Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD, EPA, etc)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XP-7866
- Substance type: white powder
- Physical state: solid
- Analytical purity: 99.5 wt% obtained by 1H-NMR
- Purity test date: 99.5 wt%
- Lot/batch No.: 10188-1 JM
- Expiration date of the lot/batch: 28 February 2015
- Storage condition of test material: room temperature in the dark
- Other:

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RccHan™:WIST supplied by Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: the animals weighed at least 200g - The weight variation did not exceed ±20% of the mean weight for each sex.
- Fasting period before study:
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Free access
- Water (e.g. ad libitum): Free access
Note: The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: Acclimatisation period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
test item moistened with distilled water prior to application
Details on dermal exposure:
TEST SITE
- Area of exposure: the back and flanks
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item.
- Time after start of exposure: 24-Hour contact period- then, 14 days of observations

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: yes - moisted with distilled water

VEHICLE: No vehicle used
Duration of exposure:
24-Hour contact period
Doses:
- One dose : 2000 mg/kg( limit test)
No. of animals per sex per dose:
5 females / 5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days - 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Frequency of observations and weighing:
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, gross lesions, body weight, motalityand any other toxicological effects
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
other: Dermal median lethal dose (LD50)
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
There were no signs 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:
There were no signs of dermal irritation

Any other information on results incl. tables

No clinical observations in none of the animales (males/females) at any observation times.

Applicant's summary and conclusion

Interpretation of results:
not classified
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. According to the results of the limit test, the test item is not classified under CLP regulation No 1272/2008.
Executive summary:

* Introduction. The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following:

• OECD Guidelines for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987)

• Method 83 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

* Method. A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mglkg bodyweight. Clinical signs and bodyweight development were monitored

during the study. All animals were subjected to gross necropsy.

* Mortality. There were no deaths.

* Clinical Observations. There were no signs of systemic toxicity.

* Dermal Irritation. There were no signs of dermal irritation.

* Bodyweight. All animals showed expected gains in bodyweight over the study period.

* Necropsy. No abnormalities were noted at necropsy.

* Conclusion. The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mglkg bodyweight.