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We are developing a computational model 
for human neural tube closure.

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With this model we think we can improve...

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the prediction of human 
developmental toxicity.

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VOICE OVER: In order to 
improve human chemical...

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and pharmaceutical safety assessment 
we need a fresh look at the way we work.

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The classical way of safety assessment...

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relies heavily on the use 
of laboratory animals...

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assuming that they were 
miniature human beings.

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However, humans may respond differently 
to toxic substances than animals.

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PIERSMA: We believe that toxicity testing 
should be improved...

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to achieve a better risk 
assessment in humans.

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We can do that by combining human data 
with new in silico as well as in vitro tools...

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to get a complete picture 
of the toxicity of chemicals.

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VOICE OVER: RIVM is working on a new 
approach for human safety assessment...

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based on ontologies.

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Ontologies describe the biology 
of human physiology and disease...

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starting at the level 
of genes and molecules.

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PIERSMA: Based on our knowledge 
of physiology and disease...

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we can actually describe what 
happens when a compound...

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affects the system all the way to the 
disease that emerges which is at the end.

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We can describe this process in so-called
adverse outcome pathways...

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in which we describe 
all the different elements...

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that lead from the initial event 
to the adverse outcome in the end.

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In order to build ontologies, 
we need extensive data mining.

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The data mining will help us 
delineate the AOPs...

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starting from the exposure situation 
to the disease state.

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And within the ontologies 
and within the AOPs...

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we will then be able to define 
what are the critical points...

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that we need to address 
in terms of a testing system.

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So we will design a battery of test systems 
that take care of all these different points...

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and then with an in silico model...

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we will translate the results 
of these in vitro models...

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into a prediction of toxicity.

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Using AOPs, we will be 
able to understand...

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how neural tube defects come about 
and how compounds affect the system.

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VOICE OVER: One of the most 
prominent neural tube-related...

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malformations in human embryos 
is spina bifida.

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Using the ontology approach...

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RIVM is working on a three-dimensional 
computer model...

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of neural tube closure 
in the developing embryo.

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PIERSMA: We have a
detailed understanding...

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of how the neural tube is 
formed in embryogenesis.

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This allows us to describe the ontology...

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to extract the AOPs and to define
what test systems we need...

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to test the effects of compounds 
on the system.

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And this combined with in silico models...

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will allow us to do a hazard and 
risk assessment of chemicals...

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using this novel, human-based system.