From the article: "To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity
screening assays to assess potential risks to man and the environment. For human health hazard assessment these
screening assays need to be translational to humans, have high throughput capability, and from an animal
welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement).
In the area of toxicology a number of cell culture systems are available but while these have some predictive
value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This
is because they often lack biotransformation capacity, multicellular or multi- organ complexity, for example, the
hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms.
To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode)
and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals
being considered for a new commercial application. Nematodes exposed to Piperazine and one of the
analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations
and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also
reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental
delays. Malformations and mortality in individual fish were also scored. Significant malformations were
most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the
higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish.
The results of the nematode and zebrafish studies were in alignment with data obtained from conventional
mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems.
The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any
significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications."