2-bromo-5-hydroxy-4-methoxybenzaldehyde

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997-11-27 to 1998-01-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study performed according to OECD 402 and EU Method B3 (Acute Toxicity Dermal) test without 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:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Remarks:

The testing facility indicated that the protocol was followed without deviation.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

The testing facility indicated that the protocol was followed without deviation.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

: from the Swiss GLP Monitoring Authorities

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

426-540-0

EC Name:

-

Cas Number:

2973-59-3

Molecular formula:

C8 H7 Br O3

IUPAC Name:

2-bromo-5-hydroxy-4-methoxybenzaldehyde

Details on test material:

- Name of test material (as cited in study report): T002019
- Molecular formula (if other than submission substance): not applicable
- Molecular weight (if other than submission substance): not applicable
- Smiles notation (if other than submission substance): not applicable
- InChl (if other than submission substance): not applicable
- Structural formula attached as image file (if other than submission substance): not applicable
- Substance type: no data
- Physical state: gray to brown powder
- Analytical purity: 91.3 % (HPLC)
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: 00265786
- Expiration date of the lot/batch: 1998 July 01 (retest test)
- Stability under test conditions: Unknown, is excluded from the Statement of compliance
- Storage condition of test material: In the original container, at room temperature, aways from direct sunlight
- Other: no data

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Janssen Pharmaceutica N.V., 00265786
- Expiration date of the lot/batch: 01-JUL-1998 (retest date)
- Purity:91.3%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In original container at room temperature away from direct sunlight.
- Solubility and stability of the test substance in the solvent/vehicle: Unknown

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HanIbm: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL., Biological Research Labolatories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: Males: 8 weeks; females: 11 weeks.
- Weight at study initiation: Male: 243-2252 g; Females: 199-218 g.
- Fasting period before study: no data
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observation
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433, batch no. 90/97 rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum. Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water (e.g. ad libitum): Community tap water from Itingen, available ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimation period: 27-Nov-1997 to 03-Dec-1997

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3 deg C
- Humidity (%): 40-70 % (values above 70% possible during cleaning)
- Air changes (per hr): air conditioned 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs light / 12 hrs dark (music played during the light period).

IN-LIFE DATES: From: 1997-11-27 To: 1997-12-18

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: back of the animals (free of fur)
- % coverage: 10 % of the total body surface
- Type of wrap if used: dressing (the dressing was wrapped around abdomen and fixed with an elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes (with lukewarm tap water and dried with disposable paper towels)
- Time after start of exposure: 24 hrs after the application the dressing was removed

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL
- Concentration (if solution): not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 g/mL

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female rats per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortaliy/viability: four times during test day 1 and once daily during days 2-15;
Body weights: on test days 1 ( prior to administration) , 8 and 15;
Clinical signs: each animal was examined for changes in appearance and behaviour four times during day 1, and once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes. All animals were killed at the end of the observation period by an intraperitoneal injection of Narcoren at a dose of at least 2.0 mL/kg/bw ( equivalent to at least 320 mg sodium pentobarbitone/kg bw) and discarded after macroscopic examinations were performed.

Statistics:

No statistical analysis were used.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: Observed over a period of 14 days.

Mortality:

No deaths occured during the study.

Clinical signs:

other: No systematic or local signs of toxicity were observed during the study period. A yellow discoloration was observed at the application site immediately after removal of the dressing up to test day 3 for the male animals and test day 6 for female animals.

Gross pathology:

No macroscopic findings were observed at necroscopy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of T002019 after single dermal administration to rats of both sexes observed over a period of 14 days is: LD50 (rat) grater than 2000 mg/kg bw.