Registration Dossier

Administrative data

Description of key information

Oral: LD50 = ca. 1047 mg/kg bw (rat, BASF test)

Dermal: LD50: ca. 2000 mg/kg bw (rabbit, occlusive)

Inhalation: LC50 = 7.01 mg/L (rat, 4h)

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
Remarks:
observation period only 7 days
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
In principle, the methods described in OECD Guideline 401 were used. Several groups of 5 and 10 rats per dose respectively were treated by gavage with preparations of the test substance in aqueous solutions with 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
Specific details on test material used for the study:
tert. Butylacrylate, stabilized with 0.02 % hydroquinone
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: own breeding
- Weight at study initiation: males: 112 - 274 g; females 108 - 200 g

ENVIRONMENTAL CONDITIONS
not reported
Route of administration:
oral: gavage
Vehicle:
other: aqueous suspension with traganth
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 - 30 %

MAXIMUM DOSE VOLUME APPLIED: 21.3 cm3/kg bw in the 5581 mg/cm3 treatment
Doses:
approx. 174; 558; 872; 1090; 1395; 1744; 2180; 2790; 5581 mg/kg bw (calculated with a density of ca. 0.87 g/cm3; original data: 200, 640, 1000, 1250, 1600, 2000, 2500, 3200 and 6400 µL/kg bw)
No. of animals per sex per dose:
5 per dose or 5 per sex per dose (see result table)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days (except the treatment group of 1090 mg/kg bw, 20 % concentration: 12 d)
- Frequency of observations: daily on workdays
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 047 mg/kg bw
Based on:
test mat.
Remarks on result:
other: original data: ca 1200 µL/kg bw
Mortality:
Mortality mostly occurred within the first two days after dosing. Animals which survived recovered within day 2 to 4. For more details see table below.
Clinical signs:
Dyspnoea, convulsive chewing, spastic gait, saltatory spasms, rolling convulsions, abdominal/lateral position several hours after application.
Body weight:
not observed
Gross pathology:
Nothing abnormal found on necropsy.

Cumulated mortality:
Dose           1hr      24hrs   48hrs    7days

174 mg/kg      0/5      0/5     0/5      0/5
558 mg/kg      0/5      0/5     0/5      0/5
872 mg/kg      0/15     1/15    2/15     2/15   
1090 mg/kg     0/20     7/20    8/20     11/20     
1395 mg/kg     0/20     12/20   12/20    11/20*
1744 mg/kg     0/10     7/10    7/10     7/10
2180 mg/kg     0/10     7/10    8/10     8/10
2790 mg/kg     0/10     10/10   10/10    10/10
5581 mg/kg     0/10     10/10   10/10    10/10

*12/20 after 12 d

Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 047 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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material: Tertiaerbutylacrylat
- Physical state: clear liquid
- Analytical purity: ca. 99.5 %
- Impurities: stabilized with 15 ppm Hydrochinonmonomethylether
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Wiga, Sulzfeld, D (SPF breeding)
- Weight at study initiation: 185 ± 15g
- Fasting: no
- Diet (ad libitum): Herilan MRH (H. Eggersmann KG, Rinteln, D)
- Water (ad libitum): tap water

ENVIRONMENTAL CONDITIONS
- standardized conditions (unspecified)
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 apparatus: permanent infusion pump (UNITA)
- Exposure chamber volume: 200 L
- Source and rate of air: 3000 - 3100 L/h
- System of generating particulates/aerosols: heatable vaporisator, electric (BASF)
- Treatment of exhaust air: vacuum system with underpressure (9.8 Pa)

TEST ATMOSPHERE
- Brief description of analytical method used: GC HP 5840 A, detector: FID; the atmosphere was absorbed with propanol-2 in two wash bottles in serial configuration; ca. 1 L/min
- Samples taken from breathing zone: yes

