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Administrative data

Description of key information

Oral: LD50 = 4895 mg/kg bw (rat) (BASF, 1962)

Inhalation: LC50 = 10.5 mg/L (rat, 4h) (Union Carbide, 1968)

Dermal: LD50 >2000 mg/kg bw (rabbit, occlusive) (BASF Corp., 1998)

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:
21 Aug - 24 Aug 1962
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Remarks:
roup-wise documentation of clinical signs was performed over the 7-day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose. The clinical signs and findings were reported in summary form.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material: Isobutyl acrylate
- Physical state: liquid
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 122-271 g
Route of administration:
oral: gavage
Vehicle:
other: aqueous emulsion with traganth
Details on oral exposure:
VEHICLE
- Amount of vehicle: 200; 1600; 3200; 4000; 5000; 6400 µL/kg bw. Calculation of concentrations (mg/kg bw) based on density of the test substance (0.89 g/mL).
Doses:
178; 1424; 2848; 3560; 4450; 5696 mg/kg bw
No. of animals per sex per dose:
5 animals/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 4 895 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the 7 day observation period in the 178 to 3560 mg/kg bw dose groups. One rat died within the first 24 hours in the 4450 mg/kg bw dose group. In the 5696 mg/kg bw dose group, all 5 rats died within the first 24 hours.
Clinical signs:
Clinical symptoms in the highest dose group were narcosis, staggering gait, apathy and abdominal position. Some animals of the other dose groups showed slight apathy after dose administration.
Gross pathology:
Kidneys were hyperemic in 4 of the sacrificed animals. No changes were observed in the deceased animals.

Dose (mg/kg bw)

No. of animals

Mortality after

1 h

24 h

48 h

7 days

5696

5

0/5

5/5

5/5

5/5

4450

5

0/5

1/5

1/5

1/5

3560

5

0/5

0/5

0/5

0/5

2848

5

0/5

0/5

0/5

0/5

1424

5

0/5

0/5

0/5

0/5

178

5

0/5

0/5

0/5

0/5

Original value reported: LD50 = 5500 µL/kg bw (corresponding to ca. 4895 mg/kg bw).

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 895 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Six rats per dose group were exposed to isobutyl acrylate vapours at metered concentrations (not checked analytically) of 1000, 2000 and 4000 ppm (corresponding to approx. 5.2, 10.5 and 21 mg/L) in a 9 liter glass exposure chamber for 4 h. The animals were observed for 14 days and the LC50 was calculated by the moving average method based on a 14-day observation period.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material: Isobutyl acrylate
- Physical state: liquid
- Lot/batch No.: 02497
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Fasting period before study: none
- Diet: Rockland diets (ad libitum)
- Water: ad libitum
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Vapours at metered concentrations, not checked analytically, were generated by feeding the liquid at a constant rate down the inside of a spirally corrugated surface of a minimally heated one inch Pyrex tube, through which metered air was passed. Resultant vapours were delivered to rats in a 9-liter glass exposure chamber.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
1000, 2000, 4000 ppm (corresponding to approximately 5.2, 10.5, 21 mg/L) Calculation of concentrations (mg/L) based on Derelanko MJ (2000). Toxicologist's Pocket Handbook, CRC Press, conversion table, p. 57.
No. of animals per sex per dose:
6
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, gross pathology
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
ca. 10.5 mg/L air
Based on:
test mat.
95% CL:
> 7.4 - < 14.8
Exp. duration:
4 h
Mortality:
No mortality was observed in 1000 ppm dose group; 3/6 animals died in 2000 ppm dose group at days 4,5,6 after exposure; all animals died in 4000 ppm dose group on the day of exposure.
Clinical signs:
other: 1000 ppm dose group: extremities irritated at 3 h of exposure; 2000 ppm dose group: eyes and noses irritated at 1 h of exposure, and gasping at 3 h of exposure; 4000 ppm dose group: Rubbing noses and keeping eyes closed immmediately, hyperactive at 30 min
Gross pathology:
Abnormalities observed through necropsy included capillary injection on all animals at the highest dose group. Consolidation of the lungs in 3 animals in the middle dose group. Nothing remarkable in the surviving animals.
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
10 500 mg/m³

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: Lot No. S8003-01-6A
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products Inc., Michigan
- Age at study initiation: approx. 15 weeks
- Weight at study initiation: 2,3 - 2,5 kg
- Housing: individually (stainless steel cages)
- Diet (e.g. ad libitum): measured amount (High Fiber Rabbit Diet 7015 (Harlan Teklad)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test material was applied to the test site in a thin uniform layer which was approximately 0.03 g/cm². The area of application (approximately 180 cm²) was covered with a 4-ply 9.5-cm x 19-cm gauze patch secured with paper tape and overwrapped with Saran Wrap® and Elastoplast® tape to provide an occlusive dressing.
Duration of exposure:
24 h
Doses:
- 2000 mg/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
- Other examinations performed: clinical signs, body weight,organ weights, pathology
Statistics:
No statistical evaluation.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
Three males and all five females exhibited weight losses of 27 to 129 g during the first week of the study. Some recovery from these weight losses were noted during the second week of the study although one additional male exhibited a 25 g weight loss from Day 7 to Day 14.
Body weight:
Clinical signs of toxicity in three male and all five females included hypoactivity, staggered gait, injected iris, and/or decreased food consumption. All animals returned to a normal appearance by Day 4 after treatment.
Gross pathology:
At necropsy, the treated skin of each animal was observed to be thickened, diffusely dark red, or had multiple, dark red, eroded areas of variable size. The subcutis of the treated skin in some animals was also observed to have dark red areas of variable size. These observations were indicative of irritation caused by the test material. There were no other visible lesions in any of the animals.
Other findings:
Dermal irritation (based on the most severe score for each animal at any time point) consisted of severe erythema and edema, marked atonia, slight desquamation, marked coriaceousness, and slight to moderate fissuring. Subcutaneous hemorrhaging, blanching, eschar, and possible necrotic areas were also observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The estimated dermal LD50 values for male and female rabbits were determined to be greater than 2,000 mg/kg.
Executive summary:

