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Description of key information

The acute oral toxicity of 3-Methylpyrazole is greater than 300 and smaller than 2000 mg/kg.
The acute inhalation LC50 for 3-Methylpyrazole is greater than 28000 mg/cm3 (highest technically achievable concentration).

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:
2012-06-06 - 2012-11-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The GLP study was conducted according to an internationally accepted guideline. All study parameters are based on the specific guideline.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
CD-1
Sex:
female
Details on test animals or test system and environmental conditions:
Species / Strain / Stock Rat (Rattus norvegicus) / CD / Crl: CD(SD)

Supplier Charles River Laboratories,
Research Models and Services,
Germany GmbH
Sandhofer Weg 7
97633 Sulzfeld
Germany

Selection of species In accordance with OECD 423; the rat is the preferred species

Sex Female

Number of animals 9 female animals

Groups 6 animals for the dose levels of 300 mg/kg b.w., 3 animals for the dose level of 2000 mg/kg b.w.

Body weight
(at start of administration) 176 - 209 g

Age
(at start of administration) Approx. 8 weeks

Route of administration:
oral: gavage
Vehicle:
other: 0.8% aqueous hydroxypropylmethylcellulose (for the dose level of 300 mg/kg only)
Doses:
300 and 2000 mg/kg b.w.
No. of animals per sex per dose:
6 animals for the dose levels of 300 mg/kg b.w., 3 animals for the dose level of 2000 mg/kg b.w.
Control animals:
no
Details on study design:
Principle of the ATC-test method
This procedure permits the identification of the 'acute-toxic-class' (ATC), a measurement of the acute toxicity by the oral route.
The test item is administered orally by gavage at a single dose level to a group of experimental animals. The dose used is selected from a series of defined dose levels. Due to the small number of animals used with this method, there is no need to perform a range finding test.
The test item is tested using a stepwise procedure, each step uses three female animals. The results of each step determine if:
o no further testing is needed,
o the next step will be performed with the same dose,
o the next step will be performed at the next higher or next lower dose level.

Starting at 2000 mg/kg b.w.
o Testing at 2000 mg/kg b.w.:
Three animals of one sex (preferably females) are treated at 2000 mg/kg b.w. (first step). If two to three animals die, testing at 300 mg/kg b.w. should be performed.
If no to one animal dies, the test item should be retested (second step) with 2000 mg/kg b.w., using three animals of the same sex.
If, in this second step, two to three animals die, testing at 300 mg/kg b.w. should be performed. If, in this second step, no to one animal dies, no further testing is necessary.

o Testing at 300 mg/kg b.w.:
If the results of the test at 2000 mg/kg b.w. indicate the need for further testing at a lower dose level.
Three female animals are treated at 300 mg/kg b.w. (first step).
If two or three animals die, testing at 50 mg/kg b.w. should be performed.
If fewer than two animals die, the test item should be retested (second step) with 300 mg/kg b.w., using three animals of the same sex.
If, in this second step, two or three animals die, testing at 50 mg/kg b.w. should be performed. If, in this second step, no to one animal dies, no further testing is necessary.



o Testing at 50 mg/kg b.w.:
If the results of the test at 300 mg/kg b.w. indicate the need for further testing at a lower dose level.
Three female animals treated at 50 mg/kg b.w. (first step).
If two or three animals die, testing at 5 mg/kg b.w. should be performed.
If fewer than two animals die, the test item should be retested (second step) with 50 mg/kg b.w., using three animals of the same sex.
If, in this second step, two or three animals die, testing at 5 mg/kg b.w. should be performed. If, in this second step, no to one animal dies, no further testing is necessary.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
yes, at 2000 mg/kg bw. all animals died prematurely
Clinical signs:
Under the present test conditions, a single oral administration of 300 mg 3-Methylpyrazole/kg b.w. did not reveal any signs of toxicity. No premature death was recorded within the test period. No signs or abnormalities were noted at necropsy.
A single oral administration of 2000 mg 3-Methylpyrazole/kg b.w. revealed reduced motility, ataxia, reduced muscle tone, dyspnoea and dorsal position in all 3 of 3 animals and lateral position in 2 animals. All animals died prematurely.
Body weight:
All surviving animals gained the expected body weight.
Gross pathology:
No signs or abnormalities were noted at necropsy.
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study 3-Methylpyrazole was examined for acute toxicity after a single oral administration to rats.
Under the present test conditions, a single oral administration of 300 mg 3-Methylpyrazole/kg b.w. did not reveal any signs of toxicity. No premature death was recorded within the test period. No signs or abnormalities were noted at necropsy.
A single oral administration of 2000 mg 3-Methylpyrazole/kg b.w. revealed reduced motility, ataxia, reduced muscle tone, dyspnoea and dorsal position in all 3 of 3 animals and lateral position in 2 animals. All animals died prematurely. No signs or abnormalities were noted at necropsy.
All surviving animals gained the expected body weight.
The LD50 value was ranked between 300 and 2000 mg/kg b.w.
Executive summary:

In this study 3-Methylpyrazole was examined for acute toxicity after a single oral administration to rats. Under the present test conditions, a single oral administration of 300 mg 3-Methylpyrazole/kg b.w. did not reveal any signs of toxicity. No premature death was recorded within the test period. No signs or abnormalities were noted at necropsy. A single oral administration of 2000 mg 3-Methylpyrazole/kg b.w. revealed reduced motility, ataxia, reduced muscle tone, dyspnoea and dorsal position in all 3 of 3 animals and lateral position in 2 animals. All animals died prematurely. No signs or abnormalities were noted at necropsy. All surviving animals gained the expected body weight. The LD50 value was ranked between 300 and 2000 mg/kg b.w.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The study is GLP compliant and has Klimisch score 1.

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
Study period:
1987-08-06 - 1988-01-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study parameters are not described in detail (size of test chamber, concentration of test substance in the test chamber).
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
inhalation: gas
Type of inhalation exposure:
not specified
Vehicle:
air
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
2065, 3380, 4180, 7930, 18750, 28110 mg/m3
No. of animals per sex per dose:
5
Control animals:
no
Sex:
female
Dose descriptor:
LC50
Effect level:
> 28 000 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality was observed.
Clinical signs:
other: No abnormal clinical signs were observed.
Gross pathology:
No macroscopic organ alterations were observed.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 for 3-Methylpyrazole is greater than 28000 mg/m3 (highest technically achievable concentration).
Executive summary:

The acute inhalation LC50 for 3-Methylpyrazole is greater than 28000 mg/m3 (highest technically achievable concentration).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
28 000 mg/m³
Quality of whole database:
The study is reliable and has Klimisch score 2.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Both available studies are reliable with Klimisch scores 1 -2 and sufficient for classification and labelling purposes. No further testing is required.


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – inhalation endpoint
Only one study available.

Justification for classification or non-classification

3 -Methylpyrazole has to be classified as Acute Tox. 4. 3-Methylpyrazole is not classified as toxic via inhalation route.