Registration Dossier

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:
1995-09-21 to 1996-03-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed under GLP and the study was conducted in general compliance with the US EPA OPP (Section 81-5) and TSCA Health Effects Test Guidelines, 40 CFR 798.4470

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: EPA Guidelines for Registering Pesticides in the U.S.(Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, Section 81-5)
Qualifier:
according to
Guideline:
other: TSCA Health Effects Test Guidelines, 40 CFR 798.4470
Qualifier:
according to
Guideline:
other: Japanese Agricultural Chemicals Laws and Regulations Testing Guidelines for Toxicology Studies published by the Society of Agricultural Chemical Industry, under the auspices of MAFF
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Y-4036
- Physical state: clear, colourless liquid
- Analytical purity: 98.3 %
- Purity test date: 1995-09-27
- Lot/batch No.: 16912-29
- Storage condition of test material: original container at room temperature, under these conditions the substance is stable for several years

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, PA
- Age at study initiation: Young adult
- Weight at study initiation: 2339 to 2705 grams
- Housing: Individual suspended wire-mesh cages. The animals were maintained by the animal husbandry staff of WIL Research Laboratories, Inc., in accordance with Standard Operating Procedures.
- Diet (e.g. ad libitum): Purina® Certified Rabbit Chow® #5322 ad libitum
- Water (e.g. ad libitum): municipal water ad libitum
- Acclimation period: a minimum of six days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67.7 - 68.1 °F)
- Humidity (%): 35.6 - 56.1%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Remarks:
none
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site

Duration of treatment / exposure:
4 h
Observation period:
Mortality: The rabbits were observed twice daily (morning and afternoon) for mortality for the duration of the study
Dermal Observation: The application sites were observed for erythema, edema and other dermal findings approximately 30 - 60 minutes and 24, 48, and 72 hours after patch removal and on day 4 if irritation persisted.
Number of animals:
6, two males and four females
Details on study design:
TEST SITE
- Area of exposure: approximately 1" x 1"
- % coverage: no data
- Type of wrap if used: a secured two-ply gauze patch that was overwrapped with a gauze binder and secured with Dermiform® tape. Plastic restraint collars were applied and remained on the animals for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towels moistened with deionized water
- Time after start of exposure: at the end of 4 hours

SCORING SYSTEM:
Dermal irritation was graded in accordance with the method of Draize:

Evaluation of Dermal Reactions

Value
Erythema and Eschar Formation

0 No erythema
1 Very slight erythema (barely perceptible, edges of area not well defined)
2 Slight erythema (pale red in color and edges definable)
3 Moderate to severe erythema (definite red in color and area well defined)
4 Severe erythema (beet or crimson red) to slight eschar formation (injuries in depth)


4 Total possible erythema score

Edema Formation

0 No edema
1 Very slight edema (barely perceptible, edges of area not well defined)
2 Slight edema (edges of area well defined by definite raising)
3 Moderate edema (raised approximately 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

4 Total possible erythema score
8 Total possible Primary Irritation Score



Descriptive Ratings
Mean Primary Dermal Irritation Index

Range of Values Descriptive Rating

0 Nonirritating
0.1 - 2.0 Slightly Irritating
2.1 - 5.0 Moderately Irritating
5.1 - 8.0 Severely Irritating

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
male
Time point:
other: 72
Score:
1
Reversibility:
fully reversible within: 1 day
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
male
Time point:
other: 72h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
female
Time point:
other: 72h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
female
Time point:
other: 72h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
female
Time point:
other: 72h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
female
Time point:
other: 72h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
male
Time point:
other: 96h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
male
Time point:
other: 72h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
female
Time point:
other: 72h
Score:
0
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
female
Time point:
other: 72h
Score:
0
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
female
Time point:
other: 72h
Score:
0
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
female
Time point:
other: 72h
Score:
0
Other effects:
One female had a body weight loss of 129 grams (5%) from day 0 to day 3. A body weight loss of this magnitude is common in animals which have been bandaged and collared for four hours, and was not attributed to test material.
There were no other remarkable body weight changes during the study period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
Very slight erythema was observed on a single male animal at 72 hours post-dose. There was no edema or other dermal findings. The irritation was reversible and completely subsided by day 4.
The primary Irritation Index was calculated to be 0.0. The test material, Y-4036, received a descriptive rating classification of nonirritating.
Executive summary:

The primary dermal irritation potential of Y-4036 was evaluated in this study with New Zealand White rabbits.

Single 0.5 -ml doses of the test material were applied to the clipped, intact skin of six albino rabbits under semi-occlusive dressings for a four-hour exposure period. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated in accordance with the method of Draize at approximately 30 -60 minutes and 24, 48 and 72 hours after patch removal and on day 4 if irritation persisted.

Very slight erythema was observed on a single male animal at 72 hours post-dose. There was no edema or other dermal findings. The irritation was reversible and completely subsided by day 4.

The Primary Irritation Index was calculated to be 0.0. The test material, Y-4036, received a descriptive ranting classification of nonirritanting.