RESUMEN
New agrochemicals must demonstrate safety to numerous ecological systems, including aquatic systems, and aquatic vertebrate toxicity is typically evaluated by using the in vivo acute fish toxicity (AFT) test. Here, we investigated two alternative in vitro assays using a cell line isolated from rainbow trout (Onchorhynchus mykiss) gill tissue: (i) adenosine triphosphate (ATP) luminescence and (ii) cell painting. The former assay measures cytotoxicity, while the latter measures changes in cellular morphology in response to chemical exposure. We assessed how well end points in these two assays predicted acute lethality (i.e., LC50 values) in independent in vivo AFT tests. When compared to results from OECD TG 249 (in vitro), we found that the ATP assay was not as predictive (R2 = 0.53) as the cell painting assay. Similarly, when compared to results from OECD TG 203 (in vivo), the cell painting was much more predictive (R2 = 0.67). Our results show that such in vitro assays are useful for fast and efficient screening alternatives to in vivo fish testing that can aid in the agrochemical discovery phase, where thousands of potential new actives are tested each year.
RESUMEN
In the realm of crop protection products, ensuring the safety of pollinators stands as a pivotal aspect of advancing sustainable solutions. Extensive research has been dedicated to this crucial topic as well as new approach methodologies in toxicity testing. Hence, within the agricultural and chemical industries, prioritizing pollinator safety remains a constant objective during the development of predictive tools. One of these tools includes computational models like quantitative structure-activity relationships (QSARs) that are valuable in predicting the toxicity of chemicals. This research uses bee toxicity data to develop artificial neural network classification models for predicting honey bee acute toxicity. Bee toxicity data from 1542 compounds were used to develop models; the sensitivity and specificity of the best model were 0.90 and 0.91, respectively. These in silico models can aid in the discovery of next-generation crop protection products. These tools can guide the screening and selection of next-generation crop protection molecules with high margins of safety to pollinators, and candidates with favorable sustainability profiles can be identified at the early discovery stage as precursors to in vivo data generation.
RESUMEN
The human population will be approximately 9.7 billion by 2050, and food security has been identified as one of the key issues facing the global population. Agrochemicals are an important tool available to farmers that enable high crop yields and continued access to healthy foods, but the average new agrochemical active ingredient takes more than ten years, 350 million dollars, and 20,000 animals to develop and register. The time, monetary, and animal costs incentivize the use of New Approach Methodologies (NAMs) in early-stage screening to prioritize chemical candidates. This review outlines NAMs that are currently available or can be adapted for use in early-stage screening agrochemical programs. It covers new in vitro screens that are on the horizon in key areas of regulatory concern. Overall, early-stage screening with NAMs enables the prioritization of development for agrochemicals without human and environmental health concerns through a more directed, agile, and iterative development program before animal-based regulatory testing is even considered.
Asunto(s)
Agroquímicos , Humanos , AnimalesRESUMEN
The toxicity and time-dependent sorption of three hydrophobic organic chemicals to Rhodococcus rhodochrous bacteria were investigated. In experiments, environmentally relevant concentrations of pentachlorophenol (PCP), hexachlorobenzene (HCB), and dichlorobiphenyl (DPCB) were applied to living (both growing and nongrowing) bacteria as well as to dead bacteria. For PCP (an ionizing chemical), bacterial growth decreased, and bacterial death increased, as the PCP concentration increased. In sorption experiments with PCP, the partition coefficient was affected by the active uptake of PCP by living but not by dead bacteria, by the death of the living bacteria because of PCP toxicity, and by saturation of site-specific sorption as the PCP concentration increased. Hexachlorobenzene (a nonionizing chemical) did not affect bacterial growth or death at all HCB concentrations investigated. In sorption experiments with HCB, the partition coefficient depended on the rate of bacterial growth relative to the sorption rate. The sorption rate depended on the state of bacterial aggregation, and this changed with time. Results for DPCB (a nonionizing chemical with an equilibrium partition coefficient similar to that of HCB) were similar to those for HCB.