Improvement of chemical carcinogenicity testing...
requires a mechanism-based approach with a reduced use of laboratory animals.
MUSIC
VOICE OVER: Carcinogenicity testing of chemical substances currently relies..
on studies in which rodents are exposed during their entire lifetime.
These studies cost a lot of money and animals.
From a scientific point of view it is known that these studies...
not always reliably predict carcinogenic hazard for humans.
Mechanisms relevant for carcinogenesis...
are traditionally divided into two categories:
genotoxic and non-genotoxic mechanisms.
And this categorisation is based on the ability of a substance...
to directly interact with genetic material.
For the assessment of genotoxic potential, a reliable testing strategy is in place.
And this testing strategy includes both in silico and in vitro methods...
and, where needed, a selected set of in vivo tests.
The assessment of carcinogenic potential however...
still requires lifetime studies using rodents.
VOICE OVER: To conceptualise a novel animal-free approach...
researchers at RIVM started with charting the underlying mechanisms...
of chemical carcinogenesis.
The approach is firmly rooted in human tumor biology...
and in-depth knowledge of mechanisms of non-genotoxic carcinogenicity.
We identified several mechanisms relevant for non-genotoxic carcinogenesis...
based on data from OECD guideline studies.
These data are publicly available through assessment reports...
from regulatory agencies.
We applied the concept of adverse outcome pathways...
to build networks of mechanisms relevant for carcinogenesis.
And these networks guide the selection of appropriate in silico and in vitro methods...
which together form an integrated strategy for carcinogenicity testing.
VOICE OVER: Replacement of the lifetime rodent study...
by a dedicated set of in vitro and in silico experiments...
will lead to a better, mechanism-based prediction...
of the risk of non-genotoxic carcinogenicity due to chemical exposure.
The current activities aimed at building AOP networks for pesticides...
which is a class of compounds that is particularly data rich...
due to legal information and data requirements.
As a next step, we will broaden the AOP networks...
and assess their relevance to humans, to ensure that ultimately...
the testing strategy for cancer risk assessment...
is applicable across different regulatory frameworks.
By having a continued dialogue with all stakeholders...
including regulators as well as industry, we aim to build confidence...
in this mechanism-based approach for cancer risk assessment.