Table 7.

Summary table of test results of in vivo gene mutation studies

Study design	Test material	Results	Reliability/Relevance	Reference
Oral
C57BL/6Jp un/p un mice In vivo DNA deletion assay in the p un locus Drinking water for 10 days to pregnant mice; 500 mg/kg	NSC: 2, TiO2 NPs (P25), 15–24 nm	Positive	2/limited	Trouiller et al. (2009)
Intraperitoneal injection
Male B6C3F1 mice Pig‐a gene mutation assay in peripheral blood reticulocytes and in total red blood cells; 0.5, 5.0 and 50 mg/kg bw per day for 3 days	NSC: 1, TiO2 NPs, anatase, ellipsoidal shape (TEM), minor axes 12.1 ± 3.2 nm	Negative	2/limited	Sadiq et al. (2012)
Intravenous injection
Gene mutation in gpt, Spi– (liver) and pig‐a (erythrocytes) Delta transgenic C57BL/6J mice; 2, 10 and 50 mg/kg bw for 4 weeks	NSC: 1, TiO2 NPs (P25), 15–24 nm	Negative	1/limited	Suzuki et al. (2016)
Gene mutation in gpt, Spi– (liver) Delta transgenic C57BL/6J mice; 0, 2, 10 and 50 mg/kg bw for 4 weeks	NSC: 1, TiO2 NPs (P25), 15–24 nm	Negative	2/limited	Suzuki et al. (2020)
LacZ mutation assay in liver and spleen C57BL/6 transgenic mice; 0, 10 and 15 mg/kg bw, i.v. on 2 days	NSC: 1, TiO2 NPs (NM‐102), 21–22 nm	Negative	1/limited	Louro et al. (2014)
Intratracheal instillation
Male Sprague–Dawley rats Pig‐a gene mutation assay in peripheral blood reticulocytes and in total red blood cells; 3 endotracheal instillation over 8 days; 0.5, 2.5 and 10 mg/kg (a total particle surface area lung deposition of 87, 437 and 1,700 cm2/lung)	NSC: 1 TiO2 NPs (P25), 15–24 nm	Negative	2/limited	Relier et al. (2017)

NSC: nanoscale considerations; NP: nanoparticle; i.v.: intravenous.