CLASS METHOD
- Rationale for the selection of the starting concentration: based on results of an inhalation hazard test
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
8.78; 7.42; 6.30; 5.35; 5.24; 2.96 mg/L (analytical concentrations, vapour)
No. of animals per sex per dose:
20
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations, weighing was performed on d0, d7 and d14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Probit analysis (Finney, 1971)
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
7.01 mg/L air (analytical)
95% CL:
6.65 - 7.45
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
7.3 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: no confidence interval calculated due to inadequate homogeneity
Sex:
male
Dose descriptor:
LC50
Effect level:
6.75 mg/L air (analytical)
95% CL:
6.3 - 7.32
Exp. duration:
4 h
Mortality:
- 8.78 mg/L: 20/20
- 7.42 mg/L: 11/20
- 6.30 mg/L: 3/20
- 5.35 mg/L: 1/20
- 5.24 mg/L: 2/20
- 2.96 mg/L: 0/20
- control: 0/20
See table for details
Clinical signs:
other: Attempts to escape, lid closure, reddish eye and nose discharge, crusted nose and eyes, accelerated or intermittend respiration, high-stepping or unstable gait, squatting posture, reduced motility, tremor, reddish ears and extremities, ruffled fur. Signs
Body weight:
Males of the 7.42 mg/L treatment had a ca. 40% lower weight gain after 14 d if compared with the control. The mean body weight gain of the females in all treatment groups was somewhat lower than the control in the first observation week, while their weight gain was comparable with the control in the second week.
See table for details
Gross pathology:
Animals that died: generally: acute heart dilatation, acute congestion hyperemia; highest dose group: liver with rare and slight broadening of the lobules; lower doses: in some animals slight acute lung dilution
Sacrificed animals: nothing abnormal found

Cumulated mortality

Dose (mg/L)

sex

after 7 d

after 14 d

8.78

male

10/10

10/10

female

10/10

10/10

7.42

male

7/10

7/10

female

4/10

4/10

6.30

male

3/10

3/10

female

0/10

0/10

5.35

male

0/10

0/10

female

0/10

0/10

5.24

male

0/10

0/10

female

2/10

2/10

2.96

male

0/10

0/10

female

0/10

0/10

control

male

0/10

0/10

female

0/10

0/10

Body weight (g)

Dose (mg/L)

sex

at d 0

after 7 d

after 14 d

Body weight gain (14d; g)

8.78

male

192

female

181

7.42

male

196

202

231

35

female

173

184

196

23

6.30

male

182

210

238

56

female

179

289

192

13

5.35

male

181

218

256

75

female

180

185

191

11

5.24

male

187

214

247

60

female

184

187

202

18

2.96

male

188

224

269

81

female

184

193

209

25

control

male

193

220

249

56

female

185

200

213

28

Interpretation of results:
Category 3 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
7 010 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
wide range of treated area size
Qualifier:
no guideline followed
Principles of method if other than guideline:
BASF Test: Before OECD guidelines were established, an internal standardized test was performed. 3 animals per sex per dose were treated for 24 h under occlusive conditions. Observations were performed on weekdays, weighing was performed several times during the observation period of 14 d.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material: Tertiaerbutylacrylat
- Physical state: clear liquid
- Analytical purity: ca. 99.5 %
- Impurities: stabilized with 15 ppm Hydrochinonmonomethylether
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gaukler, D
- Mean weight at study initiation: 2.85 kg (males); 2.92 kg (females)
- Diet (e.g. ad libitum): Ssniff

ENVIRONMENTAL CONDITIONS
not reported
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 108-247 cm2, clipped back

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.4 or 2 g/kg bw.
- Constant concentration used: yes

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Lutrol/ water
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
400, 2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7d (low dose)/ 14 d (high dose)
- Frequency of observations and weighing: observations on workdays, weighing at the beginning and the end of the test
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Mortality:
- 2000 mg/kg: 3/6 animals died
- 400 mg/kg: 0/6 animals died
see table for details
Clinical signs:
2000 mg/kg: apathy, accelerated respiration, screaming
Other findings:
Local effects: obvious primary irritation effects, which were not fully reversible within the observation period; scaling at the end of the observation period.

