Registration Dossier

Administrative data

Description of key information

The substance is harmful after acute oral or dermal exposure (Cat. 4, H302 and H312), but does not cause mortality at saturated vapour concentrations.

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
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Limit test:
no
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: overnight
- Diet: standard lab diet ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4 mL/kg bw
Doses:
males: 1.0, 2.0, 4.0 mL/kg bw
females: 0.25, 0.5, 1.0, 2.0, 4.0 mL/kg bw
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: on days 0 (prior to treatment), 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
LD50 value was calculated using the moving average method (Thompson, 1947; Weil, 1983)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 750 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Using a density of 0.936 kg/L, the calculated LD50 of 1.87 mL/kg bw is equivalent to 1750 mg/kg bw
Mortality:
Most deaths occurred at 1.5 to 2 days. However, three females died at 10 to 14 days. Survivors recovered at one to three days.

Males: 0/5, 3/5 and 5/5 of the low, middle and high dose group died
Females: 0/5, 0/5, 1/5, 2/5, 5/5 of the 0.25, 0.5, 1, 2, 4 mL/kg bw dose group died, respectively
Clinical signs:
Signs of toxicity included sluggishness, lacrimation, unkempt fur, kyphosis (in 2), prostration, a moribund appearance, diarrhea, red to brown discharge on perioral, perinasal and periurogenital fur.
Body weight:
Males: body weight gain at 1.0 mL/kg bw; bodyw eight reduced at 2.0 mL/kg bw
Females: no body weight gain at all dose levels
Gross pathology:
Dead animals: stomach abnormalities (discoloration, brown liquid or gas, gastric collapse); discoloure dlungs; brown to dark red livers, intstines, and kidneys.
Survivors: small stomachs and spleens; rough stomach surfaces, adhesion of the stomach to liver or spleen, enlarged and mottled red kidneys.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 was 1750 mg/kg bw in male and female rats. Necropsy findings in survivors revealed irritation/corrosion of the stomach and intestines.
Executive summary:

Oral toxicity was investigated in a study similar to OECD TG 401. Male and female rats (n=5 per sex per dose) were exposed against different doses of test substance up to 4 mL/kg bw (3744 mg/kg bw by calculation on basis of substance density of 0.936 kg/L). Exposed animals showed signs of toxicity including sluggishness, lacrimation, unkempt fur, kyphosis, prostration, a moribund appearance, diarrhea, red to brown discharge on perioral, perinasal and periurogenital fur. Female rats of all dose groups and male rats at doses >= 2 mL/kg bw did not gain body weight. The following findings were observed at necropsy of dead animals: stomach abnormalities (discoloration, brown liquid or gas, gastric collapse), discoloured lungs, brown to dark red livers, intstines, and kidneys. Necropsy of the surving animals revealed the following effects: small stomachs and spleens; rough stomach surfaces, adhesion of the stomach to liver or spleen, enlarged and mottled red kidneys.Using the moving average method an LD50 value of 1.87 mL/kg bw (corresponding to 1750 mg/kg bw) was calculated for male and female rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
sufficient for evaluation

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Inhalation Risk Test
GLP compliance:
not specified
Test type:
fixed concentration procedure
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 - 300 g
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: animal chmaber
- Exposure chamber volume: 100 to 152 L
- Method of holding animals in test chamber: in cage
- Source and rate of air: air in the exposure chamber
- System of generating atmosphere: 100 g of the test material was placed in the sealed exposure chamber for approx. 18 hours. A mixing fan periodically agitated the chamber atmosphere to aid in distribution of the vapour. Oxgen was added, as needed, to maintain approx. 20% of oxygen.


Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
saturation
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: on days 0 (prior to treatment), 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
none
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
8 375 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: There were no signs of toxicity and no gross lesions at necropsy.
Mortality:
No death during exposure or thereafter
Clinical signs:
None noted
Body weight:
Increase in males from 280 g on day 0 to 339 g on day 14. No significant body weight gain in females (237 g before treatment, 244 g at day 14 (all values means).
Gross pathology:
No gross lesions noted
Interpretation of results:
GHS criteria not met
Conclusions:
Male and female rats (5 per sex) survived a 6-hour whole body exposure to a saturated vapour atmosphere. There were no deaths within the 14-day observation period. There were no clinical signs of toxicity at any time, or gross lesions at terminal sacrifice. According to EC/1272/2008 table 3.1.1 the substance is not acutely toxic after inhalation.
Executive summary:

Male and female rats (5 per sex) survived a 6-hour whole body exposure to a saturated vapour atmosphere. There were no deaths within the 14-day observation period. There were no clinical signs of toxicity at any time, or gross lesions at terminal sacrifice.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
sufficient for evaluation

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
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: between 2.0 and 3.0 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: excess fluid removed
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
males: 0.5. 1.0, 2.0, 2.83, and 4.0 mL/kg bw
females: 0.5. 1.0, 1.41, 2.0, and 4.0 mL/kg bw
- Constant volume or concentration used: no
Duration of exposure:
24 hr
Doses:
males: 0.5. 1.0, 2.0, 2.83, and 4.0 mL/kg bw (i.e. 468, 936, 1872, 2649, 3744 mg/kg bw)
females: 0.5. 1.0, 1.41, 2.0, and 4.0 mL/kg bw (i.e. 468, 936, 1320, 1872, 3744 mg/kg bw)
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 0 (prior to treatment), 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin reactions at one hour, 7 days and 14 days after contact period.
Statistics:
LD50 value was calculated using teh moving average method (Thompson, 1947; Weil, 1983)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 228 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The applied volume was converted to mg/kg bw using a density of 0.936 kg/L
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 367 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The applied volume was converted to mg/kg bw using a density of 0.936 kg/L
Mortality:
Moast deaths occurred at 1.5 hours to one day; one female died at 3 days. A few affected survivors recovered after one to three days.

