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Description of key information

Oral:

The test substance was found to be practically non-toxic by the oral route of exposure, with a LD50 value of 6327 mg/kg bw for both sexes combined.

Dermal:

No signs of systemic toxicity were noted. Evaluation of local skin reactions revealed severe to slight erythema and oedema (10/10), mild to slight scaling (10/10), abraded lines well defined (2/10), atonia (1/10), haemorrhaged area (2/10) and compound residues (10/10). Individual and mean body weights increased at each recoding time following dosing. The acute dermal LD50 of dibromostyrene was greater than 2000 mg/kg bw.

Inhalation:

The study provided in this section was provided for information purposes only, and was not included for use in assessment of the toxicity of the substance.

Reactions during exposure included lacrimation, clear nasal discharge, inactivity, and rapid, shallow breathing. All animals appeared normal in the afternoon following exposure and during the 2-day observation period. The LC50 of the study was determined to be greater than the highest dose tested. No necropsy data was provided.

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:
3 December 1982 to 13 January 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Specific details have not been provided
GLP compliance:
no
Remarks:
Not-GLP but QA statement included.
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan, USA
- Age at study initiation: young adult
- Weight at study initiation: 210.1 to 272.5 g
- Fasting period before dosing: 24 hours
- Housing: individually in wire-bottomed cages suspended above the cage board that was changed three times a week
- Diet: Purina Certified Rodent Chow 5002 ad libitum (with the exception of the fasting period; re-offered 1 hour after dosing)
- Water: ad libitum
- Acclimation period: 15 to 43 days

ENVIRONMENTAL CONDITIONS
- Controlled temperature and humidity room
- Photoperiod: 12 hours light a day

IN-LIFE DATES: 3 December 1982 to 13 January 1983
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Dosages were calculated on the basis of test substance specific weight of approx 1.83 g per mL.
Food was re-offered 1 hour after dosing
Doses:
5000, 6250 and 7500 mg/kg bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
The dose level of 5000 mg/kg was used at first. Additional doses were added to allow LD50 calculation.
Statistics:
LD50 was calculated according to Litchfield and Wilcoxon (1949)
Sex:
male
Dose descriptor:
LD50
Effect level:
5 790 mg/kg bw
95% CL:
4 826 - 6 946
Sex:
female
Dose descriptor:
LD50
Effect level:
6 937 mg/kg bw
95% CL:
5 906 - 8 148
Sex:
male/female
Dose descriptor:
LD50
Effect level:
6 327 mg/kg bw
95% CL:
5 622 - 7 121
Mortality:
Deaths occurred on days 1 to 2.
5000 mg/kg bw: 1 male on day 2 (1/5 males; combined: 1/10)
6250 mg/kg bw: 1 male on day 1, 2 males on day 2 (3/5); 2 females on day 2 (2/5) (combined: 5/10)
7500 mg/kg bw: 4 males on day 1, 1 male on day 2 (5/5); 3 females on day 3 (3/5) (combined: 8/10)
Clinical signs:
On the day of dosing
5000 mg/kg bw: slight ataxia (all animals at 3 to 5 hours)
6250 mg/kg bw: slight salivation (2M at 2 to 4 hrs), slight to mild lethargy (5M at 4 to 5 hrs), moderate ataxia (5M at 5 hrs), slight to mild urine stains (1M at 5 hrs and 2F at 2 to 5 hrs), slight lethargy and ataxia (1F at 5 hrs)
7500 mg/kg bw: slight to moderate ataxia, lethargy and inactivity (all animals at 2 to 5 hrs), urine stains (1M at 3 to 4 hrs), dilated pupils, prostration (1F at 5 hrs), slight lacrimation (1F at 4 to 5 hrs).
Following days
5000 mg/kg bw: slight inactivity, lethargy and ataxia (all animals, days 1 to 3), no faeces (all animals day 1). 1M dead on day 2.
6250 mg/kg bw: anorexia (all animals, day 1), adipsia (2M and 2F, day1); severe lethargy, ataxia, inactivity, prostrate, slowed and laboured respiration, pale extremities and finally death on day 2 (2M and 1 F); urine stains, decreased defecation and lacrimation were also noted in some of these animals. One F showing the above signs recovered to appear normal by day 4. Several animals appeared slightly less affected with signs of mild to slight inactivity or lethargy, lacrimation, decreased faeces or red material around the mouth. 1M and 1F were found dead on day 2 and 2M and 2F appeared normal by day 4. 1F appeared normal on days 4 to 9, showed moderate salivation (day 10 only) and red material around the nose on days 10 and 11, and was normal by day 12.
7500 mg/kg bw: 4M dead on day 1; severe inactivity,prostration, lacrimation, decreased defecation and finally death (1M and 3F day 2). Severe lethargy and ataxia and body cold to touch was present in some of these animals. 2F recovered and appeared normal by day 5.
Body weight:
Individual and mean body weights increased at each interval after dosing, except for one female treated at 6250 mg/kg bw on day 13.
Gross pathology:
Findings ranged from no significant findings (all animals at terminal sacrifice) to stomach distended with food, forestomach with shaggy white or chalky white material present, hindstomach reddened or pale with or without focal haemorrhage, intestines reddened in decent animals from all groups.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance is practically not toxic by the oral route of exposure, with a LD50 value of 6327 mg/kg bw for both sexes combined.
Executive summary:

