Prenatal current-use pesticide exposure and children's neurodevelopment at one year of age in the Infants' Environmental Health (ISA) birth cohort, Costa Rica.

BACKGROUND: Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. OBJECTIVE: We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants' Environmental Health (ISA) birth cohort. METHODS: To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1-3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). RESULTS: We found higher prenatal urinary 2,4-D concentrations were associated with lower language (ßper ten-fold increase = -2.0, 95 % confidence interval (CI) = -3.5, -0.5) and motor (ßper ten-fold increase = -2.2, 95 %CI = -4.2, -0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (ßper ten-fold increase = -1.9, 95 %CI = -4.7, 0.8), and lower motor composite scores among boys (ßper ten-fold increase = -3.8, 95 % CI = -7.7, 0.1) but not girls (ßper ten-fold increase = 2.3, 95 %CI = -1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. DISCUSSION: Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.

Kinetic and Mechanistic Modelling of Pyrimethanil Fungicide Adsorption onto Soils of Varying Physico-chemical Properties.

Pesticide transport in the environment is impacted by the kinetics of its adsorption onto soil. The adsorption kinetics of pyrimethanil was investigated in ten soil samples of varying physicochemical properties. The highest adsorption was in the soil having the maximum silt and CaCO3 contents, pH and electrical conductance but the lowest amorphous Fe oxides and CaCl2 extractable Mn. Pseudo-second order kinetics and intra-particle diffusion model best accounted the adsorption kinetics of pyrimethanil. The equilibrium adsorption estimated by pseudo-second order kinetics (q02) was significantly and positively correlated with CaCl2 extractable Cu content (r = 0.709) while rate coefficient (k02) had a negative correlation with crystalline iron oxides content (r = -0.675). The intra-particle diffusion coefficient (ki.d.) had inverse relationship with CaCl2 extractable Mn content in soils (r = -0.689). FTIR spectra showed a significant interaction of pyrimethanil with micronutrient cations. Adsorption kinetic parameters of pyrimethanil could be successfully predicted by soil properties. The findings may help to evolve fungicide management decisions.

Fungicide Sensitivity of Colletotrichum Species Causing Bitter Rot of Apple in the Mid-Atlantic U.S.A.

Apple growers in the Mid-Atlantic region of the U.S.A. have reported increased losses to bitter rot of apple. We tested the hypothesis that this increase is because the Colletotrichum population has developed resistance to commonly used single-mode-of-action (single-MoA) fungicides. We screened 220 Colletotrichum isolates obtained from 38 apple orchards in the Mid-Atlantic region for resistance to 11 fungicides in Fungicide Resistance Action Committee (FRAC) groups 1, 7, 9, 11, 12, and 29. Eleven (5%) of these isolates were resistant to FRAC group 1 with confirmed ß-tubulin E198A mutations, and two (<1%) were also resistant to FRAC group 11 with confirmed cytochrome-b G143A mutations. Such low frequencies of resistant isolates indicate that fungicide resistance is unlikely to be the cause of any regional increase in bitter rot. A subsample of isolates was subsequently tested in vitro for sensitivity to every single-MoA fungicide registered for apple in the Mid-Atlantic U.S.A. (22 fungicides; FRAC groups 1, 3, 7, 9, 11, 12, and 29), and 13 fungicides were tested in field trials. These fungicides varied widely in efficacy both within and between FRAC groups. Comparisons of results from our in vitro tests with results from our field trials and other field trials conducted across the eastern U.S.A. suggested that EC25 values (concentrations that reduce growth by 25%) are better predictors of fungicide efficacy in normal field conditions than EC50 values. We present these results as a guideline for choosing single-MoA fungicides for bitter rot control in the Mid-Atlantic U.S.A.

A Sensitive Pyrimethanil Sensor Based on Electrospun TiC/C Film.

