Registration Dossier

Administrative data

Description of key information

Acute oral toxicity:

LD50: > 2000 mg/kg b.w.

Acute dermal toxicity:

LD50  > 2000 mg/kg b.w.

Acute toxicity inhalation: According to REACH regulation Annex VIII column 2, in addition to the oral route, information shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. The dermal route is considered as the major route of exposure for N-(3(5)-Methyl-lH-pyrazol-l-yl-methyI)-acetamid (P 70/05). In addition, as determined by the particle size distribution study, no particles are smaller than the respirable particle size of 10 μm. In conclusion further testing on vertebrate animals is not justified, thus the conduct of an acute inhalation toxicity study is not required.

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:
2007-04-27 - 2007-06-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an internationally accepted guideline. All study parameters are based on the specific guideline.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
The study room and cages were cleaned and disinfected before the animals arrived. During the study, the room and cages were cleaned at regular intervals. From the randomisation until sacrificing a single animal was housed in a Makrolon® Type 3 cage.
ALTROMIN 1324, pelleted standard diet (ALTROMIN, D-32791 Lage/Lippe) Batch: 161007/1025
With the exception of overnight fasting before oral administration and until 3 hours after administration food was available ad libitum.
Environment: air conditioned,
temperature: 22 - 25 °C,
relative humidity: 33 - 70 %, with a shortly rising on 75 %
artificial light was set to give a cycle of 12 hours light and 12 hours dark; the light phase was from 6.30 a.m. - 6.30 p.m.
The diet is delivered periodically with an accompanying certificate of analysis giving details of nutritional composition and levels of specified contaminants (heavy metals, aflatoxins and pesticides).
Route of administration:
oral: gavage
Vehicle:
other: Tylose MH 1000 in deionised water
Details on oral exposure:
Route of administration: orally, by gavage; using a metal catheter and disposable plastic syringes.
Rationale: The acute toxicity is to determine at first by the oral administration.
Doses:
2000 mg/kg body weight (b.w.)
No. of animals per sex per dose:
6 female animals
Control animals:
no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the course of investigation.
Clinical signs:
Only on the day of administration some clinical signs (squatting position, rough hair coat, impaired general condition) were observed in the animals of the second step of the study (animals 4 - 6).
Body weight:
The body weight gain of the animals was not affected by the administration of the test item.
Gross pathology:
No substance dependent pathological finding was observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyI)-acetamid (P 70/05) was tested in 6 female Charles River Wistar rats according toOECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).
The test item was administered at the single dose of2000mg/kg body weight (Limit test) by gavage.
All animals were examined for mortality, clinical signs and body weight gain. The pathological alterations of organs were examined at the end of a 14-day observation period.
None of the animals died after a single oral administration of 2000 mg/kg b.w. N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)~acetamid (P 70/05).
The LD50 p.o. rat is > 2000 mg/kg b.w.
Apart from some clinical signs on the day of administration which are signs of an impaired general condition no clinical symptoms were observed during the further course of investigation.
The body weight gain of the animals was not affected. No substance dependent pathological finding was observed.
Executive summary:

The acute oral toxicity of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyI)-acetamid (P 70/05) was tested in 6 female Charles River Wistar rats according toOECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method).

The test item was administered at the single dose of2000mg/kg body weight (Limit test) by gavage.

All animals were examined for mortality, clinical signs and body weight gain. The pathological alterations of organs were examined at the end of a 14-day observation period.

None of the animals died after a single oral administration of 2000 mg/kg b.w. N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid (P 70/05).

The LD50 p.o. rat is > 2000 mg/kg b.w.

Apart from some clinical signs on the day of administration which are signs of an impaired general condition no clinical symptoms were observed during the further course of investigation.

The body weight gain of the animals was not affected. No substance dependent pathological finding was observed.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and has Klimisch score 1.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
other:
Justification for type of information:
According to REACH regulation Annex VIII column 2, in addition to the oral route, information shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. The dermal route is considered as the major route of exposure for N-(3(5)-Methyl-lH-pyrazol-l-yl-methyI)-acetamid (P 70/05). In addition, as determined by the particle size distribution study, no particles are smaller than the respirable particle size of 10 μm. In conclusion further testing on vertebrate animals is not justified, thus the conduct of an acute inhalation toxicity study is not required.
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Study is not required.

