Reaction mass of 4-methylene-2-phenyltetrahydro-2H-pyran and 4-methyl-2-phenyl-3,6-dihydro-2H-pyran

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 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; age of animals at the start of study was not reported

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no GLP statement; no data about purity and no certificate of analysis of the test substance; no details on environmental conditions; age of animals at the start of study was not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of 4-methylene-2-phenyltetrahydro-2H-pyran and 4-methyl-2-phenyl-3,6-dihydro-2H-pyran

EC Number:

943-338-2

Molecular formula:

C12H14O

IUPAC Name:

Reaction mass of 4-methylene-2-phenyltetrahydro-2H-pyran and 4-methyl-2-phenyl-3,6-dihydro-2H-pyran

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 2-Phenyl-4-methyldihydropyran
- Physical state: Clear colourless liquid with a pungent odour
- Date received: 08 October 1980

Please note that although the substance is stated as a mono-constituent substance 2-Phenyl-4-methyldihydropyran in the report, recent analytical data has determined the substance to be a multi-constituent (Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran). As the chemical manufacturing process has not changed since the report was written, the recent analytical information is relevant to the batch which was tested.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Housing: Animals were housed individually in cages.

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
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

Six

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Eyes were not washed following instillation and the animals were released immediately.

SCORING SYSTEM: Ocular lesions were observed at 24, 48 and 72 h and 7 days after instillation and graded according to a scale comparable to OECD guideline 405.

TOOL USED TO ASSESS SCORE: Ocular reactions were read using a binocular magnifying glass. The diagnosis of corneal damage was confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eyes were examined in a dark room under UV illumination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: average of 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: average of 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: average of 24, 48 and 72 h

Score:

0.5

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: average of 24, 48 and 72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritant / corrosive response data:

- Slight redness and slight swelling of the conjunctivae were noted in 5/6 and 2/6 rabbits, respectively.
- Within 7 days, these lesions had cleared up completely.

Other effects:

None

Any other information on results incl. tables

Table 7.3.2/1: Scores for ocular lesions

Animal no.	Cornea				Iris				Conjunctivae redness				Conjunctivae chemosis
	24 h	48 h	72 h	Mean*	24 h	48 h	72 h	Mean*	24 h	48 h	72 h	Mean*	24 h	48 h	72 h	Mean*
1	0	0	0	0	0	0	0	0	1	1	0	0.67	1	0	0	0.33
2	0	0	0	0	0	0	0	0	1	0	0	0.33	0	0	0	0.00
3	0	0	0	0	0	0	0	0	1	1	0	0.67	0	0	0	0.00
4	0	0	0	0	0	0	0	0	1	1	1	1.00	1	0	0	0.33
5	0	0	0	0	0	0	0	0	1	0	0	0.33	0	0	0	0.00
6	0	0	0	0	0	0	0	0	0	0	0	0.00	0	0	0	0.00
Mean^#				0				0				0.50				0.11

*mean of scores at 24, 48 and 72 h

^#mean of scores of all 6 animals

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran is not classified as irritating to eyes according to the Directive 67/548/EEC and the CLP Regulation.

Executive summary:

In an eye irritation study conducted similarly to the OECD Guideline 405, six rabbits of the New Zealand White strain were exposed to 0.1 mL of Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran in their one eye, while the other eye remained untreated and served as control. The eyelids were then gently held together for 1 second to avoid any loss of the test material. Eyes were not washed and ocular reactions were read at 24, 48 and 72 h and 7 days following instillation using a binocular magnifying glass. The diagnosis of corneal damage was confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eyes were examined in a dark room under UV illumination. Ocular reactions were graded according to a scale comparable to the OECD Guideline 405.

Slight redness and slight swelling of the conjunctivae were noted in 5/6 and 2/6 rabbits, respectively. Within 7 days, these lesions had cleared up completely. The calculated mean scores for each individual lesion for all animals within three scoring times (24, 48 and 72 h) were as follows: 0.00 for cornea score; 0.00 for iris score; 0.50 for conjunctivae score and 0.11 for chemosis score. In this study, 2-phenyl-4-methyldihydropyran is not considered as irritating to eyes in rabbits.

Under the test conditions, Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran is not classified as irritating to eyes according to the Directive 67/548/EEC and the CLP Regulation.