Correction to: Mode of action-based risk assessment of genotoxic carcinogens.

The author would like to thank N. Bakhiya, S. Hessel-Pras, B.

Mode of action-based risk assessment of genotoxic carcinogens.

The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group.

Etoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probe.

The topoisomerase II (topo II) inhibitors etoposide (VP-16) and merbarone (MER) were investigated with the in vivo micronucleus test (MN test) combined with fluorescence in situ hybridization (FISH) using the mouse minor satellite DNA probe to discriminate MN of clastogenic and aneugenic origin. All experiments were performed with male (102/ElxC3H/El) F1 mice bred in the mouse colony of the GSF Research Center. The sample size per experimental group was five animals and 2,000 polychromatic erythrocytes (PCE) were scored per animal from coded slides in the conventional MN test.

Recommendations for statistical designs of in vivo mutagenicity tests with regard to subsequent statistical analysis.

A workshop was held on September 13 and 14, 1993, at the GSF, Neuherberg, Germany, to start a discussion of experimental design and statistical analysis issues for three in vivo mutagenicity test systems, the micronucleus test in mouse bone marrow/peripheral blood, the chromosomal aberration tests in mouse bone marrow/differentiating spermatogonia, and the mouse dominant lethal test. The discussion has now come to conclusions which we would like to make generally known. Rather than dwell upon specific statistical tests which could be used for data analysis, serious consideration was given to test design.

Dose response study for 1,3-butadiene-induced dominant lethal mutations and heritable translocations in germs cells of male mice.

Butadiene (BD) and its metabolites have extensively been studied in the EU sponsored research project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites". Within this project a dominant lethal test and a heritable translocation test were performed with male mice to study the dose-response relationships for the respective endpoints. BD concentrations of 130 and 500 ppm were tested in the dominant lethal assay by exposing male mice on 6 h/day for five consecutive days resulting in doses of 3900 and 15,000 ppmh, respectively.