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
Study period:
2007-04-27 - 2007-05-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an internationally accepted guideline. All study parameters are based on the specific guideline.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Species / Strain: rat/Wistar Crl:WI
Rationale:The rat is a suitable rodent species for acute toxicity
studies and is acceptable to regulatory authorities.
Sex:male, female (nulliparous, non-pregnant)
Supplier:Charles River Wiga GmbH,
D-97320 Sulzfeld
Hygiene status upon supply: SPF
Age at start of acclimatisation: approximately 8 weeks
Randomisation / Acclimatisation:5 days before start of dosing the animals were assigned to cages according to random numbers corresponding the planned treatment groups. In this time no signs were observed which indicated an illness or other injury.
Mean body weight at administration: Males: 218.2 g± 5.5 g (2.5%) n=5 Females: 211.8 g ± 4.6 g (2.2%) n = 5
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test item was moistened with a 0.5 % (m/v) solution of Tylose MH 1000 in deionised water, applied to the shaved skin area and covered with a layer of a gaze patch and then with aluminium foil (6.5x6.5 cm). This patch was held in contact with the skin by occlusive dressing (Elastoplast, BSN medical), single administration on May 08, 2007,7.268 - 7.48 a.m. After 24 hours the patch was removed and the application area was cleaned with deionised water.
Duration of exposure:
24 hours
Doses:
2.000 mg/kg b.w.
No. of animals per sex per dose:
5 males, 5 females
Control animals:
not required
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the animals died during the course of investigation.
Clinical signs:
None of the animals showed alterations of the general state of well-being during the course of investigation. Not any alteration of the skin at the administration area was observed.
Body weight:
The body weight gain of the animals was not affected by the administration of the test item.
Gross pathology:
There were no macroscopic pathological findings in the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
Acute dermal toxicity of N-(3(5)-MethyI-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) was tested in 5 male and 5 female Charles River Wistar rats according to OECD Guideline 402 (Acute Dermal Toxicity). The test item was applied at a single dose of 2000 mg/kg body weight to a shaved dorsal area of the trunk of the animals and was then covered with a gauze patch which was held in contact with the skin with an occlusive dressing. The exposure was for 24 hours.
Animals were examined for mortality, clinical signs, alterations of the administration area, body weight gain and pathological alterations of organs at the end of a 14-day observation period.
None of the animals died during the course of the investigation. The LD5O dermal rat is > 2000 mg/kg b.w.
Clinical signs were not observed during the observation period. Not any alteration of the skin at the administration area was observed.
The body weight gain of the animals was not affected by the test item administration. Pathological findings were not observed at necropsy.
Executive summary:

Acute dermal toxicity of N-(3(5)-MethyI-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) was tested in 5 male and 5 female Charles River Wistar rats according to OECD Guideline 402 (Acute Dermal Toxicity). The test item was applied at a single dose of 2000 mg/kg body weight to a shaved dorsal area of the trunk of the animals and was then covered with a gauze patch which was held in contact with the skin with an occlusive dressing. The exposure was for 24 hours.

Animals were examined for mortality, clinical signs, alterations of the administration area, body weight gain and pathological alterations of organs at the end of a 14-day observation period.

None of the animals died during the course of the investigation.

The LD50 dermal rat is > 2000 mg/kg b.w.

Clinical signs were not observed during the observation period.

Not any alteration of the skin at the administration area was observed.

The body weight gain of the animals was not affected by the test item administration.

Pathological findings were not observed at necropsy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and has Klimisch score 1.

Additional information

The acute oral toxicity of N-(3(5)-Methyl-lH-pyrazol-l-yl-methyI)-acetamid (P 70/05) was tested in 6 female Charles River Wistar rats according toOECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method). The test item was administered at the single dose of 2000 mg/kg body weight (Limit test) by gavage. None of the animals died after a single oral administration of 2000 mg/kg b.w. N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid (P 70/05). The LD50 p.o. rat is > 2000 mg/kg b.w.

Acute dermal toxicity of N-(3(5)-MethyI-lH-pyrazol-l-yl-methyl)-acetamid (P 70/05) was tested in 5 male and 5 female Charles River Wistar rats according to OECD Guideline 402 (Acute Dermal Toxicity). The test item was applied at a single dose of 2000 mg/kg body weight to a shaved dorsal area of the trunk of the animals and was then covered with a gauze patch which was held in contact with the skin with an occlusive dressing. The exposure was for 24 hours. None of the animals died during the course of the investigation. The LD50 dermal rat is > 2000 mg/kg b.w. Clinical signs were not observed during the observation period.

Justification for selection of acute toxicity – oral endpoint

Only one study available.

Justification for selection of acute toxicity – inhalation endpoint

Study is not required.

Justification for selection of acute toxicity – dermal endpoint

Only one study available.

Justification for classification or non-classification

Acute oral toxicity:

The respective criteria are not met.

The estimated LD50 of > 2000 mg/kg bw. is above the treshold for hazard category 4 (2000 mg/kg bw).

N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid

is therefore not classified for acute oral toxicity.

Acute toxicity via the dermal route:

The respective criteria are not met. The estimated LD50 of > 2000 mg/kg bw. is above

the treshold for hazard category 4 (2000 mg/kg bw).

N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid

is therefore not classified for acute dermal toxicity.

Acute toxicity via the inhalation route:

The dermal route is considered as the major route of exposure for N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid. In addition, as determined by the particle size distribution study, no particles are smaller than the respirable particle size of 10 μm. In conclusion further testing on vertebrate animals is not justified, thus the substance will be not classified for acute inhalation toxicity.