Developmental & Reproductive Toxicity
What is DART?
Developmental and reproductive toxicity (DART) testing is an important part of product safety assessments, looking at their potential effects on human and animal development, and on reproductive systems. Conventional DART assays use large numbers of genetically inbred mammals such as mice and rats and are time-consuming, costly, and fail to capture the potential variability in responses in the human population. Moreover, many jurisdictions including in Europe and North America are phasing out animal testing in approvals of new chemical entities. DART testing cannot be replaced by in vitro models as it requires a complete organism with reproductive organs and full life cycle.
Our unique approach
vivoVerse’s solution to this challenge is to use the well-studied nematode model organism C. elegans as a cost effective, rapid alternative in vivo model. Like rodent models, C. elegans has a fully characterized developmental timeline and a complete reproductive system. Unlike rodent models, C. elegans develops from hatched larvae to reproductively mature adult in <3 days, has an easily studied transparent body, and is not subject to any welfare regulations.
Our DART assay measures multiple developmental and reproductive phenotypes to indicate potential adverse outcomes in exposed organisms. We treat populations of age synchronized C. elegans with one or more doses of the substances of interest and allow them to develop and show relevant phenotypes. Using our proprietary automated imaging platform and AI/ML assisted image analysis, we can image and quantify these phenotypes in thousands of C. elegans to provide multi-parametric dose response assessments from large numbers of treated animals in weeks, not months.
What we can provide
- Customized assay parameters e.g. number of chemicals, doses, strains
- Quantification of effects on developmental and reproductive phenotypes including in utero embryo development and body dimensions
- Comparisons of the relative effect of multiple individual chemicals and their mixtures on DART endpoints, for lead candidate prioritization or demonstrating safety profile improvement over alternatives
- Effective concentration and LOAEL values for multiple endpoints using dose curves
- Genetically diverse populations available, better capturing population variability
- Better value for money: Multiparametric in vivo endpoints quantified for a lower cost than a single acute toxicity study in mouse
- Rapid results: A typical assay can be performed in as little as 6 weeks versus several months to >1 year for mammalian studies
- Comparable results to mammalian models: C. elegans has ~83% homology with the human proteome and shows high concordance with toxicology results from mammals (~89% with rats in most chemical spaces for developmental toxicity).
- Ethically compatible: We use an alternative model organism not subject to animal welfare regulations
- Expert guidance: An experienced multi-disciplinary team with expertise in assay design and toxicology to help design your study
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