2-(4-bromophenyl)-2-methylpropionic acid methyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed in accordance with validated guidelines and in GLP compliance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-bromophenyl)-2-methylpropionic acid methyl ester

EC Number:

450-630-9

EC Name:

2-(4-bromophenyl)-2-methylpropionic acid methyl ester

Cas Number:

154825-97-5

Molecular formula:

C11H13BrO2

IUPAC Name:

methyl 2-(4-bromophenyl)-2-methylpropanoate

Test material form:

other: liquid

Details on test material:

The test item was a liquid with a degree of purity >99,5%. The test material was stored at room temperature (range of 17-23 °C), away from direct sunlight.

Test animals

Species:

rat

Strain:

other: Rat, HanBrl: Wist (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST SYSTEM
Test system: Rat, HanBrl: Wist (SPF)
Source: RCC Ltd - Biotechnology and Animal Breeding Division - CH-4414 Fullinsdorf/Switzerland
Number of animals per group: 3 males or 3 females
Total number of animals: 3 males; 3 females
Age when treated: Males: 8 weeks
Females: 10 weeks
Identification: Unique cage card and corresponding color-coded spots on the tail.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.


HUSBANDRY
Room number: E16
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with target ranges for temperature 22 ± 3°C and for relative humidity between 30-70%. 12 hours fluorescent light/12 hours dark, music during the light period.

Accommodation: In groups of three per sex in Makrolon type-4 cages with wire mesh tops and standardized softwood bedding.
Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet - batch no. 77/01 - ad libitum. Results of analyses for contaminants are archived.
Water: Community tap-water, from Itingen ad libitum. Results of bacteriological, chemical and contaminant analyses are archived.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

The test item was suspended in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a volume of 10 mL/kg.

Doses:

Dose levels were in terms of test item as supplied unless otherwise stated by the sponsor. The preparations were made shortly before each dosing. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The mixtures were prepared using a magnetic stirrer. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer. The animals received a single oral dose of the test item by gavage at 2000 mg/kg body weight. The application volume was 10 mL/kg body weight.

No. of animals per sex per dose:

3 males or 3 females

Control animals:

no

Details on study design:

TREATMENT
The animals received a single oral dose of the test item by gavage at 2000 mg/kg body weight after being fasted for 16 to 20 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing. The application volume was 10 mL/kg body weight.
Rationale: Oral administration was considered to be an appropriate application method as it is a possible route of human exposure during manufacture, handling and use of the test item.

OBSERVATIONS
Mortality/Viability: Daily during acclimatization and twice daily during days 1-15.
Body weights: On test days 1 (pre-administration), 8 and 15.

Clinical signs: Daily during acclimatization and at least four times (see table of Mortality/Clinical Signs) on test day 1 after the test item administration. Once daily during days 2-15. All abnormalities were recorded.

PATHOLOGY - NECROPSY
All surviving 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 body weight(equivalent to at least 320 mg sodium pentobarbitone/kg body weight) and discarded after macroscopic examinations were performed. No organs or tissues were retained.
Animals which died spontaneously during the observation period were neoropsied as soon as they are found dead and any abnormalities recorded.

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.

Remarks on result:

other: median lethal dose

Mortality:

The following animals were treated and percentage of mortality was observed:
Males: 0% at 2000 mg/Kg
Females: 33% at 2000 mg/Kg
Female no. 3 was found dead on test day 2.

Clinical signs:

Lateral recumbency and marked sedation were noted in female no. 3 before it was found dead. Slightly ruffled fur (from day 1 to 4), hunched posture (day 1) and slight dyspnea (days 3, 4, 9, 10) were observed in female no. 2. Slightly ruffled fur was observed in female no. 1 and all males on test days 1 and 2.

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 observed at necropsy.

Any other information on results incl. tables

The details on individual findings are reported in the illustration attached below.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of FEXO-03 after single oral administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat) > 2000 mg/Kg bw.