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Administrative data

Description of key information

Oral (comparable to OECD 401), rat: LD50= 404 mg/kg bw 
Inhalation (comparable to OECD 403), rat, 4 h exposure: LC50 = 2.7 mg/L
Dermal (comparable to OECD 402), rabbit: LD50 = 252.5 mg/kg bw

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. Only animals who died during the observation period were necropsied. Lack of data on test substance (no analytical purity).
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
only dead animals were necropsied; no histopathology
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms
- Weight at study initiation: 200-300 g
- Fasting period before study: 18 h
- Housing: during the test period the animals were housed individually in stainless steel wire bottomed cages.
- Diet: Fisher Rat Chow; ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0-22.2
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
DOSAGE PREPARATION: 1.0 mL test material was diluted to 10.0 mL with water.

MAXIMUM DOSE VOLUME APPLIED: 0.6 mL/kg bw

Doses:
0.25 mL/kg bw corresponding to 252.5 mg/kg bw
0.35 mL/kg bw corresponding to 353.5 mg/kg bw
0.50 mL/kg bw corresponding to 505.0 mg/kg bw
0.55 mL/kg bw corresponding to 555.5 mg/kg bw
0.60 mL/kg bw corresponding to 606.0 mg/kg bw

Based on the density of Sipomer MCA: 1.01 g/cm³
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: daily
- Frequency of weighing: after fasting; surviving animals were weighed at the end of the 14-day observation period.
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs
Statistics:
The defined oral LD50 was calculated by the Litchfield-Wilcoxin method of Probit Analysis (J. Pharmacology and Experimental Therapeutics 96: 99-115, 1949).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
404 mg/kg bw
Based on:
test mat.
95% CL:
343.4 - 464.6
Mortality:
252.5 mg/kg bw: no animals died
353.5 mg/kg bw: 2 males and 2 females died
505.0 mg/kg bw: 2 males and 3 females died
555.5 mg/kg bw: 4 males and 4 females died
606.0 mg/kg bw: 5 males and 5 females died
Clinical signs:
other: No clinical signs were noted.
Gross pathology:
Necropsy revealed pulmonary haemorrhages (only dead animals were necropsied). Incidences:
353.5 mg/kg bw: 1 female
505.0 mg/kg bw: 1 male
555.5 mg/kg bw: 4 males, 2 females
606.0 mg/kg bw: 2 males, 1 females

Table 1. Acute oral toxicity.

 

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

252.5

0/0/0

---

---

0

353.5

2/0/5

---

Day 2

40

505.0

2/0/5

---

Day 3 - Day 4

40

555.5

4/0/5

---

Day 2

80

606.0

5/0/5

---

Day 2

100

Females

252.5

0/0/0

---

---

0

353.5

2/0/5

---

Day 3

40

505.0

3/0/5

---

Day 2 - Day 3

60

555.5

4/0/5

---

Day 2 - Day 3

80

606.0

5/0/5

---

Day 2- Day 4

100

LD50 = 404 mg/kg bw

                                                                                           

* first number = number of dead animals                                   

second number = number of animals with clinical signs           

third number = number of animals used
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute Oral 4, H302
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
404 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given. No details on analytical purity of the test substance. Limited details on inhalation exposure as well as on test animals and environmental conditions.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
no details on analytical purity of the test substance; limited details on inhalation exposure as well as on test animals and environmental conditions
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Remarks on duration:
pre-study: 15 min - 1 h
Concentrations:
pre-study:
1 h: 1576 ppm corresponding to 8.5 mg/L
30 min: 1810 ppm corresponding to 9.8 mg/L
15 min: 1966 ppm corresponding to 10.6 mg/L

main study:
4 h: 1000 ppm corresponding to 5.4 mg/L
4 h: 500 ppm corresponding to 2.7 mg/L
4 h: 250 ppm corresponding to 1.4 mg/L

Dose calculation was based on a molecular weight of 130.14 g/mol and a molar volume of 24.1 L/mol (at 20 °C).
No. of animals per sex per dose:
6
Control animals:
no
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 2.7 mg/L air
Based on:
test mat.
95% CL:
ca. 1.9 - ca. 3.8
Exp. duration:
4 h
Remarks on result:
other: based on a molecular weight of 130.14 g/mol and a molar volume of 24.1 L/mol (at 20 °C)
Mortality:
pre-study:
1 h (8.5 mg/L): all animals died
30 min (9.8 mg/L): 1 animal died
15 min (10.6 mg/L): no animals died

main study:
4 h (5.4 mg/L): all animals died
4 h (2.7 mg/L): 3 animals died
4 h (1.4 mg/L): no animal died
Clinical signs:
other: Within 30 min exposure to 9.8 mg/L of the test substance, animals showed laboured breathing at 10 min. Animals exposed to 8.5 and 10.6 mg/L did not show clinical signs of toxicity during the 1 h or 15 min exposure period, respectively. After 4 h exposure
Body weight:
All surviving animals showed a weight gain after exposure to the test substance at different concentrations.
Gross pathology:
After exposure to the test substance for 30 min and 1 h, rats dying prior to study termination had bright red livers and gas-filled intestinal tract. Rats surviving to study termination after 15 and 30 min exposure had no remarkable findings.
After 4-h exposure, rats dying prior to scheduled termination had slight haemorrhage of lungs and blood in intestines. For rats surviving until scheduled termination, 2 of 3 rats at 2.7 mg/L had areas of focal consolidation scattered throughout the lungs. All others showed nothing remarkable.
Other findings:
- Other observations:
1 h (8.5 mg/L): irritation of eyes at 10 min; irritation of extremities at 35 min
30 min (9.8 mg/L): irritation of eyes at 5 min; irritation of extremities at 25 min
15 min (10.6 mg/L): irritation of eyes at 5 min; irritation of nose at 10 min

