Registration Dossier

Administrative data

Description of key information

Acute toxicity - oral: A K2 key study is available (Auletta, 1979a): based on this study, the oral LD50 for male/female rats was estimated to be 2200 mg/kg body weight. The test was performed according to a method equivalent to OECD Guideline 401.
In addition, a K3 supporting study is available (van Huygevoort, 2002): based on this study, the oral LD50 for female rats was considered to exceed 2000 mg/kg body weight.
Acute toxicity - inhalation: In accordance with the specific rules for adaptation from column 1 (REACH Annex VII and VIII), no acute toxicity study needs to be conducted as the substance is classified as corrosive to the skin. Moreover, reliable data via two other routes of administration is available.
Acute toxicity - dermal: For the dermal route, a K2 key study is available (Auletta, 1979b): based on this study, the dermal LD50 for male/female rabbits was estimated to be 3300 mg/kg.

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:
1979-03-14 to 1979-04-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP study performed according to a method equivalent to OECD Guideline 401. Limited information was reported on test conditions, however sufficient animals were tested.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
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): 4236-21-35
- Substance type: Clear colourless liquid
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, Mass.
- Age at study initiation:
- Weight at study initiation: 220 to 314 grams
- Fasting period before study: approximately seventeen hours prior to administration of test material
- Housing: Following dosing, the rats were individually housed
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
No data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test material was administered by oral intubation in the form received. The dose levels were calculated according to the density provided by the sponsor as being 0.944 g/mL.
Doses:
The animals were dosed at the following dose levels: 1000, 1400, 2000, 2800 and 4000 mg/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: Bodyweights were recorded prior to fasting, at day 7 and at the termination of the study (day 14)
- Necropsy of survivors performed: yes: A gross necropsy was performed on all animals at the time of death or terminal sacrifice (day 14).
- Observations for mortality and overt signs of effect were made at 0-2 hours and at 4-6 hours following dosing and daily thereafter for fourteen days.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 200 mg/kg bw
Based on:
test mat.
95% CL:
1 900 - 2 500
Mortality:
1000 mg/kg: 1/10 animals died
1400 mg/kg: 0/10 animals died
2000 mg/kg: 2/10 animals died
2800 mg/kg: 9/10 animals died
4000 mg/kg: 10/10 animals died
Clinical signs:
Piloerection was noted at all levels throughout the observation period in the majority of the surviving animals. Motor activity decrease was evident at all levels most notably within twenty-four hours following test material administration. Also noted within the twenty-four hour period following intubation were red nasal and oral discharges and resipratory rate decrease. These signs were evident mainly at the 1000, 1400 and 2000 mg/kg dose levels.
Body weight:
All surviving animals at all dose levels exhibited weight gains during the fourteen-day post-dose observation period.
Interpretation of results:
not classified
Conclusions:
The oral LD50 for this substance is 2200 mg/kg with 95% confidence limits of 1900 to 2500 mg/kg. Based on this result, the test substance is not to be classified according to the CLP Regulation.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 200 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
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:
1979-03-28 to 1979-05-03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP study performed according to a method equivalent to OECD Guideline 402. Only 2 animals per sex and per dose tested instead of 5 as recommended in the OECD Guideline 402.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only 2 animals per sex and per dose tested instead of 5 as recommended in the OECD Guideline 402
GLP compliance:
no
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): 4236-21-35
- Substance type: Clear colorless liquid
- Physical state: Liquid
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Marland Breeding Farms, Inc., Hewitt, N.J.
- Age at study initiation: unknown
- Weight at study initiation: 2.5 to 3.1 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
The hair of each rabbit was clipped from the trunk so as to expose at least 10% of the body surface area. The skin of half of the animals (4 males, 4 females) was abraded longitudinally every 2 or 3 centimeters so as to penetrate the stratum corneum but not so deep as to disturb the derma or produce bleeding.

REMOVAL OF TEST SUBSTANCE
Following 24 hours of exposure, the sleeves were removed and observations were made for edema, erythema and eschar formation. The exposed area was then wiped free of excess test material.

TEST MATERIAL
The test material was administered as received. The dose levels were calculated based on the density of the test material which was provided by the sponsor as being 0.944 g/mL.

