tert-butyl acrylate

Endpoint summary

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

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 or test system 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:

other: Dyspnoea, convulsive chewing, spastic gait, saltatory spasms, rolling convulsions, abdominal/lateral position several hours after application.

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

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 or test system 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 air

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 or test system 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:

other: 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).