Reaction mass of sodium 3-{[3-(diethylamino)propyl]carbamoyl}-2-(dodecylamino)propanoate and sodium 3-{[3-(diethylamino)propyl]carbamoyl}-3-(dodecylamino)propanoate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14-30 March 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD guideline 402 without any deviations.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of sodium 3-{[3-(diethylamino)propyl]carbamoyl}-2-(dodecylamino)propanoate and sodium 3-{[3-(diethylamino)propyl]carbamoyl}-3-(dodecylamino)propanoate

EC Number:

939-579-8

Molecular formula:

Empirical Formula : C11H21N3O3Na C2nH4n+1 (n=4 – 9), C11H21N3O3NaC18H35, C11H21N3O3NaC18H33 Molecular formula of the two main constituents : C23H46N3O3Na

IUPAC Name:

Reaction mass of sodium 3-{[3-(diethylamino)propyl]carbamoyl}-2-(dodecylamino)propanoate and sodium 3-{[3-(diethylamino)propyl]carbamoyl}-3-(dodecylamino)propanoate

Details on test material:

- Name of test material (as cited in study report): CHIMEXANE HB
- Physical state: Yellowish thick gel
- Analytical purity: 55.9 %
- Lot/batch No.: 0126344
- Date of receipt: 28 February 2006
- Expiration date of the lot/batch: March 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: 353 ± 12 g; females: 217 ± 9 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
- Washing: Residual test item was removed using a moistened cotton pad.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- 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:

other: No clinical signs were observed.

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

Skin reactions:
- An erythema was observed in all animals from Day 2. This erythema persisted up to Day 4 in 1/5 males, Day 7 in 1/5 males and 1/5 females, Day 9 in 2/5 males and 1/5 females, Day 11 in 1/5 males and Day 12 in 3/5 females.
- An edema was observed in 4/5 males and 4/5 females from Day 2 up to Day 4.
- A dryness of the skin was observed in 4/5 males and 4/5 females from Day 5. It persisted up to Day 12 in 3/5 males and 4/5 females and up to Day 13 in 1/5 males.
- Crusts were noted in 3/5 males and 4/5 females from Day 5. They persisted up to Day 7 in 3/5 males and 2/5 females, Day 9 in 1/5 females and Day 12 in 1/5 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 HB 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 HB was tested for acute dermal toxicity in Sprague-Dawley [Rj: SD (IOPS Han)] rats in a GLP-compliant limit dose assay according to OECD guideline 402. 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. Residual test item was removed using a moistened cotton pad at the end of the 24 h exposure period. 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 recorded in 1/5 males between Days 1 and 8 and in 3/5 males and 2/5 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.

 

Some dermal changes were observed in most of the animals. They consisted of erythema, edema, skin dryness and later crusts. An erythema was observed in all animals from Day 2 up to Day 4 in 1/5 males, Day 7 in 1/5 males and 1/5 females, Day 9 in 2/5 males and 1/5 females, Day 11 in 1/5 males and Day 12 in 3/5 females. An edema was observed in 4/5 males and 4/5 females from Day 2 up to Day 4. A dryness of the skin was observed in 4/5 males and 4/5 females from Day 5 ; it persisted up to Day 12 in 3/5 males and 4/5 females, and up to Day 13 in 1/5 males. Crusts were noted in 3/5 males and 4/5 females from Day 5 up to Day 7 in 3/5 males and 2/5 females, Day 9 in 1/5 females and Day 12 in 1/5 females.

 

Under the test conditions, CHIMEXANE HB 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).