Titanium carbide (TiC) is a very significant transition metal carbide that displays excellent stability and electrical conductivity. The electrocatalytic activity of TiC is similar to noble metals but is much less expensive. Herein, carbon nanofibers (CNFs)-supported TiC nanoparticles (NPs) film (TiC/C) is prepared by electrospinning and carbothermal processes. Well-dispersed TiC NPs are embedded tightly into the CNFs frameworks. The electrochemical oxidation of pyrimethanil (PMT) at the TiC/C-modified electrode displays enhanced redox properties, and the electrode surface is controlled simultaneously both by diffusion and adsorption processes. When TiC/C is applied for PMT determination, the as-fabricated sensor shows good sensing performance, displaying a wide linear range (0.1⁻600 µM, R² = 0.998), low detection limit (33 nM, S/N = 3), and good reproducibility with satisfied anti-interference ability. In addition, TiC/C shows long-term stability and good application in natural samples. The facile synthetic method with good sensing performance makes TiC/C promising as novel electrode materials to fabricate efficient sensors.

Positive effects of an oil adjuvant on efficacy, dissipation and safety of pyrimethanil and boscalid on greenhouse strawberry.

Methylated vegetable oil adjuvants can enhance initial deposition and decrease the required dosages of pesticides sprayed on plants, so an oil adjuvant mixed with fungicides were used to prevent and control gray mold in greenhouse strawberry. As the persistence and dietary exposure risks from fungicides on strawberries after using adjuvants have not been assessed, the efficacy, dissipation and safety of pyrimethanil and boscalid in the presence and absence of a methylated vegetable oil adjuvant were evaluated. To better describe the actual use of fungicides in greenhouse strawberry, twice repeated application of fungicides were conducted follower by an optimized QuEChERS pre-treatment method. When applied at 60% of their recommended dosages with the adjuvant, the efficacy of pyrimethanil and boscalid for gray mold was similar to that shown by the treatment of 100% fungicides in absence of the adjuvant based on Duncan's Multiple-Range test, and their average residues increased to 89.0% and 89.3%, respectively. The adjuvant enhanced the accumulation effect of pyrimethanil residue by 31.7% after repeated applications, and the half-lives were similar (5.2 and 4.2 d). The adjuvant had comparable accumulation effects (1.75 and 1.83) and similar half-lives (5.4 and 5.5 d) for boscalid. In absence of adjuvant, the risk quotients (RQs) of pyrimethanil (0.41 and 0.33) and boscalid (0.49 and 0.63) after twice applications at pre-harvest interval were lower than 1. Adding the methylated vegetable oil adjuvant to fungicides would result in unprolonging half-life and acceptably low dietary exposure risk on strawberries, but lower dosage of fungicides were used.

Synthesis of Pyrimethanil-Loaded Mesoporous Silica Nanoparticles and Its Distribution and Dissipation in Cucumber Plants.

Mesoporous silica nanoparticles are used as pesticide carries in plants, which has been considered as a novel method to reduce the indiscriminate use of conventional pesticides. In the present work, mesoporous silica nanoparticles with particle diameters of 200-300 nm were synthesized in order to obtain pyrimethanil-loaded nanoparticles. The microstructure of the nanoparticles was observed by scanning electron microscopy. The loading content of pyrimethanil-loaded nanoparticles was investigated. After treatment on cucumber leaves, the concentrations of pyrimethanil were determined in different parts of cucumber over a period of 48 days using high performance liquid chromatography tandem mass spectrometry. It was shown that the pyrimethanil-loaded mesoporous silica nanoparticles might be more conducive to acropetal, rather than basipetal, uptake, and the dosage had almost no effect on the distribution and dissipation rate in cucumber plants. The application of the pesticide-loaded nanoparticles in leaves had a low risk of pyrimethanil accumulating in the edible part of the plant.

Synergistic antifungal effect and potential mechanism of Dimethomorph combined with Pyrimethanil against Phytophthora capsici.

