Reaction mass of 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate and 3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-05-21 to 1979-06-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Non-GLP study conducted similarly to OECD Guideline 405 with deviations: no data about purity and no certificate of analysis of the test substance; no details on environmental conditions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

non-GLP study; no data about purity and no certificate of analysis of the test substance; no details on environmental conditions

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

pre-GLP

Test material

Test material information

Constituent 1

Reference substance name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

EC Number:

268-259-4

EC Name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-6-yl pivalate

Cas Number:

68039-44-1

Molecular formula:

C15H22O2

IUPAC Name:

3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-6-yl pivalate

Constituent 2

Reference substance name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate

EC Number:

268-261-5

EC Name:

3a,4,5,6,7,7a-hexahydro-4,7-methano-1H-inden-5-yl pivalate

Cas Number:

68039-45-2

Molecular formula:

C15H22O2

IUPAC Name:

3a,4,5,6,7,7a-hexahydro-1H-4,7-methanoinden-5-yl pivalate

impurity 1

Reference substance name:

rel-(1R,2S,3aR,4S,5R,6aS,7R)-octahydro-1,5:2,4-dimethanopentalen-7-yl pivalate

Molecular formula:

C15H22)2

IUPAC Name:

rel-(1R,2S,3aR,4S,5R,6aS,7R)-octahydro-1,5:2,4-dimethanopentalen-7-yl pivalate

Test material form:

other: liquid, may crystalize to white solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): PM 343 Pivaloxycyclene
- Source: PPL, UK
- Physical state: Very pale clear yellow liquid
- Date received: 29 March 1979

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Age at study initiation: 8 weeks
- Weight at study initiation: 1-2 kg

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

No washing was done.

Observation period (in vivo):

15 days

Number of animals or in vitro replicates:

Three

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Ocular lesions were scored at 15 min, 4, 24, 48 and 72 h and on Days 5, 8, 9, 10, 11, 12 and 15 according to the following scale:
CORNEA
Normal……0
Any change from normal, including slight dulling of corneal luster.......0.5 (can be considered as equivalent to 1 as recommended in OECD Guideline 405)
Scattered or diffuse areas of opacity, or loss of corneal epithelium, iris clearly visible….…1
Easily discernible, greyish, translucent areas, details of iris slightly obscured….…2
Grey-white areas, no details of iris visible, size of pupil barely discernible……..3
Complete corneal opacity, iris not discernible…..…4

IRIS
Normal…0
Any divergence from normal, congestion of iridial vessels, deepening on folds……+ (can be considered as equivalent to 1 as recommended in OECD Guideline 405)

CONJUNCTIVAE
Redness (palpebral and bulbar conjunctivae and nictitating membrane)
Vessel normal……0
Some vessel definitely injected……1
Diffusion, crimson red, individual vessel not easily discernible……2
Diffuse beefy red……3

CHEMOSIS
No swelling……0
Any swelling above normal……1
Obvious swelling with partial eversion of eyelids……2
Swelling with lids about half closed…..…3
Swelling with lids more than half closed………4

TOOL USED TO ASSESS SCORE: Slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: for undiluted test item

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: for undiluted test item

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: for undiluted test item

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: for undiluted test item

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: for undiluted test item

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: for undiluted test item

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: for undiluted test item

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: for undiluted test item

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: for undiluted test item

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: for undiluted test item

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: for undiluted test item

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: for undiluted test item

Irritant / corrosive response data:

- Moderate corneal opacities, affecting up to all cornea, were noted in all 3 rabbits. These reactions were associated with moderate corneal swelling.
- All animals had slight to moderate conjunctivitis and 2/3 animals had slight to moderate discharge.
- One animal healed by Day 4, one by Day 9 and one by Day 15.

Other effects:

None

Any other information on results incl. tables

Table 7.3.2/1: Individual ocular examinations and mean values of the scores recorded for each animal (24, 48 and 72 h) after instillation of undiluted test item

Rabbit No.	Region of eye	Scores
		15 min	4 h	24 h	48 h	72 h	Day 5	Day 8	Days 9-12	Day 15	Mean
											(24, 48 and 72 h)
1	Corneal opacity	-	-	1	1	1	1	-	1	N	1.0
	Iris	-	-	0	0	0	0	-	0	0	0.0
	Conjunctivae: Redness	1	1	1	2	1	1	-	0	0	1.3
	Conjunctivae: Chemosis	0	0	1	0	0	0	-	0	0	0.3
2	Corneal opacity	-	-	1	1	N	-	-	-	-	0.7
	Iris	-	-	0	0	0	-	-	-	-	0.0
	Conjunctivae: Redness	1	1	1	1	0	-	-	-	-	0.7
	Conjunctivae: Chemosis	0	1	1	0	0	-	-	-	-	0.3
3	Corneal opacity	-	-	1	1	1	-	N	-	-	1.0
	Iris	-	-	0	0	0	-	0	-	-	0.0
	Conjunctivae: Redness	1	1	1	1	0	-	0	-	-	0.7
	Conjunctivae: Chemosis	0	1	1	0	0	-	0	-	-	0.3

 N: No information about the symbol was reported by the author. In the text, it was mentioned that one animal healed by Day 4, one by Day 9 and one by Day 15 therefore 'N' was considered as equivalent to zero for the calculation of mean scores.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the test conditions, PM 343 Pivaloxycyclene is classified as ‘Irritating to eyes (Category 2)’ according to the CLP Regulation. It is not classified as irritating to eyes according to the Directive 67/548/EEC.

Executive summary:

In an eye irritation study conducted similarly to the OECD Guideline 405, 0.1 mL of the undiluted test item, PM 343 Pivaloxycyclene, was instilled into one eye of 3 rabbits. The eyes were examined and the changes were scored at 15 min, 4, 24, 48 and 72 h and on Days 5, 8, 9, 10, 11, 12 and 15.

Single application of the undiluted preparation caused moderate corneal opacities, affecting up to all cornea, in all 3 rabbits. These reactions were associated with moderate corneal swelling. All animals had slight to moderate conjunctivitis and 2/3 animals had slight to moderate discharge. One animal healed by Day 4, one by Day 9 and one by Day 15. Mean individual scores at 24, 48 and 72 h for the 3 animals after exposure to undiluted item were 1.0, 0.7, 1.0 for cornea score; 0, 0, 0 for iris score; 1.3, 0.7, 0.7 for conjunctivae score and 0.3, 0.3, 0.3 for chemosis score.

Under the test conditions, PM 343 Pivaloxycyclene is classified as ‘Irritating to eyes (Category 2)’ according to the CLP Regulation.