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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 13 to April 17, 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Study performed similar to OECD Guideline 404.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Remarks:
The study meets the requirements of 40 CFR Part 160 with the following exception: stability, characterization, identity and verification of the test item concentration as received and tested are the responsbility of the sponsor.

Test material

Constituent 1
Chemical structure
Reference substance name:
1-[2-(allyloxy)ethyl-2-(2,4-dichlorophenyl)-1H-imidazolium hydrogen sulphate
EC Number:
261-351-5
EC Name:
1-[2-(allyloxy)ethyl-2-(2,4-dichlorophenyl)-1H-imidazolium hydrogen sulphate
Cas Number:
58594-72-2
Molecular formula:
C14H14Cl2N2O.H2O4S
IUPAC Name:
1-[2-(2,4-DICHLOROPHENYL)-2-(PROP-2-EN-1-YLOXY)ETHYL]-1H-IMIDAZOLE SULFATE (1:1)
Test material form:
solid: particulate/powder
Details on test material:
- Product names: FUNGAFLOR® 75C / FUNGAFLOR® 75SP / FUNGAZIL® 750SP / FUNGAFLOR® 75PS / FUNGAZIL® 75SP / FUNGAFLOR® 750SP
- Reference number: JNJ-2634372-ABI / R027180 (product code)
- Physical state: solid
- Appearance: beige solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: ZR027180PUE201/ PSL Code Number E71118-2H
- Expiration date of the lot/batch: October 15, 2003
- Purity test date: no data


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: no data
- Stability under test conditions: Expected to be stable for the duration of testing.
- Solubility and stability of the test substance in the solvent/vehicle: Soluble in water (>500 g/L)

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Prior to application, the test item was moistened to achieve a dry paste by preparing a 90% w/w mixture in distilled water. Five tenths of a gram of the test item (dry weight basis) was placed on a 1 inch x 1inch, 4-ply gauze pad and applied to one 6 cm2 intact dose site.
- Final preparation of a solid: The sample was applied as a 90% w/w mixture in distilled water.

Test animals

Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Davidson's Mill Farm, South Brunswick, NJ
- Age at study initiation: Adult
- Weight at study initiation: no data
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the Guide for the Care and Use of Laboratory Animals DHEW (NIH) No. 86.23. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Pelleted Purina Rabbit Chow #5326.
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by automatic water dispensing system.
- Acclimation period: 18 or 46 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8-22.8° C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hour light/12 dark cycle

IN-LIFE DATES: no data

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
distilled
Controls:
other: Untreated skin areas were used as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 gram of test item (dry weight basis)


Duration of treatment / exposure:
4 hours
Observation period:
up to 72 hours
Number of animals:
2 males and 4 females
Details on study design:
TEST SITE
- Area of exposure: Dorsal area and trunk. On the day prior to application, a group of animals was prepared by clipping (Oster model #A2-small) the dorsal area and the trunk.
- % coverage: one 6 cm2 area
- Type of wrap if used: Micropore tape
The test material was applied to approximately to 1 inch x 1 inch, 4-ply gauze pad and applied to one 6 cm2 intact dose site on each animal. The pad and entire trunk of each animal were then wrapped with a semi-occlusive 3 inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test sites were gently wiped with water and a clean towel to remove residual test item.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days)
- Skin reactions were recorded at 1, 24, 48 and 72 hours after administration
- Cage side observations: once daily during the test period.

SCORING SYSTEM:
The dermal irritation was assessed according to the Draize Standard Skin Irritation Grading Scale
- Primary Dermal Irritation Index (PDII) was classifed as follows:
PDII Classification
Less than 2.0 Slightlly irritating
2.0-5.0 Moderately irritating
Greater than 5.0 Severly irritating






Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
8
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: PDII reported in the study and included in this IUCLID entry was calculated across the 24, 48, and 72 h timepoints
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.37
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.13
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
One rabbit was free from dermal irritation throughout the study. Within twenty-four hours of patch removal, very slight to well-defined erythema was noted at five of six treated sites. Two rabbits also exhibited ver slight edema. The overall incidence and severity of irritation decreased with time. All affected animals were free from erythema and edema within 72 hours.

Any other information on results incl. tables

All animals appeared active and healthy.  Apart from the dermal irritation noted, there were no other signs of gross toxicity, adverse pharamologic effects or abnormal  behavior.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the classification system used, the Imazalil sulfate, is classified as slightly irritating to the skin when moistened with distilled water prior to application.

Under the conditions of this study, the Primary Irritation Index (PII) was 0.7, indicating that the test substance is a mild irritant. Based on the mean scores for erythema and edema at 24, 48 and 72 hours and the criteria of the CLP Regulation, the substance is considered as non irritant to the skin (score < 2.3).