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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:
guideline study
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.
Key result
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:
other: 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 ora
Gross pathology:
No signs or abnormalities were noted at necropsy.
Interpretation of results:
Category 4 based on GHS criteria
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 - < 2 000 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
Details on test animals or test system and environmental conditions:
Male Wistar rats of a departmental breeding strain with a minimum age of 60 days were used for the study. Before the start of the experiment, the animals lived in an area of 1270 cm3 with 10 individuals each and received food and water (communal tap network) ad libitum.
The ambient temperature was adjustable in the range of 20± 3°C, the humidity was averagely 80 %. The ambient noise level was in the range of 65 -80 dB. The experimental animals had lived under natural light conditions since birth.

The animals used had a mean body mass of 257 ± 19,8 g .
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
The experimental set-up for inhalation tests with one component consists of the following components: compressed air bottle, pressure reducing valve and 2 needle valves from Zimmermann, vaporiser (capillary, frit) with thermostated liquid holder, thermostat, glass transition piece and distributor for the exposure chamber. The vapour-air mixture of the investigated substance was produced by compressed air flow at a total air flow rate of 200 l/h. The inhalation time was 4 hours.

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
Key result
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 air
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.

A study for acute dermal toxicity does not need to be conducted since the substance is classified as corrosive to skin.

Justification for classification or non-classification

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