Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted using OECD guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

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))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Sponsors identification: FR-720
Description: Off white powder
Batch number: 10-11-08-4
Date received 10 November 2011
Exp date February 2013
Storage conditions room temperature in the dark
Bromine content: 67.1-68.1%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Five males and five females (Wistar; RccHan:WIST) supplied by Harlan laboratories UK.
On receipt the animals were randomly allocated to cages. Females were nulliparous and non-pregnant.
After acclimatisation of at least five days the animals were selected at random and given a number unique within a study by ink marking on the tail and a number written on a cage card. At the start of the studythe animals weighed at least 200g and were 8-12 weeks of age. The weight variation did not exceed ± 20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed ihdividually during the 24 hr exposure period and in groups of five by sex for the reminder of the study.
Free access to drinking water and food was allowed throughout the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. The rate of air exchange was at least 15 changes per hr and the lightning was controlled by a time switch to give 12 hr continous light and 12 hr darkness.



Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Remarks:
arachis oil BP
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair. The appropriate amount of test item was moisten with arachis oil BP and applied evenly as possible to an area of shorn skin. A piece of surgical gauze was placed over the the treatment area and semi-occluded with a piece of self adhesive bandage. Theanimals were caged individually for the 24 hr exposure period. Shortly after dosing the dressings were examined to ensure that they were securly in place.After the 24 hr contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with a suitable solvent to remove any residual test item. The animals were returned to group housing for the reminder of the study period.

Duration of exposure:
24 hr contact period
Doses:
2000mg/kg test substance
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:
The animals were observed for deaths and signs of toxicity 0.5, 1, 2 and 4 hr after dosing and subsequently once daily for 14 days.
After removal of the dressings and subsequently once daily for 14 days, the test sites were examimed for the evidence of primary irritation and scored according to draize JH (1977) "Dermal and Eye Toxicity Tests" In : Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, washington DC p. 31.
Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoractic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
no sign of systemic toxicity
Body weight:
All animals showed expected gains in bodyweight over the study period
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
Dermal reactions: Very slight erythema was noted at the test site of all males and three females. Small superficial scattered scabs were also noted at the test site of one female. There were no signs of dermal irritation noted at the test sites of two females.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

Acute dermal toxicity was conducted in Wistar rats using the following guidelines, OECD 402; Method B3 Acute Toxicity; OPPTS 870.1200.

A group of five males and five females was given a single 24 hr semi-occluded dermal application at a dose of 2000 mg/kg bodyweight. clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No deaths, no signs of systemic toxicity and no abnormalities were evident at the end of the experiment.

All animals showed expected gaind in bodyweight and very slight erythema was noted at the test sites of eight animals.