Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

γ-Butyrolactone (GBL) has been extensively studied for mutagenicity both in vitro and in vivo. Overwhelming, responses in genetic toxicology studies have been negative (see below) except for one study, but only in the presence of S9 (Loveday, 1986). The weight of the evidence indicates that GBL is not genotoxic.

Published results for in vitro studies, with and without metabolic activation (unless noted otherwise) are summarized as follows (NTP, 1992 unless otherwise noted):

- Escherichia coli: no DNA damage or gene mutation

- Salmonella Typhimurium: no DNA damage or gene mutation (also in Hawthorne, 1983 and Japan MHLW, 2000)

- Yeast: no mitotic gene conversion or aneuploidy induction

- Rat liver epithelial cells without S9: did not induce chromosome aberrations

- HeLa Cells: did not induce unscheduled DNA repair

- Chinese Hamster V79 Cells: did not induce gene mutations

- Human fibroblasts: did not induce gene mutations

- Chinese Hamster Ovary cells: positive only in the presence of S9 (Loveday, 1986)

Results of published in vivo studies are as follows (NTP, 1992 unless otherwise noted):

- Drosophila melanogaster (males): no sex-linked recessive lethal mutations in germ cells

- Drosophila melanogaster (females): no genetic damage to somatic cells (Vogel, 1993)

- Mice (males): no abnormalities in sperm heads

- Mice (females): negative for induction of micronuclei in bone marrow cells

Short description of key information:

Results in vivo: negative

Results in vitro: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Gamma butyrolactone has been extensively studied for mutagenicity both in vitro and in vivo. Overwhelming, responses in genetic toxicology studies have been negative except for one study, but only in the presence of S9. The weight of the evidence indicates that GBL is not genotoxic. Based on this evidence, 1,4-butanediol would not be rated as a mutagen under either the EU DSD classification system (EU Directive 67/548/EEC) or the EU CLP classification system (EU Regulation 1272/2008).