Fluoroacetate in plants - a review of its distribution, toxicity to livestock and microbial detoxification

Fluoroacetate producing plants grow worldwide and it is believed they produce this toxic compound as a defence mechanism against grazing by herbivores. Ingestion by livestock often results in fatal poisonings, which causes significant economic problems to commercial farmers in many countries such as Australia, Brazil and South Africa.Several approaches have been adopted to protect livestock from the toxicity with limited success including fencing,toxic plant eradication and agents that bind the toxin. Genetically modified bacteria capable of degrading fluoroacetate have been able to protect ruminants from fluoroacetate toxicity under experimental conditions but concerns over the release of these microbes into the environment have prevented the application of this technology.Recently, a native bacterium from an Australian bovine rumen was isolated which can degrade fluoroacetate. This bacterium, strain MFA1, which belongs to the Synergistetes phylum degrades fluoroacetate to fluoride ions and acetate. The discovery and isolation of this bacterium provides a new opportunity to detoxify fluoroacetate in the rumen. This review focuses on fluoroacetate toxicity in ruminant livestock, the mechanism of fluoroacetate toxicity,tolerance of some animals to fluoroaceate, previous attempts to mitigate toxicity, aerobic and anaerobic microbial degradation of fluoroacetate, and future directions to overcome fluoroacetate toxicity.

A New Method for Detection and Identificationof Sodium Fluoroacetate and Fluoroacetamideby NMR Spectroscopy

Nuclear magnetic resonance (NMR) is well known for its capacity to identify thestructure of chemical compounds. But, as we know, it has not yet been used in thedetection and identification of fluorine-containing toxicants in complicated matrixes.Here some efforts were made in this area to apply this powerful technique totoxicological analysis. Sodium fluoroacetate and fluoroacetamide are two fluorine-containing rodenticidesof high toxicity. Their determination in samples related to intoxication is

Structure-guided protein design of fluoroacetate dehalogenase for kinetic resolution of rac-2-bromobutyric acid

R-2-Bromobutyric acid is a very important intermediate for the synthesis of agrochemicals and pharmaceuticals.Bioresolution of rac-2-bromobutyric acid(rac-2-BBA)provides a promising process for R-2-bromobutyric acid(R-2-BBA)production.The fluoroacetate dehalogenase(FAcD)has been always studied in the defluorination process.We found that FAcD RPA1163 showed detectable activity but no enantioselectivity towards rac-2-BBA.The iterative saturation mutagenesis(ISM)of FAcD RPA1163 resulted in a mutant H155V/W156R/Y219M,which catalyzed the kinetic resolution of rac-2-BBA to produce R-2-BBA with enhanced activity and enantioselectivity(99.3%ee).The high preference for S-2-bromobutyric acid(S-2-BBA)is of synthetic value.Molecular docking analysis indicated that the H155V/W156R/Y219M mutation reduced steric hindrance and broadened the halide pocket.It is not only the steric hindrance but also the electrostatic environment that has an effect on the activity and enantioselectivity.

Acute Inhalation Toxicity Study of 2-Fluoroaceta mide in Rats

One of the most potent rodenticides is 2_fluoroacetamide (2_FA). Toxicity of this chemical is well documented. However, its inhalation toxicity data is not available in the literature. Hence, \{acute\} inhalation toxicity study was carried out by exposing male and female rats to aerosols of 2_FA at different concentrations for 4 h in a dynamically operated whole body inhalation exposure chamber. During and after the inhalation exposure the rats were less active, and showed mild tremors and convulsions. At higher concentrations the rats died after 2_3 days. The estimated 4_h LC 50 for male and female rats was 136.6 and 144.5 mg·m -3 respectively. Exposure to 0.7 LC 50 for 4 h duration showed an increase in the liver weight of male and female rats 7 days after exposure. Various haematological and biochemical variables determined were within the normal limits. However, histological findings showed injured lung as indicated by desquamation and necrosis of the epithelium of the respiratory tract. Marked hypertrophy of hepatocytes displaying strong acidophilic granulated cytoplasm was observed. Focal dilatation of renal proximal tubules in kidney with cytoplasmic vacuolation, and irregularly placed pyknotic nuclei were seen. The present study shows that 2_FA is a highly toxic chemical through the inhalation route based on the LC 50 value. Consequently necessary precautions should be taken during its handling.

Vertebrate pesticide risk assessment by indigenous communities in New Zealand

In New Zealand,the vertebrate pesticide sodium fluoroacetate(Compound 1080)is aerially applied in baits for control of the brush-tailed possum Trichosurus vulpecula(Kerr,1792).Maori,the indigenous people of New Zealand,have raised concerns about 1080 impacts on culturally-important species.Here,we outline two steps taken to help Maori assess 1080 risk.First,field research was undertaken to determine if naturally-occurring plants utilized by a Maori community for food and medicine would take up 1080 from baits.Single baits were placed at the base of individual plants of two species,pikopiko(Asplenium bulbiferum)and karamuramu(Coprosma robusta).Plants were sampled at various times up to 56 days,and samples were analyzed for 1080 content.No 1080 was detected in any of the pikopiko samples,whereas 1080 was detected in karamuramu,at a maximum concentration of 5 ppb after seven days,and 2.5 ppb after 14 days.This concentration decreased to 0 at 28 days,indicating that 1080 was not persistent.The results of the present study suggest there is negligible risk of humans being poisoned by consum-ing plants that have taken up 1080 from baits.To allay community concerns that minute concentrations of 1080 might influence the medicinal properties of plants,it is suggested that a withholding period of 30 days after 1080 control operations could be adopted.Second,after further consultation we undertook a review of the scientific literature relating to 1080 impacts on additional non-target species of cultural importance to Maori.The information was presented on an interactive foodweb database that allowed the collection and presentation of a large volume of complex information about 1080 in a holistic and pictorial fashion.This database was presented to many Maori communities throughout New Zealand,and feedback was overwhelmingly positive.The database is likely to play a key role in informing these communities about 1080,and is seen as an important new tool to help these communities make their own risk assessments.