Registration Dossier

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test 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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Chemical name: N-(3(5)-Methyl-1 H-pyrazol-1 -yl-methyl)-acetamid
Code of the sponsor: P 70/05 Formula: C7H11N3O
Description: white, amorphous solid
Purity: > 99 % (HPLC and NMR)

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

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.