Extensive evaluation of a new LC-MS-MS method to quantify monofluoroacetate toxin in the kidney.

Monofluoroacetate is a highly lethal toxin that causes death by inhibiting cellular adenosine triphosphate (ATP) production. The heart and brain are the primary target organs. Acute death is attributed to cardiac fibrillation and/or convulsions. Although it occurs naturally in some plants, a major source of animal intoxication is access to sodium monofluoroacetate (NaMFA) pesticide, which continues to be a concern in the USA and around the world despite restricted use in some countries including the USA. There are also concerns about misuse of this pesticide for malicious poisoning. Currently, a tissue-based diagnostic method for NaMFA intoxication in animals is lacking. There is a critical need by the veterinary diagnostic community for a simple, sensitive and reliable tissue-based diagnostic test to confirm NaMFA poisoning in animals. We have developed and extensively evaluated a sensitive novel liquid chromatography combined with tandem mass spectrometry method suitable for this purpose. The limits of detection and limits of quantitation are 1.7 and 5.0 ng/g, respectively. The accuracy and precision met or exceeded expectations. The method performance was verified using the incurred kidney obtained from animal diagnostic cases. This novel kidney-based method is now available for clinical use and can help with diagnostic purposes, including detecting potential issues related to animal foods.

Reversible leukoencephalopathy caused by 2 rodenticides bromadiolone and fluoroacetamide: A case report and literature review.

RATIONALE: With the easy access, rodenticide poisoning has been a public health problem in many countries. Characteristics of central nervous system (CNS) lesions induced by rodenticides are scarcely reported. PATIENT CONCERNS: We presented a case of a 40-year-old man with seizure and consciousness disorder, coagulation dysfunction, and symmetric lesions in white matter and corpus callosum. DIAGNOSIS: He was diagnosed with rodenticide poisoning due to bromadiolone and fluoroacetamide. INTERVENTIONS: He was treated with vitamin K, hemoperfusion, acetamide, and calcium gluconate. OUTCOMES: His leukoencephalopathy was reversed rapidly with the improvement of clinical symptoms. LESSONS: This report presented the impact of rodenticide poisoning on CNS and the dynamic changes of brain lesions, and highlighted the importance of timely targeted treatments.

Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical.

Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing a specific antibody to FAM is not only critical for the development of a fast diagnostic but also a potential treatment. However, achieving this goal is a great challenge, mainly due to the very low molecular weight of FAM. Here, we design two groups of FAM haptens for the first time, maximally exposing the fluorine or amino groups, with the aid of linear aliphatic or phenyl-contained spacer arms. Interestingly, whereas the hapten with fluorine at the far end of the hapten did not induce an antibody response to FAM, the hapten with an amino group at the far end and phenyl-contained spacer arm triggered a significantly specific antibody response. Finally, a monoclonal antibody (mAb) named 5D11 was successfully obtained with an IC50 value of 97 µg mL-1 and negligible cross-reactivities to the other nine functional and structural analogs.

Methylene blue and monosodium glutamate improve neurologic signs after fluoroacetate poisoning.

Fluoroacetate (FA) is a tasteless, odorless, water-soluble metabolic poison with severe toxicological effects. Characterized in the mid-1900s, it has been used as a rodenticide but is comparably lethal to all mammals. Many countries have restricted its use, and modern-day accidental human exposures are rare, but recently, concerns have been raised about its application as a chemical weapon with no known antidote. A combined treatment of methylene blue (MB), an antioxidant, and monosodium glutamate (MSG), a precursor of the citric acid cycle substrate alpha-ketoglutarate, has been recommended as an effective countermeasure; however, no peer-reviewed articles documenting the efficacy of this therapy have been published. Using a rodent model, we assessed the effects of MB and MSG on the neurologic, cardiac, and pulmonary systems. Transcriptomic analysis was used to elucidate inflammatory pathway activation and guide bioassays, which revealed the advantages and disadvantages of these candidate countermeasures. Results show that MB and MSG can reduce neurologic signs observed in rats exposed to sodium FA and improve some effects of intoxication. However, while this strategy resolved some signs of intoxication, ultimately it was unable to significantly reduce lethality.

Plasma fluoroacetic acid concentrations: Symptoms, hematological, and biochemical characteristics in patients with fluoroacetic acid poisoning in the emergency department.

