Registration Dossier

Administrative data

Description of key information

Oral (similar to OECD TG 401), rat: LD50 = 12 828 mg/kg bw (male)
Dermal (similar to OECD TG 402), rabbit: LD50 = 15 200 mg/kg bw (male)
Inhalation: no reliable data available

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report)
Principles of method if other than guideline:
Only limited information on procedure and results is given in the study report. The test material was administered by stomach intubation to Wistar-derived male rats.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-4 weeks
- Weight at study initiation: 90-120 g
- Fasting period before study: none
- Diet: appropriate diet ad libitum (not further specified)
- Water: ad libitum (not further specified)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg
Doses:
0.5, 1, 2, 4, 8, and 16 mL/kg bw, equivalent to 475, 950, 1900, 3800, 7600, and 15200 mg/kg bw (calculated based on a density of 0.95 g/cm³)
No. of animals per sex per dose:
5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 along with the 95% confidence limits was calculated by the moving average method based on a 14 day observation period.
Sex:
male
Dose descriptor:
LD50
Effect level:
12 825 mg/kg bw
Based on:
test mat.
95% CL:
>= 551 - <= 3 192
Remarks on result:
other: (equivalent to 13.5 mL/kg bw (95% CL 5.38 - 33.6 mL/kg bw); calculated based on a density of 0.95 g/cm³)
Sex:
male
Dose descriptor:
LD0
Effect level:
475 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (equivalent to 0.5 mL/kg bw; calculated based on a density of 0.95 g/cm³)
Mortality:
- 16 mL/kg bw: 3/5 (all animals died 30-35 min after dosing)
- 8 mLl/kg bw: 1/5 (animal died on day 7 post-dosing)
- 4 mL/kg bw: 2/5 (animals died 20 min after dosing and on day 1); repeated for confirmatory purpose: deaths 2/5 on days 0 and 1
- 2 mL/kg bw: 2/5 (deaths occured 15 and 20 min after dosing)
- 1 ml/kg bw: 1/5 (animal died 30 min after dosing)
- 0.5 mL/kg bw: 0/5
Clinical signs:
- 16 mL/kg bw: Sluggish (survivers) at 35 min; salivation
- 8 mL/kg bw: Diarrhoea at day 1
- 4 mL/kg bw: Salivation; repeated for confirmatory purpose: Unsteady gait; salivation 5 min after dosing; survivors recovered after 1 day.
- 2 mL/kg bw: Unsteady gait; salivation at 8 min
- 1 mL/kg bw: Salivation (the animal that died)
- 0.5 ml/kg bw: no clinical signs were observed during the study period.
Body weight:
Mean body weight changes seen throughout the study period were:
- 16 mL/kg bw: 64 g (21 and 107 g)
- 8 mL/kg bw: 107 g (94 to 123 g)
- 4 mL/kg bw: 112 g (100 to 126 g); repeated for confirmatory purpose: 125 g (121 to 134 g)
- 2 mL/kg bw: 120 g ( 112 to 125 g)
- 1 mL/kg bw: 123 g (119 to 132 g)
- 0.5 mL/kg bw: 102 g (71 to 125 g)
No further details are given in the study report.
Gross pathology:
In victims, the stomach was gas-filled, the glandular portions were injected, and the intestines were injected or contained blood.
In survivors, nothing remarkable was observed.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for acute oral toxicity according to a test protocol that is comparable to the appropriate OECD test guideline, but without GLP compliance. The test material was administered by stomach intubation to 5 male rats each dose group. The LD50 was determined to be 12825 mg/kg bw. The predominant clinical signs detected were salivation, unsteady gait, sluggishness, and diarrhoea. No deaths and no clinical signs throughout the study period were observed at 425 mg/kg bw. Based on this data, classification for acute oral toxicity according to EC/1272/2008 is not warranted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
12 825 mg/kg bw
Quality of whole database:
The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP. However, no test material purity is stated in the study report.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
There are no reliable data for the inhalation route. However, there is one study with a reliability score of 4.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-5 months
- Fasting period before study: none
- Diet: appropriate diet ad libitum (not further specified)
- Water: ad libitum (not further specified)
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: impervious sheeting

