(pentabromophenyl)methyl acrylate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03/04/2003-29/05/2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP comparable to OECD guideline

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Principles of method if other than guideline:

/

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: within an interval of +/-20% of the mean initial bodyweight of the first treated group except for animal number 5-2 whose bodyweight was approximately +22% of the mean initial bodyweight of the first treated group. This deviation was considered not to affect the purpose or integrity of the study.
- Fasting period before study: an overnight fast immediately before dosing and for approximately 3-4 hours after dosing
- Housing: in groups in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-25°C
- Humidity (%):30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12 hrs dark/12hrs light

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle:5, 30, 200, 200, 500 mg/ml
- Amount of vehicle (if gavage): calcultated according to the fasted bodyweight at the time of dosing.


MAXIMUM DOSE VOLUME APPLIED: 10


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: using all available information on the toxicity of the test material, 50mg/kg was chosen at the starting dose.

Doses:

50, 300, 2000, 2000, 5000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy, mortality

Statistics:

/

Preliminary study:

/

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: no signs of systemic toxicity

Gross pathology:

No abnormalities were noted at necropsy

Other findings:

/

Conclusions:

The acute oral medial lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 5000mg/kg bodyweight.

Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

• OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001)
• United States Enviro

nmental Protection Agency Health Effects Test Guidelines OPPTS 870.1100 Acute Oral Toxicity, 2002

Method.

A group of three fasted females was treated with the test material at a dose level of 50 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 300, 2000 and 5000 mg/kg bodyweight. Dosing was performed sequentially. The test material was administered orally as a suspension in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 5000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02/03/2012-04/04/2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP comparable to OECD guideline

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

yes

Remarks:

only one dose level was conducted

Principles of method if other than guideline:

/

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: RccHan: WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation:8-12 weeks
- Weight at study initiation: 200-350g
- Housing: in groups of three by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks and cardboard 'fun tunnels".
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light): 12hrs light/12hrs dark

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: chambers from ADG Developments Ltd., Hitchin, Herts, UK
- Exposure chamber volume: 30 litres
- Method of holding animals in test chamber: in a tapered, polycarbonate restraining tube
- Method of conditioning air: compressed air was passed through a water tap and respiratory quality filter
- System of generating particulates/aerosols:SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany)
- Method of particle size determination: Marple Personal Cascade Impactor (Westech IS Ltd., Beds, UK)
- Temperature, humidity, pressure in air chamber: temperature and relative humidity were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd., Beds, UK)

TEST ATMOSPHERE
- Brief description of analytical method used: the gravimetric method used glass fibre filters placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump. Each filter was weighed before and after samling in order to calculate the weight of collected test item. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration.
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: determined three times during the exposure period
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD = 2.80 μm, GSD = 2.22

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: 1.0mg/l as the mean achieved concentration was 102% of target and no deaths occured, no further levels were required.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by weight difference

Duration of exposure:

4 h

Concentrations:

1.0 mg/l

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:at hourly intervals during exposure, immediatly on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

/

Preliminary study:

/

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.02 mg/L air (analytical)

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Signs of hunched posture, pilo-erection and red/brown staining around the snout are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded during exposure. These observation

Body weight:

All male animals and two females exhibited slight bodyweight losses on the first day post-exposure. Reasonable bodyweight development was noted for all animals during the remainder of the recovery period.

Gross pathology:

No macroscopic abnormalities were detected

Other findings:

/

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

No deaths occured in a group of six rats exposed to a mean achieved atmosphere concentration of 1.02mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4hr LC50) of FR-1025M, in the RCCHan:WIST strain rat was greater than 1.02mg/L (GHS - Category 4, > 1-5mg/L.

Executive summary:

INTRODUCTION

A study was performed to assess the acute inhalation toxicity of the test item. The method was compatible with that described in the OECD No. 436, with the exception that only one dose level was conducted.

METHODS

A group of six RccHan:WIST strain rats (three males, three females) was exposed to a dust atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period.

RESULTS

The mean achieved atmosphere concentration was 1.02 mg/L (Std. Dev.: 0.05mg/L, nominal: 9.64 mg/L)

An example calculation for determining test atmosphere concentration is shown below:

Sample number	Time (mins)	Filter weights (mg)		Difference (mg)	Sample volume (L)	Concentration (mg/l)
		Pre-sample	Post-sample
1	5	32.57	36.61	4.04	4	1.01

The characteristics of the achieved atmosphere were as follows:

Mean achieved atmosphere concentration (mg/L)	Mean mass median aerodynamic diameter (µm)	Inhalable fraction (% < 4µm)	Geometric standard deviation
1.02	2.80	67.4	2.22

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 020 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09/04/2003-23/4/2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP comparable to OECD guideline

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Principles of method if other than guideline:

/

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200g
- Housing: in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hrs light, 12hrs dark

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flank
- % coverage: 10%
- Type of wrap if used: surgical gaze and semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000mg/kg
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

5000mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

/

Preliminary study:

/

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: no signs of systemic toxicity

Gross pathology:

no abnormalities

Other findings:

Dermal reaction: no signs of dermal irritation

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 5000mg/kg bw

Executive summary:

INTRODUCTION

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following:

* OECD 402

* EU method B3

* OPPTS 870.1200

METHOD

A group of ten animals was given a single, 24 -hour, semi-occluded dermal application of undiluted test material to intact skin at a dose level of 5000mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

MORTALITY: There were no deaths

CLINICAL OBSERVATIONS: no signs of systemic toxicity

DERMAL IRRITATION: no signs of dermal irritation

BODYWEIGHT: all animals showed expected gains in bodyweight over the study period, except for one female treated at a dose level of 5000mg/kg that showed a bodyweight loss during the first week and expected gain in bodyweight over the second week.

NECROPSY: no abnormalities were noted at necropsy

CONCLUSION: The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 5000mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
The most recent study

Justification for selection of acute toxicity – inhalation endpoint
One study available

Justification for selection of acute toxicity – dermal endpoint
One study available

Justification for classification or non-classification

Based on the results of the studies, the substance does not need to be classified according to CLP-Regulation (EC) No 1272/2008