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Description of key information

Acute toxicity - oral: A reliable, K1 key acute oral toxicity test was performed in male and female Sprague Dawley rats according to a method equivalent to OECD Guideline 401 (Mallory VT, 1983). The oral LD50 for male and female rats was determined to be 1344 mg/kg bw.

Acute toxicity - inhalation: An acute inhalation study does not need to be conducted as the substance is classified as corrosive to the skin (according to REACH, Annex VIII section 8.5, column 2). In addition, reliable acute oral and acute dermal toxicity studies are available.

Acute toxicity - dermal: An reliable, K1 key acute dermal toxicity test was performed in male and female New Zealand White rabbits according to a method equivalent to OECD Guideline 402 (Mallory VT, 1983b). The dermal LD50 was determined to be 3570 mg/kg bw.

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:
6 September 1983 - 23 September 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-23-1
- Substance type: Organic
- Physical state: Clear liquid
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration.
- Other: Specific gravity = 0.890 g/mL
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hilltop Lab Animals, Inc. Scottdale, Pennsylvania
- Weight at study initiation: 180 - 360 grams after fasting; the weight variation in animals or between groups did not exceed ± 20%
- Fasting period before study:18 hours
- Housing: Animal rooms: Separate isolation by test system; rats housed in groups, according to sex, or individually in stainless steel 1/2 wire mesh cages. Size in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum96+
- Acclimation period: Five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Dose-range finding study:
In a dose-range finding study, four fasted animals, two per sex, were administered the test article at 1000, 2000, 4000 and 8000 mg/kg, orally by gavage.
LD50 determination:
In the acute oral toxicity study, five groups of ten rats (5 males and 5 females) were administered at dose levels of 800, 1000, 1250, 1600 and 2000 mg/kg by oral gavage.
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 7 and 14, body weights were recorded
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs:
The rats observed at approximately 1, 2, 4 and 24 hours after dosing and twice daily for 14 days for pharmacotoxic, CNS effects and mortality.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 344 mg/kg bw
Based on:
test mat.
95% CL:
1 153 - 1 567
Sex:
male
Dose descriptor:
LD50
Effect level:
1 332 mg/kg bw
Based on:
test mat.
95% CL:
1 066 - 1 663
Sex:
female
Dose descriptor:
LD50
Effect level:
1 357 mg/kg bw
Based on:
test mat.
95% CL:
1 173 - 1 570
Mortality:
None of the animals died at 800 mg/kg
One of ten died at 1000 mg/kg
Two of ten died at 1250 mg/kg
Nine of ten died at 1600 mg/kg
Ten of ten died at 2000 mg/kg
Clinical signs:
Signs observed included decreased activity, decreased body tone, chromodacryorrhea, piloerection, ptosis, poor grooming, red exudate around the oral and nasal cavities, abnormal gait, abnormal stance, ataxia, body drop, tremors, semi-prostration, and prostration.
Gross pathology:
Necropsy of animals dying on study revealed the stomach mucosa desquamated, dark red cecum and distended intestines. Intestines and bladders were fluid-filled and black in color. Hemorrhagic thymus, congested lungs and dark adrenals were also observed. Hemorrhagic thymus, congested lungs and dark adrenals were also observed. Terminal necropsy revealed one animal with dark foci on the kidneys. No visible lesions were observed in the remaining animals.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based upon the results of the acute oral toxicity study in rats, the calculated oral LD50 for male and female rats treated with the substance was determined to be 1344 mg/kg with 95% confidence limits of 1153 to 1567 mg/kg. Therefore, the substance is to be classified as acute oral toxicant category 4 according to the criteria laid down in the CLP Regulation.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 344 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
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:
31 October, 1983 - 29 November, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-23-1
- Substance type: clear liquid
- Physical state: liquid
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration
- Other: Order No.: J-171
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sgarlat's Rabbitry, Harvey's Lake, Pennsylvania
- Weight at study initiation: 2 - 3 kilograms
- Fasting period before study: no data
- Housing: Rabbits were housed individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk, dorsal area
- % coverage: no less than 20% of the dorsal body surface area was available for application of the test article
- Type of wrap if used: A layer of gauze was wrapped around the animals to cover the dosed area. The animals were wrapped with rubber dam and an ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Following the 24 hour period of exposure, the rubber dam and ace bandage were removed. The test site was washed to remove any remaining material.
Duration of exposure:
24 hours
Doses:
dose-range finding study: 1000, 3000, 5000 and 8000 mg/kg
definitive dermal LD50 determination: 2500, 3200, 4000 and 5000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and clinical signs were recorded at 30 minutes, 2 and 4 hours after the 24 hour period of exposure, and twice daily thereafter for fourteen days.
- Necropsy of survivors performed: yes
Statistics:
The LD50 was determined by the method of Litchfield and Wilcoxon (1949), JPET 96: 99-114
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 570 mg/kg bw
Based on:
test mat.
95% CL:
2 900 - 4 380
Mortality:
None of the rabbits died at 2500 mg/kg, two of four rabbits died at 3200 and 4000 mg/kg, and four of four died at the 5000 mg/kg dose level.
Clinical signs:
Signs observed included necrosis and edema of the application sites, decreased activity, ptosis, cyanosis, loss of righting, semiprostration, body drop, ataxia, abnormal stance and abnormal gait. A lack of defecation at 24 hours post treatment was also observed.
Gross pathology:
Necropsy of the animals dying on study revealed hemorrhages of the muscle layers at the application sites, discolored thymus and dark fluid-filled bladders. Terminal necropsy revealed hemorrhages in the muscle layers at the application sites. The liver was adhered to the abdominal wall in one rabbit.

