2-ethoxyethyl methacrylate

Endpoint summary

Description of key information

Acute oral toxicity:
Oral LD50 (rat, male/female) > 2000 mg/kg bw; OECD Guideline 401; GLP compliant, RL1
Supporting studies:
Oral LD50 (mouse, male/female) > 8200 mg/kg bw (95% c.i. 5200 – 13300 mg/kg bw); equivalent to OECD Guideline 401; pre-GLP, RL2 (Basic data given: comparable to guidelines)
Oral LD50 (rat, sex not given) > 5000 mg/kg bw; pre-GLP, RL3 (Documentation insufficient for assessment)
Acute dermal toxicity:
Dermal LD50 (rat, male/female) > 2000 mg/kg bw; OECD Guideline 402; GLP compliant, RL1

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:

1993-07-08 to 1993-07-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24th February 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley ICO: OFA-SD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: app. 6 weeks
- Weight at study initiation: 189 ± 2 g (males), 158 ± 8 g (females)
- Fasting period before study: app. 18 h before and 4 h after dosing
- Housing: in groups of 5 by sex during treatment, polycarbonate cages covered with a stainless steel lid
- Diet (e.g. ad libitum): pelleted diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±20
- Air changes (per hr): app. 13
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

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
- Frequency of observations and weighing: bodyweights were recorded on days 1 (=day of treatment), 5, 8, 15; clinical signs: several times following application; at least once daily thereafter
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: mortality: 0/10

Mortality:

No deaths occurred during the observation period.

Clinical signs:

No clinical signs were observed during the study period.

Body weight:

The body weight gain of the animals had slowed down slightly between days 1 and 5. Thereafter, between days 5 and 8, an increase of the body weight gain was noted. During the second week of the observation period, the body weight gain of the animals was normal.

Gross pathology:

Macroscopic examination of the main organs of the animals sacrificed at the end of the study revealed no apparent abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 for ETMA in rats is > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to OECD guideline 401, adopted 24 February 1987, groups of fasted app. 6 week old Sprague-Dawley ICO: OFA-SD rats (5/sex) were given a single oral dose of ETMA (99.94% a.i.) by gavage at a dose level of 2000 mg/kg bw and observed for 14 days.

No deaths occurred during the observation period.

No clinical signs were observed during the study period.

The body weight gain of the animals had slowed down slightly between days 1 and 5. Thereafter, between days 5 and 8, an increase of the body weight gain was noted. During the second week of the observation period, the body weight gain of the animals was normal. 

Macroscopic examination of the main organs of the animals sacrificed at the end of the study revealed no apparent abnormalities.

 

Oral LD50 (rat, male/female) > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality (Klimisch score = 1). This finding is supported by further studies (pre-GLP, RL2/3).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Study period:

1993-07-06 to 1993-07-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24th February 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley ICO: OFASD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: app. 8 weeks
- Weight at study initiation: 248 ± 8 g (males), 218 ± 7 g (females)
- Fasting period before study: no
- Housing: individually during treatment, polycarbonate cages covered with a stainless steel lid
- Diet (e.g. ad libitum): pelleted diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5x6 cm (females), 5x7 cm (males)
- % coverage: 10% body surface area
- Type of wrap if used: gauze patches were held in contact with the skin by means of
adhesive hypoallergic aerated semi-occlusive dressing and restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no (no residual test substance was observed after patch removal)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

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
- Frequency of observations and weighing: bodyweights were recorded on days 1 (=day of treatment), 5, 8, 15; clinical signs: several times following application; at least once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: necropsy of dead animals

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: 20% mortality at this dose level

Mortality:

2/5 females were found dead 24 hours after treatment without any preclinical signs.

Clinical signs:

No clinical signs and cutaneous reactions were observed during the study.

Body weight:

Between days 1 and 5, a decrease in body weight was noted for 1/5 males, the bodyweight gain was slightly reduced for 1/5 males and 2/5 females. The body
weight of these animals showed an improvement during the remainder of the observation period. This finding was probably due to the stress caused by the experimental conditions and was not attributed to treatment with the test substance
The body weight gain of the surviving animals was normal.

Gross pathology:

Macroscopic examination of the main organs of the animals found dead during the study or sacrificed at the end of the study revealed no apparent abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 for ETMA in rats is >2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study according to OECD guideline 402, adopted 24 February 1987, 5 male and 5 female app. 8 weeks old Sprague-Dawley ICO: OFASD rats were dermally exposed to ETMA (99.94% a.i.) for 24 hours under a semiocclusive dressing to approx. 10% of body surface area at a single dose of 2000 mg/kg bw. Animals then were observed for 14 days.

2/5 females were found dead 24 h after treatment without any preclinical signs.

No clinical signs and cutaneous reactions were observed during the study.

Between days 1 and 5, a decrease in body weight was noted for 1/5 males, the bodyweight gain was slightly reduced for 1/5 males and 2/5 females. The body weight of these animals showed an improvement during the remainder of the observation period. This finding was probably due to the stress caused by the experimental conditions and was not attributed to treatment with the test substance. The body weight gain of the surviving animals was normal.

Macroscopic examination of the main organs of the animals found dead during the study or sacrificed at the end of the study revealed no apparent abnormalities.

 

Dermal LD50 (rat, male/female) > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality (Klimisch score = 1).
Only one study available, but no adverse effects also for other routes at highest dose/conc. tested

Additional information

Reliable, relevant and adequate data are available for the acute oral and dermal toxicity of ETMA.

