation temperatures (i.e., 12 ± 1 °C and 23 ± 2 °C). Furthermore, we address challenges associated with the usability and interpretation of in vitro data to support the decision making within the regulatory bioaccumulation assessment in bridging the gap between in silico methods and in vivo studies. According to our results, four of the tested substances (i.e., chlorophacinone, coumatetralyl, bromadiolone, and difenacoum) exhibited significant intrinsic clearance (p < .001) in the RT-S9 assay. Overall, the observed metabolism was (very) slow and clearance rates were temperature-dependent. Whether the determined in vitro biotransformation rate had a substantial influence on the predicted bioconcentration factor during extrapolation was subject to the lipophilicity of the test substance. Further improvements of existing concepts are needed to overcome uncertainties in the prediction of bioconcentration factors for chemicals such as anticoagulants.

Long-term trends of second generation anticoagulant rodenticides (SGARs) show widespread contamination of a bird-eating predator, the Eurasian Sparrowhawk (Accipiter nisus) in Britain.

Second generation anticoagulant rodenticides (SGARs) are widely used to control rodents around the world. However, contamination by SGARs is detectable in many non-target species, particularly carnivorous mammals or birds-of-prey that hunt or scavenge on poisoned rodents. The SGAR trophic transfer pathway via rodents and their predators/scavengers appears widespread, but little is known of other pathways of SGAR contamination in non-target wildlife. This is despite the detection of SGARs in predators that do not eat rodents, such as specialist bird-eating hawks. We used a Bayesian modelling framework to examine the extent and spatio-temporal trends of SGAR contamination in the livers of 259 Eurasian Sparrowhawks, a specialist bird-eating raptor, in regions of Britain during 1995-2015. SGARs, predominantly difenacoum, were detected in 81% of birds, with highest concentrations in males and adults. SGAR concentrations in birds were lowest in Scotland and higher or increasing in other regions of Britain, which had a greater arable or urban land cover where SGARs may be widely deployed for rodent control. However, there was no overall trend for Britain, and 97% of SGAR residues in Eurasian Sparrowhawks were below 100 ng/g (wet weight), which is a potential threshold for lethal effects. The results have potential implications for the population decline of Eurasian Sparrowhawks in Britain. Fundamentally, the results indicate an extensive and persistent contamination of the avian trophic transfer pathway on a national scale, where bird-eating raptors and, by extension, their prey appear to be widely exposed to SGARs. Consequently, these findings have implications for wildlife contamination worldwide, wherever these common rodenticides are deployed, as widespread exposure of non-target species can apparently occur via multiple trophic transfer pathways involving birds as well as rodents.

Monitoring the hepatic residues of cis- and trans-diastereoisomers of second generation anticoagulant rodenticides reveals a different bioaccumulation of diastereoisomers in the food chain of the Réunion harrier (Circus maillardi).

The Réunion harrier is an endangered raptor and endemic species to the Réunion Island. Second generation anticoagulant rodenticides (SGARs) are widely used pesticides on the island in order to control rodent populations. The latter are responsible for the transmission of leptospirosis to humans, the damage of sugarcane crops, and the decline of endemic endangered birds. SGARs are very persistent chiral pesticides and consequent secondary exposure or poisoning of the Réunion harrier has been observed (73% of prevalence in a group of 58 harriers). Commercial formulations of SGARs are a mixture of trans- and cis-diastereoisomers. Both diastereoisomers of all SGARs have been shown to inhibit coagulation function with the same potency. On the other hand, they have been shown to have a significant difference in terms of tissue-persistence. This difference has led to residue levels in rats with a significantly lower proportion of one of the isomers compared to the bait composition. In this study, residue levels of the diastereoisomers of all SGARs were evaluated in the livers of 58 harrier carcasses. The respective concentrations and proportions of cis- and trans- diastereoisomers of all SGARs are presented. cis-Brodifacoum and trans-bromadiolone had the highest concentrations (up to 438 and 573 ng/g ww respectively), while trans-brodifacoum was less than 46 ng/g and cis-bromadiolone was barely detected. cis-Difenacoum showed the highest prevalence and the highest concentration was 82 ng/g ww, while trans-difenacoum was never detected. This study demonstrated that only cis-brodifacoum and trans-bromadiolone (and cis-difethialone, but with a low prevalence) had hepatic concentrations above a toxic threshold. The cis- and trans-diastereoisomers of SGARs had differential bioaccumulation in the food chain of the Réunion harrier compared to commercial baits. This suggests that a change of the proportions of SGARs diastereoisomers in baits could reduce the risk of secondary poisoning of predators, but maintain primary toxicity.