(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

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

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: WIGA, Sulzfeld
- Age at study initiation: ca. 12 weeks
- Weight at study initiation: mean male animals: 220 g, mean female animals: 180 g
- Fasting period before study: 16 hours before the study, water ad libitum
- Housing: 5 animals in V-II-A-steel-meshcages, typ DK-III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26 °C
- Humidity (%): 45-75%
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE (0.5% aqueous carboxymethyl cellulose)
- Concentration in vehicle: 50%
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: Aqueous formulation corresponds to the physiological medium

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

5000 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: weighing was performed on day 0, day 2-4, day 7 and day 13, clinicals signs were checked after
application during the first 15 minutes, at 15 and 30 minutes, after 1, 2, 4 and 5 hours, then twice on working days and once a day on weekends
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

one male animal died on day 2 and one female animal died on day 1, total 2/10 animals died

Clinical signs:

other: dyspnoe, apathy, staggering, scrubby fur, salivation, bad general condition

Gross pathology:

dead animals:
heart: acute dilatation of the prechambers, acute congestive hyperanemia
stomach/intestine: vascula injection, intestine: atonic
sacrificed animals:
stomach: gastroesophageal vestibule thickened, sporadic agglutination of the gastroesophageal vestibule with the peritoneum.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test item after oral aclministration was found to be greater than 5,000 mg/kg body weight in rats.

Executive summary:

The study was performed to assess the acute toxicity following oral administration in Wistar rats in a study performed similar to OECD 401 guideline (GLP not specified).

Single doses of 5,000 mg/kg body weight of the test material preparations in aqueous carboxymethyl cellulose (5%) were given to 5 male and 5 female fasted rats by gavage. One day after substance administration, 1 male and 1 female rat died. The dead animals showed gross pathology findings at the heart (acute dilatation of the prechambers, acute congestive hyperanemia), stomach (vascular injection) and intestine (atonic). In animals surviving the observation period of 14 days gross pathology findings at the stomach were investigated and included gastroesophageal vestibule thickened, sporadic agglutination of the gastroesophageal vestibule with the peritoneum. Clinical signs observed throughout the study were dyspnoe, apathy, staggering, scrubby fur, salivation and bad general condition. The mean body weights of the administration groups increased throughout the study period.

Under the conditions of this study, the median lethal dose of the test item after oral administration was found to be greater than 5,000 mg/kg body weight in rats.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Jan. 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

yes

Remarks:

occlusive, only 8 days of observation, 72 h observation timepoint missing

GLP compliance:

not specified

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Weight at study initiation: male: 3.18 kg, female: 3.14 kg
- Housing: individually in stainless steel cages with wire mesh floor, 40 cm x 51 cm
- Diet: ca. 130 g per animal and day; Ovator Solikanin 4 MM; Muskator-Werke
- Water: ca. 250 ml per day and animal; tap water and deionized water
- Acclimation period: at least 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26 °C
- Humidity (%): 50 - 80 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

at least 15 h before exposure

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of the same animals

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

8 days

Number of animals:

2 animals

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of the exposure with lutrol and lutrol/water (1:1)
- Time after start of exposure: after 4 hours of exposure


SCORING SYSTEM: according to Draize/ as described in OECD guideline 404

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 48 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 48 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 48 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 48 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the substance was not irritating to the skin under the tested conditions. However, mild skin effects were observed.

Executive summary:

The present skin irritation study was performed similar to OECD guideline 404 (GLP not specified, reliability 2) with two Vienna White rabbits (f/m). The animals were treated for 4 h with the undiluted test substance under occlusive conditions and the skin reactions were observed for a period of 8 days. Mild skin effects were seen after exposure. The value for edema formation was 1 over all animals tested and 1 for individual animals. The value for erythema formation was 1.5 over all animals tested and 2 in the first animal and 1 in the second animal. In one animal, erythema formation was not fully reversible at the end of the observation period on day 8.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Principles of method if other than guideline:

BASF-Test
The inhalation hazard test demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at the temperature chosen for vapor generation (usually 20°C). Groups of rats were sequentially exposed to the vapors, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted disc in a glass cylinder for different time periods.
No analytical determination of the atmosphere concentrations was performed. The nominal concentration usually can be calculated as quotient of the amount of the test substance weight loss during exposure. Group-wise documentation of clinical signs was performed over the 14 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period in surviving animals.

GLP compliance:

not specified

Test type:

other: Inhalation Risk Test

Test material

Test material information

Constituent 1

Reference substance name:

(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

EC Number:

256-032-2

EC Name:

(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

Cas Number:

42978-66-5

Molecular formula:

C15 H24 O6

IUPAC Name:

(1-methyl-1,2-ethanediyl)bis[oxy(methyl-2,1-ethanediyl)] diacrylate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Wiga, Sulzfeld, Germany
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 180 - 250 g
- Housing: 3 animals per cage in Becker D III cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 2°C
- Humidity (%): 50+-5 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

see: any other informations on materials and methods

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

7 h

Concentrations:

The dose, based on the a vapor pressure of ca. 0.000044 hPa at 20 °C, computes to ca. 0.00054 mg/l.

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were checked daily for clinical signs
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross-pathology

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.001 mg/L air

Exp. duration:

7 h

Remarks on result:

other: All 12 animals exposed to the test material survived.

Mortality:

no deaths, all 12 animals survived the 14 days post exposure

Clinical signs:

other: wiping of the snout

Body weight:

no data

Gross pathology:

without findings

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

All 12 animals survived the inhalation risk test, where the animals were exposed to a saturated vapor of the test substance (concentration ca. 0.00045 mg/l) for 7 hours.

Executive summary:

The acute inhalation toxicity was investigated in an Inhalation Risk test with rats (reliability 2). The test was performed in principle as described in OECD test guideline 403 (GLP not specified). It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at 20 °C. Young adult laboratory rats, 6 per sex, were exposed sequentially to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 7 hours. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as 0.000545 mg/l based on the vapor pressure. Group-wise documentation of clinical signs was performed over a 14 day study period. All animals survided inhalative exposure and showed no gross pathology findings. Clinical symptoms soley included wiping of the snout throughout expsoure.

Based on the study findings no acute inhalation toxicity can be concluded for animals expsosed to a saturated vapor of the test item.