Fluoroacetic acid (FAcOH) was once a highly toxic rodenticide widely used in the world. In the past, studies on the toxicity of FAcOH have focused on animal experiments. The toxicity of FAcOH to humans and the changes of FAcOH in plasma have not been studied. Therefore, the present study aimed to describe the changes of plasma FAcOH concentrations, hematological, and biochemical characteristics in patients with FAcOH intoxication. According to clinical symptoms, 68 patients from the emergency department were divided into different groups: convulsion group, unconsciousness group, death group, and control groups. Plasma FAcOH concentrations, hematological, and biochemical parameters were investigated. Results demonstrated that patients in the convulsion group and the unconsciousness group had a significant increase (p < 0.01) in the level of neuron-specific enolase (NSE), creatine kinase MB (CKMB), glucose (GLU), and white blood cell count (WBC) and a significant decrease (p < 0.01) in serum potassium compared with the control group, respectively. Moreover, patients in the death group had a significant increase (p < 0.01) in the level of NSE, CKMB, N-terminal pro-brain natriuretic peptide, GLU, and WBC and a significant decrease (p < 0.01) in serum potassium and total calcium compared with the survival group. The concentrations of FAcOH in plasma in the convulsion group, the unconsciousness group, and the death group were 72.31 ± 42.29, 118.33 ± 55.41, and 163.78 ± 43.32 µg/mL, respectively. These changes and the plasma FAcOH concentrations may increase our understanding of the toxicity of FAcOH to humans and may help doctors to judge the clinical prognosis of patients with FAcOH intoxication.

Sodium fluoracetate's poisoning, a case report

Sodium fluoroacetate, known as compound 1080, was discovered in Germany during the Second World War. Used as a rodenticide, however, as it is an odorless and tasteless substance, with a lethal dose in humans of 2 mg / kg, it was withdrawn from the market in some countries, including Colombia, however, it is obtained illegally. This substance has biochemical and physiological effects at the cellular level that alter the transport of citrate at the mitochondrial level, generating accumulation of lactic acid and alteration in the use of glucose. The clinical manifestations are nonspecific, there is no cardinal symptom. Therefore, its diagnosis is made due to high clinical suspicion, associated with establishment of exposure to the compound, since paraclinical confirmation is difficult to perform in a timely manner. We present a case report of intentional ingestion in an adolescent, associated added infection to the bloodstream by methicillin- sensitive Staphylococcus aureus (MSSA), who developed multiple complications and the need for support in the Intensive Care Unit (ICU) with satisfactory outcome. Not having a specific antidote, she was treated with ethanol to increase the level of acetate, thus offering an alternative substrate to the Krebs cycle and may offer benefits in the acute treatment of these patients. Patient with sodium fluoroacetate poisoning and kidney failure, receiving renal replacement therapy with a favorable evolution and survival at discharge from the intensive care unit of a third-level hospital in the city of Pereira, Risaralda, Colombia. Sodium fluoroacetate poisoning is relatively rare and can cause acute kidney injury and multi-organ failure with a high rate of complications and death. A case of self-inflicted poisoning that received early continuous renal replacement therapy with a favorable outcome in terms of survival and discharge from the intensive care unit of a third-level hospital in the city of Pereira, Risaralda, Colombia was presented

No disponible

Herbaspirillum seropedicae as a degrading bacterium of monofluoroacetate: effects of its inoculation in goats by ingesting Amorimia septentrionalis and the concentrations of this compound in plants sprayed with the bacterium / Herbaspirillum seropedicae como bactéria degradadora de monofluoroacetato de sódio: efeitos de sua inoculação em caprinos ingerindo Amorimia septentrionalis e nas concentrações deste composto em plantas pulverizadas com a bactéria

