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Estimating the carcinogenic potency of chemicals from the in vivo micronucleus test

Schatting van de carcinogene potency van chemische stoffen uit de in vivo micronucleus test

Synopsis

The RIVM has developed a faster method for estimating the carcinogenic potency of compounds, using less animals than with existing methods.

Currently, the degree to which a substance is carcinogenic is estimated from the number of tumors found in animals in long-term studies. These long-term studies are necessary because the development of tumors is a slow process. Normally, these studies take two years and make use of many animals (around 400). Prior to deciding whether to perform a long-term study, short term-studies are always performed to examine if a compound causes DNA damage. The presence of DNA damage (a positive result in short-term test) is generally indicative that a compound might be carcinogenic. Long-term studies are therefore performed to confirm whether a compound is carcinogenic or not, and to assess how potent the substance is in inducing tumors (carcinogenic potency).

Research at the RIVM has shown that short-term studies can not only provide an indication as to whether a compound causes DNA damage, but also can provide an estimate of the carcinogenic potency of a chemical. With this new approach, long-term studies can be avoided. This is of interest given the international aim for reducing animal use and long-term studies.

In this new method, a comparison was made between the concentration that induced a selected degree of DNA damage in short-term studies and the concentration at which a selected percentage of animals developed tumors. Results demonstrated a relationship between concentrations in short- and longterm studies, thus providing the possibility to use short-term studies to obtain an indication of the carcinogenic potency of chemicals.
 

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