Aim 6: Environmental & Animal Toxicity Assessment

Our Toxicity Assessment aim evaluates the environmental and biological safety of new bioactive compounds compared with traditional products. Through comprehensive testing in computational, in vitro, and in vivo models, we aim to ensure that these compounds are safe for environmental and agricultural use.

Research Goals & Approach

1. Computational Environmental Impact Assessment

We employ computational models to assess the environmental impact of candidate compounds, focusing on their persistence, bioaccumulation, and acute toxicity. Using the U.S. Environmental Protection Agency’s CompTox Chemical Dashboard, we gather and analyze data on these parameters to prioritize compounds for deeper toxicological evaluation. This computational approach provides an efficient, high-throughput screening mechanism that identifies potentially hazardous compounds early in the development process. By integrating this information, we establish a baseline understanding of each compound’s environmental profile, ensuring that further in vivo and in vitro testing is both targeted and impactful.

2. Zebrafish and Human Cell Toxicity Testing

Zebrafish embryos serve as a widely accepted model for assessing reproductive and developmental toxicity due to their rapid development, large brood sizes, and transparent embryos. Using established protocols, we conduct concentration-response assessments to determine lethal concentration, inhibitory concentration, and no adverse effect levels. These tests evaluate the impact of candidate compounds on mortality, hatching success, structural development, and neurobehavioral responses under environmentally and physiologically relevant conditions. Complementing these in vivo studies, high-throughput screening assays using human cell lines assess cell viability and potential human health impacts. This dual-platform strategy offers comprehensive insights into the toxicity profiles of the compounds, comparing their effects to those of legacy pesticides to identify safer alternatives.

3. Mechanistic Toxicity Analysis

To uncover the molecular mechanisms underlying observed toxic effects, we perform RNA sequencing on zebrafish embryos exposed to candidate compounds. This analysis highlights the activation or suppression of pathways involved in steroid hormone biosynthesis, antioxidant responses, lipid peroxidation, and inflammation. Bioinformatic pipelines, employing KEGG and Gene Ontology databases, facilitate exploratory and targeted analyses of gene expression changes. These mechanistic studies provide valuable insights into the compounds’ biological interactions, enabling us to pinpoint specific modes of toxicity and refine compound designs for minimized adverse effects.

4. Cross-Species Toxicity Testing

Through collaborations with experts in neurotoxicology, immunotoxicology, and carcinogenesis, we expand toxicity testing to additional model systems. For example, neurotoxic effects are evaluated using Caenorhabditis elegans, a model nematode, to assess compound impacts on mortality and movement. Similarly, immunotoxic and carcinogenic assessments are conducted with human cell lines and specialized assays. This cross-species approach offers a broader understanding of the compounds’ impacts on various biological systems, ensuring that findings are applicable to diverse ecological and health contexts. These collaborative efforts enhance the robustness of our toxicity assessments, fostering the development of compounds that are both effective and environmentally safe.

Our assessment of environmental and animal toxicity, screened in silico and conducted in zebrafish—a model for ecotoxicology and human health.

Outcomes & Impact

Our assessments ensure that new bioactive compounds offer a safer alternative to existing products. We aim to confirm that these compounds have limited acute toxicity, reduced long-term effects, and lower risks of endocrine disruption. This rigorous testing supports the development of safe, environmentally friendly solutions for sustainable agriculture.