Herbaspirillum seropedicae is a nitrogen-fixing bacterium capable of using toxic compounds as a source of carbon. Bacteria with this capacity can be used to make animals resistant to plant poisoning containing monofluoroacetate (MFA), such as Amorimia septentrionalis. The aim of this study was to evaluate if H. seropedicae is efficient in the degradation of MFA present in A. septentrionalis and if the inoculation of this bacterium in goats confers protection to A. septentrionalis intoxication. Two experiments were performed: in the first experiment 12 goats were divided into 2 groups. Goats in Group 1 were orally administered a solution containing the H. seropedicae bacterium for 10 days. From day 10 onwards, they received a daily dose of 5g/kg of A. septentrionalis with the bacteriauntil clinical signs of intoxication were observed. Group 2 goats received only the plant at the same dose, also until the observation of clinical signs of intoxication. The amount of MFA found in A. septentrionalis used in the experiment with goats was 1.6±0.058μg/mg. The total plant dose ingested by all goats in Group 1 was 80.83±12.81g/kg (129.33±20.50mg/kg MFA), which were significantly greater ​​(p<0.05) than those of Group 2 goats (39.16±19.08g/kg plant and 62.66±30.53mg/kg MFA). Group 1 goats took an average of 16.16±2.56 days to develop clinical signs of intoxication, significantly longer (p=0.0012) than Group 2 goats (7.83±3.81 days). Two Group 2 goats died on the same day that they developed clinical signs of intoxication. At necropsy of these two animals, no significant changes were observed. In the second experiment, samples of A. septentrionalis were sprayed with a solution containing H. seropedicae. Before and eight days after spraying, the samples were pressed and dried for quantitation of MFA. The amount of MFA present in samples of A. septentrionalis 8 days after spraying with H. seropedicae was significantly lower (p=0.017) than that found prior to spraying. It can be concluded that administration of H. seropedicae in goats is capable of causing greater resistance to A. septentrionalis intoxication, and spraying the plant with this bacterium significantly reduces the amount of MFA in the plant.(AU)

Herbaspirillum seropedicae é uma bactéria fixadora de nitrogênio, capaz de utilizar compostos tóxicos como fonte de carbono. Bactérias com essa capacidade podem ser utilizadas para tornar os animais resistentes à intoxicação por plantas que contém monofluoroacetato (MFA), como Amorimia septentrionalis. O objetivo do presente estudo é avaliar se H. seropedicae é eficiente na degradação do MFA presente em A. septentrionalis e se a inoculação dessa bactéria, em caprinos, confere proteção à intoxicação por A. septentrionalis. Foram realizados dois experimentos: no primeiro experimento foram utilizados 12 caprinos, divididos em dois grupos. Os caprinos do Grupo 1 receberam diariamente, oralmente, uma solução contendo a bactéria H. seropedicae durante 10 dias. A partir do décimo dia passaram a receber, diariamente, além da solução com a bactéria 5g/kg de A. septentrionalis até a observação de sinal clínico de intoxicação. Os caprinos do Grupo 2 receberam apenas a planta na mesma dose, também até que a observação de sinais clínicos de intoxicação. A quantidade de MFA encontrada em A. septentrionalis utilizada no experimento com caprinos foi de 1,6± 0,058µg/mg de planta em média. A dose total de planta ingerida por todos os caprinos do Grupo 1 foi de 80,83±12,81g/kg (129,33±20,50mg/kg de MFA), valores significativamente maiores (p<0,05) do que os dos caprinos do Grupo 2 (39,16±19,08g/kg de planta e 62,66± 30,53mg/Kg de MFA). Os caprinos do Grupo 1 demoraram em média 16,16 ±2,56 dias para desenvolver sinais clínicos da intoxicação, período significativamente maior (p=0,0012) que os caprinos do Grupo 2 (7,83±3,81dias). Dois caprinos do Grupo 2 morreram no mesmo dia que desenvolveram sinais clínicos da intoxicação. Na necropsia desses dois animais não foram observadas alterações significativas. No segundo experimento, amostras de A. septentrionalis foram pulverizadas com uma solução contendo a bactéria H. seropedicae. Antes e oito dias após a pulverização, as amostras foram prensadas e secas para posterior quantificação do MFA. A quantidade de MFA presente nas amostras de A. septentrionalis oito dias após a pulverização com H. seropedicae foi significativamente menor (p=0,017) do que a encontrada antes da pulverização. Pode-se concluir que a administração de H. seropedicae em caprinos é capaz de causar uma maior resistência à intoxicação por A. septentrionalis, e a pulverização da planta com esta bactéria reduz significativamente a quantidade de MFA na planta.(AU)

Techniques for prevention and control of poisoning by sodium monofluoroacetate (MFA)-containing plants in ruminants / Técnicas para prevenção e controle da intoxicação em ruminantes por plantas que contém monofluoroacetato de sódio

