Acetamide, N,N'-(ethenylmethylsilylene)bis[N-ethyl-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 April - 25 June, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[ethenyl(N-ethylacetamido)methylsilyl]-N-ethylacetamide

EC Number:

643-078-7

Cas Number:

87855-59-2

Molecular formula:

C11 H22 N2 O2 Si Si(CH3)(CH=CH2)[N(CH2CH3)(C(=O)CH3)]2

IUPAC Name:

N-[ethenyl(N-ethylacetamido)methylsilyl]-N-ethylacetamide

Test material form:

solid: compact

Details on test material:

Identilication: ZMA T Number 4094103 (Supplied as Dow Corning® 1·6008)
Lot Number: 091217
Expiration Date: 26 Dec 2010
Source: Korea Biogen Co., Ltd., 690 Sinduk·Ri, Suugname·Myuan, Chuna·City, Chungnam, 330·893, Korea
CAS Number: Not provided
Physical Description: Amber liquid as dctcnnined by HES Study Number 11429·101
Stability: Stable in absence of water, moisture, or humid air
Purity: According to information provided by the submitter, the test article to be treated as a mono·constituent, but the area percent
for one of the components, methyl vinyl bis(nethylacetamido )silane was detennined as part of the characterization (HES Study Number 11429-101). The result was 77.9 ± 003 area % purity.
Solubility: As test article will be applied neat, information not applicable
Characterization: HES Study Number 11429,· 101
Storage Conditions: Room temperature according to infonnation provided by samplc submitter
Archive: A reserve sample was not retained for this study.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Duration of treatment / exposure:

The dose of one-tenth of a milliliter of test article was placed in the lower conjunctival sac of the right eye. The eyelids were held gently together for about one second.

Observation period (in vivo):

Ocular irritation scoring: Prior to randomization, prior to dosing, and approximately 1 hour, 24 hours, 48 hours, 72 hours and seven days, 14 days, and 21 days post dose.

Number of animals or in vitro replicates:

Three males

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: D7108

Time point:

other: 24 Hour

Score:

1

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: D7108

Time point:

other: 48 Hour

Score:

1

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal: D7108

Time point:

other: 72 Hour

Score:

2

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 / 48 / 72 Hour

Score:

1.3

Max. score:

2

Results 5

Irritation parameter:

other: area of cornea

Basis:

animal: D7108

Time point:

other: 24 Hour

Score:

4

Results 6

Irritation parameter:

other: area of cornea

Basis:

animal: D7108

Time point:

other: 48 Hour

Score:

2

Results 7

Irritation parameter:

other: area of cornea

Basis:

animal: D7108

Time point:

other: 72 Hour

Score:

1

Results 8

Irritation parameter:

other: area of cornea

Basis:

mean

Time point:

other: 24 / 48 / 72 Hour

Score:

2.3

Max. score:

4

Results 9

Irritation parameter:

iris score

Basis:

animal: D7108

Time point:

other: 24 Hour

Score:

0

Results 10

Irritation parameter:

iris score

Basis:

animal: D7108

Time point:

other: 48 Hour

Score:

0

Results 11

Irritation parameter:

iris score

Basis:

animal: D7108

Time point:

other: 72 Hour

Score:

0

Results 12

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 / 48 / 72 Hour

Score:

0

Max. score:

0

Results 13

Irritation parameter:

conjunctivae score

Basis:

animal: D7108

Time point:

other: 24 Hour

Score:

2

Results 14

Irritation parameter:

conjunctivae score

Basis:

animal: D7108

Time point:

other: 48 Hour

Score:

3

Results 15

Irritation parameter:

conjunctivae score

Basis:

animal: D7108

Time point:

other: 72 Hour

Score:

3

Results 16

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 / 48 / 72 Hour

Score:

2.7

Max. score:

3

Results 17

Irritation parameter:

chemosis score

Basis:

animal: D7108

Time point:

other: 24 Hour

Score:

4

Results 18

Irritation parameter:

chemosis score

Basis:

animal: D7108

Time point:

other: 48 Hour

Score:

3

Results 19

Irritation parameter:

chemosis score

Basis:

animal: D7108

Time point:

other: 72 Hour

Score:

2

Results 20

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 / 48 / 72 Hour

Score:

3

Max. score:

4

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the substance (Supplied as Dow Coming® 1-6008) elicits irreversible damage to the eyes of rabbits.

Executive summary:

This study was designed to assess the potential irritant and/or corrosive effects of ZMAT Number 4094103 (Supplied as Dow Corning(R) 1-6008) in rabbits when administered by a single ocular dose. The study design was based on Organisation for Economic Co-operation and Development (OECD) Test Guideline Number: 405: Acute Eye Irritation/Corrosion (2002) and United States Environmental Protection Agency (USEPA) Health Effects Test Guideline Office of Prevention, Pesticides and Toxic Substances (OPPTS) 870.2400: Acute Eye Irritation (1998). Animals ordered for use on this study were examined to determine if they had any eye irritation, ocular defects, or pre-existing corneal injury. Animals were found to be free of ocular lesions and were assigned to the study and randomized to determine dose order. Dosing was performed within 24 hours of the prescreen examination. The eyes were examined again prior to dosing to determine if any ocular irritation was present. The dose of one-tenth of a milliliter of test article was placed in the lower conjunctival sac of the right eye. The eyelids were held gently together for about one second. The other eye, which remained untreated, served as the control. When the first animal was dosed, significant corneal peeling was noted immediately after dosing. Therefore no other animals assigned to the study were dosed as corneal peeling following test article administration suggests that the test article could be corrosive to the eye. To minimize pain and discomfort, the treated animal had a topical analgesic, Tetracaine, administered immediately after dosing and at two additional times at two hour intervals. Tetracaine was administered to the control eye to ensure that any irritation in the test eye wasn't the result of its administration. At the one hour post dose administration observation, an eye examination with a penlight was performed. No residual test article was noted in the test eye; but there was notable eye irritation. Observations noted were grade 1 opacity over three quarters of the surface of the eye, grade 1 iris score, grade 3 conjunctivae (redness), and grade 3 chemosis (swelling). Over 50% of the cornea epithelium was peeled from the surface of the test eye. Subsequent examinations of the eyes were made at approximately 24, 48, 72 hours and 7, 14, and 21 days after exposure. Eyes were further examined subsequent to the day of dosing by application of fluorescein dye. One drop of fluorescein dye was dropped directly onto the cornea, and excess reagent removed by flushing with physiological saline. The maximum amount of peeling in the test eye confirmed by fluorescein staining was 90%. The peeling was no longer apparent 21 days following dose administration, but a grade 4 opacity covering less than a quarter of the surface of the eye was noted. Pannus was also noted on 7, 14, and 21 days post dose administration. The iris effects were not noted at these observation intervals; and remaining findings were grade 1 by 21 days post dose administration. The mean ocular irritation scores for 24, 48, and 72 hour post test article administration intervals was 1.3 for opacity, 2.3 for area of opacity, 2.7 for conjunctivae (redness), and 3.0 for chemosis (swelling). As administration of the test article resulted in irreversible tissue damage, no other animals assigned to the study were dosed. The animal assigned to the study survived until the end of the 21 day experimental phase. No notable body weight loss was apparent at the end of the experimental phase. Under the conditions of the test, ZMAT Number 4094103 (Supplied as Dow Corning? 1-6008) elicits irreversible damage to the eyes of rabbits.