Methyl 4-bromobenzoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-11-6 to 2002-2-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 4-bromobenzoate

EC Number:

210-596-6

EC Name:

Methyl 4-bromobenzoate

Cas Number:

619-42-1

Molecular formula:

C8H7BrO2

IUPAC Name:

methyl 4-bromobenzoate

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 051101-Sa
- Expiration date of the lot/batch: 2002-11-1
- Purity test date: 2001-11-12



STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient temperature
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle: Hydrolysis is possible


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was supended in 0.1% CMC. The supensions were prepared freshly before administration and were administered within 10 minutes after the preparation.
- Final preparation of a solid: The test substance was supended in 0.1% CMC. The supensions were prepared freshly before administration and were administered within 10 minutes after the preparation.

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River WIGA, D-97633
- Age at study initiation: Approximately 8 weeks at the time of the administration
- Weight at study initiation: See Table 2
- Housing: Single cagin in Makrolon cages type III. Wire mesh lids. Sanitation of cages once a week
- Diet (e.g. ad libitum): Altromin 1324 forte, gamma irradiated with 25 kGy 60CO, ad libitum. Exception: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterward. Random samples of the feed are analysed for contaminants by Altromin
- Water (e.g. ad libitum): Tap water from an automatic waterin system, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2
- Humidity (%): 47.7
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: The tst substance was suspendet in 0.1% CMC
- Amount of vehicle (if gavage): The dose volume was 10 mL per kg body weight. The individual dose volumes were calculatet using the body weights determined on the day of the administration
- Lot/batch no. (if required): Article No. C-5013


MAXIMUM DOSE VOLUME APPLIED: The dose volume was 10 mL per kg body weight


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no prior information on the toxicity of the test substance was avaliable, a starting dose of 200 mg of the test substance per kg body weight was chosen. The further proceeding was in accordance with the guideline/directive

Doses:

200 mg per kg body weight to male rats
200 mg per kg body weight to female rats
2000 mg per kg body weight to male rats
2000 mg per kg body weight to female rats

No. of animals per sex per dose:

200 mg per kg body weight to male rats (3 animals)
200 mg per kg body weight to female rats (3 animals)
2000 mg per kg body weight to male rats (3 animals)
2000 mg per kg body weight to female (3 animals)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study

Clinical signs:

other: The findings, with an onset shortly after the administration and lasting until a maximum of 6 h p.a. were: - central nervous effects: sedation This effect may also be due to discomfort. - Signs of discomfort: chromodacryorrhoea

Gross pathology:

The animals were killed by CO2 asphyxia 14 days p.a. and subjected to a necrospsy including a gross pathological examination.

Any other information on results incl. tables

Table1: Synopsis of the results

 

Dose (mg/kg)	Sex	Animal Nos.	Number of animals Exposed              affected          deceased
200	m	11, 12, 13	3	0	0
200	f	16, 17, 18	3	0	0
2000	m	21, 22, 23	3	3	0
2000	f	26, 27, 28	3	0	0

 

 

Table 2: Body weights and body weight gain.

 

Dose mg/kg Sex	Animal No.	Body weight (g)   Before        7 days       14 days      death administer   p.a.              p.a.				Body weight gain (g)   0-7 days     7-14 days      p.a.            p.a.
200 m	11	193	284	344	-	91	60
	12	205	296	365	-	91	69
	13	197	291	352	-	94	61
	mean SD	198 6	290 6	354 11	- -	92 2	63 5
200 f	16	169	209	217	-	40	8
	17	165	205	223	-	40	18
	18	170	203	211	-	33	8
	mean SD	168 3	206 3	217 6	- -	38 4	11 6
2000 m	21	204	300	365	-	96	65
	22	207	295	364	-	88	69
	23	207	284	343	-	77	59
	mean SD	206 2	293 8	357 12	- -	87 10	64 5
2000 f	26	183	215	223	-	32	8
	27	166	206	219	-	40	13
	28	167	199	214	-	32	15
	mean SD	172 10	207 8	219 5	- -	35 5	12 4

 

Table 3: Observations in life.

 

Findings	Dose mg/kg sex	No. of the affected animals	Observation time (p.a.) first         last	Maximum grade of severity
Normal at any time	200, m	11, 12, 13	0h            14d	-
	200, f	16, 17, 18	0h            14d	-
	2000, f	26, 27, 28	0h            14d	-
chromodacryorrhoea	2000, m	21	4h            6h	low
sedation	2000, m	21 22 23	0,5h         4h 1h            2h 1h            2h	low low low

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

This acute oral study is considered to be reliable. It does satisfy the guideline requirement for an acute oral study OECD 423 in the rat.