Monofluoroacetate (MFA)-containing plants cause sudden death associated with exercise in ruminants, and are responsible for significant losses in Brazilian livestock, estimated at 500,000 bovine deaths annually. Most of the times, the control and treatment of this type of poisoning are not efficient, because disease evolution is superacute, usually causing the death of the animal. Due to the difficulty in controlling this intoxication, several studies have suggested alternatives to prevent it, mainly by making animals resistant to the MFA present in these plants or by avoiding their consumption. This literature review addresses the techniques used experimentally to control the poisoning of ruminants by plants containing MFA. The first studies carried out in Brazil demonstrated that goats and sheep that continuously receive non-toxic doses of plant containing MFA show greater resistance to poisoning than untreated animals, and that this resistance can be transmitted by ruminal fluid transfaunation, suggesting that poisoning occurs due to the presence of bacteria that hydrolyze MFA in the rumen. Based on this hypothesis, several MFA-hydrolyzing bacteria were isolated (Enterococcus faecalis, Bacillus sp., Paenibacillus sp., Burkholderia sp., Cupriavidus sp., Staphylococcus sp., Ancylobacter sp., Ralstonia sp., Stenotrophomonas sp., Pigmentiphaga kullae, and Ancylobacter dichloromethanicus). When some of these bacteria were administered intraruminally, they provided the animal with a different level of protection against poisoning. However, it was observed that protection is gradually lost when the bacterium administration is interrupted. Consequently, to obtain more efficient protection, these bacteria should be administered continuously, probably in the form of probiotics. In another assay, MFA was administered to sheep at non-toxic doses to test the hypothesis that this substance could induce the multiplication of bacteria that hydrolyze it in the rumen. There was no increase in resistance to poisoning after administration of MFA; however, no signs of poisoning were observed when animals received trifluoroacetate and no clinical signs were verified when they were challenged with toxic doses of MFA; in contrast, all control animals presented clinical signs. These results suggest that trifluoroacetate induces the proliferation of MFA-degrading bacteria, and can be used in intoxication prophylaxis. The conditioned food aversion technique, using lithium chloride, has been successfully used experimentally to prevent ruminants from ingesting plants that contain MFA. Another alternative tested was the spraying of Amorimia septentrionalis with the endophytic bacterium Herbaspirillum seropedicae, which degrades MFA, resulting in decreased concentration of this compound in the plants. In conclusion, several experimental techniques have been proved efficient in the control and prophylaxis of MFA-containing plant poisoning; however, none of these techniques are available commercially. Further experiments, mainly in the field, should be carried out to adapt some of these techniques to the conditions of extensive breeding in the numerous areas where MFA-containing plants occur.(AU)