Synergistic effect of dimethomorph (DIM) and pyrimethanil (PYM) was evaluated using the Wadley method and the molecular mechanism of the antifungal effects of the combined treatment was systematically investigated. DIM+PYM had a synergistic effect on Phytophthora capsici, with the synergistic effect being observed at 5:1, at which the synergy coefficient was 1.8536. The mycelia of the pathogen treated with DIM+PYM were branched, uneven in thickness, and swollen. Moreover, scanning electron microscopy (SEM) revealed that DIM+PYM caused mycelium breaks, swelling, and apex enlargement, while transmission electron microscopy (TEM) revealed structural damage, cavities, and cell membrane morphological abnormalities. DIM+PYM inhibited the growth of mycelia, destroyed the cell membrane, interfered with energy metabolism, reduced protein and sugar content. Additionally, the transcriptome and metabolome of fungi treated with DIM+PYM changed significantly; specifically, there were 1571 differentially expressed genes and 802 differential metabolites. DIM+PYM may mainly damage the cell membrane, energy, protein, soluble sugar pathways.

Review: Progress towards research on the toxicology of pyrimethanil.

Pyrimethanil is a persistent environmental pollutant that poses a significant threat to human health. In this review, we summarize the fungicidal mechanism of pyrimethanil and its toxicological effects on aquatic organisms and mammals, as well as its impact on growth and development as an endocrine disruptor. Additionally, we investigate the metabolism of pyrimethanil in mammals and its molecular mechanism in the occurrence of Alzheimer's disease. Furthermore, this review outlines the influence of climate change on the toxicity of pyrimethanil, emphasizing the need to consider the impact of mixtures of multiple compounds on human health. Finally, we propose several promising future directions for pyrimethanil research, believing that there is a better understanding of the interaction between pyrimethanil and organisms, as well as the development of techniques to remove pyrimethanil, may be the best approach to eliminating the threat posed by this compound.

Water-Stable Cd-MOF with fluorescent sensing of Tetracycline, Pyrimethanil, abamectin benzoate and construction of logic gate.

Due to the indiscriminate abuse of pesticides and antibiotics has caused serious threats to the environment and human and animal bodies, the detection of antibiotics and pesticides has attracted widespread attention in recent years. Herein, a novel 2D Cd (II)-MOF, [Cd(L)0.5(1,2-bimb)] (Cd-L-1,2-bimb), [H4L = 1, 1'-ethylbiphenyl -3, 3', 5, 5'- tetracarboxylic acid, 1, 2-bimb = 1, 2-bis[(1H-imidazol-1-yl) methyl] benzene] is synthesized. Cd-L-1,2-bimb has excellent stability in different organic solvents and in the range of pH 1.1-12.5. Cd-L-1,2-bimb exhibits high selectivity, high sensitivity, and fast luminescent response to pesticides [pyrimethanil (PTH, LOD = 2.2 µM) and abamectin benzoate (AMB, LOD = 2.39 µM)] and antibiotic contaminants tetracycline (TET, LOD = 0.13 µM). Cd-L-1,2-bimb displays discriminative fluorescence when detecting AMB and PTH, and is an implication logic gate. Finally, the possible detection mechanism of Cd-L-1,2-bimb toward different pollutants is also further investigated. This MOF-based multifunctional sensor opens up new prospects for environmental monitors.

Changes to Soil Microbiome Resulting from Synergetic Effects of Fungistatic Compounds Pyrimethanil and Fluopyram in Lowbush Blueberry Agriculture, with Nine Fungicide Products Tested.

