Registration Dossier

Administrative data

Description of key information

A 90-d study by oral route have been performed on the test material. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

A 90-day dietary repeat dose toxicity study has been performed on Hedione. This study complies with the recommendations of the OECD Guidelines for Testing of Chemicals n° 408.It was designed to investigate the systemic toxicity of the test material when administered orally, via dietary admixture, to Sprague-Dawley CD® rats (10/sex/group) at dose levels of 10, 50, and 100 mg/kg bw/ day for a period of 90 days. Control animals (10/sex) received untreated standard laboratory diet.

 

Clinical observations and body weight measurements were performed on all animals pretest and weekly during the study period. Ophthalmoscopic examinations were conducted on all animals pretest and at termination of the dosing period. Food consumption was evaluated weekly beginning one week prior to initiation of dosing. Test substance intake measurements were performed weekly beginning one week after initiation of dosing. Motor activity, functional observational battery and ophthalmology observations were performed pretest and during the twelfth week of dosing.

 

After 3 months of treatment, hematology, coagulation and clinical chemistry evaluations were performed, surviving animals were euthanatized, selected organs were weighed and organ/body weight and organ/brain weight ratios calculated. Complete macroscopic postmortem examinations were performed on all animals, and histopathological evaluation of all tissues was conducted for animals in the 0 and 100 mg/kg/day groups.

 

Administration of dietary concentrations of 10, 50 and 100 mg/kg/day of ST 08 C99 to Sprague-Dawley rats for up to 90 days did not result in any adverse toxicological effects. Therefore, the NOEL (No-Observable-Effect-Level) was 100 mg/kg/day.

Justification for classification or non-classification

There were no treatment-related deaths; no significant functional changes in any organ system; no significant effects on hematology or urinalysis parameters; no significant gross or histopathological organ damage; and no increase in necrosis, fibrosis or granuloma formation in vital organs in male and female rats exposed to up to 100 mg/kg bw/day. Based on the evidence of this study, Hedione is not classified for “Specific Target Organ Toxicity – Repeated Exposure” according to Directive 67/548/EEC, UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.