As plantas que contém monofluoroacetato (MFA) causam morte súbita associada ao exercício em ruminantes, e são responsáveis por grandes perdas na pecuária brasileira, estimadas em 500.000 mortes de bovinos anualmente. O controle e tratamento desse tipo de intoxicação, na maioria das vezes, não apresenta eficiência, visto que a evolução da doença é superaguda, e geralmente ocasiona a morte do animal. Devido à dificuldade no controle dessa intoxicação, diversos estudos sugerem alternativas para preveni-la, principalmente tornando os animais resistentes ao MFA presente nessas plantas ou evitando seu consumo. O objetivo do presente trabalho é fazer uma revisão bibliográfica das técnicas utilizadas experimentalmente para controlar a intoxicação de ruminantes por plantas que contém MFA. Nos primeiros trabalhos realizados no Brasil, foi determinado que caprinos e ovinos que recebem continuadamente doses não tóxicas de planta que contém MFA apresentam maior resistência a intoxicação que animais não tratados e que essa resistência pode ser transmitida por transfaunação de fluído ruminal, sugerindo que a mesma ocorre devido a presença de bactérias que hidrolisam MFA no rúmen. Com base nessa hipótese foram isoladas diversas bactérias que hidrolisam MFA (Enterococcus faecalis, Bacillus sp., Paenibacillus sp., Burkholderia sp., Cupriavidus sp., Staphylococcus sp., Ancylobactersp., Ralstoniasp., Stenotrophomonas sp., Pigmentiphaga kullae e Ancylobacter dichloromethanicus). Quando algumas dessas bactérias foram administradas intraruminalmente conferiram diferentes graus de proteção contra a intoxicação. No entanto foi observado que a proteção se perde gradualmente quando se deixa de administrar a(s) bactéria(s). Em consequência, para obter uma proteção mais eficiente essas bactérias deveriam ser administradas continuadamente, provavelmente na forma de probiótico. Em outro ensaio administrou-se MFA a ovinos em doses não tóxicas para testar a hipótese de que esta substância poderia induzir a multiplicação de bactérias que hidrolisam o mesmo no rúmen. Não houve um aumento da resistência a intoxicação após a administração de MFA; no entanto quando foi administrado trifluoroacetato, os animais não desenvolveram nenhum sinal de intoxicação e quando desafiados com doses tóxicas de MFA não apresentaram sinais clínicos, pelo contrário todos os animais controles apresentaram sinais clínicos. Esses resultados sugerem que o trifluoroacetato induz a proliferação de bactérias que degradam MFA e pode ser utilizado para a profilaxia da intoxicação. A técnica da aversão alimentar condicionada, utilizando cloreto de lítio, tem sido empregada experimentalmente, com sucesso, para evitar que ruminantes ingiram plantas que contém MFA. Outra alternativa testada foi a pulverização de Amorimia septentrionalis com a bactéria endofítica Herbaspirullum seropedicae, que degrada MFA, resultando na diminuição da concentração deste composto na planta. Conclui-se que há diversas técnicas que experimentalmente tem demonstrado eficiência no controle e profilaxia das intoxicações por plantas que contém MFA; no entanto, nenhuma dessas técnicas está disponível comercialmente. Futuros experimentos, principalmente, a campo, deverão ser realizados para adaptar alguma(s) dessas técnicas as condições de criação extensiva nas numerosas áreas onde ocorrem plantas que contém MFA.(AU)

Neonatal mortality associated with sodium monofluoracetate in kids fed with colostrum from goats ingesting Amorimia septentrionalis / Mortalidade neonatal associada ao monofluoroacetato de sódio em cabritos alimentados com colostro de cabras ingerindo Amorimia septentrionalis

Sudden deaths after colostrum ingestion in kids and lambs born to mothers grazing in areas with Amorimia septentrionalis have been reported in the Brazilian northeastern semi-arid region, in Paraíba state. This study aimed to determine whether the sodium monofluoracetate (MF) contained in A. septentrionalis is eliminated in milk, causing the death of kids. After confirming gestation on the 25th day after mating, 26 goats were randomly distributed into three groups. In Group 1, eight goats received fresh leaves of A. septentrionalis in daily doses of 1g/kg body weight, administered at three different periods during gestation: from days 91 to 100, 116 to 125, and from day 140 until delivery day. In Group 2, consisting of 10 females, eight goats received 1g/kg body weight of A. septentrionalis dried and milled leaves, fed daily from the 140th day of gestation until delivery. The other two goats of this group did not ingest the plant during gestation and after delivery the colostrum supplied to their kids was replaced by colostrum of goats from that same group that had ingested the plant. Eight goats from Group 3 (control) did not ingest A. septentrionalis. Seven goats from Group 1 showed signs of poisoning from 2nd to 8th days of plant administration, in all periods, and recovered within 7 to 12 days. Another goat presented severe clinical signs and was submitted to euthanasia in extremis. Two goats aborted. Four kids, from two goats, received colostrum and, after 15 minutes, presented depression, breathing wheezing, lateral recumbence, bleating, and death. Two goats gave birth at night; the two kids were found dead and, at necropsy, it was verified that they were born alive. The last goat in this group gave birth to two kids which showed no signs of poisoning after colostrum ingestion. In Group 2, the eight goats that ingested dry leaves of the plant presented tachycardia and engorgement of the jugular veins; six aborted, and the kids of the other two goats died immediately after delivery without ingesting colostrum. The three kids of the two goats that did not ingest the plant during gestation did not show signs of poisoning after ingesting colostrum from the goats that had ingested the plant. In Group 3, all females kidded normally and the kids showed no signs of poisoning. Ten leaf samples of A. septentrionalis contained 0.00074% ±0.00018 MF. These results demonstrate that the MF of A. septentrionalis is eliminated in colostrum and may cause the death of kids. As in previous reports, the plant also caused abortion.(AU)