Lowbush blueberries (Vaccinium spp.) are a crop of economic significance to Atlantic Canada, Quebec, and Maine. The fruit is produced by the management of naturally occurring plant populations. The plants have an intimate relationship with the soil microbiome and depend on it for their health and productivity. Fungicides are an important tool in combatting disease pressure but pose a potential risk to soil health. In this study, amplicon sequencing was used to determine the effects of six fungistatic compounds both alone and in combination via nine commercially available fungicide products on the bacterial and fungal microbiomes associated with lowbush blueberries and to study whether these effects are reflected in crop outcomes and plant phenotypes. One fungicide, Luna Tranquility, a combination of fluopyram and pyrimethanil, was found to impart significant effects to fungal and bacterial community structure, fungal taxonomic abundances, and bacterial functions relative to control. The two fungicides which contained fluopyram and pyrimethanil as single ingredients (Velum Prime and Scala, respectively) did not induce significant changes in any of these regards. These results suggest the possibility that these microbiome changes are the result of the synergistic effect of fluopyram and pyrimethanil on soil microbiomes. While these results suggest a significant disruption to the soil microbiome, no corresponding changes to crop development and outcomes were noted. Ultimately, the majority of the fungicides analysed in this trial did not produce significant changes to the soil microbiome relative to the untreated group (UTG). However, one of the fungicide treatments, Luna Tranquility, did produce significant changes to the soil ecosystem that could have longer-term effects on soil health and its future use may merit additional investigation onto its ecotoxicological properties.

Modification of the existing maximum residue levels for pyrimethanil in table grapes, garlic and honey.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Ascenza Agro S.A. submitted a request to the competent national authority in Greece to modify the existing maximum residue levels (MRL) for the active substance pyrimethanil in table grapes, garlic and honey. The data submitted in support of the request were found to be sufficient to derive MRL proposals for table grapes, garlic and honey. Adequate analytical methods for enforcement are available to control the residues of pyrimethanil 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 long-term intake of residues resulting from the use of pyrimethanil according to the reported agricultural practice is unlikely to present a risk to consumer health.

Self-Assembled Nanoparticles of a Prodrug Conjugate Based on Pyrimethanil for Efficient Plant Disease Management.

Self-assembled nanotechnology is a promising strategy for improving the effective utilization of pesticides due to its distinct advantages. Herein, an amide-bonded prodrug conjugate based on pyrimethanil (PYR) and butyric acid (BA) was successfully synthesized by the nucleophilic substitution reaction and subsequently self-assembled into spherical nanoparticles (PB NPs) with an average size of 85 nm through the solvent exchange method without using any toxic adjuvant. The results showed that PB NPs based on PYR and BA had a synergistic antimicrobial activity against S. sclerotiorum on plant leaves due to good photostability, low volatilization, good surface activity, and improved retention. Additionally, PB NPs could be used by plant cells as nutrients to promote the growth of plants and thus reduced the toxicity of PYR to plant. Therefore, this prodrug conjugate self-assembly nanotechnology would provide a promising strategy for improving the effective utilization rates of pesticides and reducing their toxicities to plants.

Fabrication and Characterization of Antifungal Hydroxypropyl-ß-Cyclodextrin/Pyrimethanil Inclusion Compound Nanofibers Based on Electrospinning.

Pyrimethanil (PMT) is an anilinopyrimidine bactericide with poor water solubility, which limits its applications. To improve the physical and chemical properties of PMT, hydroxypropyl-ß-cyclodextrin/pyrimethanil inclusion compound nanofibers (HPßCD/PMT-IC-NFs) were fabricated via electrospinning. A variety of analytical techniques were used to confirm the formation of the inclusion compound. Scanning electron microscopy image displayed that HPßCD/PMT-IC-NF was homogeneous without particles. Thermogravimetric analysis indicated that the formation of the inclusion compound improved the thermostability of PMT. In addition, the phase solubility test illustrated that the inclusion compound formed by PMT and HPßCD had a stronger water solubility. The antifungal effect test exhibited that HPßCD/PMT-IC-NF had better antifungal properties. The release experiment confirmed that HPßCD/PMT-IC-NF had a sustained-release effect, and the release curve conformed to the first-order kinetic model equation. In short, the fabrication HPßCD/PMT-IC-NF inhibited improved solubility and thermostability of PMT, thus promoting the development of pesticide dosage form to water-based and low-pollution direction.

Exposure to pyrimethanil induces developmental toxicity and cardiotoxicity in zebrafish.