 

Acute oral toxicity

In an acute oral toxicity study according to OECD guideline 401, adopted 24 February 1987, groups of fasted app. 6 week old Sprague-Dawley ICO: OFA-SD rats (5/sex) were given a single oral dose of ETMA (99.94% a.i.) by gavage at a dose level of 2000 mg/kg bw and observed for 14 days.

No deaths occurred during the observation period. No clinical signs were observed during the study period. The body weight gain of the animals had slowed down slightly between days 1 and 5. Thereafter, between days 5 and 8, an increase of the body weight gain was noted. During the second week of the observation period, the body weight gain of the animals was normal.

Macroscopic examination of the main organs of the animals sacrificed at the end of the study revealed no apparent abnormalities.

Oral LD50 (rat, male/female) > 2000 mg/kg bw.

 

This is supported by the following studies:

In an acute oral toxicity study similar to OECD guideline 401, groups of fasted, CFLP mice (20 - 23 g), 5/sex were given a single oral dose of undiluted ETMA (no information on purity) at dose levels of 0, 4.0, 6.4, 8.0, 10.0, 12.6, 16.0 mL/kg bw, corresponding to ca. 3850, 6160, 7700, 9600, 12100 and 15400 mg/kg bw (based on the density of 0.9632 g/cm³) and observed for 14 days.

Up to a dose of 6.4 mL/kg bw no deaths occurred. 3/5 males and 2/5 females died in the 8 mL/kg bw dose group, 2/5 males and 2/5 females died in the 8.0 mL/kg bw dose group, 5/5 males and 3/5 females died in the 12.6 mL/kg bw dose group, and 4/5 males and 4/5 females died in the 16.0 mL/kg bw dose group.

Signs of reaction to treatment included lethargy and piloerection. These signs were accompanied by fine body tremors in mice at 8 mL/kg bw and by diuresis and increased salivation in mice treated at 10 and 16 mL/kg bw. Recovery of the survivors was apparently complete within 7 days after treatment.

Slightly depressed body weight gains were observed during the first week of observation in mice treated with 16 mL/kg bw, but returned to normal during the second week.

Autopsy of the animals that dies during treatment revealed darkening of the liver and kidneys and injection of vessels of the abdominal viscera. Terminal necropsy findings of the surviving animals were normal. 

Oral LD50 > 8.6 mL/kg bw (95% c.i. 5.4 – 13.8 mL/kg bw), corresponding to 8200 mg/kg bw(95% c.i. 5200 – 13300 mg/kg bw).

 

In an acute oral toxicity study albino rats were given a single oral dose of ETMA(98.8% a.i.)in corn oil at doses of 3000 and 5000 mg/kg bw. The observation period was not given in the study report.

No mortality occurred. In the 3000 mg/kg bw dose group one animal was sensitive to touch 24 h after dosing. In the 5000 mg/kg bw dose group two animals were slightly hunched and sensitive to touch 24 h after dosing. No other signs of toxicity were observed.

The oral LD50 of ETMA in rats was > 5000 mg/kg bw.

Acute inhalation toxicity

A study on acute inhalation toxicity is unjustified in accordance to REACH regulation Annex VIII, column 2 due to exposure considerations as well as in accordance to REACH regulation Annex XI due to scientific considerations. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Furthermore, systemic toxicity relevant to humans did not appear in acute by oral or dermal exposure. Considering the exposure probability and the available information on the intrinsic toxic activity of the substance, an inhalative systemic toxicity risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is not scientifically necessary. Thus, also animal welfare is respected according to REACH intentions.

 

Acute dermal toxicity

In an acute dermal toxicity study according to OECD guideline 402, adopted 24 February 1987, 5 male and 5 female app. 8 weeks old Sprague-Dawley ICO: OFASD rats were dermally exposed to ETMA (99.94% a.i.) for 24 hours under a semiocclusive dressing to approx. 10% of body surface area at a single dose of 2000 mg/kg bw. Animals then were observed for 14 days.

2/5 females were found dead 24 h after treatment without any preclinical signs.

No clinical signs and cutaneous reactions were observed during the study.

Between days 1 and 5, a decrease in body weight was noted for 1/5 males, the bodyweight gain was slightly reduced for 1/5 males and 2/5 females. The body weight of these animals showed an improvement during the remainder of the observation period. This finding was probably due to the stress caused by the experimental conditions and was not attributed to treatment with the test substance. The body weight gain of the surviving animals was normal.

Macroscopic examination of the main organs of the animals found dead during the study or sacrificed at the end of the study revealed no apparent abnormalities.

Dermal LD50 (rat, male/female) > 2000 mg/kg bw.

There are no data gaps in acute toxicity. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.

Consistency of data on read-across chemicals:

A fully reliable study is available for acute oral toxicity of ETMA, so read across is not employed for this endpoint.

The source substances 2-Ethoxyethanol and Methcrylic acid were of similarly low toxicity after single administration. Diluted Methacrylic acid had an LD50 of >2000 mg a.i./kg bw (25% dilution in water or 10% dilution in corn oil). The LD50 of 2-ethoxyethanol was 3000 mg/kg bw in rat and 1400 mg/kg bw in guinea pigs.

The comparable outcome of the acute toxicity studies conducted with the target substance and the source substances supports the read-across hypothesis.

Justification for classification or non-classification

Based on the available data, ETMA does not need to be classified for acute toxicity according to regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.