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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28.11.2002 - 06.01.2003

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: OECD Guidelines for the Testing of Chemicals, Number 423 "Acute Oral Toxicity - Acute Toxic Class Method", adopted 17 December 2001 . Directive 96/54/EEC, 8.1 tris "Acute Oral Toxicity-Acute Toxic Class Method", September 30, 1996.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

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: Retest date 30-JUNE-2003
- Storage condition of test material: at room temperature, in the dark

Test animals

Species:

rat

Strain:

other: HanBrl: Wist (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Anima! Breeding Division, CH-4414 Füllinsdorf I Switzerland
- Age at study initiation: Males: 9 weeks, Females: 12 weeks
- Weight at study initiation: males: 247 - 267g, femals: 190 - 192 g
- Fasting period before study: approximately 18 hours
- Housing: Makroion type-4 cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Under Iabaratory conditions, after health examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light/ 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE

- Amount of vehicle (if gavage): 10 ml/kg body weight

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 femals / 3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality / Viability: Daily during acclimatization and twice daily during days 1-15.
Weighing: On test days 1 (prior to administration), 8 and 15
Clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during
days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was used

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study

Clinical signs:

Slightly ruffled fur was noted in all female animals from test day 4 to 6 and in all male
animals from test day 6 to 7.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and age.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median Iethal dose of BROMHEXINE HYDROBROMIDE after singleoral administration
to rats of both sexes, observed over a period of 14 days is:
LDso (rat): greater than 2000 mg/kg body weight