Registration Dossier

Administrative data

Description of key information

90-Day NOAEL (Oral, rat): 225 mg/kg bw

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
225 mg/kg bw/day

Additional information

In a 90-day subchronic toxicity study on rats and mice exposed by oral gavage to γ-Butyrolactone (NTP, 1992), no substance-related gross or microscopic lesions were observed at doses up to 900 mg/kg bw (rats) and 1050 mg/kg bw (mice), given 5 days per week. For male rats, a NOAEL of 225 mg/kg bw was reported based on decreased mean body weights and weight gains, and complete mortality of male rats at 900 mg/kg bw. For female rats, a NOAEL of 450 mg/kg bw was reported based on 1 death in the high dose group. For mice, a NOAEL of 525 mg/kg bw was reported based on decreased mean body weights and weight gains in males and increased mortality in males and females at the 1050 mg/kg bw dose.

Further study of repeat dose toxicity was performed by NTP in conjunction with a 2 year cancer bioassay with rats and mice (NTP 1992). See carcinogenicity section.

Justification for classification or non-classification

In a 90-day subchronic toxicity study on rats and mice exposed by oral gavage to γ-Butyrolactone, no substance-related gross or microscopic lesions were observed at doses up to 900 mg/kg bw (rats) and 1050 mg/kg bw (mice). A NOAEL of 225 and 450 mg/kg bw was reported for male and female rats, respectively based on decreased mean body weights and weight gains in the mid and high dose males, and on mortality in the high dose males and females. For mice, a NOAEL of 525 mg/kg bw was reported based on decreased mean body weights and weight gains in males and increased mortality in males and females at the 1050 mg/kg bw dose. Gamma butyrolactone does not meet the requirements for classification under the EU DSD (EU Directive 67/548/EEC) nor would classification for Specific Target Organ Toxicity, repeated exposure, be required under the EU CLP criteria (EU Regulation 1272/2008).