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
25 April 2013, PDF |
46 pages |
Hernandez LG, van Benthem J, Slob W
RIVM Report 340700007
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.