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

Skin irritation / corrosion

Administrative data

Endpoint:

skin 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: see 'Remark'

Remarks:

Non-GLP study conducted similarly to OECD Guideline 404 with deviations: no data about purity and no certificate of analysis of the test substance; no details on environmental conditions; occlusive patches applied for 24 h and scored at 24 and 72 h after application; observations not followed until the reversibility of the effects

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

no GLP statement; no data about purity; no certificate of analysis of test substance; no details on environmental conditions; occlusive patches applied for 24 h and scored at 24 and 72 h after application; observations not followed until the reversibility

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-methyl dihydropyran 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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Age at study initiation: Adult

Test system

Type of coverage:

occlusive

Preparation of test site:

other: intact or abraded skin

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

72 h

Number of animals:

12 rabbits (6 with intact skin and 6 with abraded skin)

Details on study design:

- Area of exposure: Back of the animals
- % coverage: Test substance (0.5 mL) was applied under a surgical patch (1 inch x 1 inch) to the intact or abraded skin site on each animal.
- Type of wrap used: The patches were fixed to the application site by means of adhesive tape and the entire trunk of the rabbits was wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.

REMOVAL OF TEST SUBSTANCE
- After an exposure period of 24 h, the patches and the applied material were removed.

SCORING SYSTEM:
- Skin reactions were scored at 24 and 72 h after application according to Draize scoring system (1944).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 24 and 72 h

Score:

1.3

Max. score:

4

Reversibility:

no data

Remarks on result:

other: intact skin

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 24 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

no data

Remarks on result:

other: intact skin

Irritant / corrosive response data:

- After 24 h, very slight or well-defined erythema was generally noted in animals.
- After 72 h, very slight erythema, slight to distinct scaliness and very slight oedema were noted in 4/12 rabbits.
- After 24 and 72 h, focal haemorrhages were noted on the abraded skin of one rabbit. It was stated by the author that this rabbit had an abnormally sensitive skin.
- No distinct differences were noted between the reactions on the intact skin and abraded skin.

Other effects:

None

Any other information on results incl. tables

Table 7.3.1/1: Skin irritation data for individual rabbits

Rabbit number	Irritation scores (Intact skin)
	24 h		72 h		Mean (24 and 72 h)
	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
1	2	1	1	1	1.5	1.0
2	1	0	2	0	1.5	0.0
3	2	0	1	1	1.5	0.5
4	1	0	1	0	1.0	0.0
5	1	0	1	0	1.0	0.0
6	1	0	1	0	1.0	0.0
Mean (all 6 animals)					1.3	0.3

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 skin according to the Directive 67/548/EEC and the CLP Regulation.

Executive summary:

In a primary dermal irritation study performed similarly to OECD Guideline 404, 12 New Zealand White rabbits were dermally exposed to 0.5 mL of Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran, under an occlusive patch (1 inch X 1 inch) to intact or abraded skin of the dorsal region. After an exposure period of 24 h, the patches and the applied material were removed and skin reactions were scored by Draize method. A second reading was recorded 48 h later (72 h after application). Irritation scores at 48 h after application were derived using the worst case scores recorded at 24 or 72 h.

After 24 h, very slight or well-defined erythema was generally noted in animals. After 72 h, very slight erythema, slight to distinct scaliness and very slight oedema were noted in 4/12 rabbits. After 24 and 72 h, focal haemorrhages were noted on the abraded skin of one rabbit. It was stated by the author that this rabbit had an abnormally sensitive skin. No distinct differences were noted between the reactions on the intact skin and abraded skin.

The calculated mean scores for each individual lesion for all animals within scoring times (24 and 72 h) were as follows: 1.3 for erythema score (intact skin) and 0.3 for oedema score (intact skin).

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 skin according to the Directive 67/548/EEC and the CLP Regulation.