At RIVM, we use the zebrafish embryo as a whole organism model...
to test the effects of substances on various outcomes and diseases.
VOICE OVER: Toxicity testing of chemical substances is increasingly based...
on mechanisms of toxicity that are structured in adverse outcome pathways...
describing the chain of events leading to toxicity or disease.
To study the effect of chemical exposure...
on an adverse outcome...
in vitro and in silico assays are used or being developed...
to represent the different key events along the AOP.
With knowledge on the relationships between the individual key events...
the integration of the data from these assays will predict...
whether exposure in the end will lead to an adverse outcome.
For certain diseases it is known...
that toxicity relies on the interaction between different organs or cell types.
Prediction of such toxicity requires...
the use of more complex assays and models to cover the interplay.
VOICE OVER: To understand what exposure to a certain toxicant...
means for humans...
whole organisms are needed in addition to simple in vitro models.
There are only few models available for this purpose...
before entering the realm of in vivo rodent studies.
And the zebrafish embryo is one of them.
HEUSINKVELD: Reasons for the increased recognition...
of the zebrafish as a useful model for toxicological research...
are related to its fast development, transparent body...
and above all: great resemblance of human biology.
The zebrafish only takes five days...
from a fertilised egg to fully developed organism.
This timeframe allows for the study of many developmental processes...
using multiple readouts...
such as morphological scoring and imaging techniques...
to monitor functional endpoints in living organisms.
VOICE OVER: At RIVM, the zebrafish embryo model is used...
as whole organism model for testing the effect of chemical substances...
on several adverse outcomes and diseases.
HEUSINKVELD: We use it, for example, to study the effect of chemicals...
on the nervous system and its development...
using motor activity and behaviour as an endpoint.
The same endpoint is also used to study the addictiveness of substances...
such as drugs.
Other techniques that are applied are imaging techniques and transcriptomics...
to study effects on skeletal development, liver disease...
and to explore the assessment strategies for chemical mixtures.
As such, zebrafish are used...
as a higher tier complex model in AOP-based testing strategies.
When applied correctly...
the combination of in vitro and in silico techniques with zebrafish embryos...
shows great potential to reduce the need for toxicity testing...
in higher tier animals such as rodents.