2-Propenoic acid, 2-methyl-, tris(1-methylethyl)silyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 April 2010 to 22 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Recent study conducted by a GLP certified laboratory in accordance OECD, EPA and EU guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

EC Number:

700-182-8

Cas Number:

134652-60-1

Molecular formula:

C13 H26 O2 Si

IUPAC Name:

Tripropan-2-ylsilyl 2-methylprop-2-enoate

Details on test material:

- Name of test material (as cited in study report): TIS-M
- Lot/batch No.: 9925
- Storage condition of test material: Room temperature, under nitrogen, continuously protected from all lights
- Date of manufacture: 23 September 2009
- Expiry date: 02 December 2010

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft. 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: ~11 weeks old (adult)
- Weight at study initiation: Body weight range at the beginning of the life phase: 2633-2728 g end of the life phase: 2823-3055 g
- Fasting period before study: No information
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet: Animal received PURINA Base – Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum.
- Water: The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 19 April 2010 To: 22 April 2010

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye of each animal served as the control.

Amount / concentration applied:

TEST MATERIAL

- Amount(s) applied: 0.1 ml

- Concentration: Undiluted

Duration of treatment / exposure:

Not applicable - test material was not removed.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 male animals

Details on study design:

Application of the Test Item
Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals that had a normal eye condition and any with ocular lesions were rejected. An initial test was performed using one animal. The test item was instilled into the conjunctival sac of the left eye. The eyelids were held closed for several seconds to prevent the loss of the test item. The contralateral eye served as the control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made according to a six point scale. After consideration of the ocular responses produced in the first animal, two additional animals were treated.

Clinical Observations
The eyes were examined at 1, 24, 48 and 72 hours after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of ill- health during the study were recorded. At the end of the observation period, each animal was sacrificed by intramuscular injections of CP-Ketamin 10% and CP-Xylazine 2% followed by iv. Euthasol® 40% anaesthesia. Death was verified by checking pupil and cornea reflex, absence of respiration and pulse.

Scoring and Assessment of Local Reaction
The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002).

Measurement of Body Weight
Individual body weight was recorded at the beginning and end of the experiment.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

Mean

Time point:

other: Overall at 24. 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hrs

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

3

Reversibility:

other: Not applicable

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

3

Reversibility:

other: Not applicable

Results 13

Irritation parameter:

other: Discharge

Basis:

animal #1

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

3

Reversibility:

other: Not applicable

Results 14

Irritation parameter:

other: Discharge

Basis:

animal #2

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

3

Reversibility:

other: Not applicable

Results 15

Irritation parameter:

other: Discharge

Basis:

animal #3

Remarks:

Mean

Time point:

other: Overall at 24, 48 and 72 hrs

Score:

0

Max. score:

3

Reversibility:

other: Not applicable

Irritant / corrosive response data:

See tables below.
Initial Pain Reaction (IPR) was not observed in the animals. One hour after the application, conjunctival redness (score 1) and conjunctival discharge (score 1) was observed in all animals. At 24 hours after treatment, conjunctival redness (score 1) was observed in one animal. At 48 hours after treatment there were no clinical signs observed. At 72 hours after treatment, there were no clinical signs observed. As there were no clinical signs observed, the study was terminated after the 72 hour observation. During the study, the control eye of all animals was symptom-free.

Other effects:

None
There was no mortality observed during the study.
The body weight and body weight change were considered to be normal with no indication of treatment related effect.

Any other information on results incl. tables

INDIVIDUAL SCORES FOR OCULAR IRRITATION

Table 1. Time of Observation: Day 0

Time	Animal No.	Score of irritation								IPR
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
1 hour	00805	1	0	1	0	0	0	0	-	0
	00849	1	0	1	0	0	0	0	-	0
	00848	1	0	1	0	0	0	0	-	0

Table 2. Time of observation: Day 1

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
24 hours	00805	1	0	0	0	0	0	0	-
	00849	0	0	0	0	0	0	0	-
	00848	0	0	0	0	0	0	0	-

Table 3. Time of observation: Day 2

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
48 hours	00805	0	0	0	0	0	0	0	-
	00849	0	0	0	0	0	0	0	-
	00848	0	0	0	0	0	0	0	-

Table 4. Time of observation: Day 3

Time	Animal No.	Score of irritation
		Conjunctivae			Opacity of cornea		Iris	Control eye	Other sign
		R	CH	D	OD	OE	R
72 hours	00805	0	0	0	0	0	0	0	-
	00849	0	0	0	0	0	0	0	-
	00848	0	0	0	0	0	0	0	-

MEAN VALUES OF EYE IRRITATION (24, 48, 72 hour reading)

Table 5. Mean values

Animal Number	Sex	Cornea Opacity	Iris	Conjunctivae
				Redness	Chemosis	Discharge
00805	male	0.00	0.00	0.33	0.00	0.00
00849	male	0.00	0.00	0.00	0.00	0.00
00848	male	0.00	0.00	0.00	0.00	0.00

Abbreviations:

R = Redness, CH = Chemosis, D = Discharge, NT = Can not be scored, OD =  Opacity degree of density, OE =   Extension of opaque area, IPR =  Initial pain reaction, - =  No data

Table 6. Body weight data

Animal Number	Beginning of study(g)	At the end of study(g)	Body weight gain(g)
00805	2728	3030	302
00849	2633	2823	190
00848	2701	3055	354

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item TIS-M, applied to rabbit eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 48 hours. According to Regulation (EC) No 1272/2008, TIS-M does not require classification as an eye irritant.

Executive summary:

An acute eye irritation study of the test item TIS-M was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002).

The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A volume of 0.1 mL of the test item was administered as a single dose. The eyes were examined at 1, 24, 48 and 72 hours after the application. Initial Pain Reaction (IPR) was not observed in the animals. One hour after the application, conjunctival redness (score 1) and conjunctival discharge (score 1) was observed in all animals. At 24 hours after treatment, conjunctival redness (score 1) was observed in one animal. At 48 hours after treatment there were no clinical signs observed. At 72 hours after treatment, there were no clinical signs observed. As there were no clinical signs observed, the study was terminated after the 72 hour observation. During the study, the control eye of all animals was symptom-free. The general state and behavior of animals were normal throughout the study period. The body weight and body weight change were considered to be normal with no indication of treatment related effect.

The animal’s individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows: chemosis : 0.00, 0.00, 0.00 discharge : 0.00, 0.00, 0.00 redness : 0.33, 0.00, 0.00 cornea opacity : 0.00, 0.00, 0.00 iris : 0.00, 0.00, 0.00.

The test item TIS-M, applied to the rabbits eye mucosa, caused significant conjunctival irritant effects at one hour which were reduced at 24 hours after application. The effects were fully reversible within 48 hours. According to Regulation (EC) No 1272/2008, TIS-M does not require classification as an eye irritant.