Registration Dossier

Administrative data

Description of key information

The substance is of low acute toxicity by the oral roure (LD50 values reported are >2000-4290 mg/kg bw) and also by the dermal route (LD50 6400 mg/kg bw).  Acute toxicity by inhalation is not investigated due to the low volatilty of the substance; this is not considered to be a relevant expousre route and a waiver is proposed according to Column 2 of Annex VIII of the REACH Regulation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
4 290 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
6 400 mg/kg bw

Additional information

Acute oral toxicity

The oral LD50 of e-Caprolactone was determined in Wistar rats in a GLP study according to EU Method B.1 (Snoeji & Buse-Pot, 1992). A single dose of 2000 mg/kg bw e-Caprolactone was administered to the rats via a stomach tube, observations were made for 14 days and autopsy was performed at the end of the observation period. Two out of 5 females rats died within 2 days of dosing, but no male rats died. The clinical signs observed were mostly indicative of effects on motor coordination, muscle tone, autonomic and central nervous system; signs appeared within 30 minutes after dosing and disappeared within 3 days. Autopsy did not reveal any macroscopic abnormality that was thought to be treatment related. The acute oral LD50 of the substance was therefore found to be >2000 mg/kg bw under the conditions of this study.

The acute oral toxicity of ε-caprolactone was determined in groups of 5 male Carworth-Wistar rats (Smyth et al, 1954; Carpenter, 1953). ε-caprolactone was administered orally by gavage as a 10% aqueous solution at doses of 2000, 4000 and 8000 mg/kg bw and animals observed for 14 days. Deaths occurred at teh two highest dose levels. Signs of toxicity were apparent within 4 hours of dosing and included narcosis, prostration, ruffed coats and sluggishness. Autopsies of decedents revealed congestion of the lungs, mottling of livers, pale kidneys and gastrointestinal tract irritation. The LD50 was calculated to to be 4290 (3070 -5980) mg/kg bw under the conditions of this study.

Acute toxicity: inhalation

A waiver is proposed in accordance with Column 2 of Annex VIII of the REACH Regulation. Inhalation exposure is unlikely as the vapour pressure of the substance is 0.81 Pa at 25°C. An older and non-standard study (Smyth et al,1954; Carpenter, 1953) indicates that the only treatment-related effects in rats following exposure to air saturated with the substance for 8 hours was slight skin irritation. No additional testing is proposed for reasons of animal welfare. Worker inhalation exposure is not likely to be significant given the low vapour pressure and the effects of exposure will be limited by local irritation.

Acute toxicity: dermal

The acute dermal toxicity of ε-caprolactone was determined in groups of 4 male New Zealand White rabbits (Smyth et al, 1954; Carpenter; 1953). The test substance was applied to the clipped skin of the trunk, covering approximately 10% of the body surface. The test substance was held in place for 24 hours using an impervious plastic film. After removal of the dressing, the rabbits were observed for 14 days for mortality. Deaths occurred at 10000 ml/kg bw (4/4) and at 5000 mL/kg bw (1/4). Skin erythema was produced, and autopsies revealed congested haemorrhagic lungs, and extremely congested livers. The acute dermal LD50 was 5.99 (4.27 -8.42) mL/kg bw; calculated to be equivalent to 6400 (4570 -9000) mg/kg bw.

Justification for classification or non-classification

The substance is shown to be of low acute toxicity by the oral and dermal routes of exposure; inhalation exposure is unlikely due to the low volatilty of the substance and no testing is proposed for this route of exposure. The available data do not indicate that the substance requires classification for acute toxicity according to Dircetive 67/548/EEC and Regulation (EC) No 1272/2008 (the CLP Regulation).