Sub-structure-based category formation for the prioritisation of genotoxicity hazard assessment for pesticide residues: Sulphonyl ureas.

In dietary risk assessment, residues of pesticidal ingredients or their metabolites need to be evaluated for their genotoxic potential. The European Food Safety Authority recommend a tiered approach focussing assessment and testing on classes of similar chemicals. To characterise similarity and to identify structural alerts associated with genotoxic concern, a set of chemical sub-structures was derived for an example dataset of 74 sulphonyl urea agrochemicals for which either Ames, chromosomal aberration or micronucleus test results are publicly available. This analysis resulted in a set of seven structural alerts that define the chemical space, in terms of the common parent and metabolic scaffolds, associated with the sulphonyl urea chemical class. An analysis of the available profiling schemes for DNA and protein reactivity shows the importance of investigating the predictivity of such schemes within a well-defined area of structural space. Structural space alerts, covalent chemistry profiling and physico-chemistry properties were combined to develop chemical categories suitable for chemical prioritisation. The method is a robust and reproducible approach to such read-across predictions, with the potential to reduce unnecessary testing. The key challenge in the approach was identified as being the need for pesticide-class specific metabolism data as the basis for structural space alert development.

Identification of sulfonylurea biodegradation pathways enabled by a novel nicosulfuron-transforming strain Pseudomonas fluorescens SG-1: Toxicity assessment and effect of formulation.

Nicosulfuron is a selective herbicide belonging to the sulfonylurea family, commonly used on maize culture. A bacterial strain SG-1 was isolated from an agricultural soil previously treated with nicosulfuron. This strain was identified as Pseudomonas fluorescens and is able to quantitatively dissipate 77.5% of nicosulfuron (1mM) at 28°C in the presence of glucose within the first day of incubation. Four metabolites were identified among which ASDM (2-(aminosulfonyl)-N,N-dimethyl-3-pyridinecarboxamide) and ADMP (2-amino-4,6-dimethoxypyrimidine) in substantial proportions, corresponding to the hydrolytic sulfonylurea cleavage. Two-phase dissipation kinetics of nicosulfuron by SG-1 were observed at the highest concentrations tested (0.5 and 1mM) due to biosorption. The extend and rate of formulated nicosulfuron transformation were considerably reduced compared to those with the pure active ingredient (appearance of a lag phase, 30% dissipation after 10days of incubation instead of 100% with the pure herbicide) but the same metabolites were observed. The toxicity of metabolites (standardized Microtox® test) showed a 20-fold higher toxicity of ADMP than nicosulfuron. P. fluorescens strain SG-1 was also able to biotransform two other sulfonylureas (metsulfuron-methyl and tribenuron-methyl) with various novel pathways. These results provide new tools for a comprehensive picture of the sulfonylurea environmental fate and toxicity of nicosulfuron in the environment.

Toxicity assessment of the maize herbicides S-metolachlor, benoxacor, mesotrione and nicosulfuron, and their corresponding commercial formulations, alone and in mixtures, using the Microtox(®) test.

The Microtox(®) test, using the prokaryote Vibrio fischeri, was employed to assess the toxicity of the maize herbicides S-metolachlor, benoxacor, mesotrione and nicosulfuron, and their formulated compounds: Dual Gold Safeneur(®), Callisto(®) and Milagro(®); alone and in mixtures. For each compound we obtained original IC50 values, with consistent higher toxicities for formulated compounds compared to active ingredients alone. Mixtures of the four herbicides, prepared according to application doses encountered in agriculture, were found to be toxic at a lower concentration than single molecules. Mesotrione and nicosulfuron mixture appeared to be highly toxic to V. fischeri, however, this recommended post-emergence combination for maize crops got its toxicity decreased in formulated compound mixtures, suggesting that chemical interactions could potentially reduce the toxicity. Data comparisons to theoretical models showed a good prediction of mixture toxicity by Concentration Addition concept. Results seemed to exclude any synergistic effects on V. fischeri for the tested herbicide mixtures. Additional work coupling these bioassay data to ecosystemic level studies (aquatic and soil compartments) and data on additives and degradation products toxicity, will help to fill the gap in our knowledge of the environmental impact of these xenobiotics and in the choice of a more sustainable use of pesticides.

Assessment of the toxicity of triasulfuron and its photoproducts using aquatic organisms.

The toxicological effects of the sulfonylurea herbicide triasulfuron and its photoproducts were assessed on four aquatic organisms. Toxicity varied with tested organism and with triasulfuron irradiation time. Triasulfuron and its photoproducts had no significant effects on the crustacean (Cladocera) Daphnia magna (causing 50% effective concentration [EC50] [48 h] = 49 +/- 1 mg/L) and the marine bacteria Vibrio fischeri (EC50 [30 min] > 100 mg/L). In contrast, primary producers (the duckweed Lemna minor, the microalgae Pseudokirchneriella subcapitata, and Chlorella vulgaris) were very sensitive to triasulfuron (EC50s < 11 microg/L). For these organisms, triasulfuron photoproducts were less toxic than the parent compound but the residual toxicity observed still represented a potential environmental hazard.