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Administrative data

Description of key information

No mortality occurred in a well-conducted GLP guideline study (OECD TG 401) at the dose level of 2000 mg/kg. Therefore, the acute oral LD50 of this substance is

considered to be higher than 2000 mg/kg bw.
No mortality occurred in a well-conducted GLP guideline study (OECD TG 402) at the dose level of 2000 mg/kg. Therefore, the acute dermal LD50 of this substance is

considered to be higher than 2000 mg/kg bw.
According to a report on the acute 4-hour inhalation toxicity in rats the acute inhalation LC50 of this substance is considered to be 620 mg/m³. The reliability of this value

is not assignable since no sufficiently detailed data were available for assessment.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Original report is only available in Japanese. The translation is in progress. Therefore, the report is cited by a peer-reviewed OECD SIDS.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Specific details on test material used for the study:
TEST MATERIAL:
Name of test material: 2-(dimethylamino)ethyl methacrylate
Species:
rat
Strain:
other: Crj:CD(SD)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
0 (Vehicle), 500, 1000, 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No deaths occurred in any of the treated groups.
Gross pathology:
At necropsy, raised patches in the forestomach were observed in males of the 2000 mg/kg group.
Other findings:
Histopathologically, papillomatous hyperplasia in the forestomach was apparent.
Interpretation of results:
GHS criteria not met
Executive summary:

A single oral toxicity study revealed a LD50 value of above 2000 mg/kg bw for the substance in both sexes.

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
Remarks:
Restrictions: purity of TS not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
observation period 4 weeks
GLP compliance:
no
Test type:
standard acute method
Specific details on test material used for the study:
TEST MATERIAL:
- Name of test material (as cited in study report): 2-(dimethylamino)ethyl methacrylate
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: S. IVANOVAS GmbH & Co., Med. Versuchstierzuchten K.G., Postfach 7, D-7964 Kißlegg/Allgäu)
- Age at study initiation: males 52 days, females 70 days
- Weight at study initiation: 170-180 g
- Fasting period before study: 15-16 hours
- Housing: single housing in Makrolon cages (Type II)
- Diet: ALTROMIN 1323 (Altromin GmbH, Postfach 285, D-4937 Lage/Lippe) ad libitum except during fasting period
- Water: tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±0.5
- Humidity (%): 60±3
Route of administration:
oral: gavage
Doses:
1.00, 1.26, 1.59, 2.00, 2.52, 3.18, 4.00, 5.04, 6.35 ml/kg
(933, 1176, 1483, 1866, 2351, 2967, 3732, 4702, 5925 mg/kg; calculated from original data using density of 0.933 g/cm³)
No. of animals per sex per dose:
10
Details on study design:
- Duration of observation period following administration: 4 weeks
- Observations: behaviour, food consumption, body weight gain
- Necropsy of survivors performed: yes
Statistics:
Calculation of LD50 according to LITCHFIELD and WILCOXON.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 659 mg/kg bw
Remarks on result:
other: calculated from original data using density of 0.933 g/cm³
Sex:
male
Dose descriptor:
LD50
Effect level:
2 706 mg/kg bw
95% CL:
> 2 333 - < 3 079
Remarks on result:
other: calculated from original data using density of 0.933 g/cm³
Sex:
female
Dose descriptor:
LD50
Effect level:
2 612 mg/kg bw
95% CL:
> 2 333 - < 2 986
Remarks on result:
other: calculated from original data using density of 0.933 g/cm³
Mortality:
Dead occured within 24 hours after administration of the TS (within 1-24 hours after tonoclonic spasms). The lowest dose that caused death was 2.00 ml/kg (1866 mg/kg).
Clinical signs:
Sedation, food consumption decreased, ataxia, dyspnoea, comatose condition, tonoclonic spasms. Surviving animals recovered within 2-4 days.
Gross pathology:
Hemorrhagic mucous membrane of the stomach in dead animals. Survivors showed no pathologic signs.

Acute oral toxicity in rats:

 

Dose*

(mg/kg)

No. of males/females

Decrease in food consumption

(%, group mean)

Decrease in body weight gain

(%, group mean)

Mortality after

24 h

14 d

d 1

d 2

d 14

d 1

d 2

d 14

m

f

m

f

933

10/10

4

0

6

0

2

3

0

0

0

0

1176

10/10

36

6

0

4

6

2

0

0

0

0

1483

10/10

46

4

6

2

4

6

0

0

0

0

1866

10/10

38

6

2

4

2

6

3

3

3

3

2351

10/10

56

26

4

0

0

6

4

5

4

5

2967

10/10

58

20

8

4

8

10

6

6

6

6

3732

10/10

68

31

5

6

4

8

6

7

6

7

4702

10/10

86

48

6

2

8

8

8

8

8

8

5925

10/10

100

-

-

6

-

-

10

10

10

10

* calculated from original data using density of 0.933 g/cm³; m = males, f = females, d = day

Interpretation of results:
Category 5 based on GHS criteria
Executive summary:

The acute oral LD50 in rats was calculataed to be 2612 mg/kg bw based on the results obtained in female rats. The LD50 in female rats is slightly lower than in male rats.