Mortes súbitas, após a ingestão do colostro, em cabritos e cordeiros nascidos de mães que pastejam em áreas com Amorimia septentrionalis são relatadas no semiárido da Paraíba. O objetivo deste trabalho foi determinar se o monofluoracetato de sódio (MF) contido em Amorimia septentrionalis é eliminado pelo leite, causando a morte dos cabritos. Após a confirmação da gestação no 25º dia após a cobertura, 26 cabras foram aleatoriamente distribuídas em três grupos. No Grupo 1, oito cabras receberam folhas frescas de A. septentrionalis em doses diárias de 1g/kg de peso vivo, administradas em três períodos diferentes durante a gestação: entre os dias 91 a 100, 116 a 125 e do 140º dia até o parto. No Grupo 2, composto por 10 fêmeas, oito cabras receberam 1g/kg de peso vivo de folhas secas e trituradas de A. septentrionalis, fornecida diariamente do 140º dia de gestação até o parto. As outras duas cabras desse grupo não ingeriram a planta durante a gestação e, ao parirem, o colostro fornecido aos seus cabritos foi substituído pelo colostro de cabras, desse mesmo grupo, que ingeriram a planta. Oito cabras do Grupo 3 (controle) não ingeriram A. septentrionalis. Sete cabras do Grupo 1 apresentaram sinais de intoxicação entre o 2º e 8º dia de administração da planta, em todos os períodos, e se recuperavam em 7 a 12 dias. Outra apresentou sinais clínicos graves e foi eutanasiada in extremis. Duas cabras abortaram. Quatro cabritos, oriundos de duas cabras, receberam colostro e, após 15 minutos, apresentaram depressão, respiração ofegante, decúbito lateral, berros e morte. Dois cabritos, nascidos de duas cabras que pariram durante a noite, foram encontrados mortos e os achados de necropsia permitem afirmar que nasceram vivos. A outra cabra desse grupo pariu dois cabritos que, mesmo mamando o colostro, não apresentaram sinais de intoxicação. No Grupo 2, as oito cabras que ingeriram a planta seca apresentaram taquicardia e ingurgitamento das veias jugulares; seis abortaram e os cabritos das outras duas morreram imediatamente após o parto, sem ingerir colostro. Os três filhotes das duas cabras que não ingeriram a planta durante a gestação não apresentaram sinais de intoxicação após ter ingerido colostro das cabras que tinham ingerido a planta. No Grupo 3, todas as fêmeas pariram normalmente e os filhotes não apresentaram sinais de intoxicação. Dez amostras de folhas de A. septentrionalis continham 0,00074% ± 0,00018 de MF. Estes resultados demonstram que o MF de A. septentrionalis, além de causar abortos, é eliminado pelo colostro podendo causar a morte dos cabritos.(AU)

Multiple episodes of 1080 (sodium monofluoroacetate) intoxication in a California calf-raising operation.

Over a 1-y period, a California calf-raising operation experienced 4 separate episodes of sudden death in 4-6-mo-old steers. Each episode occurred in 1-3 contiguous pens on 1 of 3 properties owned by the operation, but eventually all 3 properties were involved. In each episode, animals appeared normal at the evening feeding but at the subsequent morning feeding were found dead or dying. Remaining live calves had a stiff gait and were often dribbling urine, but did not show respiratory signs until they were down and agonal. At postmortem examination, calves consistently had moderate-to-large numbers of ecchymotic and suffusive hemorrhages on the epicardial surface and moderate-to-large amounts of fluid in the pericardial sac. Pulmonary edema and/or moderate amounts of watery fluid in the thoracic and abdominal cavities were present in a smaller percentage. On histologic examination, the myocardium had variable myofiber degeneration characterized by hypereosinophilia and fragmentation with mild interstitial infiltrates. Testing of heart and liver samples for monensin found levels lower than in previous cases of monensin toxicity. Rumen content was negative for oleandrin and grayanotoxins. Sodium monofluoroacetate (trade name: 1080) was consistently detected at ⩾10 ppb in kidney and liver, and was concluded to be the cause of the intoxication.

Analysis of monofluoroacetic acid in human plasma by UFLC-MS/MS and its application in patients with sodium monofluoroacetate or monofluoroacetamide poisoning.

