Bicyclo[2.2.1]heptane, 2-ethyl-5-methoxy-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 09 May 1988 and 23 May 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

403-610-9

EC Name:

-

Cas Number:

122795-41-9

IUPAC Name:

1-ethyl-3-methoxytricyclo[2.2.1.0²,⁶]heptane; 2-ethyl-5-methoxybicyclo[2.2.1]heptane; 2-ethyl-6-methoxybicyclo[2.2.1]heptane

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Buckmasters, Henham, Hertfordshire, England.
- Age at study initiation: Approximately 12 to 15 weeks
- Weight at study initiation: 2.9 to 3.3 kg
- Housing: The rabbits were individually housed in metal cages with perforated floors
- Diet: Free access to SDS Standard Rabbit Diet.
- Water: Free access to tap water

ENVIRONMENTAL CONDITIONS
- Temperature:: Animal room temperature was maintained at approximately 19°C
- Humidity: 30-70%.
- Air changes: Approximately 19 air changes per hour
- Photoperiod: Lighting was controlled to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and was used for control purposes.

Amount / concentration applied:

A 0.1 ml aliquot of ethyl methoxy norbornane was placed into the lower everted lid of one eye of each animal.

Duration of treatment / exposure:

Up to 1 hour

Observation period (in vivo):

Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation.

Number of animals or in vitro replicates:

3

Details on study design:

The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage or conjunctival inflammation.

A 0.1 ml aliquot of ethyl methoxy norbornane was placed into the lower everted lid of one eye of each animal.

The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated and served as a control.

Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation. Observation of the eyes was aided by the use of a handheld torch.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #137

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: #138

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal: #139

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal: #137

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

iris score

Basis:

animal: #138

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal: #139

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #137

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 7 d

Results 8

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: #138

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 3 d

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: #139

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 10

Irritation parameter:

chemosis score

Basis:

animal: #137

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 d

Results 11

Irritation parameter:

chemosis score

Basis:

animal: #138

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

chemosis score

Basis:

animal: #139

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 d

Irritant / corrosive response data:

The numerical scores awarded to the ocular reactions elicited by Neoproxen are given in Table 1
One of the animals gave a "positive" response.
No corneal damage or iridial inflammation were observed.
A diffuse crimson colouration of the conjunctivae accompanied by obvious swelling with partial eversion of the eyelids was observed in one of the animals. Mild conjunctival irritation only was observed in the other two animals. The reactions had resolved two, three or seven days following instillation of the test substance.

Any other information on results incl. tables

Table 1: Ocular reactions elicited by ethyl methoxy norbornane

Rabbit number and sex	Region of eye		One hour	Day after instillation					Result Positive (+) Negative (-)
				1	2	3	4	7
137♂	Cornea		0	0	0	0	0	0	+
	Iris		0	0	0	0	0	0
	Conjunctivae	Redness	2	1	0	0	0	0
		Chemosis	2	1	0	0	0	0
138♂	Cornea		0	0	0	0	0	0	-
	Iris		0	0	0	0	0	0
	Conjunctivae	Redness	1	1	0	0	0	0
		Chemosis	1	0	0	0	0	0
139♂	Cornea		0	0	0	0	0	0	-
	Iris		0	0	0	0	0	0
	Conjunctivae	Redness	1	0	0	0	0	0
		Chemosis	1	1	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

other: Not irritating according to EU CLP (EC 1272/2008 and its amendments).

Conclusions:

Neoproxen is not considered to be irritating to eyes.

Executive summary:

The irritant effects of Neoproxen to the rabbit eye was assessed in a GLP study according to OECD Guideline No. 405. Slight effects on conjunctivae were observed in all animals only at day 1.