In an acute oral toxicity study, groups of 5 male and 5 female Sprague-Dawley rats received single oral doses of the undiluted test substance at 5000, 6250 or 7500 mg/kg bw after a fasting period of 24 hours. Food was re-offered 1 hour after dosing. Deaths occurred on days 1 and 2. A single male rat died in the group treated at 5000 mg/kg bw. A total of 5 animals (3 males and 2 females) died in the group treated at 6250 mg/kg bw. A total of 8 animals (5 males and 3 females) died in the group treated at 7500 mg/kg bw. Signs of toxicity were noted in all treated animals; survivors appeared normal by day 4 (5000 and 6250 mg/kg bw) or day 5 (7500 mg/kg bw). Individual and mean body weights increased at each interval afetr dosing, with the exception of a single female treated at 6250 mg/kg bw on day 13. No significant macroscopic findings were noted at termination for surviving animals, while stomach distended with food, forestomach with shaggy white or chalky white material present, hindstomach reddened or pale with or without focal haemorrhage, intestines reddened were observed in decent animals from all groups.

The LD50 was calculated to be 6327 mg/kg bw for both sexes combined.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 327 mg/kg bw
Quality of whole database:
The quality of the database is high.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
6 to 8 November 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
other: Regulations of MTB, Code of Federal Regulations, Vol. 49, Part 173.343(2), 1976
Deviations:
not specified
Principles of method if other than guideline:
Two groups of 5 male Sprague-Dawley rats were exposed, whole body, to the material via inhalation at different but consecutive times. Target concentration was 2 mg/L. Nominal concetrations were 3.1 mg/L and 2.8 mg/L for the first and second group, respectively. The test material was nebulized into a a 37.5 L glass exposure chamber with a DeVilbsis continuous flow nebulizer. The test material was stored in refrigerator until the hour of exposure. The nebulization rate was maintained at 11.7 mg/min, while the air exchange rate within the chanber was maintained at 3.8 L/min for the first group. The nebulization rate was maintained at 10.0 mg/min, while the air exchange rate within the chanber was maintained at 3.6 L/min for the second group. Animals were observed during the 1 hour exposure and for 2 days thereafter. Body weights were recorded just prior to exposure and again on test days 2 and 3. No necropsy was performed.
GLP compliance:
no
Remarks:
but QA statement included in the report
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries, Inc., Madison, Wisconsin
- Age at study initiation: 8 weeks
- Weight at study initiation: 292 to 319 g
- Housing: individually
- Diet (e.g. ad libitum): Purina Rat Chow ad libitum except during the 1 hour exposure
- Water (e.g. ad libitum): ad libitum except during the 1 hour exposure
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
Temperature controlled quarters (no more details available)

IN-LIFE DATES: From: 6 To: 8 November 1980
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
Exposures were conducted in a 37.5 L glass exposure chanber. Air flow through the chamber was provided with a wet test meter, and vacum pump. An air tube containing a desiccate was connected into the line of the air flow system between the exhaust port of the chamber and the wet test meter. This collected or filtered out the test material which was contained within the atmosphere that was exhausted from the chamber. The test material was administered into the chamber near the junction of the air inlet port, which usually allows the test material and incoming air to mix evenly within the chamber at the top before being drawn down and around the animals.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 h
Concentrations:
Target 2 mg/L. Nominal 3.1 and 2.8 mg/L.
No. of animals per sex per dose:
5 males per group
Control animals:
no
Details on study design:
Animals were examined during the 1 hour exposure and for 2 days therefater. Body weight was recorded prior to exposure and on days 2 and 3. No necropsy was performed.
Statistics:
None
Sex:
male
Dose descriptor:
LC50
Effect level:
> 2 mg/L air (nominal)
Exp. duration:
1 h
Remarks on result:
other: target concentration
Mortality:
No mortality occurred.
Clinical signs:
other: Reactions during exposure included lacrimation, clear nasal discharge, inactivity, and rapid, shallow breathing. All animals appeared normal in the afternoon following exposure and during the 2-day observation period.
Body weight:
Mean body weights showed an increase in both groups during the 3 days of test. Individual values showed minimal body weight losses in 3 rats of the first group on day 2, followed by body weight gains on day 3.
Gross pathology:
Not applicable
Interpretation of results:
other: not a Class "B" poison
Remarks:
Criteria used for interpretation of results: other: Regulations of MTB, Code of Federal regulations, Vol. 49, Part 173.343(2), 1976
Conclusions:
The acute inhalation LC50 (1 hour) of dibromostyrene was higher than 2 mg/L (target concentration).
Executive summary:

In an acute inhalation study, two groups of 5 male rats were exposed whole-body to a target concentration of 2 mg/L. Nominal concetrations were 3.1 and 2.8 mg/L, respectively, for the first and second group. Animals were observed during exposure and for 2 days thereafter. Body weight was recoded prior to exposure and on days 2 and 3. No necropsy was performed.

