Registration Dossier

Administrative data

Description of key information

In a subacute oral toxicity study performed in accordance with OECD guideline No 407 and in compliance with Good Laboratory practices,  the administration to CD rats of the test material, at dosages of 15, 150 and 1000 mg/kg/day was not associated with any evidence of toxicity.  The No-Observe-Effect Level (NOEL) was considered to be 1000 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
Limit test:
no
Species:
rat
Strain:
other: CD® (SD) IGS BR
Sex:
male/female
Route of administration:
oral: gavage
Details on results:
CLINICAL SIGNS AND MORTALITYThere were no deaths and no clinical signs related to the treatment with the test material.BODY WEIGHT AND WEIGHT GAINBodyweight gain was considered to be unaffected by treatment.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)Food consumption was considered to be unaffected by treatment.FOOD EFFICIENCYFood conversion efficiency was considered to be unaffected by treatment.HAEMATOLOGYThere were no haematologival changes which were considered to be related to treatment.A few inter-group differences attained statistical significance but there were minor, seen in one sex only and were considered to have arisen by chance.CLINICAL CHEMISTRYNo clinical chemistry changes which were considered to be related with treatment.NEUROBEHAVIOURThere were no inter-group differences in arena observations that were considered to be associated with treatment.Landing footsplay and grip strength measurements showed some inter-group variation during week 4 of treatment and some differences achieved statistical significance. There were, however, no consistent trends and many of the differences were apparent before commencement of treatment, an association with treatment was therefore discounted. Motor activity was unaffected by treatment.ORGAN WEIGHTSOrgan weights were unaffected by treatment.GROSS PATHOLOGYMacroscopic examination of animals killed on completion of the treatment period did not reveal any treatment-related findings.HISTOPATHOLOGY: NON-NEOPLASTICThere were no microscopic findings which were attributable to treatment with the test material. All microscopic findings were considered to be incidental and of no toxicological importance.
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
28-day oral toxicity study complete and sufficient to fulfill the REACh annex VIII requirements

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available (further information necessary)

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a sub-acute study performed according to OECD 407 guideline and in compliance with Good Laboratory Practices, test material diluted in 1.0% methylcellulose in purified water was administered by oral gavage to three groups of rats (5/sex) at 15, 150 and 1000 mg/kg bw/day for four weeks. A control group received vehicle alone at the same volume-dosage (10 mL/kg bw/day).

There were no deaths, no clinical signs related to treatment and no evidence of neurotoxicity during the weekly functional battery test. Bodyweight, food consumption and food conversion efficiency were not affected by treatment. There were no haematological or blood chemistry changes related to treatment. Organ weights were unaffected by treatment and there were no macroscopic or microscopic findings which were attributable to the treatment with the test material.

The No-Observed-Effect Level (NOEL) was considered to be 1000 mg/kg bw/day.


Justification for classification or non-classification

As there is no evidence of toxicity in a subacute study, no classification for repeated dose toxicity is warranted according to regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.