Monofluoroacetic acid (FAcOH), was once widely used in baits as a rodenticide in agriculture. For intentional and unintentional misuses, the incidence of FAcOH poisoning has increased in recent years. Organic fluorine rodenticides such as sodium monofluoroacetate and monofluoroacetamide, the analogs of FAcOH, can easily be converted to FAcOH in vivo and cause injury. It is urgent to establish a simple and sensitive analytical method of FAcOH in human plasma and applied to clinical poison analysis. In this paper, an ultra-fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method was developed for determination of FAcOH in patient plasma. We used isotopic labelled FAcOH-13C2, D2 as the internal standard (IS). Plasma samples were simply precipitated with acetonitrile and the supernatant was injected directly for analysis. The chromatographic column was Phenomenex Luna® Silica column (100 × 2 mm, 3 µm), FAcOH was eluted by isocratic elution with a mobile phase of acetonitrile-water contains 5 mM ammonium formate with 0.2% formic acid. The retention time of FAcOH was 2.31 min A good linear response was from 0.25 to 200 µg/mL, with a correlation coefficient of r = 0.9980. The limit of detection was 0.05 µg/mL. The recoveries at three spiking levers were 89.51-93.03% with relative standard deviations ranged between 2.55-3.61%. This new method has been successfully applied to monitor 31 cases of patients suspected with sodium monofluoroacetate or monofluoroacetamide poisoning.

Sodium fluoroacetate toxicity: a case report of malicious poisoning in dogs across a Phoenix, Arizona neighborhood.

In May 2016, thirteen dogs housed in backyards within a single neighborhood were reported to have developed convulsions and died within a 24 h period. An investigation of the scene by law enforcement resulted in submission of eight dogs for postmortem examination. It was suspected that a rapid acting toxin was the cause of death. A gas chromatography-mass spectrophotometry (GC-MS) protocol combined with thin-layer chromatography that allows screening for common convulsants failed to identify a toxin in either pooled gastric content or liver samples from select cases. After consultation with a veterinary toxicologist, sodium fluoroacetate poisoning was investigated. Sodium fluoroacetate, also known as 1080, is a pesticide that was available in the United States from the 1940's to the 1970's, but since 1972 has been banned or under EPA restricted use. When gastric content was re-tested using a GC-MS protocol with selective fluoroacetate ion monitoring and carbon 14 radiolabeling to facilitate quantification, 379 ppb sodium fluoroacetate was detected in a pooled gastric content sample. In spite of its banned status, sodium fluoroacetate remains a rarely reported cause of malicious poisoning in domestic dogs in the United Sates. This compound is highly toxic and is capable of causing death in dogs, humans, other mammals, and insects in ingested quantities as small as a few droplets. Even when geographic or historical proximity to a source is not evident, this intoxication should be considered in dogs exhibiting compatible clinical signs.

Treatment of severe fluoroacetamide poisoning in patient with combined multiple organ dysfunction syndrome by evidence-based integrated Chinese and Western medicines: A case report.

RATIONALE: Fluoroacetamide poisoning is the acute and severe disease of human, which leads to nervous, digestive, and cardiovascular system damage or even death in a short period of time. PATIENT CONCERNS: We report a case of a 65-year-old woman with loss of consciousness, nausea, and vomiting who was sent to the hospital by passers-by. DIAGNOSIS: She was diagnosed with severe fluoroacetamide poisoning with combined multiple organ dysfunction syndrome. INTERVENTIONS: When the diagnosis was unclear, we gave gastric lavage, support and symptomatic treatment, and closely with the vital sign. When the diagnosis was clear, based on the evidence of retrieved, muscle injection of acetamide, calcium gluconate, and vitamin C. Traditional Chinese medicine aspect, oral administration of mung bean soup of glycyrrhizae and Da-Cheng-Qi decoction enema. OUTCOMES: By setting reasonable treatment for patients, she had no special discomfort and complications after treatment. Besides, through 1-month follow-up, it was confirmed that the treatments were effective. LESSONS: Evidence-based integrated Chinese and Western medicines can effectively improve the therapeutic effects in severe fluoroacetamide-poisoned patients with combined MODS.

Earwax: A clue to discover fluoroacetate intoxication in cattle.