Cumulative mortality

Dose (mg/kg bw)

sex

after 1 h

after 24 h

after 48 h

after 7 d

after 14 d

2000

male

0/3

1/3

1/3

1/3

1/3

female

0/3

1/3

2/3

2/3

2/3

400

male

0/3

0/3

0/3

0/3

female

0/3

0/3

0/3

0/3

Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral exposure route:

Groups of 5 to 20 rats were administered orally doses of 174, 558, 872, 1090, 1393, 1744, 2180, 2790 or 5581 mg/kg bw. (The original doses were 0.2; 0.64; 1.0; 1.25; 1.6; 2.0; 2.5; 3.2; 6.4 mL/kg bw.) Animals were observed for 7 days after dose administration. The mortality rate was 0/5, 0/5, 2/15, 11/20, 12/20, 7/10, 8/10, 10/10 and 10/10. Mortality mostly occurred within the first two days after dosing. Animals which survived recovered within days 2 to 4. Clinical signs of toxicity were dyspnoea, convulsive chewing, spastic gait, saltatory spasms, rolling convulsions, abdominal/lateral position several hours after dose administration (BASF 1964). The LD50 was determined to be approx. 1047 mg/kg bw.

Dermal exposure route:

Scientifically acceptable studies suitable for the hazard assessment of tert-butyl acrylate are available on rabbits as well as rats. The undiluted test substance was applied for 24 hours under occlusive conditions to the clipped back of rabbits. Test dosages were 400 and 2000 mg/kg bw. Whereas no animal (0/6 rabbits) died in the lower dose, 3 of 6 rabbits died in the 2000 mg/kg group (BASF 1979). The LD50 for rabbits was determined to be approx. 2000 mg/kg bw. Observed clinical symptoms were apathy and accelerated respiration. In addition, obvious primary irritation effects that were not fully reversible within the observation period of 14 days were recorded. The test substance was also administered under occlusive conditions for 24 hours to the clipped back of rats. Test dosages were 1000, 2000, and 4000 mg/kg bw. No animal died within the observation period of 14 days. Clinical signs in all animals of the highest dose group were seen directly after test substance application and included temporary local erythema, apathy, unsteady gait, irregular respiration and tremor (BASF 1979). The LD50 in rats was found to be > 4000 mg/kg bw.

Inhalation exposure route:

Groups of 10 rats per sex were exposed by whole-body exposure to vapour concentrations of 2.96, 5.24, 5.35, 6.30 7.42 or 8.78 mg/L (analytically determined) for 4 hours and observed for 14 days (BASF 1979). The mortality rate was 0/20, 2/20, 1/20, 3/20, 11/20 and 20/20. Mortality occurred within the first day, except in the 5.24 mg/L dose group where one animal died on day 9. Observed clinical symptoms were avoidance response, eyelid closure, eye and nasal discharge, as well as crusty noses and eyes, rapid and irregular respiration, unsteady gait, prone position, piloerection, decreased motility, tremor, reddened ears and extremities. These signs occurred in a concentration dependent manner mainly within the first day. The LC50 was determined to be 7.01 mg/L/4 h (analytically determined).

In inhalation hazard tests, where rats were exposed to a saturated vapour atmosphere (at 20 °C), no mortality occurred in animals exposed for 30 minutes (0/12 rats) whereas all animals (6/6 rats) exposed for 1 hour died (BASF 1979). The animals exhibited severe irritation of the nasal mucosa indicative of a respiratory irritant.

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

Justification for classification or non-classification

Based on an oral LD50 of 1047 mg/kg bw, a dermal LD50 of 2000, and an inhalation LC50 of 7.01 mg/L the substance is classified as Acute Tox. 4 H302: Harmful if swallowed, Acute Tox. 4 H312: Harmful if in contact with skin, and Acute Tox. 3, H331: Toxic if inhaled in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and GHS classification (GHS UN rev.6, 2015).