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Administrative data

Description of key information

Guinea pig. Not sensitising. OECD 406; Reliability = 2

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is used for read-across and therefore has been assigned a reliability of 2 (reliable with restrictions). Otherwise the study has a reliability of 1 (reliable without restriction).
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance dimethylpyrazole differs from the target substance pyrazole in the addition of 2 methyl groups in the 1 and 4 position. This minor modification is unlikely to impede the reactivity of the source substance as compared to the target substance.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
All information available on source and target materials are provided in the section "test material" in IUCLID.

3. ANALOGUE APPROACH JUSTIFICATION
The read-across from pyrazole to dimethylpyrazole is specified for the endpoint of sensitisation. A weight-of-evidence is conducted to assess the sensitising properties of pyrazole. On the one hand, the structurally closely related dimethylpyrazole does not give rise for concern with regard to sensitization. On the other hand, QSAR modelling was performed to further evaluate and probe the sensitizing properties of the test substance. Also the QSAR modelling prediction is "not sensitizing". Therefore, the sensitization concern is considered adequately addressed, overall there is no concern for sensitization.

4. DATA MATRIX
endpoint-specific read-across combined with QSAR-modelling - please refer to the respective IUCLID datasets for more information.
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Data from a maximation test conducted with dimethylpyrazole are available.
Species:
guinea pig
Strain:
other: Pirbright White, Dunkin Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River GmbH - Wiga, Kisslegg, FRG
- Age at study initiation: young adult animals
- Weight at study initiation: 331-373 g
- Housing: Makrolon, type IV
- Diet (e.g. ad libitum): Kliba Labordiät 341 (Kaninchen-Meerschweinchen-Haltungsdiät); ad libitum
- Water (e.g. ad libitum): Water ad libitumn (tap water; about 2 g of ascorbic acid per 10 L water was added to the drinking water twice a week)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
water
Concentration / amount:
Intradermal induction:
test substance 1% in 0.9% aqueous NaCl-solution or in Freund's adjuvant/0.9% aqueous NaCl-solution (1 : 1) or 0.9% aqueous NaCl-solution
Percutaneous induction:
test substance unchanged
Challenge:
test substance 75% in aqua bidest.
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Intradermal induction:
test substance 1% in 0.9% aqueous NaCl-solution or in Freund's adjuvant/0.9% aqueous NaCl-solution (1 : 1) or 0.9% aqueous NaCl-solution
Percutaneous induction:
test substance unchanged
Challenge:
test substance 75% in aqua bidest.
No. of animals per dose:
control group: 5 (2 control groups); test group: 10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE

INTRADERMAL INDUCTION:
- No. of exposures: 6 intradermal injections in groups of two per animal
- Site: shoulder
- Duration: 24h

Injections for the test group:
A) front row: 2 injections each of 0.1 ml Freund's adjuvant without test substance emulsified with
0.9% aqueous NaCl-solution in a ratio of 1 :1
B) middle row: 2 injections each of 0.1 ml of the test substance formulation
C) back row: 2 injections each of 0.1 ml Freund's adjuvant / 0.9% aqueous NaCl-solution (1 :1)
with test substance

Injections for control groups 1 and 2:
- The animals were given the same injections (A, B,C) but without test substance, only with the formulating agent.

PERCUTANEOUS INDUCTION:

- Percutaneous induction was carried out one week after intradermal induction.
The animals were exposed to about 0.3 g of the test substance.
- The control groups were not treated, since the test substance was applied unchanged and thus no solvent was used.
Duration of exposure:
- 48 hours
Site of application:
- shoulder, same area as in the case of the previous intradermal application
Readings:
- 48 h after the beginning of application
Assessment of skin findings:
- analogous to the pretest

B. CHALLENGE EXPOSURE

Challenge: 21 days after intradermal induction.
the animals were exposed to about 0.15 g of the test substance formulation.

- treatment of the test group and of control group 1 with the test substance formulation (control group 2 remained untreated).

Duration of exposure:
- 24 hours
Site of application:
- intact flank (occlusive dressing)
Readings:
- 24 and 48 h after the removal of the patch

Assessment of skin findings according to Draize, J.H. (1959).



Positive control results:
A positive control (reliability check) with a known sensitizer is not included in this study. However, a separate study is performed twice a year in the laboratory. The positive control with Alpha-Hexylcinnamaldehyde, techn. 85% showed that the test system was able to detect sensitizing compounds under the laboratory conditions chosen.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
test substance 75% in aqua bidest.
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
test substance 75% in aqua bidest.
No. with + reactions:
0
Total no. in group:
10
Interpretation of results:
GHS criteria not met
Conclusions:
1,4-Dimethylpyrazole does not have a sensitizing effect on the skin of the guinea pig in the Maximization Test under the test conditions chosen.
Executive summary:

A guinea pig maximization test was conducted in accordance with OECD Guideline 406. No sensitization was observed at the 24 and 48 hour challenges. Therefore, the test substance not considered to be a skin sensitizer.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There is no study available for pyrazole concerning skin sensitization. However, read-across to 1,4 -dimethylpyrazole has been performed. In a GLP-compliant guideline study (according to OECD TG 406), 1,4 -dimethylpyrazole showed no skin sensitizing properties. Moreover, pyrazole does not show a sensitizing alert (protein binding) in QSAR modelling (OECD Toolbox v.1.0). Therefore, no sensitsing potential is expected.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

There was no evidence of dermal sensitisation in guinea pigs using a structurally similar analogue. Moreover, the test substance does not show a sensitizing alert (protein binding) in QSAR modelling (OECD Toolbox v.1.0). Therefore, the substance does not need to be classified for skin sensitisation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.