ABSTRACT
In this paper, we present analytical methodologies for the determination of the thiazolidine fungicide flutianil (trade name GATTEN) and its primary metabolite OC56635 in hemp cannabis matrices. A total of nine crop matrices were tested: whole seed, fiber, flower buds, hemp hearts, hemp seed oil, hemp meal, hemp flour, ethanol extracted CBD resin (CBD-E), and supercritical CO2 extracted CBD resin (CBD-C). Processing of the CBD-E and CBD-C crop fractions was carried out in-house using methods detailed herein. Field sample analysis utilized sequential extractions, stacked solid phase extraction (SPE) column cleanups, and evaporation to prepare the samples for LC-MS/MS quantitation. Method validations for each fraction were carried out using untreated hemp matrices over a minimum of three levels, with lowest levels of method validation (LLMV) of 0.010 µg/g for all fractions except the CBD resins, for which LLMV was 0.020 µg/g. Flutianil-treated samples from nine field sites were collected from several crop production regions and analyzed to determine the distribution of incurred flutianil and OC56635 residues within the different hemp matrices. This data was generated in support of nationwide registration with the United States Environmental Protection Agency (USEPA).
Subject(s)
Cannabis , Fungicides, Industrial , Tandem Mass Spectrometry , Cannabis/chemistry , Tandem Mass Spectrometry/methods , Fungicides, Industrial/analysis , Fungicides, Industrial/chemistry , Pesticide Residues/analysis , Chromatography, High Pressure Liquid/methods , Solid Phase Extraction/methods , Food Contamination/analysis , Seeds/chemistry , Liquid Chromatography-Mass SpectrometryABSTRACT
The conclusions of EFSA following the peer review of the initial risk assessment carried out by the competent authority of the rapporteur Member State Belgium, for the pesticide active substance flutianil, are reported. The context of the peer review was that requested by the European Commission following the submission and evaluation of confirmatory information with regard to the endocrine disruption potential of the substance. The conclusions were reached on the basis of the evaluation of the representative uses of flutianil as a fungicide on grapevine and ornamental crops. Assessments not finalised, together with the missing information identified as being required by the regulatory framework, are listed.
ABSTRACT
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant OAT Agrio Co. Ltd submitted a request to the competent national authority in Belgium (originally the United Kingdom) to set import tolerances for the active substance flutianil in various crops. The data submitted in support of the request were found to be sufficient to derive MRL proposals for apples, cherries, strawberries, cucumbers and courgettes. For melons, data gaps were identified which precluded the derivation of MRL proposals. Adequate analytical methods for enforcement are available to control the residues of flutianil in the commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of flutianil according to the reported agricultural practices is unlikely to present a risk to consumer health. It is to be noted that the consumer risk assessment could not be finalised with regard to the potential presence of soil metabolite OC 56635 in rotational crops. The reliable end points appropriate for use in regulatory risk assessment are presented.
ABSTRACT
Flutianil, a fungicide effective only on powdery mildew, was previously reported to affect the host cell's haustorial formation and nutrient absorption. Studies were conducted to investigate flutianil's primary site of action on Blumeria graminis morphology using transmission electron microscope (TEM) observation and RNA sequencing (RAN-seq) techniques. TEM observation revealed that flutianil caused the extra-haustorial matrix and fungal cell wall to be obscured, without remarkable changes of other fungal organelles. RNA-seq analysis indicated that, unlike other powdery-mildew fungicides, flutianil did not significantly affect the constantly expressed genes for the survival of B. graminis. Genes whose expression is up- or downregulated by flutianil were found; these are the three sugar transporter genes and various effector genes, mainly expressed in haustoria. These findings indicate that the primary site of action of flutianil might be in the haustoria.
ABSTRACT
Flutianil, chemically characterized as a cyano-methylene thiazolidine, showed antifungal activity against powdery mildew on various crops but not any other plant pathogens tested. Flutianil showed high residual and translaminar activities and rainfastness against Podosphaera xanthii. It also exhibited curative activity against P. xanthii on cucumber at an extremely low concentration of 10 mg/L. There was no cross-resistance between flutianil and other existing fungicides. Morphological studies revealed that flutianil did not inhibit the early infection behavior of Blumeria graminis f. sp. hordei i.e., conidium bursting, primary and appressorial germinations, appressorium development and hook formations, but it did inhibit haustorium formation and further fungal development. Nutrient absorption by haustoria and subsequent secondary hyphal elongation was inhibited by flutianil but not by the fungicide that showed a similar inhibitory pattern up to the haustorium formation stage of the infection process. These findings suggest that flutianil might have a novel mode of action.
ABSTRACT
Flutianil was discovered as a novel fungicide chemically characterized as a cyano-methylene thiazolidine. This chemical showed particularly high fungicidal activities against powdery mildew on various crops. Optimization of the fungicidal performance of the series of synthesized chemicals finally led to the identification of flutianil, which could control powdery mildew diseases. In this report, details of the structure-activity relationships from the lead compound to flutianil are described.
ABSTRACT
We have evaluated the toxicity of flutianil, which was developed by OAT Agrio. Flutianil shows low toxicity, no carcinogenicity, no reproductive toxicity, and no genotoxicity. Based on these results, the ADI of flutianil has been set at 2.4 mg/kg bw/day with a safety factor of 100.
ABSTRACT
Following the publication of the EFSA conclusion on flutianil in 2014, the rapporteur Member State (RMS), the United Kingdom, launched a formal process for harmonising the classification of flutianil. The Committee for Risk Assessment (RAC) of the European Chemicals Agency (ECHA) finalised a RAC opinion on the proposed harmonised classification of flutianil in 2016. For some hazard classes, the harmonised classification proposed by the RAC was different than the provisional classification used in the EFSA conclusion. It should be noted that this difference was based on new information and does not constitute a scientific divergence as per Article 30 of Regulation (EC) No 178/2002. This statement updates the EFSA conclusion to consider the harmonised classification as proposed by the RAC. Concerns are clarified.