Isobutyl Acrylate, was evaluated for its acute dermal toxicity potential in male and female rabbits of the Hra:(NZW)SPF strain when administered as a single topical application at a level of 2,000 mg/kg of body weight. No mortality was observed during the study. The estimated dermal LD50 values for male and female rabbits were determined to be greater than 2,000 mg/kg. Clinical signs of toxicity included hypoactivity, staggered gait, decreased food consumption, and injected iris, all of which were transient in nature. All animals returned to a normal appearance by Day 4 after treatment. Body weight losses from 27 to 129 g were observed in three males and all five females during the first week. Some recovery from these weight losses were noted during the second week with the exception that one additional male exhibited a 25 g weight loss from Day 7 to Day 14. The test material produced severe dermal irritation which was probably associated with the observed weight losses. At necropsy, the treated skin of each animal was observed to be thickened, diffusely dark red, or had multiple, dark red, eroded areas of variable size. The subcutis of the treated skin in some animals was also observed to have dark red areas of variable size. These observations were indicative of irritation caused by the test material. There were no other visible lesions in any of the animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw

Additional information

Oral exposure route:

In an acute toxicity study (BASF, 1962) groups of 5 rats were administered doses of 178, 1424, 2848, 3560, 4450, 5696 mg/kg bw by gavage and observed for 7 days for lethality and clinical signs of intoxication. No mortality was observed during the 7 day observation period in the 178 to 3560 mg/kg bw dose groups. One rat died within the first 24 hours in the 4450 mg/kg bw dose group. In the 5696 mg/kg bw dose group, all 5 rats died within the first 24 hours. The LD50 was found to be approx. 4895 mg/kg bw. Clinical symptoms in the highest dose group were narcosis, staggering gait, apathy and abdominal position. Some animals of the other dose groups showed slight apathy after dose administration. At necropsy, hyperemia of the kidneys was found in 4 of the sacrificed animals.

Other studies reported an LD50 of 6639 mg/kg bw in rats without clinical symptoms (Union Carbide, 1968) and 6292 mg/kg bw (clinical signs: heavy breathing at the highest dose level of 17800 mg/kg bw) (Union Carbide, 1971; Carpenter et al. 1974). The LD50 in mice was 2910 mg/kg bw, the observed symptoms were piloerection, narcosis and laboured breathing (BASF, 1962). Tanii (1982) reported an LD50 of 6105 mg/kg bw (no information about clinical symptoms).

 

Inhalation exposure route:

The inhalation 4-hr LC50 for rats was determined to be 2000 ppm (corresponding to approx. 10.5 mg/L) (Union Carbide, 1968). Groups of six rats were exposed to test item vapours at metered concentrations of 1000, 2000 and 4000 ppm (corresponding to approx. 5.2, 10.5 and 21 mg/L). No mortality was observed in the 1000 ppm dose group; 3/6 animals died at 2000 ppm on days 4, 5, 6 after exposure; all animals died in the high dose group on the day of exposure. Clinical signs were gasping and irritation of eyes, nose, respiratory tract and extremities. The animals of the high-dose group were hyperactive 30 min after the exposure and prostrate after 1-1.5 h after exposure. Necropsy findings included capillary injection and consolidation of the lungs.

Another 4-hr LC50 for rats is reported to be 2828 ppm (corresponding to approx. 14.8 mg/L), clinical symptoms were irritation to eyes, extremities and respiratory tract, gasping and hypersensitivity to stimuli in the tested concentrations of 2000 and 4000 ppm (10.5 and 21 mg/L) (Union Carbide, 1971; Carpenter 1974).

In an inhalation hazard test, saturated vapours of the test item (37.3 mg/L) were extremely irritating to the eyes, nose and skin (Union Carbide, 1968).

 

Dermal exposure route:

The estimated dermal LD 50 for male and female rabbits were determined to be greater than 2000 mg/kg (BASF Corp., 1998), in a study performed according to OECD TG 402 under GLP, when administered as a single topical application at a level of 2000 mg/kg of body weight. No mortality was observed, clinical signs of toxicity included hypoactivity, staggered gait, decreased food consumption and injected iris. At necropsy, the treated skin of each animal was observed to be thickened, diffusely dark red, or had multiple, dark red, eroded areas of variable size (irritation caused by the test material).

Justification for classification or non-classification

Harmonised Classification - Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation)

H312: Harmful in contact with skin.

H332: Harmful if inhaled.