Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxicological information

Skin sensitisation

Currently viewing:

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.