Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 March - 11 May 2006
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in compliance with OECD guideline 402 with deviations: temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
temperature and relative humidity recorded in the animal room were sometimes outside of the target ranges
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Reference substance 001
Cas Number:
9022-76-8
Details on test material:
- Name of test material (as cited in study report): CHIMEXANE NB
- Physical state: Brownish viscous liquid
- Analytical purity: 98.5 %
- Lot/batch No.: 0129336
- Date of receipt: 27 February 2006
- Expiration date of the lot/batch: February 2007
- Storage condition of test material: At room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: Males: 326 ± 6 g; females: 212 ± 4 g
- Housing: Housed individually in polycarbonate cages
- Diet: SsniffR/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 µm), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal area, approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females
- % coverage: Approximately 10 % of the total body surface area
- Undiluted test item was placed on a hydrophilic gauze pad and then applied on the clipped skin. The test item and the gauze pad were held in contact with the skin for 24 h by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- No residual test item was observed on removal of the dressing.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.06 mL/kg
- Constant volume or concentration used: Yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
- Sighting test: 1/sex
- Main test: 4/sex
Control animals:
other: historical control data
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: Animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until Day 15. From Day 2, any local cutaneous reaction was recorded.
Bodyweight was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: Yes; all animals were killed by carbon dioxide asphyxiation on Day 15 and all animals were subjected to a macroscopic examination.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed.
Body weight:
- When compared to historical control animals, a slightly reduced body weight gain was seen in 3/5 males and 4/5 females between Days 8 and 15.
- Overall body weight gain of the other animals was similar to that of historical control animals.
Gross pathology:
- No macroscopic abnormalities were observed at necropsy.
Other findings:
Skin reactions:
- An erythema was noted in all animals from Day 2. It persisted up to Day 6 in 1/5 males, up to Day 7 in 1/5 females, up to Day 8 in 3/5 males, up to Day 10 in 1/5 males and up to Day 12 in 4/5 females.
- An edema was observed in all animals from Day 2. It persisted up to Day 5 in 4/5 males and 4/5 females and up to Day 7 in 1/5 males and 1/5 females.
- A dryness of the skin was noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. It persisted up to Day 12 in 2/5 males and 1/5 females and up to Day 14 in 3/5 males and 4/5 females.
- Crusts were noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. They persisted up to Day 8 in 2/5 males, Day 10 in 1/5 males, Day 12 in 1/5 males and 2/5 females and Day 15 (end of the observation period) in 1/5 males and 2/5 females.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, CHIMEXANE NB should not be classified according to the criteria of the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).
Executive summary:

CHIMEXANE NB was tested for acute dermal toxicity in Sprague-Dawley [Rj: SD (IOPS Han)] rats in a limit dose assay according to OECD guideline 402 and in compliance with GLP. Groups of rats (5/sex) were administered a single dermal dose of undiluted test material at 2000 mg/kg bw on clipped skin (approximately 10 % of the total body surface area) using a semi-occlusive patch held in place for 24 h. Examinations for mortality, clinical signs, body weight gain and dermal reactions were performed during a 14-day observation period. All surviving animals were necropsied at the end of the observation period.

No deaths and clinical signs occurred during the observation period. When compared to historical control animals, a slightly reduced body weight gain was seen in 3/5 males and 4/5 females between Days 8 and 15. Overall body weight gain of the other animals was similar to that of historical control animals. At necropsy, macroscopic examination of main organs showed no abnormalities. The acute dermal combined LD50 was greater than 2000 mg/kg bw.

An erythema was noted in all animals from Day 2. It persisted up to Day 6 in 1/5 males, up to Day 7 in 1/5 females, up to Day 8 in 3/5 males, up to Day 10 in 1/5 males and up to Day 12 in 4/5 females. An edema was observed in all animals from Day 2. It persisted up to Day 5 in 4/5 males and 4/5 females and up to Day 7 in 1/5 males and 1/5 females. A dryness of the skin was noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. It persisted up to Day 12 in 2/5 males and 1/5 females and up to Day 14 in 3/5 males and 4/5 females. Crusts were noted on Day 6 in 4/5 males and 4/5 females and on Day 8 in 1/5 males and 1/5 females. They persisted up to Day 8 in 2/5 males, Day 10 in 1/5 males, Day 12 in 1/5 males and 2/5 females and Day 15 (end of the observation period) in 1/5 males and 2/5 females.

Under the test conditions, CHIMEXANE NB should not be classified according to the criteria of the Annex VI of the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).