Laut OECD SIDS: LD50 ist 2656 mg/kg bw (beide Geschlechter)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Specific details on test material used for the study:
TEST MATERIAL:
- Name of test material (as cited in study report): Dimethylaminoethyl methacrylate (MADAME)
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: ICO: OFA-SD (IOPS Caw)
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: mean males 255±3 g, mean females 228±8 g
- Housing: in groups of 4 to 7 of the same sex per cage in sterilizable polycarbonate cages (48 x 27 x 20 cm) during the acclimatization period and individually in sterilizable polycarbonate cages (35.5 x 23.5 x 19.3 cm) during the study
- Diet: certified pellet diet "Rats - Mice sustenance ref. A04 C" (U.A.R., 91360 Villemoisson-sur-Orge, France) ad libitum
- Water: filtered tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±20
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The day before treatment, the dorsal area of each animal was clipped with an electric clipper on an area of 6 x 8 cm. Only animals with healthy intact skin were used for the study. The TS in its original form was applied at a dose level of 2000 mg/kg at a volume taking into consideration that the specific gravity (SG) of the TS was 0.933 directly to an area of skin representing approximately 10% (5 x 6 cm for the females and 5 x 7 cm for the males) of the body surface of the animal. This was calculated according to Meeh's formula (AFNOR-TO3-23 Standard, August 1980, France). A hydrophilic gauze patch was then applied to the skin. The TS and the gauze patch were held in contact with the skin for 24 hours by means of an adhesive hypoallergic aerated semi-occlusive dressing attached to a restraining bandage. This dressing prevented the ingestion of the TS by the animal. No residual TS was observed at removal of the dressing.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: The body weight gain of the treated animals was compared to a reference curve of the C.I.T. control animals with the same initial weight.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality was checked frequently just after application of the TS and then at least twice a day during the 14-day observation period. The animals were observed for clinical signs frequently after application of the TS and at least once a day during the observation period. The animals were individually weighed just before application of the TS and then on days 5, 8 and 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occured at the dose level of 2000 mg/kg.
Clinical signs:
Within 72 hrs of application of the test substance, hypokinesia, sedation and dyspnea were observed and had reversed on day 5. Local signs of marked irritations were noted during the study.
Body weight:
The body weight gain of the animals was not influenced by the treatment.
Gross pathology:
The macroscopic examination revealed no abnormalities in the animals sacrificed at the end of the study. Signs of cutaneous irritation had eversed.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test substance administered by dermal route in rats is higher than 2000 mg/kg.
Executive summary:

The LD50 of the test substance administered by dermal route in rats is higher than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

There were various studies on the acute toxicity of the test substance by different administration routes. In total, eleven reports on the acute toxicity via oral, dermal, inhalation or intraperitoneal routes to rats, mice or rabbits were reviewed.

Oral exposure route:

As for oral toxicity, the study by the Ministry for Health and Welfare, Japan (MHW Japan, 1998) was considered to be the most reliable because it was well conducted according to OECD TG 401 in compliance with GLP and was therefore identified as the key study. In this study, SD rats (5/sex/dose) were administered doses of 0 (vehicle), 500, 1000, 2000 mg/kg bw by gavage. Although raised patches and papillomatous hyperplasia in die forestomach were observed, no death occurred in the 2000 mg/kg bw dose group. The LD50 after oral application is considered to be greater than 2000 mg/kg bw. This result is supported by an acute oral toxicity study in rats from Roehm, where an LD50 of 2659 mg/kg was determined (Roehm, 1978).

Two other acute oral LD50 values in rats were reported to be equal to 1550 mg/kg bw (Kirk-Othmer, 1978 -1984) or greater than 1751 mg/kg bw (Izmerov, 1982). The reliability of these two studies is not assignable.

Dermal exposure route:

As for dermal toxicity, the study on rats by Atochem was identified as the key study (Atochem, 1992). This study was conducted in accordance with OECD TG 402 in compliance with GLP. At 2000 mg/kg dose in rats, no mortality was observed although symptoms of hypokinesia, sedation, dyspnoea and skin irritation were observed. The dermal acute lethal dose is considered to be greater than 2000 mg/kg bw.

Inhalation exposure route:

Due to low vapour pressure (0.58 hPa at 20°C) and the exclusion of spray applications, inhalation is not a relevant pathway of exposure. Regarding acute toxicity by inhalation, a LC50 of 0.62 mg/L (620 mg/m³) after a 4-hour inhalation of the test substance in rats and a LC50 of 1.8 mg/L (1800 mg/m³) after a 2-hour inhalation of the test substance in mice were reported (Izmerov, 1982). However, the reliability of these values is not assignable since no sufficiently detailed data were available for assessment.

Other exposure routes (intraperitoneal):

As to the acute toxicity by intraperitoneal (i.p.) administration, LC50 values ranging from 25 mg/kg bw to 310 mg/kg bw were reported in three studies with rats or mice (Kirk-Othmer, 1978 -1984; Paulet, 1975; NTIS, 1986). The severest value for the intraperitoneal acute toxicity was 25 mg/kg bw for mice (NTIS, 1986).

Justification for classification or non-classification

In the key study for acute oral toxicity the LD50 of the test substance was determined to be higher than 2000 mg/kg (MHW Japan, 1998). Based on these data, no classification of the test substance is required. There are no reliable data considering acute inhalation toxicity. Based on the data from acute dermal toxicity studies no classification of the test substance is required. Accordingly, the following classification of the test substance concerning acute toxicity is proposed:

GHS classification according to Annex I 1272/2008 CLP (EU GHS):

- Oral route: No classification

- Dermal route: No classification.

- Inhalation route: No classification.

However, the test substance is listed in Annex I of the Directive 67/548/EEC and in Annex VI of CLP regulation 1272/2008 (EU-GHS). Accordingly, in spite of the contradictory database, the test substance has to be classified as follows:

GHS classification according to Annex VI 1272/2008 CLP (EU GHS):

- Oral route: Acute toxicity - Cat. 4*

- Dermal route: Acute toxicity - Cat. 4*

- Inhalation route: No classification.