Registration Dossier

Administrative data

Description of key information

A 90-day rat inhalation study demonstrates local irritation (as indicated by effects on the eyes and nose) in the absence of any systemic toxicity at an exposure concentration of 45 ppm (203 mg/m3).  A local NOAEC of 15 ppm (70 mg/m3) is therefore derived for this study; a systemic NOAEC of 203 mg/m3 is derived.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
70 mg/m³
Study duration:
subchronic
Species:
rat

Additional information

Repeated dose oral toxicity

In a proprietary study not summarised here but summairsed in the OECD SIDS (2006) missing (Hermansky et al, 1991. E-Caprolactone given by drinking water to rats at levels of 500, 2000 and 5000 ppm in a 14-day study did not result in any treatment-related clinical signs of toxicity, clinical pathology findings, organ weight changes, necropsy observations or histopathological findings. E-Caprolactone affected food and water consumption (due to palatability effects ) as weIl as body weight gain at the level of 5000 ppm only. The NOAEL was 2000 ppm, which is equivalent with a dose 152 and 184 mg/kg bw for males and females, respectively.

A waiver is proposed according to Column 2 of Annex VIII and IX of the REACH Regulation. Oral exposure is not a relevant route of exposure; the toxicity of the substance by a relevant route of exposure (inhalation) has been adequately investigated. Additional studies are therefore not scientifically justified and cannot be supported for reasons of animal welfare.

Repeated inhalation toxicity

In a 90 -day stduy ( Norris & Kintigh, 1992), two groups of rats were exposed to e-Caprolactone vapour for 6 hours per day, 5 days per week, for 13 weeks, at concentrations of either 15 or 45ppm. A third group acted as the control group and was exposed to air only. The rats were sacrificed after the final exposure (14 week sacrifice). Two additional groups of rats were exposed (at the same time as the three groups sacrificed at week 14) to the 0 and 45ppm concentrations for 6 hours per day, 5 days per week, for 13 weeks, then allowed a 4 week recovery period prior to sacrifice (18 week sacrifice). There were no mortalities during the study, and no effects were observed in opthalmology, water consumption or body weights at the 14 and 18 week sacrifices, or in organ weights and urinalysis at the 14 week sacrifice. Significant changes in food consumption, haematologic and urinalysis values, and organ weights observed in the 45 ppm group were not considered to be exposure related, due to the delayed onset and nature of the changes. The only observations thought to be directly related to exposure were the instances of perinasal and periocular encrustation and eyelid swelling in a small number of males in the 45 ppm group at the 14 week sacrifice, however no histopathologic evidence of skin inflammation was noted in these regions. The NOAEC for systemic toxicity is therefore 45 ppm (203 mg/m3); some evidence of slight irritation was seen at this concentration, leading to a NOAEC for irritation of 15 ppm (70 mg/m3).

Repeated dose toxicity: dermal

A waiver is proposed according to Column 2 of Annex VIII and IX of the REACH Regulation. The toxicity of the substance by a relevant route of exposure (inhalation) has been adequately investigated. Addtional studies are therefore not scientifically justified and cannot be supported on animal welfare grounds

Justification for classification or non-classification

The available data indicate that the substance is of low toxicity and do not indicate that the substance requires classification according to Directive 67/548/EEC and Regulation (EC) No 1272/2008 (the CLP Regulation).