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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methylpyrazole
EC Number:
231-445-0
EC Name:
4-methylpyrazole
Cas Number:
7554-65-6
Molecular formula:
C4H6N2
IUPAC Name:
4-methyl-1H-pyrazole
Details on test material:
- Name of test material (as cited in study report): 4-Methylpyrazol
- Description: pale yellow liquid
- Storage conditions: at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Weight at study initiation: 2.8 ± 0.2 kg
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm)
- Diet: ad libitum, 112 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France)
- Water: ad libitum, water filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animal
Amount / concentration applied:
Application volume: 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: right flank
- Type of wrap if used: The substance was placed on dry gauze pad. The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and restraining bandage.

REMOVAL OF TEST SUBSTANCE
- No residual substance was observed on removal of the dressing
- Time after start of exposure: 4 hours

SCORING SYSTEM: THe skin was examined approximately 1, 24, 48 and 72 hours after removal of the dressing.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24 - 72 hours
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Necrosis was observed.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
4
Max. score:
4
Remarks on result:
other: Necrosis was observed; The animal was sacrificed 24 hours after exposure, because of the severe reaction.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24 - 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 - 72 hours
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: Necrosis was observed.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 hours
Score:
4
Max. score:
4
Remarks on result:
other: Necrosis was observed; The animal was sacrificed 24 hours after exposure, because of the severe reaction.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24 - 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
In one animal (#2), a severe erythema, a severe oedema and cutaneous necrosis were observed on days 1 and 2. This animal was killed for ethical reasons on day 2. In a second animal (#3), a very slight or well-defined erythema was recorded between day 1 and day 4. Dryness of the skin was noted between day 5 and day 7. In the third animal (#1), a very slight to moderate erythema and very slight or slight oedema were noted from day 1 up to day 9. A slight cutaneous necrosis (0.5 cm diameter) was observed in this animal from day 1 up to day 5. Dryness of the skin and crusts were then recorded at the treatment site and persisted up to the end of the observation period.

A microscopic examination of a skin sample taken from the sacrificed animal (#2) showed the following microscopic findings:
- moderate epidermal necrosis, as assessed by nuclear pycnosis and strong eosinophilia of nuclei and cytoplasms; in addition a focal cleft within necrotic epidermis was seen
- moderate heterophil infiltration in the uppermost papillary dermis,
- moderate pilo-sebaceous atrophy (hair follicles, sebaceous glands, arrector-pili muscles),
- slight collagen degradation of the dermis extending to lower part of reticular dermis,
- slight congestion of the blood vesseis in die middle/lower part of reticular dermis,
- slight hemorrhage in the dermis (middle part/lower part of reticular dermis).

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information