No mortality occurred. Reactions during exposure included lacrimation, clear nasal discharge, inactivity, and rapid, shallow breathing. All animals appeared normal in the afternoon following exposure and during the two days after exposure. Mean body weight increased duirng the 3 days of test.

The LC50 (1 hour) of dibromostyrene was greater than 2 mg/L (target concentration).

Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

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:
10 to 23 November 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Clerco Reasearch Farms, Cinicinnati, Ohio
- Age at study initiation: youg adults
- Weight at study initiation: 1.85 to 2.55 kg
- Housing: individually in steel wire-bottomed cages suspended above cage board that was changed three times a week.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow #5322 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): checked daily
- Humidity (%): checked daily
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

IN-LIFE DATES: From: 10 To: 23 November 1982
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hrs before treatment the back of the rabbits were clipped free of hair with an Oster small animal clipper. Individual dose amounts were calculated using day 0 body weights taken prior to dosing and considering specific gravity of the test substance of 1.83 g. Just prior to the application of the test material the skin test site of each animal was abraded by making a series of parallel epidermal abrasions, every 2 or 3 cm longitudinally with a 25-gauge hypodermic needle. These abrasions were made sufficiently deep to penetrate the stratum corneum but not to disturb the derma or produce bleeding. The required dose amount of liquid was measured in a disposable sterile syringe and applied to the test site. A glass stirring rod was used to distribute the test material evenly over the exposure site (approx. 240 cm2). Each test site was immediately occluded with a layer of 4-ply gauze, two single layersthick. The trunk of the rabbit was wrapped with rubber latex dental dam and the denatl dam taped at the edges with 1 inch Micropore tape to form an airtight occlusive wrap. The test material remained in contact for 24 hours. At the end of this period the dressing were removed and the residual test material gently wiped off with a paper towel.
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Statistics:
None needed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
No signs of systemic toxicity were noted. Evaluation of local skin reactions revealed severe to slight erythema and oedema (10/10), mild to slight scaling (10/10), abraded lines well defined (2/10), atonia (1/10), haemorrhaged area (2/10) and compound residues (10/10).
Body weight:
Individual and mean body weights increased at each recoding time following dosing.
Gross pathology:
No abnormality was detected at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of dibromostyrene was greater than 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study, 5 male and 5 female New Zealand rabbits received a single dermal application of dibromostyrene at 2000 mg/kg bw under occlusive conditions. Exposure lasted 24 hours. Animals were observed for 14 days following treatment.

No mortality occurred during the study. Only skin reactions but no systemic clinical signs were noted. All animals gained weight during the study.

The acute dermal LD50 was greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The quality of the database is high.

Additional information

Oral:

Briggs M.C., LeQuire M., Kingerly A.F. and Mayhew D.A. (1983) was used as the key study to fulfil the data requirement for acute toxicity via the oral route. The methodology employed in the study was comparable to the OECD guideline 403 and was considered adequate for assigning classification. The study was assigned a reliability score of 1.

Thompson GW (1980) was provided as a supporting study for information purposes. The study confirms that the LD50 is greater that the highest dose tested, thought the highest dose in this study is not sufficient for classification. The study was assigned a reliability score of 2.

 

Dermal:

Briggs M.C., LeQuire M., Kingerly A.F. and Mayhew D.A. (1983) was selected as the key study to fulfil this data requirement. The study was performed in compliance with GLP and the methods followed were similar to the OECD guideline 402. The study was accordingly assigned a reliability of 1. The study Thompson GW (1980) was provided as supporting information to the key study. Although the study was not tested up to the doses required for classification, no toxicity was observed during the study up to the highest dose.

 

Inhalation:

Biesemeier J.A. (198) was provided for information purposes only. The study only dosed up to 2 mg/L and is therefore not adequate for classification purposes.

Justification for selection of acute toxicity – oral endpoint

Two acute oral toxicity studies were available. The key study was selected, as the dosing levels were sufficient for classification and labelling and risk assessment purposes. As the supporting study did not include doses beyond 50 mg/kg, the study was provided only as supplementary information.

Justification for selection of acute toxicity – inhalation endpoint

A supporting study was provided for information purposes, however the maximum dose level applied was not sufficient for classification and labelling and risk assessment purposes.

Justification for selection of acute toxicity – dermal endpoint

Two acute dermal toxicity studies were available. The key study was selected, as the dosing levels were sufficient for classification and labelling and risk assessment purposes. As the supporting study did not include doses beyond 200 mg/kg, the study was provided only as supplementary information.

Justification for classification or non-classification

According to the criteria in directive 67/548/EEC and regulation (EC) No 1272/2008, the substance does not meet the criteria for classification as acutely toxic.