Pyrimethanil is a broad-spectrum fungicide commonly used in the prevention and treatment of Botrytis cinerea. However, little information is available in the literature to show the toxicity of Pyrimethanil to cardiac development. In this study, we used an experimental animal model to explore the developmental and cardiac toxicity of Pyrimethanil in aquatic vertebrates; we exposed zebrafish embryos to Pyrimethanil at concentrations of 2, 4, and 6 mg/L from 5.5 to 72 h post fertilisation. We found that Pyrimethanil caused a decrease in the hatching rate, heart rate, and survival rate of zebrafish embryos. Pyrimethanil exposure also resulted in pericardial and yolk sac edema, spinal deformity, and heart loop failure. Moreover, Pyrimethanil increased reactive oxygen stress levels and heightened the activity of superoxide dismutase and catalase. Alterations were induced in the transcription of apoptosis-related genes (p53, Bax, Bcl2, Casp 9, and Casp6l1) and heart development-related genes (Tbx2b, Gata4, Myh6, Vmhc, Nppa, Bmp2b, Bpm 4, and Bpm 10). Our data showed that the activation of Wnt signalling by BML-284 could partially rescue the malformed phenotype caused by Pyrimethanil. Our results provide new evidence for Pyrimethanil's toxicity and the danger of its residues in the environment and agricultural products.

Residues of anilinopyrimidine fungicides and suspected metabolites in wine samples.

The coexistence of the anilinopyrimidine fungicides pyrimethanil (PYR) and cyprodinil (CYP), and suspected metabolites in wine samples was investigated by liquid chromatography (LC) with tandem mass spectrometry (MS/MS), based on triple quadrupole (QqQ) and quadrupole time-of-flight (QTOF) MS instruments. For the first time, quantitative data obtained after solid-phase extraction (SPE) of wine samples have demonstrated the systematic presence of 4-hydroxyanilino derivatives of PYR and CYP in wines containing residues of parent fungicides, at concentrations from 0.2 to 58 ng mL-1. Higher concentration ratios (hydroxylated derivative/active fungicide) were measured in red than in white wines, particularly in case of PYR. On average, the concentrations of PYR-4OH were twice those measured for PYR in red wines. A targeted search of hydroxyl derivatives in wine extracts by LC-QTOF-MS showed the existence of additional hydroxylation positions in the pyrimidine ring and/or in the alkyl substituents bond to this cycle in the structure of both anti-botrytis fungicides. Moreover, free and glycosylated forms of the hydroxylated metabolites for both fungicides coexist in wine samples. In case of CYP, it is proved that hydroxylated and glycosylated metabolites are already present in grapes before vinification.

A sensitive pyrimethanil sensor based on porous NiCo2S4/graphitized carbon nanofiber film.

With the extensive use of pesticides, the problem of pesticide residues has become people's concern. In this work, NiCo2S4 nanoneedle arrays grown on an electrospun graphitized carbon nanofiber film (NiCo2S4/GCNF) is successfully prepared by a simple two-step hydrothermal method, and further applied to detection of fungicide pyrimethanil (PMT). NiCo2S4 arrays exhibit a unique core-shell structure with rough surface, providing abundant electrochemically active sites exposed to the electrolyte. The NiCo2S4/GCNF modified electrode displays excellent electrocatalytic activity, and the electrode surface is controlled both by diffusion and adsorption processes. When applied to PMT determination, NiCo2S4/GCNF sensor displays wide linear range from 0.06 to 800 µM with low detection limit (20 nM). Furthermore, the as-proposed sensor also displays other outstanding advantages, including simple preparation, low cost, perfect reproducibility and good application in practical samples. Such attracting analytical properties could be attributed to high electrocatalytic activity of NiCo2S4 and superior electrical conductivity of GCNF frameworks. In addition, the detailed oxidation mechanism of PMT at NiCo2S4/GCNF electrode was also studied. The results indicate that NiCo2S4/GCNF is a promising platform for PMT sensors.

In Vitro Effects of Pesticides on European Foulbrood in Honeybee Larvae.

