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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-conducted study performed under GLP to current guideline with adequate test material characterization.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
None

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Standard Laboratory Conditions. Air-conditioned with 10 - 15 air changes per hour, and continuously monitored environment with ranges for room
temperature 22 ± 3 °C and for relative humidity between 30 - 70% (values above 70% during cleaning process possible), automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.

Accommodation: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (J. Rettenmaier & Söhne GmbH & Co. KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) including paper enrichment (Enviro-dri from Lillico, Biotechnology, Surrey / UK).

Diet: Pelleted standard Harlan Teklad 2914C rodent maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland), batch no. 82/09 (B0770), was available ad libitum. Results of respective analyses for contaminants are included in Appendix I.

Water: Community tap-water from Itingen was available ad libitum in water bottles. Results of bacteriological assay, chemical and contaminant analyses of respective samples are included in Appendix II.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This formulation trial is excluded from the statement of compliance.

The dose formulations were prepared shortly before each dosing occasion using a magnetic stirrer.

The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer. Food was provided again approximately 3 hours after dosing.
Doses:
The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 16.5 to 17.25 hours (access to water was permitted). The dosing volume was 10 mL/kg body weight.
No. of animals per sex per dose:
Six
Control animals:
no
Details on study design:
None
Statistics:
None

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
In one female, slight shivering was noted 3 hours post treatment. Otherwise, no clinical signs were observed until the end of the observation period.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of di-tert-butyl peroxide (CAS# 110-05-4) after single oral administration to female rats, observed over a period of 14 days is > 2000 mg/kg.
Executive summary:

Two groups, each consisting of three female RccHan:WIST (SPF) rats, were treated with di-tertbutyl peroxide (CAS# 110-05-4) by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in corn oil at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2 - 15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study period. In one female, slight shivering was noted 3 hours post treatment. Otherwise, no clinical signs were observed until the end of the observation period. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. The median lethal dose of di-tert-butyl peroxide (CAS# 110-05-4) after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight