Registration Dossier

Administrative data

Description of key information

Butyl acrylate is of low toxicity after a single ingestion and short term skin contact. Butyl acrylate is of moderate toxicity after short-term inhalation.
Oral: LD50 = 3150 mg/kg bw (rat, BASF Test)
Dermal: LD50: 2000 - 3024 mg/kg bw (rabbit, occlusive)
Inhalation: LC50 = 10.3 mg/L (rat, OECD TG 403)

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:
other: Basic data given: study report which meets basic scientific principles.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
BASF test: In principle, the methods described in OECD Guideline 401 were used.
5-10 rats per dose were treated by gavage with preparations of the test substance in 10 % traganth. Group-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
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
other: Aqueous traganth emulsion
Doses:
2.040, 3.160 and 5.010 ml/kg bw (corresponding to 1840, 2840 and 4510 mg/kg bw) Calculation of concentrations (mg/kg bw) based on density of the test substance (0.90 g/ml).
No. of animals per sex per dose:
5-10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Other examinations performed: clinical signs
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 3 150 mg/kg bw
Mortality:
One, 2 and 8 animals died in the dose groups of 1832, 2838 and 4500 mg/kg bw, respectively.
Clinical signs:
1832 mg/kg bw: only piloerection on the day after substance administration
2838 mg/kg bw: piloerection, staggering gait, one rat had diarrhea
4500 mg/kg bw: piloerection, labored breathing, abdominal position, crawling gait.
Gross pathology:
1832 mg/kg bw: mottled lung surface, thymus haemorrhagic, spleen congested
2838 and 4500 mg/kg bw: hyperemia of medulla renalis was observed.
Other findings:
- Histopathology: low grade of fatty degeneration was observed in liver of one animal in 2838 mg/kg bw dose group.

Dose (mg/kg bw)

No. of animals

Mortality

1 h

24 h

48 h

7 days

1832

5

0/5

1/5

1/5

1/5

2838

5

0/5

2/5

2/5

2/5

4500

10

0/10

4/10

8/10

8/10

Original value reported: LD50 = 3.5 ml/kg bw (corresponding to ca. 3150 mg/kg bw)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 150 mg/kg bw
Quality of whole database:
Study equivalent to OECD 401.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
BASF test: This test was performed in principle as described in OECD Guideline 403.
Ten male and ten female rats (Sprague-Dawley) were exposed by whole body exposure to butyl acrylate vapour analyzed concentrations of 5.9, 8.1, 11.27, 11.4, 15.7, 17.4 and 24.2 mg/l. The animals were not fasted prior to exposure to the vapors of the substance. The animals were observed over a 14 day period after exposure.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SPF-Zucht, WIGA, Sulzfeld
- Weight at study initiation: 185±15 g
- Diet: Herilan MRH, H . EGGERSMANN KG, ad libitum
- Water: Tap 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
Exposure concentrations of butyl acrylate were generated by pumping liquid butyl acrylate at constant rates using an infusion pump (UNITA I, B. BRAUN) into glass vaporization flasks heated to 80°C, the vapors were mixed with fresh air and transmitted to the exposure chamber.


CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation chamber made from glass and steel
- Exposure chamber volume: 200 l


TEST ATMOSPHERE
- Brief description of analytical method used: The butyl acrylate air mixture was measured continuously using a flame ionization detector (FID). Apparatus used was FID total hydrocarbons analyzer (CARLO ERBA).
- Samples taken from breathing zone: yes


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.9, 8.1, 11.27, 11.4, 15.7, 17.4 and 24.2 mg/l
No. of animals per sex per dose:
10
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, histopathology
Statistics:
Statistical analysis were made according to Probit-Analysis, D.J. Finney, 1971.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
11.9 mg/L air
Exp. duration:
4 h
Mortality:
No animals died in the low dose group. Two out of 20, 5/20, 11/20, 18/20, 18/20 and 20/20 died in the 8.1, 11.27, 11.4, 15.7, 17.4 and 24.2 mg/l dose groups, respectively.
Clinical signs:
All the animals showed symptoms of toxicity which included strong irritation to mucous membrane and panting.
Body weight:
Dose related decrease in body weight was observed in all animals.
Gross pathology:
Acute dilatation and acute hyperemia in the heart; spotted haemorrhages, slight edema and acute emphysema in lungs were observed in the deceased animals. Similar lesions of lungs as in deceased rats were in the killed animals.

Concentration (mg/l)

Mortality

Analytical

Nominal

Male

Female

24.2

21.6

10/10

10/10

17.4

17.2

10/10

8/10

15.7

15.8

8/10

10/10

11.4

16.2

9/10

2/10

11.27

12.6

2/10

3/10

8.1

9.6

1/10

1/10

5.9

7.2

0/10

0/10

1 . LC50 (4 h) for male and females rats = 11.9 mg/ l air (2275 ppm)

2 . LC50 (1 h) for male and females rats = 47.6 mg / l air (9090 ppm)*

3 . LC50 (4 h) for male rats = 11.2 mg / l air (2140 ppm)

4 . LC50 (1 h) for male rats = 45.0 mg / l air (8555 ppm)*

5 . LC50 (4 h) for female rats = 12.6 mg / l air (2405 ppm)

6 . LC50 (1 h) for female rats = 50.0 mg / l air (9625 ppm)*

* calculated from 4h LC50 values

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
10 300 mg/m³
Quality of whole database:
Study equivalent to OECD 403

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:
other: Basic data given: study report which meets basic scientific principles. Original document not available.
Principles of method if other than guideline:
Male albino rabbits were applied with the undiluted test substance under impervious sheeting on the clipped intact skin of the trunk. The animals were immobilized during the 24-hour contact period. Thereafter, excess fluid was removed to prevent ingestion.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
no data
No. of animals per sex per dose:
The total number of animals was 12.
Control animals:
not specified
Sex:
male
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Clinical signs:
Iritis occurred in the eyes during the 24 hour exposure period with butyl acrylate.
Gross pathology:
Livers were found to be mottled, with prominent acini; kidneys and spleens were congested in victims.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
Study equivalent to OECD 402

Additional information

Oral exposure route:

In an acute toxicity  study conducted by BASF AG (1958) groups of 5 - 10 rats were administered doses of 1840, 2840 and 4510  mg/kg bw by gavage and observed for 7 days for lethality and clinical signs of intoxication. The mortality rate was 1/5, 2/5 and 8/10 in the low, mid and high dose groups, respectively. The LD50 was found to be approx. 3150 mg/kg bw. Clinical symptoms were unspecific: staggering gait, piloerection, diarrhea, and in the high dose group only labored breathing, and abdominal position. At necropsy, hyperemia of the medulla renalis was found in the mid and high dose group animals. In another oral gavage study with male rats, a LD50 of 9050 mg/kg bw was determined (Union Carbide, 1971).

Other acute oral LD50 values in rats, rabbits and mice were described mostly without additional data and ranged between 1800 and 8145 mg/kg bw (Union Carbide 1950, Carpenter 1974, Vernot 1977, BASF AG 1958, Tanii 1982). In addition, four other studies were available, but for three of them reliability was unknown (klimisch 4) and one was considered to be unreliable (klimisch 3).

Inhalation exposure route:

In an acute inhalation study conducted according to a protocol similar to OECD TG 403 groups of 10 Sprague-Dawley rats per sex were exposed by head-nose exposure to vapour concentrations of 2.7, 3.6, 4.96, 6.8, 8.1, 12.1 and 16 mg/L (analyzed) for 4 hours and observed for 14 days (BASF AG 1980). The mortality rate was 0/20, 0/20, 0/20, 1/20, 4/20, 13/20 and 20/20, respectively. Clinical signs of toxicity ranged from no symptoms in the lowest dose group; spasmodically breathing, prone position, irregular gait, eye and nasal discharge and piloerection in the middle dose groups; to dyspnoea, trembling and closed eyelids in the high dose group. At necropsy, acute dilatation and hyperemia of the heart, spotted haemorrhages and acute emphysema in lungs and broaden grey-brown periphery of hepatic lobules were observed in the deceased animals. The 4- hour rat LC50 was 10.3 mg/L.

There are several acute vapour inhalation toxicity studies available involving Sprague-Dawley rats, NMRI mice, and Chinese hamsters conducted by BASF AG (1979) according to an internal method equivalent to OECD guideline 403. The studies were performed with fasted and non-fasted animals, but tests with fasted animals are not taken into consideration for the hazard assessment, since fasting represents a physiological stress situation and is not in accordance with the guideline. Nonetheless, the effect values from the six studies were all in the same range, between 6.4 (hamster, non-fasted) and 13.3 (rat, fasted) mg/L. Other acute inhalation toxicity tests in rats mostly without additional data were performed and reported similar or higher values than reported by the key study. In addition, five other studies were available, but for all of them reliability was unknown (klimisch 4).

Dermal exposure route:

The undiluted substance was applied for 24 hours to the intact skin of rabbits under occlusive conditions. The dermal rabbit LD50 values ranged from 2000 mg/kg to 3024 mg/kg (3.36 mL/kg) body weight (Union Carbide 1950, Union Carbide 1971). Erythema and necrosis of the skin were apparent. Iritis occurred in the eyes of the exposed rabbits during the 24 hour exposure period with butyl acrylate. At necropsy, livers were found to be mottled and grayish, with prominent acini; kidneys, spleens and intestines as well as their mesenteries were congested in victims. Occasionally bloody urine was found in the deceased animals.

Sokal et al. (1980) reported LDLo values for rat and rabbit of 1700 mg/kg bw, and Vernot et al. (1977) found a dermal LD50 in rabbits of 5660 mg/kg bw. BASF AG (1958) reported a value of >180 mg/kg bw, which was the only dose tested. In addition, two other studies were available, for one of them the reliability was unknown (klimisch 4) and the other was considered to be unreliable (klimisch 3).

Taking all the presented data into consideration, Butyl acrylate was concluded to be of low toxicity after a single ingestion and short-term skin contact. Butyl acrylate is of moderate toxicity after short-term inhalation.

Justification for classification or non-classification

CLP classification (Regulation (EC) No 1272/2008):

- Inhalation route (vapour): Acute Category 4