Neonicotinoid and fungicide exposure has been linked to immunosuppression and increased susceptibility to disease in honeybees (Apis mellifera). European foulbrood, caused by the bacterium Melissococcus plutonius, is a disease of honeybee larvae which causes economic hardship for commercial beekeepers, in particular those whose colonies pollinate blueberries. We report for the first time in Canada, an atypical variant of M. plutonius isolated from a blueberry-pollinating colony. With this isolate, we used an in vitro larval infection system to study the effects of pesticide exposure on the development of European foulbrood disease. Pesticide doses tested were excessive (thiamethoxam and pyrimethanil) or maximal field-relevant (propiconazole and boscalid). We found that chronic exposure to the combination of thiamethoxam and propiconazole significantly decreased the survival of larvae infected with M. plutonius, while larvae chronically exposed to thiamethoxam and/or boscalid or pyrimethanil did not experience significant increases in mortality from M. plutonius infection in vitro. Based on these results, individual, calculated field-realistic residues of thiamethoxam and/or boscalid or pyrimethanil are unlikely to increase mortality from European foulbrood disease in honeybee worker brood, while the effects of field-relevant exposure to thiamethoxam and propiconazole on larval mortality from European foulbrood warrant further study.

Pyrimethanil Ionic Liquids Paired with Various Natural Organic Acid Anions for Reducing Its Adverse Impacts on the Environment.

In this study, nine pyrimethanil ionic liquids (PILs) were synthesized through an acid-base reaction with nine naturally derived organic acid anions to improve the physicochemical properties and reduce the environmental adverse impacts. The PILs presented lower volatilization, higher photostability, better soil adsorption capacity, and improved fungicidal activity relative to pyrimethanil. When the length of the carbon chains in the anions was increased, the PILs showed better properties in terms of melting point, water solubility, volatility, and surface tension. The photostabilities and fungicidal activities of the PILs were significantly improved when cyclic compounds were used as the paired anion ions. With enhanced physicochemical properties and better fungicidal activity, PIL7 was selected as the best alternative to pyrimethanil. The intrinsic disadvantages of pyrimethanil could be surmounted using the system developed in the study; thus, ILs could have immense potential in the development of eco-friendly and efficient fungicides in the future.

Aquatic mesocosms exposed to a fungicide in warm and cold temperate European climate zones: Long-term macroinvertebrate response.

At present, the European Union legislation facilitates the use of similar pesticides among European Member States, thereby assuming that biodiversity and ecosystems have equal sensitivities to contaminants throughout the whole of Europe. However, with this assumption, fundamental environmental and biological differences between climatic zones are being ignored in Environmental Risk Assessment. Such differences may strongly influence the behaviour of contaminants, their effects on biodiversity and on the natural functioning of ecosystems. Furthermore, toxicity testing in European ecoregions other than cold-temperate has largely depended on standardized tests using cold-temperate species and conditions, which may lead to a false estimation of risks to organisms from other ecoregions. The present study aim was to determine the response of freshwater macroinvertebrate communities to the fungicide pyrimethanil by conducting aquatic mesocosm experiments in two different ecoregions with different climates: cold-temperate (Frankfurt, Germany) and warm-temperate (Coimbra, Portugal). The results indicate that the community in the cold-temperate climate was more sensitive to the fungicide in comparison to the warm-temperate community. This difference was most likely related to a different rate of fungicide disappearance, which was slower in the colder climate. Based upon our results we discuss important implications for improving Environmental Risk Assessment across climate zones and under present-day global climate change scenarios.

Modification of the existing maximum residue level for pyrimethanil in cucurbits with edible peel.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Arysta LifeScience Benelux SPRL submitted a request to the competent national authority in Italy, to modify the existing maximum residue level (MRL) for the active substance pyrimethanil in cucurbits with edible peel. The data submitted in support of the request were found to be sufficient to derive a MRL proposal for cucurbits with edible peel. Adequate analytical methods for enforcement are available to control the residues of pyrimethanil on 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 pyrimethanil according to the reported agricultural practice is unlikely to present a risk to consumer health.