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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
GPMT
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1990-09-19 to 1990-10-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Adopted May 12, 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: The US Federal Register Vol. 50, No.188, subpart 798.4100
Version / remarks:
September 27, 1985
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: US EPA: Pesticide Assessment Guidelines, Subdibision F - Hazard Evaluation: Human and Domestic Animals - Series 81-6: Dermal Sensitization
Version / remarks:
Addendum 4 on Data Reporting (January 1988)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: Agricultural Chemicals Law and Regulations Japan (II); Testing Guidelines for Toxicology Studies, pp. 27-29: Dermal Sensitization Toxicity Study
Version / remarks:
January 28, 1985
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The Murine Local Lymph Node Assay (LLNA) is the first-choice method for in vivo testing according to the REACH Regulation. However, this reliable GMPT was performed before entry into force of the REACH Regulation

Test material

Constituent 1
Chemical structure
Reference substance name:
1-[2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole
EC Number:
252-615-0
EC Name:
1-[2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole
Cas Number:
35554-44-0
Molecular formula:
C14H14Cl2N2O
IUPAC Name:
(±)-1-(β-allyloxy-2,4-dichloro-phenylethyl) imidazole / (±)-allyl 1-(2,4-dichlorophenyl)-2-imidazol-1-ylethyl ether
Test material form:
solid: crystalline
Details on test material:
- Physical state: crystalline solid
- Appearance: Yellow to brown crystalline solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: G3A561
- Expiration date of the lot/batch: Not specified
- Purity: 98.1%
- Manufacturing Date: 1989-01-23


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in closed containers.
- Solubility and stability of the test substance in the solvent/vehicle: The stability of imazalil in 1% sesam oil (with or without FCA), 10% petrolatum, and 5% petrolatum was controlled and guaranteed. All mixes were prepared for immediate use.


In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Test facility permanent non-inbred laboratory colony
- Females (if applicable) nulliparous and non-pregnant: not applicable
- Age at study initiation: Not specified
- Weight at study initiation: 300-400g
- Housing: Housed in an air-conditioned room and placed individually in numbered metallic cages. The cages were placed in racks.
- Diet (e.g. ad libitum): "Hope-farms" standardized pellets administrated in slef-raising hoppers and fed ad libitum.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: One-week
- Indication of any skin lesions: No

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): Not specified
- IN-LIFE DATES: From: 1990-09-19 To:1990-10-13

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: sesam oil
Concentration / amount:
1%
Day(s)/duration:
day 0
Adequacy of induction:
other: produced no necrosis at the injection site
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
10%
Day(s)/duration:
day 7; 48h occlusive patch
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
5%
Day(s)/duration:
day 21; 24 hours occlusive patch
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
2 main groups (vehicle induced and imazalil induced) of 20 animals each.
Details on study design:
RANGE FINDING TESTS:
The formulations used were chosen based upon a screen test which indicated that the 1% solution in sesam oil alone produced no necrosis at the injection site. The 10% powder in petolatum produced a slight erythema at the application site whereas the 5% powder in petrolatum did not result in erythema when applied to the skin of guinea-pigs during 24h under occlusive patch.

MAIN STUDY
A. INTRADERMAL INDUCTION - Day 0
- No. of exposures: Once
- Site: depilated nuchal area
- Concentrations:

The following injections were given:
- 2 injections of 0.1 mL of Freund's complete adjuvant blended with an equal amount of water
- 2 injections of 0.1 mL of the test article formulation close to the first 2 injections
- 2 injections of 0.1 mL of the test article formulation emulsified with Freund's complete adjuvant

Test groups: 1% solution in sesam oil
Control group: 100% sesam oil

B. EPICUTANEOUS INDUCTION - Day 7
- The test article and vehicle formulations were held in contact with the skin under an occlusive patch during 48 hours.
- The vehicle-induced group received the vehicle formulations.
- Scoring was perfromed 24 hours later.

C. CHALLENGE EXPOSURE - Day 21
- Two weeks after the epicutaneous induction a formulation of 5% imazalil in pertrolatum was applied epicutaneously on the left shaved flank under occlusive patch during 24 hours.

Challenge controls:
not specified
Positive control substance(s):
yes
Remarks:
DNCB

Results and discussion

Positive control results:
A positive sensitizer, DNCB was additionally evaluted in a separate study (Exp no. 2216). A 100% sensitization rate was obtained 48 and 72h.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% test item in petrolatum
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
5% test item in petrolatum
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
Vehicle only
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
vehicle only
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
100% sensitization rate
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Remarks on result:
positive indication of skin sensitisation
Remarks:
100% sensitization rate

Any other information on results incl. tables

Observations

All guinea-pigs survived the study. Body weights, which were recorded prior to and at the end of the study, were comparable between groups.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
As appears from these data and when compared to the results of the positive control study with DNCB (exp no. 2216) where a 100% sensitization rate was obtained 48 and 72h.
Based on the sensitization rate obtained after the challenge exposure, the study director classified the test item as weak sensitizer (sensitization rate between 0 and 8%). However accroding to the criteria laid out in the CLP regulation, Imazalil should not be classified as skin sensitizer.

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