Suitability of the use of the intraperitoneal route in the in vivo micronucleus test to evaluate the genotoxicity of hair dyes

New in vivo data cannot be generated for cosmetics. New safety assessments for genotoxicity must rely on in vivo data from the in vivo Mammalian Erythrocyte Micronucleus (MN) Test generated before the ban. Many used intraperitoneal (i.p.) administration, which is no longer recommended without scientific justification. Therefore, we investigated whether these studies are still valid for evaluating genotoxicity of hair dyes. Small to medium size molecules, including hair dyes, are preferentially absorbed via the portal vein and undergo first-pass metabolism, whereas large molecules are taken up by the lymphatics directly into the systemic circulation. Plasma concentrations of small molecules are generally similar, if not higher, after i.p. than after p.o. administration. Importantly, outcomes from in vivo MN Test using the i.p. and p.o. routes were equivalent. Most genotoxic carcinogens with positive outcomes in the in vivo MN Test were administered by i.p. injection. Differences between in vivo genotoxicity assay results using administration routes are attributed to the Mode of Action and/or tissue-specific effects. In conclusion, the i.p. route achieves sufficiently high internal exposure i.e., in the plasma and bone marrow. Therefore, legacy OECD test guideline compliant studies using the i.p. route are valid for current safety assessments of hair dyes. • Suitability of intraperitoneal (i.p.) route for toxicology studies investigated • Hair dyes given by i.p. injection undergo first-pass metabolism in liver • Focus on in vivo Mammalian Erythrocyte Micronucleus (MN) Test • in vivo MN Test results of known carcinogens via i.p. and p.o. routes equivalent • i.p. route achieves sufficiently high internal exposure for MN Test