The test material was held in contact with the skin by an 8-ply gauze wrapping and a sleeve made of impervious plastic sheeting designed to contain the dose without leakage or undue pressure. Collars designed to prevent the ingestion of the test material were worn by all animals throughout the study.
Duration of exposure:
24 hours
Doses:
2000, 2800, 4000 and 5600 mg/kg
The dose levels were calculated based on the density of the test material which was provided by the sponsor as being 0.944 g/mL.
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: Body weights were recorded initially, on day 7 and at the termination of the study (day 14)
- Necropsy of survivors performed: yes: A gross necropsy was performed on spontaneous deaths.
- Observations for mortality and overt signs of effect were made at 0-2 and 4-6 hours following dosing, and daily thereafter for fourteen days.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Based on:
test mat.
95% CL:
2 200 - 4 400
Mortality:
at 2000 mg/kg: 0/4 animals died
at 2800 mg/kg: 2/4 animals died
at 4000 mg/kg: 2/4 animals died
at 5600 mg/kg: 4/4 animals died
Clinical signs:
At the twenty-four hour dermal observation the majority of the animals at all levels exhibited severe erythema accompanied by necrotic skin and moderate edema.
Physical signs noted in the majority of animals at all dose levels during the fourteen-day post-dose observation period were clear nasal discharge, piloerection and motor activity decrease.
Body weight:
During the two-week observation period the majority of the surviving animals showed no change in weight or a slight weight gain.
Interpretation of results:
not classified
Conclusions:
The dermal LD50 of the substance was estimated to be 3300 mg/kg with 95% confidence limits of 2200 to 4400 mg/kg. The substance is not to be classified according to the CLP Regulation
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 300 mg/kg bw

Additional information

Acute toxicity: oral

Auletta (1979a) investigated the acute oral toxicity of 1000, 1400, 2000, 2800 and 4000 mg/kg in 5 male/female Sprague-Dawley albino rats. After 14 days of observation following mortalities were observed: at 1000 mg/kg 1/10 animals died, 1400 mg/kg 0/10 animals died, 2000 mg/kg 2/10 animals died, 2800 mg/kg 9/10 animals died, 4000 mg/kg 10/10 animals died. Piloerection was noted at all levels throughout the observation period in the majority of the surviving animals. Motor activity decrease was evident at all levels most notably within twenty-four hours following test material administration. Also noted within the twenty-four hour period following intubation were red nasal and oral discharges and respiratory rate decrease. These signs were evident mainly at the 1000, 1400 and 2000 mg/kg dose levels.

All surviving animals at all dose levels exhibited weight gains during the fourteen-day post-dose observation period. This study was selected as key study. In addition, a K3 supporting acute oral toxicity study was conducted in rats and the acute oral LD50 observed in this study was observed to be > 2000 mg/kg (van Huygevoort, 2002).

Acute toxicity: dermal

For the dermal route, a K2 key study is available (Auletta, 1979b). New Zealand White rabbits were exposed to 2000, 2800, 4000 and 5600 mg/kg of the substance. After 14 days of observation following mortalities were observed: at 2000 mg/kg: 0/4 animals died; at 2800 mg/kg: 2/4 animals died; at 4000 mg/kg: 2/4 animals died; at 5600 mg/kg: 4/4 animals died. At the twenty-four hour dermal observation the majority of the animals at all levels exhibited severe erythema accompanied by necrotic skin and moderate edema. Physical signs noted in the majority of animals at all dose levels during the fourteen-day post-dose observation period were clear nasal discharge, piloerection and motor activity decrease. During the two week observation period the majority of the surviving animals showed no change in weight or a slight weight gain. Based on this study, the dermal LD50 for male/female rabbits was estimated to be 3300 mg/kg.

Acute toxicity: inhalation

No acute inhalation toxicity study was performed.

Justification for classification or non-classification

Based on one K2 study (Auletta, 1979a), the oral LD50 for male/female rats was estimated to be 2200 mg/kg body weight. According to the criteria of the CLP Regulation, the substance does not have to be classified for acute oral toxicity as the LD50 value is > 2000 mg/kg bw.

Based on one K2 study (Auletta, 1979b), the dermal LD50 for male/female rabbits was estimated to be 3300 mg/kg body weight. According to the criteria of the CLP Regulation, the substance does not have to be classified for acute dermal toxicity as the LD50 value is > 2000 mg/kg bw.