An innovative method was developed to detect fluoroacetate poisoning in cattle by headspace/gas chromatographic analysis of earwax samples of intoxicated cattle. Samples were collected from 2 groups of cattle subjected to induced fluoroacetate intoxication, each group receiving a different dose of acetamide (antidote). Monofluoroacetic acid was detected in samples of intoxicated cattle in concentrations inversely proportional to the dose of acetamide. Thus, earwax analysis represents a successful approach for detection and monitoring of fluoroacetate poisoning.

Lessons learned from poisoning cases caused by 2 illegal rodenticides: Tetramine and fluoroacetamide.

BACKGROUND: Tetramine (tetramethylene disulphotetramine, TETS) and fluoroacetamide (FAA) are known as illegal rodenticides with high toxicity to animal species and human beings, which could lead to severe clinical features, including reduction of consciousness, convulsions, coma, and even death. METHODS AND RESULTS: We presented 2 cases that involved rodenticides poisoning. Even though the patients showed severe manifestations, they were initially misdiagnosed, resulting in 2 persons finally died from TETS and FAA poisoning in homicide cases. CONCLUSION: From the clinical and forensic experience of these 2 cases, we suggest that physicians should consider TETS and FAA poisoning when patients present generalized seizures, especially in some cases without clear cause and diagnosis of disease. Early diagnosis and treatment are essential for positive management and criminal investigation in intentional poisoning cases. Moreover, clinical toxicology education should be reinforced.

An outbreak of sodium fluoroacetate (1080) intoxication in selenium- and copper-deficient sheep in California.

Sodium fluoroacetate is an organofluorine compound toxic to mammals, insects, and birds, currently registered for use only in livestock protection collars as a predacide in some North American states, with restricted use in California. A flock of 445 lambs and ewes in California were moved into a native pasture on a municipal refuse disposal site. Within 24 hours, 14 ewes were found dead, and the remaining sheep were moved off the site. Both ewes and lambs exhibited disoriented running, followed by apparent blindness, weakness, ataxia, coma, and death. Over the next 4 days, 63 ewes and 80 lambs died with a peak at 3 days after grazing the suspect pasture (157/445, 35% mortality). Two dead 4-month-old lambs and 2 ewes were submitted to the California Animal Health and Food Safety laboratory for necropsy. Grossly, there were bilateral diffuse pulmonary congestion and edema, hydrothorax and hydropericardium with fibrin clots, and multifocally extensive areas of epicardial petechiae, ecchymoses, and pallor. In 1 ewe, there was regional caudodorsal pulmonary hemorrhage and intraluminal tracheal clotted blood. Microscopically in all cases, there was multifocal acute myocardial degeneration and necrosis with nonsuppurative pleocellular myocarditis. Sodium fluoroacetate was detected in kidney from a lamb and a ewe at 27.5 and 12.5 parts per billion, respectively. All sheep were selenium deficient, and concurrent copper deficiency was diagnosed in 3. The pathological and toxicological findings were consistent with 1080 poisoning, possibly exacerbated by micronutrient deficiency. This outbreak raised an alert about the use of restricted products with potential lethal effect in animals in California.

Defluorination of sodium fluoroacetate by bacteria from soil and plants in Brazil.

The aim of this work was to isolate and identify bacteria able to degrade sodium fluoroacetate from soil and plant samples collected in areas where the fluoroacetate-containing plants Mascagnia rigida and Palicourea aenofusca are found. The samples were cultivated in mineral medium added with 20 mmol L(-1) sodium fluoroacetate. Seven isolates were identified by 16S rRNA gene sequencing as Paenibacillus sp. (ECPB01), Burkholderia sp. (ECPB02), Cupriavidus sp. (ECPB03), Staphylococcus sp. (ECPB04), Ancylobacter sp. (ECPB05), Ralstonia sp. (ECPB06), and Stenotrophomonas sp. (ECPB07). All seven isolates degraded sodium-fluoroacetate-containing in the medium, reaching defluorination rate of fluoride ion of 20 mmol L(-1). Six of them are reported for the first time as able to degrade sodium fluoroacetate (SF). In the future, some of these microorganisms can be used to establish in the rumen an engineered bacterial population able to degrade sodium fluoroacetate and protect ruminants from the poisoning by this compound.