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Description of key information

In a  reliable skin irritation/corrosion study, a single irritation was found. The irritation was reversible and completely subsided by day 4. The primary Irritation Index was calculated to be 0.0. The test material  received a descriptive rating classification of nonirritating. 
In a reliable eye irritation study, the Maximum Average Score of the substance was 5.2 at one hour post-instillation. All irritations were reversible and completely subsided by termination (day 3) or earlier. The test material received a descriptive rating classification of nonirritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
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
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
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
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-09-21 to 1996-03-5
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 81-4) and TSCA Health Effects Test Guidelines, 40 CFR 798.4500
Qualifier:
according to
Guideline:
other: US EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Aminals, Section 81-4.
Qualifier:
according to
Guideline:
other: TSCA Health Effects Test Guidelines, 40 CFR 798.4500
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, PA
- Age at study initiation: Young adult
- Weight at study initiation: 2379 to 2688 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): 67.9 - 68.1 °F)
- Humidity (%): 38.2 - 61.1%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml/right eye
Duration of treatment / exposure:
1 second. The test material was placed directly into the cupped lower conjunctival sac of the rabbit´s right (test) eye. The eyelid was held closed for approximately one second after instillation. Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls. The eyes of all rabbits remained unwashed.
Observation period (in vivo):
1, 24, 48 and 72 hours after dosing
Number of animals or in vitro replicates:
6, three males and three females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize scale for scoring ocular lesions, as published in the guidelines in Subsection F. Hazard Evaluation: Human and Domestic Animals distributed in 1982 and the OECD Guidelines for Testing of Chemicals distributed in 1987.

TOOL USED TO ASSESS SCORE: After 1, 24,48 and 72 hours after dosing both eyes of the rabbits were examined macroscopically for ocular irritation using a hand-held penlight. In addition sodium fluorescein and ultraviolet light were used prior to the study initiation and after 72h.
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 1 h
Score:
5.2
Reversibility:
fully reversible within: 72h
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 24h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 48h
Score:
0.7
Reversibility:
fully reversible
Irritation parameter:
other: M.A.S - Maximum Average Score
Basis:
mean
Time point:
other: 72h
Score:
0

An iris reaction was noted in the treated eye of one animal. Minor conjunctival irritation was noted for all rabbits.

       0.1 ml/right eye, unwashed                Examination intervals                   
 Animl  Sex  Tissue        1h        24h        48h       72h* 
 19702  M Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  1  0  0  1  0  0  0  0  0
 19853  M  Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  0  0  0  0  0  0  0  0  0
 19855  M  Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  0      0      0      0    
    Conjunctiva (R-C-D)  1  1  0  1  0  0  0  0  0  0  0  0
 19870  F  Cornea (O-A)  0  0    0  0    0  0    0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  0  0  0  0  0  0  0  0  0
 19871  F  Cornea (O-A)  0  0    0  0    0  0    0  0  
     Iris  1      0      0      0    
     Conjunctiva (R-C-D)  1  1  0  0  0  0  0  0  0  0  0
 19872  F  Cornea (O-A)  0  0    0  0    0    0  0  
     Iris  0      0      0      0    
     Conjunctiva (R-C-D)  1  1  1  1  0  0  1  0  0  0  0  0
                           
 Total    

 31.0      

       6.0        4.0       0.0 
 Mean          5.2          1.0        0.7        0.0

O = Opacity; A = Area; R = Redness; C = Chemosis; D = Discharge

*Fluorescein solution applied

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Draize scale for scoring ocular lesions
Conclusions:
The Maximum Average Score for Y-4036 was 5.2 at one hour post-instillation. An iris reaction was noted in the treated eye of one female animal. There were no corneal findings. Minor conjunctival irritation was noted for all rabbits. All irritation was reversible and completely subsided by termination (day 3) or earlier.
Executive summary:

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

Single 0.1 -ml doses of the test material were instilled into the lower conjunctival sac of the right eye of three male and three female albino rabbits. The eyelids were held closed for approximately one second and released. Left eyes were manipulated in a similar manner as the right eyes and served as contralateral controls. The eyes of all rabbits remained unwashed.

The eyes were examined for ocular reactions in accordance with the method of Draize at approximately one, 24, 48 and 72 hours after dosing. Sodium fluorescein was used to aid in revealing possible corneal damage at 72 hours.

The Maximum Average Score of Y-4036 was 5.2 at one hour post-instillation. An iris reaction was noted in the treated eye of one female animal. Minor conjunctival irritation was noted for all rabbits. There were no corneal findings. All irritation was reversible and completely subsided by day 3 or earlier.

There were no deaths or remarkable changes in body weights during the study period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The irritation studies did not indicate that the substance is irritant or corrosive.

Justification for classification or non-classification

Based on reliable in vivo skin and eye irritation data, 2 -(3,4 -epoxycyclohexyl)ethyltriethoxy silane does not meet the criteria for classification as irritant according to EU Directive 67/548/EEC and Regulation 1272/2008.