4 h (5.4 mg/L): irritation of eyes at 20 min; irritation of extremities at 25 min
4 h (2.7 mg/L): irritation of eyes at 5 min; irritation of extremities at 1-1/2 h
4 h (1.4 mg/L): irritation of eyes; irritation of extremities at 2-1/2 h

Exposure to 1.4 mg/L or approximately 10% of saturated vapour for a few minutes may cause ocular irritation. A longer exposure to this vapour concentration may cause skin irritation. Experimentation with rats indicates that prolonged exposure to this vapour could lead to irritation of the mucous membranes and skin and pulmonary injury.

Table 1. Acute inhalation toxicity

Exposure time

Dose
[mg/L]

Toxicological results*

Observation of clinical signs

Time of death

Mortality (%)

Pre-study

1 h

8.5

6/0/6

---

Days 1 and 2

100

30 min

9.8

1/6/6

at 10 min

Day 1

17

15 min

10.6

0/0/6

---

---

0

Main study

4 h

5.4

6/6/6

at 2 h

Days 1 and 2

100

4 h

2.7

3/6/6

at 4 h

Days 1 and 3

50

4 h

1.4

0/0/6

at 4 h

---

0

LC50 = 2.7 mg/L

*first number = number of dead animals

second number = number of animals with clinical signs

third number = number of animals used

Table 2. Body weight changes

Exposure time

Dose [mg/L]

Weight Change*

Pre-study

1 h

8.5

N/A

30 min

9.8

+++++

15 min

10.6

++++++

Main study

4 h

5.4

N/A

4 h

2.7

+++

4 h

1.4

++++++

*all surviving animals

+ = animals with weight gain


Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
CLP: Acute Inhal 3, H331
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
2 700 mg/m³ air
Physical form:
inhalation: vapour

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: Comparable to guideline study with acceptable restrictions. No details on analytical purity of the test substance. Occlusive test conditions and limited details on test animals and environmental conditions.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no details on analytical purity of the test substance; occlusive test conditions; limited details on test animals and environmental conditions
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: animals were housed in immobilization devices in inhalation chambers with heads protruding into the study room to prevent inhalation of the substance. After treatment, animals were returned to their standard housing.

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped trunk of the rabbit under a cotton pad
- Type of wrap if used: the entire trunk was then wrapped in an impervious Vinylite covering.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was washed.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 0.125, 0.25 and 0.5 mL/kg
Duration of exposure:
24 h
Doses:
0.125 mL/kg bw corresponding to 126.25 mg/kg bw
0.25 mL/kg bw corresponding to 252.5 mg/kg bw
0.5 mL/kg bw corresponding to 505 mg/kg bw

Based on a test substance density of 1.01 g/cm³.
No. of animals per sex per dose:
4
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, body weight
Statistics:
The LD50 value was calculated via the probit method.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 252.5 mg/kg bw
Based on:
test mat.
95% CL:
ca. 171.7 - ca. 373.7
Remarks on result:
other: based on a density of 1.01 g/cm³
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 0.25 mL/kg bw
Based on:
test mat.
95% CL:
0.17 - 0.37
Mortality:
126.25 mg/kg bw: no animal died
252.5 mg/kg bw: 2 animals died
505.0 mg/kg bw: all animals died
Clinical signs:
other: No clinical signs of toxicity were observed in the animals at any dose level.
Gross pathology:
At gross pathology, mottled liver was found.
Other findings:
- Other observations:
No skin irritation was observed in the surviving animals treated with 252.5 and 505 mg/kg bw.

Table 1. Acute dermal toxicity

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

126.25

0/0/4

---

---

0

252.5

2/0/4

---

Day 1

50

505

4/0/4

---

Day 2

100

LD50 = 252.5 mg/kg bw

  *first number = number of dead animals

second number = number of animals with clinical signs

third number = number of animals used

Table 2. Body weight changes

Dose [mg/kg bw]

Weight Change*

126.25

+++-

252.5

+-

505

N/A

*all surviving animals;

+ = animals with weight gain

- = animals with weight loss

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
CLP: Acute dermal 3, H311
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
252.5 mg/kg bw

Additional information

Oral

In an acute oral toxicity study, rats were administered 2-methoxyethyl acrylate via gavage (Shapiro, 1980). 5 rats per sex and dose received the following dose levels: 252.5, 353.3, 505.0, 555.5, 606.0 mg/kg bw. The mortality was 0, 2, 2, 4 and 5 for males and 0, 2, 3, 4 and 5 for females, respectively, listed by increasing dose levels. Autopsy of dead animals revealed pulmonary haemorrhages. No clinical signs were noted. Based on the results, the oral LD50 in rats was 404 mg/kg bw.

