Registration Dossier

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test 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

Test material

Constituent 1
Chemical structure
Reference substance name:
3-methylpyrazole
EC Number:
215-925-7
EC Name:
3-methylpyrazole
Cas Number:
1453-58-3
Molecular formula:
C4H6N2
IUPAC Name:
3-methyl-1H-pyrazole
Test material form:
other: liquid

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

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.