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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

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:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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 material was a liquid with a degree of purity >99%.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Body weight at the commencement of the study: male 223-249 g and female 209-220 g. 5 male and 5 female animals were used.
The animals were derived from a controlled full barrier maintained breeding system (SPF).

The animals were barrier maintained (semi-barrier) in an air conditioned room
- temperature: 22 ± 3 °C
- Rel. humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x/hour
- Feeding ad libitum, ssniffRIM-H, 10 mm Vl534-000, complete diet for rats/mice- maintenance, totally-pathogen-free (TPF)
- Free access to tap water (drinking water, municipal residue control, microbiol. controlled periodically)
- The animals were kept in Macrolon cages on Lignocel bedding
- Certificates of food, water and bedding are filed at BSL Bioservice
- Adequate acclimatization period

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The test item was applied as a single dose, uniformly over an area which was approx. 10% of the total body surface. The test item was held in contact with the skin with a gauze-dressing and no-irritating tape and was fixed with additional dressing in a suitable manner.

Duration of exposure:

24 h

Doses:

The test item was applied at a single dose (2000 mg/kg bw) by applying uniformly over an area which was approx. 10% of the total body surface.

No. of animals per sex per dose:

5 male animals (HsdRccHan : WIST rats) and 5 female animals (HsdRccHan: WIST rats) were used.

Control animals:

not required

Details on study design:

Animals were observed for 14 days after dosing. A careful clinical examination was made at least twice on the day of dosing and once a day thereafter.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
At the end of the observation period the animals were sacrificed by an overdosage of pentobarbital.
All animals were subjected to gross necropsy. All gross pathological changes were recorded.
Individual reactions of each animal were recorded at each observation time. Toxic response data were recorded by sex and dose level. Nature, severity and duration of clinical observations were described. Body weight changes were summarized in tabular form. Necropsy findings were described.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels:
no treatment related effects observed

Body weight:

Weight gain of all animals was within the expected range

Gross pathology:

Effects on organs:
no treatment related effects observed

Other findings:

Signs of toxicity (local):
no treatment related effects observed

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Considering the reported data of this dermal toxicity test it can be stated that the test item FEXO-03 has no acute dermal toxic characteristics. The dermal LD50 was determined to be > 2000 mg/kg bw.

Executive summary:

The test item was administered topically at a single dose (2000 mg/kg bw) by applying uniformly over an area which was approx. 10% of the total body surface. 5 male animals (HsdRccHan : WIST rats) as well as 5 female animals (HsdRccHan: WIST rats) were used. The test item was held in contact by an occlusive dressing with the skin throughout a 24-hour period. The occlusive dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner. At the end of the exposure, residual test item was removed by using tap water. A careful clinical examination was made at least twice on the day of dosing and once a day thereafter. At the end of the observation period the animals were sacrificed and necropsy was carried out to record gross pathological changes. No clinical signs of toxicity were observed throughout the observation period. Except for acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection no special gross pathological changes were found in any animals. Weight gain of all animals was within the expected range (table 1). Therefore, according to the intemationally accepted guidelines, a sufficient estimation of the acute dermal toxicity of the test item FEX0-03 was provided.