A step-by-step approach for assessing acute oral toxicity without animal testing for additives of quasi-drugs and cosmetic ingredients

Hajime Kojima; Tokio Nakada; Akiko Yagami; Hiroaki Todo; Jihei Nishimura; Mio Yagi; Keiko Yamamoto; Mariko Sugiyama; Yoshiaki Ikarashi; Hitoshi Sakaguchi; Masahiko Yamaguchi; Morihiko Hirota; Sakiko Aizawa; Shota Nakagawa; Shigenobu Hagino; Masato Hatao

doi:10.1016/j.crtox.2022.100100

A step-by-step approach for assessing acute oral toxicity without animal testing for additives of quasi-drugs and cosmetic ingredients

Curr Res Toxicol. 2022 Dec 23:4:100100. doi: 10.1016/j.crtox.2022.100100. eCollection 2023.

Authors

Affiliations

¹ National Institute of Health Sciences, Japan.
² Showa University Fujigaoka Hospital, Japan.
³ Fujita Health University School of Medicine, Japan.
⁴ Josai University, Japan.
⁵ Pharmaceuticals and Medical Devices Agency, Japan.
⁶ Skin Safety Case Information Network, Japan.
⁷ Japan Cosmetic Industry Association, Japan.

Abstract

Animal testing of cosmetic ingredients and products has been banned in the European Union since 2013. However, in Japan, the application of new quasi-drugs requires the generation of data on acute oral toxicity through animal testing. A weight of evidence approach for assessing oral toxicity was challenged. This approach used a combination of safety data, including a neutral red uptake cytotoxicity assay using BALB/c3T3 cells (3T3-NRU cytotoxicity assay), which can assess the acute oral toxicity of quasi-drugs or cosmetic ingredients. We conclude that the step-by-step approach can be used to assess test substances that cause low acute oral toxicity, such as the median lethal dose (LD 50) > 2000 mg/kg, thereby avoiding animal testing.

Keywords: 3T3-NRU cytotoxicity assay; Acute oral toxicity; EURL ECVAM; NICEATM; Non-animal; OECD.

Publication types

Review