Males: all animals (5/5) of the two highest dose groups (4 and 2.83 mL/kg bw) died, no mortalities occurred at lower dose levels
Females: all animals (5/5) of the two highes dose groups (4 and 2 mL/kg bw) died, two animals (2/5) of the mid dose group (1.41 mL/kg bw) died, no animals died at the lower dose groups
Clinical signs:
Local efefcts: erythema, edema, necrosis, desquamation, alopecia, ulceratins, scabs.
Sluggishness, unsteady gait, prostration, red discharge on the perinasal and perianal fur were among the signs of toxicity noted.
Body weight:
Males: body weight gain in groups at 0.5 and 1.0 mL/kg bw; no body weight gain at 2.0 mL/kg.
Females: body weight gain in groups at 0.5 and 1.0 mL/kg bw; no body weightgain at 1.41 mL/kg bw. Complete mortality at higher dose levels.
Gross pathology:
Findings included a few discoloured lungs; red to tan livers; grey stomachs; stomachs and/or intestines with black foci; small instetsines fileld with red liquid (in 2); dark purple or red kidneys; dark red thymuses; and bladders filled with blood.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute dermal LD50 was 2228 mg/kg bw in male and 1367 mg/kg bw in female rabbits.Changes noted in internal organs suggest dermal absorption of the acid and irritation/corrosion of the organs.
Executive summary:

Dermal toxicity was investigated in a study similar to OECD TG 405. Male and female white rabbits (n=5 per sex per dose) were exposed for 24 h against different doses of test substance up to 4 mL/kg bw (3744 mg/kg bw by calculation on basis of substance density of 0.936 kg/L). Exposed animals showed local effects like erythema, edema, necrosis, desquamation, alopecia, ulceratins, and scabs. Clinical sign in treated animals were sluggishness, unsteady gait, prostration, red discharge on the perinasal and perianal fur. Body weight did not increase in animals which received more than 1 mL/kg bw. At necropsy discoloured lungs, red to tan livers, grey stomachs, stomachs and/or intestines with black foci, small instetsines fileld with red liquid (in 2), dark purple or red kidneys, dark red thymuses, and bladders filled with blood were observed. The acute dermal LD50 was 2228 mg/kg bw in male and 1367 mg/kg bw in female rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 367 mg/kg bw
Quality of whole database:
sufficient for evaluation

Additional information

Oral toxicity was investigated in a study similar to OECD TG 401. Male and female rats (n=5 per sex per dose) were exposed against different doses of test substance up to 4 mL/kg bw (3744 mg/kg bw by calculation on basis of substance density of 0.936 kg/L). Exposed animals showed clinical signs of toxicity as well as pathological findings at necropsy. Female rats of all dose groups and male rats at doses >= 2 mL/kg bw did not gain body weight. Using the moving average method an LD50 value of 1.87 mL/kg bw (corresponding to 1750 mg/kg bw) was calculated for male and female rats (Union Carbide, 1992).

Male and female rats (5 per sex) survived a 6-hour whole body exposure to a saturated vapour atmosphere. There were no deaths within the 14-day observation period. There were no clinical signs of toxicity at any time, or gross lesions at terminal sacrifice (Union Carbide, 1992).

Dermal toxicity was investigated in a study similar to OECD TG 405. Male and female white rabbits (n=5 per sex per dose) were exposed for 24 h against different doses of test substance up to 4 mL/kg bw (3744 mg/kg bw by calculation on substance density of 0.936 kg/L). Exposed animals showed local effects like erythema, edema, necrosis, desquamation, alopecia, ulceratins, and scabs. Clinical sign in treated animals were sluggishness, unsteady gait, prostration, red discharge on the perinasal and perianal fur. Body weight did not increase in animals which received more than 1 mL/kg bw. At necropsy discoloured lungs, red to tan livers, grey stomachs, stomachs and/or intestines with black foci, small instetsines fileld with red liquid (in 2), dark purple or red kidneys, dark red thymuses, and bladders filled with blood were observed. The acute dermal LD50 was 2228 mg/kg bw in male and 1367 mg/kg bw in female rabbits (Union Carbide, 1992).

Justification for classification or non-classification

Based on the available experimental data classification of the substance as acutely toxic after oral ingestion (Cat. 4; Harmful if swallowed, H302) and after dermal application (Cat. 4, Harmful in contact with skin, H312) is recommended according to the criteria of Regulation (EC) No. 1272/2008. No classification for acute toxicity after inhalation is necessary.