2,4-Dibromo-6-[(cyclohexyl-methyl-amino)-methyl]-phenylamine hydrobromide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14.11.2002 - 30.12.2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study procedures described in this report meet or exceed the requirements of the following guidelines: Directive 92/69 EEC, 8.4. "Acute Toxicity - Skin Irritation", July 31 , 1992. OECD Guidelines for Testing of Chemicals, Section 4, number 404 "Acute Dermal irritation / Corrosion", adopted April 24, 2002.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dibromo-6-{[cyclohexyl(methyl)amino]methyl}aniline hydrobromide

EC Number:

617-191-7

Cas Number:

81060-07-3

Molecular formula:

C14H20Br2N2 x HBr

IUPAC Name:

2,4-dibromo-6-{[cyclohexyl(methyl)amino]methyl}aniline hydrobromide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): BROMHEXINE HYDROBROMIDE
- Physical state: White powder
- Lot/batch No.: 02070864
- Expiration date of the lot/batch: JUN-2003
- Storage condition of test material: at room temperature, away from direct sunlight.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France
- Age at study initiation: 12 - 13 weeks
- Weight at study initiation: 2061 - 2142g
- Housing: stainless steel cages
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum
- Acclimation period: Under Iabaratory conditions after health examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C,
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g moistened with approximately 0.1 ml of purified water

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: (ca. 4 cm x 4 cm)
- Type of wrap if used: gauze patch covered with a semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm tap water
- Time after start of exposure: 1, 24, 48 and 72 hours after the removal of gauze patch

SCORING SYSTEM:
EEC Commission Directive 92/69/EEC, July 31, 1992

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Any other information on results incl. tables

VIABILITY/MORTALITY/CLINICAL SIGNS

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

IRRITATION

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

COLORATION

No staining by the test item of the treated skin was observed

CORROSION

No irreversible alterations of the treated skin were obseNed nor were corrosive effects evident on the skin

BODY WEIGHTS

Animal No. 73 showed a slight body weight loss (0.4%) during the obseNation period. The reason for this weight loss could not be established due to the short duration of the study. The body weights of all other rabbits were considered to be within the normal range of variability.

NECROPSY

No necropsy was performed on the animals sacrificed at termination of Observation

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001 /59/EC of
August 06, 2001 ), BROMHEXINE HYDROBROMIDE is considered to be "not irritating" to
rabbit skin