Registration Dossier

Administrative data

Description of key information

The oral LD50 was ca. 1144 mg/kg bw in rats. A LD50 value of 400 < LD50 < 640 mg/kg bw was observed for rabbits after acute dermal exposure. No mortality after 8 h exposure to the saturated vapour-air-mixture. 

Key value for chemical safety assessment

Acute toxicity: via oral route

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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:
preGLP, pre-OECD guidelines, observation period 7 days
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
BASF-test: The study was conducted according to an internal BASF method which in principle is comparable to the OECD Guideline 401. A test group consisting of 5 animals/sex was treated by single gavage application with an aqueous solution of the test substance. The animals were observed for mortality and for clinical symptoms of toxicity. At the end of the observation period of 7 days, the surviving animals were sacrificed for the purpose of necropsy; animals that died during the observations period also were subjected to necropsy.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: US rats
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: the test substance was administered as a 2-20% aqueous solution.
Doses:
200, 400, 800, 1000, 1250 and 1600 µl/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 144 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (original value is 1100 µl/kg bw)
Mortality:
200 and 400 µl/kg bw: no deaths after 7 days
800 µl/kg bw: 2/10 animals after 7 days
1000 µl/kg bw: 7/10 animals after 7 days
1250 µl/kg bw: 5/10 animals after 7 days
1600 µl/kg bw: all animals died after 7 days
Clinical signs:
Tonic cramps
Body weight:
Normal body weight growth
Gross pathology:
No abnormal findings
Interpretation of results:
Category 4 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 144 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Low attainable concentration due to the low vapour pressure, when the test substance is evaporated at 20°C, which is below cut off values for classification / any limit concentration.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
BASF-test: Test was performed in principle as described in OECD Guideline 403. The test demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at the temperature chosen for vapour generation (20°C). 3 rats per sex were exposed sequentially to the vapours, generated by bubbling 200 l/h air through a substance column of about 5 cm above a fritted glassdisc in a glass cylinder for 8 h. The documentation of clinical signs was performed over a period of 7 days. In order to verify the results, the test was repeated once. Calculatted saturated vapour concentration for 1-methylimidazole: 0.0412*MW*VP = 0.0412 * 82.1038 g/mol * 0.3514 hPa = 1.2 mg/L)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
8 h
Concentrations:
saturated vapour at 20 ºC (calculated saturated vapour concentration: 1.2 mg/L)
No. of animals per sex per dose:
3
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: days 1 and 7
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC0
Effect level:
other: saturated vapour at 20 ºC (calculated saturated vapour concentration: 1.2 mg/L)
Based on:
test mat.
Exp. duration:
8 h
Mortality:
None of the animals died.
Clinical signs:
Signs of escape behaviour and distinct irritation of mucous membranes.
Body weight:
Normal body weight growth.
Gross pathology:
No effects.
Interpretation of results:
other: The inhalation of a saturated vapour-air-mixture represents an unlikely acute hazard.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
1 200 mg/m³

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:
comparable to guideline study with acceptable restrictions
Remarks:
pre-GLP, pre-OECD guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
BASF-test (application on intact skin, for 24 hours, under occlusion)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
Vienna White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: M .GAUKLER, 6050 Offenbach
- Weight at study initiation: males 3.1 kg, femalses 3.0 kg
- Diet: Ssniff K, standard diet for rabbits and guinea pigs (Fa. INTERMAST GMBH, Soe) and Ovator Solikanin (Fa. Muskator-Werke, Düsseldorf) ad libitum
- Water: ad libitum
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 110 cm2 (clipped skin)
- Type of wrap if used: inert foil fixed with a adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water or a water/Lutrol solution
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
250, 400 and 640 mg/kg bw
No. of animals per sex per dose:
3 (250 and 640 mg/kg bw) and 6 (400 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: 1 h and 1, 2, 7 and 15 days
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
400 - 640 mg/kg bw
Based on:
test mat.
Mortality:
250 mg/kg bw: no mortality occurred
400 mg/kg bw: 2/6 males and 0/6 females
640 mg/kg bw: 1/3 males and 3/3 females
Clinical signs:
Resorptive intoxications symptoms:
apathy, accelerated breathing, spasms, salivation, excess lacrimation, narrowed pupils

Local irritation symptoms:
Besides obvious redness of the skin and edema at the end of the observation period necrotic changes in the skin and persistent edema were observed.
Body weight:
No effects
Gross pathology:
Animals which died during the study: dilatation of the heart and hyperemia in the lungs. In the animals which were sacrified at the end of the study no effects were observed.
Other findings:
Skin findings: firstly, erythema and edema. During the observation period necrosis was observed.
Interpretation of results:
Category 3 based on GHS criteria
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
400 mg/kg bw

Additional information

Oral toxicity

In an oral toxicity study, according to internal standard (a protocol comparable to OECD guideline 401), US-rats (5/sex/dose) were administered 1-methylimidazol at 200, 400, 800, 1000, 1250 and 1600 µl/kg bw (equivalent to ca. 208 to 1664 mg/kg bw) by single dose (gavage) followed by a 7-day observation period (1966). No mortality was observed after exposure to 200 and 400 µl/kg bw. At 800 µl/kg bw, 2/10 animals died after 7 days, at 1000 µl/kg bw, 7/10 animals died after 7 days, at 1250 µl/kg bw, 5/10 animals after 7 days and at 1600 µl/kg bw, all animals died after 7 days. The LD50 was ca. 1144 mg/kg bw. Clinical signs included tonic cramps. No abnormal findings were noted at necropsy.

 

Dermal toxicity

In an acute dermal toxicity study, according to internal standard (a protocol comparable to OECD guideline 402), male and female Vienna White rabbits were exposed to 250 (3 animals/sex), 400 (6 animals/sex) and 640 (3 animals/sex) mg/kg bw 1-methylimidazol by dermal application (area of exposure: 110 cm2 (clipped skin)) for 24 hours under an occlusive dressing followed by a 15 day observation period (1981). Clinical signs included: apathy, accelerated breathing, spasms, salivation, excess lacrimation and narrowed pupils. No mortality occurred at 250 mg/kg bw, at 400 mg/kg bw 2/6 males and 0/6 females died and at 640 mg/kg bw 1/3 males and 3/3 females died. The LD50 value was determined to be: 400 < LD50 < 640 mg/kg bw. In animals which died during the study dilatation of the heart and hyperemia in the lungs was observed.

 

Inhalation toxicity

In an acute inhalation toxicity study, according to internal standard (a protocol comparable to OECD guideline 403) in which rats (n=3/sex) were exposed to a saturated vapour of 1-methylimidazol at 20 ºC for 8 hours, no deaths were observed during a 7-day observation period (1966). Due to the low vapour pressure, the technically highest attainable concentration is approximately 1.2 g/m3 when the test substance is evaporated at 20°C (concentration not determined), which is below cut off values for classification / any limit concentration.

Justification for classification or non-classification

The available acute oral and dermal toxicity data warrants classification Cat. 4; H302 and Cat. 3; H311 according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.