Dose-range finding study:

Signs observed included necrosis, edema, ptosis, semiprostration, decreased activity, body drop, abnormal gait and cyanosis. None of the rabbits died at the 1000 or 3000 mg/kg dose levels. One of two rabbits died at the 5000 mg/kg dose level and tow of two died at 8000 mg/kg.

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the observations made in the acute dermal toxicity study in rabbits, the calculated dermal LD50 for test article 5601-23-1 was determined to be 3570 mg/kg with 95% confidence limits of 2900 to 4380 mg/kg.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 570 mg/kg bw

Additional information

Acute toxicity: oral

Mallory VT (1983) investigated the acute oral toxicity via gavage of 800, 1000, 1250, 1600 and 2000 mg test substance/kg in male/female Sprague-Dawley rats (5 animals per sex and per dose) (equivalent to OECD guideline 401). None of the animals died at 800 mg/kg, 1 of 10 animals died at 1000 mg/kg, 2 of 10 animals died at 1250 mg/kg, 9 of 10 animals died at 1600 mg/kg and all 10 animals died at 2000 mg/kg. Clinical signs observed included decreased activity, decreased body tone, chromodacryorrhea, piloerection, ptosis, poor grooming, red exudate around the oral and nasal cavities, abnormal gait, abnormal stance, ataxia, body drop, tremors, semi-prostration, and prostration. Necropsy of animals dying on study revealed the stomach mucosa desquamated, dark red cecum and distended intestines. Intestines and bladders were fluid-filled and black in color. Hemorrhagic thymus, congested lungs and dark adrenals were also observed. Terminal necropsy revealed one animal with dark foci on the kidneys. No visible lesions were observed in the remaining animals. The acute oral LD50 for male and female rats treated with the test substance was determined to be 1344 mg/kg with 95% confidence limits of 1153 to 1567 mg/kg.

Acute toxicity: inhalation

No reliable studies were available for the inhalation route. An acute inhalation study does not need to be conducted as the substance is classified as corrosive to the skin (according to REACH, Annex VIII section 8.5, column 2). In addition, reliable acute oral and acute dermal toxicity studies are available.

Acute toxicity: dermal

Mallory VT (1983b) investigated acute dermal toxicity of the test substance in New Zealand White male/female rabbits (2 animals per sex and per dose) after 24 hours of exposure to either 2500, 3200, 4000 and 5000 mg/kg bw (equivalent to OECD guideline 402). None of the rabbits died at 2500 mg/kg, two of four rabbits died at 3200 and 4000 mg/kg, and four of four died at the 5000 mg/kg dose level. Signs observed included necrosis and edema of the application sites, decreased activity, ptosis, cyanosis, loss of righting, semi prostration, body drop, ataxia, abnormal stance and abnormal gait. A lack of defecation at 24 hours post treatment was also observed. Necropsy of the animals dying on study revealed hemorrhages of the muscle layers at the application sites, discolored thymus and dark fluid-filled bladders. Terminal necropsy revealed hemorrhages in the muscle layers at the application sites. The liver was adhered to the abdominal wall in one rabbit. After 14 days of observation, the acute dermal LD50 for the test substance was determined to be 3570 mg/kg with 95% confidence limits of 2900 to 4380 mg/kg.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study and according to the criteria of the CLP Regulation, the test substance should be classified as an acute oral toxicant category 4 (H302).

The test substance should not be classified for acute dermal toxicity based on the available data and the criteria of the CLP Regulation (exceeds classification per CLP Regulation).

No data were available to decide on the classification for the inhalation route.