The acute toxicity of the test substance was further assessed in a study similar to OECD 401, in which 5 male rats per group received the test substance via oral gavage at dose levels of 252.5, 1010 and 2020 mg/kg bw (Union Carbide Corporation, 1968). Mortalities were observed in 4/5 animals and 5/5 animals treated with 1010 and 2020 mg/kg bw, respectively. No mortalities were observed in animals administered the lowest dose (252.5 mg/kg bw). However, at this dose level, sluggish behaviour was observed in the animals during the 14-day observation period. In all surviving animals of the 252.5 and 1010 mg/kg bw/day, no effects on body weights were noted. At necropsy, congestion was observed in the lungs and the abdominal viscera of treated animals. Based on the probit method, the oral LD50 value in rats was calculated to be 818 mg/kg bw.

 

Inhalation

The acute inhalation toxicity of 2-methoxyethyl acrylate was investigated in male rats using a whole body exposure system (Union Carbide Corporation, 1968). In a preliminary test, 6 animals per group were exposed to the test substance at target concentrations of 10.4, 9.6 and 8.4 mg/L for periods of 15 min, 30 min and 1 h, respectively. Since mortalities already occurred at 9.6 mg/L, concentrations used in the main study were lowered to 5.3, 2.7 and 1.3 mg/L and animals (6 per concentration) were exposed to the test substance for 4 h. At 2.7 and 5.3 mg/L, mortalities were observed between Days 1 and 3 in 3/6 and 6/6 animals, respectively. No mortality occurred in animals treated with 1.3 mg/L up to the end of the 14-day observation period. Clinical signs observed in the animals involved swollen abdomen, laboured breathing and gasping. Furthermore, irritation of the eyes, nose and extremities was noted during exposure to the test substance. Necropsy of rats dying during the study revealed slight haemorrhage of lungs and blood in intestines. In two of the three surviving rats at 2.7 mg/L areas of focal consolidation scattered throughout the lungs were observed at necropsy. All others showed nothing remarkable. Body weights in all surviving animals were not affected by treatment. Based on the results, the LC50 value in rats was 2.7 mg/L.

 

Dermal

The acute dermal toxicity of 2-methoxyethyl acrylate was assessed in a study similar to OECD 402 at dose levels of 126.25, 252.5 and 505 mg/kg bw (Union Carbide Corporation, 1968). The undiluted test substance was applied for 24 h to the clipped trunk of 4 rabbits per dose under occlusive conditions (Union Carbide Corporation, 1968). After 24 h exposure, test substance was removed by washing the treated skin area and animals were observed during a period of 14 days. Mortality occurred at dose levels of 252.5 and 500 mg/kg bw in 2/4 and 4/4 animals, respectively. No clinical signs were observed in any treated animal during the study, but skin irritation was noted in all surviving animals treated with 252.5 and 505 mg/kg bw. Necropsy revealed mottled liver in the treated animals. At 126.25 mg/kg bw, 3/4 animals showed body weight gain and one animal exhibited a loss in body weight. Of the 2 surviving animals treated with 252.5 mg/kg bw, one showed gain and one showed loss in body weight. Based on the results, the dermal LD50 value in rabbits was determined to be 252.5 mg/kg bw.

Justification for classification or non-classification

Harmonised classification


2-methoxyethyl acrylate was inserted into the ATP15. The following classification applies:



  • Acute Oral Tox. 4 - H302: Harmful if swallowed

  • Acute Inhalation Tox. 3 - H331: Toxic if inhaled


 


Details:


Acute toxicity via Oral route:


Based on the available information, the substance is classified under category 4 according to the CLP and the GHS as the lowest LD50 (rats) is 404 mg/kg bw.


 


Acute toxicity via Inhalation:


Based on the available information, the substance is classified under category 3 according to the CLP and the GHS as the lowest LC50 (rats) is 2.7 mg/L.


 


Self-classification:


In addition to the Harmonised classification, the other acute-related toxicity hazards have been assessed:


 


Acute toxicity via Dermal route:


Based on the available information, the test item is classified under category 3 according to the CLP as the LD50 (rabbits) is 252.5 mg/kg bw.


 


Specific target organ toxicity: single exposure (Oral):


The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects other than mortality were observed immediately or delayed after exposure. No classification is required. 


The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study. 


Specific target organ toxicity: single exposure (Dermal):


The classification criteria according to the CLP and the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects other than mortality were observed. No classification is required. 


The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study. 


Specific target organ toxicity: single exposure (Inhalation):


The classification criteria according to the CLP and the GHS as specific target organ toxicant (STOT) – single exposure, inhalation are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects other than mortality were observed. No classification is required. 


The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute inhalation toxicity study. 


Aspiration hazard:


The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.