Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 August 2013 to 28 November 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: extremely viscous amber liquid
- Analytical purity:
- Lot/batch No.: E00031-68-1
- Expiration date of the lot/batch: 16 October 2010
- Storage condition of test material:room temperature in the dark, under nitrogen

Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- lot/batch No.of test material: E00031-633
- Retest date of the lot/batch: 30 January 2013
- Purity test date: >/= 99%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient temperature, in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS:
- Source: Charles River UK Limited, Manston Road, Maragate, Kent, UK
- Age at study initiation: 8 to 10 weeks old
- Weight at study initiation: Males between 325.3 and 353.0 g; females between 231.4 and 251.3 g
- Idenitification: Manual ear punch
- Preparation: Hair was clipped from dorsal area of the trunk, avoiding abrading the skin, the day before dosing
- Fasting period before study: Not specified
- Housing: In groups of 5 of the same sex and the beginning of acclimatisation and then transferred into single housing before dosing.
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENT:
- Cage: Suspended polycarbonate cages with stainless steel. Woodshavings as bedding.
- Temperature: Approximately 20°C
- Humidity: Approximately 52% to 67%
- Photoperiod: 12 hour light/dark cycle (light hours 0700 h to 1900 h)
- Air changes: At least 10 air changes per hour

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test item was applied directly onto the clipped dorsal area and spread uniformally. The test item was then covered with semi-occlusive tape and secured with non-irritating occlusive tape.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
not required
Details on study design:
- Preparation: Animals housed separately and clipped before dosing
- Observations: All animals were checked for clinical changes at least 4 times on the day of dosing and daily for 14 days thereafter. Mortality/moribundity checks were performed twice a day.
- Body weight: Days 1 (before dosing), 8 and 15.
- Necropsy: All animals were euthanised on Day 15.
Statistics:
None

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no unscheduled deaths.
Clinical signs:
There were no signs of reaction to treatment during any of the observation timepoints.
Body weight:
Weight gain was considered acceptable for rats of this age and strain.
Gross pathology:
One female (No. 7) was found to have dark foci to all lobes of the lungs. As this observation is common in this strain of rat, it is not considered to be related to the test item.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
As all animals survived and the median lethal dose (LD50) is greater than 2000 mg/kg, this study is considered to be relevant, reliable and adequate for risk assessment and for classification purposes.
Executive summary:

The purpose of this study is to evaluate the adverse effects of EXP0700332 following dermal exposure for 24 hours. Male and female Sprague-Dawley rats were housed in groups up to five animals of the same sex, then separated into single housing and clipped before dosing. The dose of the test item was calculated on the day of dosing. 2000 mg/kg of test item was applied topically to each animal on the clipped dorsal area and spread as evenly as possible. The dosed area was then covered with a gauze patch which was secured with semi-occlusive tape and non-irritating occlusive tape, wrapped around the trunk. The females were dosed 5 days after the males. After 24 hours, the patches and tape were removed and the dosing sites were delinated and cleaned with mineral oil. The animals were observed for 14 days thereafter for signs of reaction. The body weight of the rats were recorded weekly and all animals were subjected to necropsy examinations on Day 15. There were no clinical signs of reaction to treatment, no unscheduled deaths, no abnormal findings in the necropsy and the body weights of all animals were considered acceptable for rats of this strain and age.