REMOVAL OF TEST SUBSTANCE
- Washing (if done): excess fluid was removed to prevent ingestion (not further specified)
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
2, 4, 8, and 16 mL/kg bw, equivalent to 1900, 3800, 7600, and 15200 mg/kg bw (calculated based on a density of 0.95 g/cm³)
No. of animals per sex per dose:
4 animals (not further specified)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin irritation
Statistics:
The LD50 along with the 95% confidence limits was calculated by the moving average method based on a 14 day observation period.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
15 200 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 187.5 - <= 193 800
Remarks on result:
other: (equivalent to 16.0 ml/kg bw (95% CL 1.25 -204 ml/kg bw); calculated based on a density of 0.95 g/cm³)
Sex:
not specified
Dose descriptor:
LD0
Effect level:
1 900 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (equivalent to 2.0 ml/kg bw; calculated based on a density of 0.95 g/cm³)
Mortality:
- 16 ml/kg bw: 2/4 (both deaths occured on day 3)
- 8 ml/kg bw: 1/4 (animal died on day 11 post-dosing); repeated for confirmatory purpose: deaths 2/4 (animals died on days 2 and 3)
- 4 ml/kg bw: 1/4 (animal died on day 2 post-dosing)
- 2 ml/kg bw: 0/4
Clinical signs:
- 16 ml/kg bw: Erythema, oedema, necrosis, ecchymosis, fissuring, desquamation at 14 days; Prostrate at 1 day
- 8 ml/kg bw: Erythema, oedema, ecchymosis, scabs at 14 days; repeated for confirmatory purpose: Oedema, necrosis at 24 h, scabs on survivors at 14 days; Prostrate at 1 day
- 4 ml/kg bw: Oedema, necrosis, scabs at 14 days, one prostate at 24 h
- 2 ml/kg bw: Ecchymosis, oedema, necrosis
Body weight:
Mean body weight changes seen throughout the study period were:
- 16 ml/kg bw: -108 g (-397 and 182 g)
- 8 ml/kg bw: 5 g (-268 to 150 g); repeated for confirmatory purpose: 19 g (-130 to 168 g)
- 4 ml/kg bw: 26 g (-281 to 223 g)
- 2 ml/kg bw: 109 g (-13 to 208 g)
No further details are given in the study report.
Gross pathology:
In victims, the lungs were red, the livers mottled bright red and tan, the kidneys were found to be mottled tan and red, the spleens appeared dark, the stomacs were injected or opaque.
In survivors, nothing remarkable was observed.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for acute dermal toxicity according to a test protocol that is comparable to the appropriate OECD test guideline, but without GLP compliance. The test material was occlusively administered to 4 rabbits each dose group. The LD50 was determined to be 15200 mg/kg bw. The predominant clinical signs detected were signs of irritation/corrosion, such as erythema, oedema, and necrosis. No deaths occured at 1900 mg/kg bw, but still signs of skin irritation were noted. Based on this data, classification for acute dermal toxicity according to EC/1272/2008 is not warranted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
15 200 mg/kg bw
Quality of whole database:
The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP. However, no test material purity is stated in the study report.

Additional information

Acute toxicity: oral

In the available key study (Bushy Run Research Center, 1981) the test item was tested according to a test protocol that is similar to the OECD TG 401, but without compliance with GLP. 5 male Wistar rats each group received the undiluted test material at doses of 475, 950, 1900, 3800, 7600, and 15 200 mg/kg bw via gavage. No deaths occurred and no signs of toxicity were observed at the low dose of 475 mg/kg bw. At higher doses, deaths occured and salivation, unsteady gait, diarrhoea, and sluggishness were observed. At the high dose, 3/5 animals died 30-35 min after dosing. Macroscopic evaluation revealed that in victims, the stomach was gas-filled, the glandular portions were injected, and the intestines were injected or contained blood. In survivors, nothing remarkable was observed. The LD50 was determined to be 12 825 mg/kg bw.

Acute toxicity: dermal

In the available key study (Bushy Run Research Center, 1981) the test item was tested for acute dermal toxicity according to a test protocol that is comparable to the OECD test guideline 402, but without GLP compliance. The test material was occlusively administered to 4 male New Zeeland White rabbits each dose group for 24 h. The LD50 was determined to be 15 200 mg/kg bw. The predominant clinical signs detected were signs of irritation/corrosion, such as erythema, oedema, and necrosis. No deaths occurred at 1900 mg/kg bw, but still signs of skin irritation were noted.

Acute toxicity: inhalation

No reliable data is available for acute toxicity via inhalation. In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2 of REACH Annex VIII) does not need to be conducted as reliable data via the oral and dermal routes are available. Nevertheless, supporting data derived from a summary report is available (Bushy Run Research Center, 1981). In this non-guideline study, which was not compliant to GLP, the test item was tested for acute inhalation toxicity. Substantially saturated vapour did not cause any deaths or signs of toxicity in any of the male rats after 6 h of exposure. The LC50 was found to be >vapour saturation at 25°C.


Justification for classification or non-classification

The available data is reliable and suitable for classification. Based on this data, classification for acute toxicity according to EC/1272/2008 is not warranted.