(pentabromophenyl)methyl acrylate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23/2/2004-15/03/2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP comparable to OECD guideline

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

deviations from the minimum level of temperature occurred. Based on laboratory historical data, deviations were considered not to have affected the study integrity.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

deviations from the minimum level of temperature occurred. Based on laboratory historical data, deviations were considered not to have affected the study integrity.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

yes

Remarks:

deviations from the minimum level of temperature occurred. Based on laboratory historical data, deviations were considered not to have affected the study integrity.

Principles of method if other than guideline:

/

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

PBB-MA

IUPAC Name:

PBB-MA

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): PBB-mA

- Substance type:Monomer
- Physical state: white to of-white powder
- Analytical purity: 99.7
- Lot/batch No.: 030198
- Expiration date of the lot/batch: 14/11/2004 (allocated by NOTOX, 1 year after receipt of the test substance
- Stability under test conditions: not indicated
- Storage condition of test material: room temperature in the dark

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River FRance, L'Abresle Cedex, France
- Age at study initiation: +/- 10weeks
- Weight at study initiation: /
- Housing:Individual in labelled Macrolon cages (type I: height 12.5cm) containing purified sawdust as bedding material.
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days i groups in polycarbonate cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C):17.9-23.1°C
- Humidity (%): 41-64%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12hrs dark/12hrs light

IN-LIFE DATES: From: To:

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

Preliminary test: 100%, 50%, 25%, 10%, 5%, 2.5%, 1%
Main study: 5%, 25%, 50%

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
The highest test substance concentration selected for the main study was a 50% concentration

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method:
- Criteria used to consider a positive response: SI >= 3

TREATMENT PREPARATION AND ADMINISTRATION:
Induction (Days 1,2,3):
Experimental animals:
The dorsum surface of both ears was epidermally treated (25μl/ear) with the test substance concentration, at approximately the same time each day.
Vehicle control animals:
The control animals were treated the same as the experimental animals, except that, instead of the test substance, the vehicle alone was administered.

Treatment Day 6:
All animals; Each animal was injected via the tail vein with 0.25ml of sterile phosphate buffered saline (PBS) containing 20μCi of 3H-methyl thymidine.
After approximately five hours, all animals were killed by intr peritoneal injection with an overdose of pentobarbital. The draining lymph node of each ear was excised. The relative size of the nodes was estimated by visual examination and abnormalities of the nodes were recorded. The nodes were pooled for each animal in 3ml PBS.

Statistics:

If possible an EC3 value was determined, using linear interpolation

Results and discussion

Positive control results:

/

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: SI values for the substance concentrations 5, 25 and 50% were 8.8, 15.0, 3.5 respectively.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: MEAN DPM/animal values were 1181, 2020 and 471 for resp. 5, 25 and 50% test substance respectively

Any other information on results incl. tables

Induction phase: No irritation was observed in any of the animals examined.

Macroscopy: The majority of nodes were equal in size, except for the nodes of some animals of the 5% and 25% groups. No other macroscopic abnormalities of the nodes were noted.

Body weights: Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The slight body weight loss, noted in some animals, was considered not toxicologically significant.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The SI values calculated for the substance concentrations 5, 25 and 50% were 8.8, 15.0 and 3.5 respectively. These data showed a dose-response and it was considered that there is sufficient evidence that the substance elicts a SI >=3. No EC value could be calculated.

Based on these results and according to the recomendations made in the test guidelines, PBB-MA should be regarded as a skin sensitizer.

Executive summary:

Test substance concentration selected for the main study were based on the results of a preliminary study. In the main study, three groups of five experimental animals were epidermally exposed to a 5%, 25% and 50% concentration respectively on three consecutive days. Five vehicle control animals were similarly treated, but with vehicle alone (acetone/olive oil (4:1 v/v).

Three days after the last exposure, all animals were injected with H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised.

After precipitating the DNA of the lymph node cells, radioactivity measurements were done.

The majority of nodes were equal in size, except for the nodes of some animals of the 5% and 25% groups.

Mean DPM/animal values for the experimental groups treated with test substance concentrations 5, 25 and 50% were 1181, 2020 and 471 respectively. The mean DPM/animal value for the vehicle control group was 135.

The SI values calculated for the susbtance concentrations 5, 25 and 50% were 8.8, 15.0 and 3.5 resp.

These data showed a dose-response and it was considered that there is sufficient evidence that the substance elicts a SI>=3. No EC3 value could be calculated.

Based on OECD 429, EC B.42 and OPPTS 870.2600, PBB-MA should be regarded as a skin sensitiser.