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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 Dec to 31 Dec 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
other: Standard acute dermal method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Identification: di-tert-butyl peroxide (CAS# 110-05-4)
Trade name: Trigonox B
Description: Liquid
Batch Number: 0904130207
Purity: 99%
Stability of Test Item: Stable under storage conditions.
Expiry Date: May 1, 2011
Storage Conditions: In a freezer (-20+/-5°C) away from direct sunlight.
Safety Precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Animals: Rat, RccHanTM: WIST(SPF)
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Laboratories B.V.
Kreuzelweg 53
5961 NM Horst / The Netherlands
Total Number of Animals: 5 males and 5 females
Age at Treatment: Males: 8 weeks / Females: 12 weeks
Body Weight Range at Treatment: 241.1 g – 272.1 g (males) / 183.7 g – 208.9 g (females)
Identification: Unique cage number and corresponding color-coded spots on the tail. The animals were marked at acclimatization start.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
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.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface.
Only those animals without injury or irritation on the skin were used in the test.
On test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusivedressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Application volume/kg body weight: 2 mL
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels. Thereafter, the reaction sites were assessed.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight/day
No. of animals per sex per dose:
5 males / 5 females
Control animals:
not required
Details on study design:
Five male and five female RccHan:WIST (SPF) rats were treated with di-tert-butyl peroxide (CAS# 110-05-4) at 2000 mg/kg by dermal application. The test item was applied undiluted as delivered from the Sponsor at a volume dosage of 2 mL/kg. The application period was 24 hours.

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 at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2 - 15. Local signs were noted once daily from test day 2 - 15. Mortality/viability was recorded within the first 30 minutes and at 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.

NECROPSY:
All animals were killed at the end of the observation period by an intraperitoneal injection pentobarbitone at a dose of at least 2.0 mL/kg body weight and discarded after macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs were performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.

DATA COMPILATION:
Body weights were recorded on-line.

Mortality/viability, clinical and local dermal signs were compiled into the Tox Control Computer System during recording and/or recorded on data sheets.

Macroscopic findings were compiled into the Tox Control Computer System during recording.

The Tox Control Computer System (Tox Control-Lims) had been validated with respect to data collection, storage and retrievability.
Statistics:
None performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were evident during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
Dermal sores were noted on the skin of a single male rat (no. 1)
Other findings:
Generalized erythema, slight in degree, was noted in two males after removal of the semi-occlusive bandage 24 hours after administration. This finding persisted in one of the two males on the following day. Erythema was not seen in any animal from day 4 onwards.

Slight desquamation was noted in one male on the last two observation days.

No dermal changes were seen in the remaining two males or in the females.

Applicant's summary and conclusion

Interpretation of results:
not classified
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 dermal administration to rats of both sexes, observed over a period of 14 days (LD50) is greater than 2000 mg/kg body weight
Executive summary:

Five male and five female RccHan:WIST (SPF) rats were treated withdi-tert-butyl peroxide (CAS# 110-05-4)at 2000 mg/kg by dermal application. The test item was applied undiluted as delivered from the Sponsor at a volume dosage of 2 mL/kg. The application period was 24 hours.

 

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs withinthe first 30 minutesand at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2 - 15. Local signs were noted once daily from test day 2 - 15. Mortality/viability was recorded withinthe first 30 minutesand at 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.

 

No deaths occurred during the study.

 

No clinical signs were evident during the course of the study.

 

The body weight of the animals was within the range commonly recorded for this strain and age.

 

Local effects included slight generalized erythema initally in two males after removal of the semi-occlusive bandage 24 hours after administration. This finding persisted in one of the two males on the following day. Erythema was not seen in any animal from day 4 onwards. Slight desquamation was noted in one male on the last two observation days. No dermal changes were seen in the remaining two males or in the females.

 

Dermal sores were noted on the treated skin of one male (no. 1) and were considered to be related to the treatement with the test item.