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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed in 1991 before the alternative OECD guidelines (LLNA and in vitro test methods) were set into force.

Test material

Constituent 1
Chemical structure
Reference substance name:
diethyl 1-(2,4-dichlorophenyl)-5-methyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylate
EC Number:
603-923-2
Cas Number:
135590-91-9
Molecular formula:
C16H18Cl2N2O4
IUPAC Name:
diethyl 1-(2,4-dichlorophenyl)-5-methyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylate

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF breeding colony
- Age at study initiation: about 4 weeks
- Weight at study initiation: 262.4 g mean
- Housing: in fully air-conditioned rooms in Makrolon cages (Type 4) on soft wood granulate, in groups of 5 animals
- Diet (e.g. ad libitum): Altromin 3112 for guinea pigs and rabbits, ad libitum
- Water (e.g. ad libitum): tap water in plastic bottles, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
Intradermal induction: 5 %
Epicutaneous induction: 25%
Day(s)/duration:
48 h (epicutaneous)
Challenge
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
25%
Day(s)/duration:
24 h
No. of animals per dose:
20 (in test groups), 10 (controls)
Details on study design:
RANGE FINDING TESTS:
In a dermal-occlusive test for primary skin irritation, 25, 5 and 1% in paraffin were applied to the left flank of two guinea pigs. The hair on the right and left flanks of the animals was removed mechanically. 0.5 mL of the test substance preparation was applied to a 2 x 2 cm cellulose
patch, which was then fixed to the left flank and covered occlusively for 24 hours with a bandage and film. 24 hours after removal of the patches, the treated skin areas were examined for erythema and oedema.

No irritation occurred after application of any of the tested concentrations.
For this reason the 25% concentration was selected for the main study.

To determine the tolerance of intradermal injections, each of the following preparations was administered twice by intradermal injection to 3 guinea pigs. The injection sites (sites 1, 2 and 3) were all within a dorsal area measuring 2 x 4 cm in the vicinity of the shoulder.
Site 1: 2 x 0.1 ml 5.0% in paraffin
Site 2: 2 x 0.1 ml 1.0% in paraffin
Site 3: 2 x 0.1 ml 0.2% in paraffin

The injections with the 5% substance preparation in paraffin caused very slight to well-defined erythema and slight oedema. The injection sites for the 1% and 0.2% preparations showed very slight to well-defined erythema and (very) slight oedema.
Based on this preliminary test, the 5% preparation in paraffin was selected for the intradermal injections in the main test.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal day 1 and epicutaneously day 8)
- Test groups: Intradermal: 50% Freund's adjuvant alone, test substance in paraffin, test substance in 50% Freund's adjuvant; epicutaneous: test substance in paraffin
- Control group: Intradermal: 50% Freund's adjuvant alone, paraffin only, 50% Freund's adjuvant alone; epicutaneous: paraffin only
- Site: dorsal area 4 x 6 cm in the vicinity of the shoulders.
- Frequency of applications: 7 days
- Duration: day 1 to day 8
- Concentrations: Intradermal 5% test substance, epicutaneous 25 % test substance


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Test groups: test substance epicutaneously
- Control group: test substance epicutaneously
- Site: shaved left flank, shaved right flank remained untreated
- Concentrations: 25% test substance
- Evaluation (hr after challenge): 48 and 72
Challenge controls:
The control group actually is a challenge control.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 5% intradermal, 25% epicutaneous; challenge: 25% epicutaneous
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
very slight erythema
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
induction: 5% intradermal, 25% epicutaneous; challenge: 25% epicutaneous
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
very slight erythema, dry rough skin, fine scales
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
25% challenge
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25% challenge
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no effects
Remarks on result:
no indication of skin sensitisation
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

The treated animals showed no clinical signs of intoxication at any time during the study. The intradermal injections with Freund's adjuvant (with and without test substance) caused moderate oedema, well-defined to moderate erythema. The injection site revealed white discoloured areas, and the skin was encrusted and scabbed. After dermal induction treatment the tissue of these injection sites became necrotic or developed open wounds in the control as well as in the treatment group. The body weight gains of the treated animals were not impaired.

Challenge:

48 and 72 hours after removal of the occlusive bandage, 4 out of 20 animals in the treated group (20%) showed dermal reactions in the form of very slight erythema, whereas no signs of dermal irritation were noticed in the control group. Additionally the skin surface was dry, rough and covered with fine scales.

Conclusion:

Based on the results of this study, Hoe 107892 00 ZC97 0001 is non-sensitising, and thus not subject to labelling requirements according to the criteria for classification in Directive 83/467/EEC.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Conclusions:
CLP: Not classified