2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: CFR, title 16, section 1500.42

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Test material

Test material information

Constituent 1

Reference substance name:

2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

EC Number:

233-487-5

EC Name:

2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

Cas Number:

10196-49-3

Molecular formula:

C6H15NOSi

IUPAC Name:

2,2,4-trimethyl-1,4,2-oxazasilinane

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht, Extertal 1
- Weight at study initiation: 2.6 kg (average)
- Housing: each animal in separate cage
- Diet (e.g. ad libitum): mümmel z (sniff / Soest), ad libitum
- Water: ad libitum
- Acclimation period: 7-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18°C
- Humidity (%): 40% r.h.
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 100 µL

Duration of treatment / exposure:

not applicable (eye was not rinsed after treatment)

Observation period (in vivo):

24/48/72 hours as well as 8 days after start of treatment.

Number of animals or in vitro replicates:

6 males

Details on study design:

SCORING SYSTEM:
Scoring according to "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, 1959, p.51".

TOOL USED TO ASSESS SCORE: ophthalmoscope 24/48/72 hours (fluorescein after 8 days; not considered for scoring)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1-#3,#6

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 48 hrs

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: #4,#5

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

iris score

Basis:

animal: #1-#6

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not reversible

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal: #2,#4

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

not fully reversible within: 48 hrs

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal: #3,#5,#6

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Results 7

Irritation parameter:

chemosis score

Basis:

animal: #1,#2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Results 9

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 10

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not reversible

Results 11

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Irritation effects were observed in all animals and at all irritation parameters. No effect was fully reversible and most effects were not reversible at all. Opthalmoscopic fluorescine observations on eyes rinsed with NaCl 8 days after treatment showed worsen cornea opacity score of 3.33 (average of animals #1-#6).

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
24 h	2/2/2/1/1/2	1/1/1/1/1/1	2/3/2/3/2/2	2/2/2/3/3/2
48 h	1/1/1/1/1/1	1/1/1/1/1/1	3/2/2/2/2/2	2/2/3/3/3/3
72 h	1/1/1/1/1/1	1/1/1/1/1/1	3/2/2/2/2/2	2/2/3/3/4/2
Average 24h, 48h, 72h	1.33/1.33/1.33/1/1/1.33	1/1/1/1/1/1	2.67/2.33/2/2.33/2/2	2/2/2.67/3/3.33/2.33
Reversibility*)	n.c./n.c./n.c./n./n./n.c.	n./n./n./n./n./n.	n./n.c./n./n.c./n./n.	n./n./n./n./n./n.
Average time (unit) for reversion	48 hrs	--	--	--

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In this study, the test substance showed irreversible effects on the eyes.

Executive summary:

In a primary eye irritation study performed in accordance with the Code of Federal Regulations, Title 16, Section 1500.42 (Test for eye irritants), the test substance was instilled into the right eye’s conjunctival sac of adult male albino rabbits (strain New Zealand White) followed by lid close for 1 second. The treated eyes were not washed after treatment. The left untreated eyes served as controls.

Animals then were observed for 8 days with score relevant observations being carried out at 24/48/72 hours after treatment.  Irritation was scored by the method described in “The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA, 1959, p.51”.

Irritation effects were observed in all animals and at all irritation parameters. No effect was fully reversible and most effects were not reversible at all. Opthalmoscopic fluorescine observations on eyes rinsed with NaCl 8 days after treatment showed worsen cornea opacity score of 3.33 (average of animals #1-#6). In this study, the test substance is a strong eye irritant (GHS Cat 1).

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Damage 1 (H318: Causes serious eye damage) is justified.