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ZeClinics has developed a broad service portfolio for safety and efficacy studies of new cosmetic compounds with zebrafish fertilized eggs; a tool that bridges the gap between in vitro and clinical cosmetic trials in line with the 3Rs and recommended by the European Commission. All our studies are performed under stringent pharmaceutical standards.
The main 4 advantages you achieve by using zebrafish embryos for cosmetic compound development are:
Stabulation of zebrafish requires less space and is cheaper than mice because adult zebrafish are smaller and are housed in large groups – up to 70 animals per tank versus only five mice per cage. This is one of the reasons making zebrafish more affordable than mammal research models. In addition, zebrafish pairs produce hundreds of offspring larvae per mating, providing a huge sample size, when compared to rodents. Moreover, larva size is only 5 mm, allowing the use of multiwell plates for separating experimental samples. Finally, drugs are administered in the swimming water, requiring lower amounts of compounds and reducing enormously the time invested in injecting drugs into rodents. All these features allow testing several conditions (different drugs and concentrations) in parallel and, overall, shortening the experimental time and cost, if compared with equivalent assays in rodents.
Zebrafish larvae are among the most informative, straightforward, and better characterized experimental models. Their optical transparency and ex-utero development, combined with a growing battery of fluorescent tissue-specific transgenic lines, allow direct in vivo visualization of cells, tissues, organs, and embryonic development under different chemical and genetic perturbations to perform simultaneous drug safety and efficacy assays.
Zebrafish embryos represent an ideal model for the screening of large compound libraries and streamlining the drug development process. The small size and the high number of zebrafish progeny allow parallel and reproducible testing of several drugs and dosages in simple multiwell plates and make it ideal for high throughput assays. In addition, the large sample size provides strong statistical power.
Zebrafish and humans have a high genetic homology, as well as high physiological and functional conservation. More than 70% of human genes have a zebrafish orthologue gene. This percentage goes up to 82% when considering human disease-associated genes. In addition, zebrafish show sensitivity, specificity, and accuracy in line with mammalian models. These biological features have positioned the zebrafish as an ideal tool for the study of diseases, biological processes, and drug effects. Indeed, it allows us to assess with certainty the role of a gene in the context of disease and the possible toxicity or effects a compound could have when administered to humans.
The zebrafish model fulfills the purpose of reducing, refining, and replacing the use of experimental animal models. Most of our research is conducted with zebrafish larvae before 5 days post fertilization, meeting the standards set by the European Commission Directive of 2010. The zebrafish model represents a viable alternative that bridges the gap between in vitro and mammal models and can lead to a reduction of animals used in later research phases.
Our toxicology assays with zebrafish fertilized eggs provide a valuable alternative for in vivo safety assessment of new cosmetic molecules before clinical trials.
In accordance with current regulations, our toxicology services are aligned with the 3Rs principle at multiple levels. To begin with, zebrafish larvae up to 5 days post fertilization (dpf) are considered in vitro models (Directive 2010/63/EU of the European Parliament and the Council). Secondly, the efficient nature of the model facilitates the execution of sequential/simultaneous assays, which produce more information from each test subject and require fewer individuals; therefore also having a positive impact on the 3Rs.
Zebrafish’s rapid and external development allows it to have differentiated tissues and fully functional organ systems, characteristics of higher vertebrate organisms, before being considered an animal by regulatory bodies. Thanks to that, zebrafish embryos are able to provide organ-focused data, a feature only shared by organoids among other non-animal models (most of which are in vitro/tissue-based/ex vivo). This represents a comparative advantage vs in vitro cellular assays.
Zebrafish embryos’ transparency makes it possible to do non-invasive assessments and allows easy monitoring, which is especially useful for developmental toxicology studies. The real advantage of acute toxicology assays for cosmetics is tissue/cell in vivo visualization. The fact that those cells/tissues are part of a living, fully functional organism makes these in vivo readouts much more representative and informative. Absorption, distribution, metabolism, and excretion of novel molecules may be better assessed within a living organism than with in vitro models, due to the impact of background physiological and biochemical processes (i.e. liver detoxification pathways) which are not present in single-cell models.
Zebrafish show high genetic homology (in 82% of human disease-causing genes), as well as high conservation histologically, physiologically, and in most organ systems. That makes toxicology and bioavailability studies in zebrafish embryos more translatable and predictable than other in vitro approaches.