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

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study conducted similarly to OECD Guideline 406 with deviations: no data about purity and no certificate of analysis of the test substance; individual weights of animals were not reported

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

no GLP statement; no data about purity and no certificate of analysis of the test substance; individual weights of animals were not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 300-400 g
- Source: Bantin and Kingman, Hull, Yorks
- Housing: Housed in grid-floor cages
- Diet (e.g. ad libitum): SGP diet (Labsure A.F. Limited, Poole, UK); ad libitum
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 h artificial light / 12 h dark

Route:

intradermal and epicutaneous

Vehicle:

water

Remarks:

for injections B.P.

Concentration / amount:

Preliminary test:
- Intradermal injections: 1 and 5 % (v/v) in liquid paraffin B.P.

Main test:
- Intradermal induction exposure: 5 % (v/v) in water for injections B.P.
- Topical induction and challenge exposures: 100 % (undiluted)

Route:

epicutaneous, occlusive

Vehicle:

water

Remarks:

for injections B.P.

Concentration / amount:

Preliminary test:
- Intradermal injections: 1 and 5 % (v/v) in liquid paraffin B.P.

Main test:
- Intradermal induction exposure: 5 % (v/v) in water for injections B.P.
- Topical induction and challenge exposures: 100 % (undiluted)

No. of animals per dose:

Preliminary test: 2 males
Main test: 12 males in treatment group and 10 males in control group

Details on study design:

PRELIMINARY TEST:
- Intradermal injection: Two male guinea pigs received intradermal injections of test material at concentrations of 1 and 5 % (v/v) in liquid paraffin B.P. and evaluated for local reactions at 7 days after injection.

MAIN STUDY
A. INDUCTION EXPOSURE: INTRADERMAL
- No. of exposures: One
- Test groups: Intradermally injected with 2 injections each of 0.1 mL of Freund’s adjuvant alone, 5 % (v/v) test material in vehicle and 5 % (v/v) test material emulsified in adjuvant on Day 1.
- Treated control group: Intradermally injected with 2 injections each of 0.1 mL of Freund’s adjuvant alone, vehicle alone and adjuvant mixed with vehicle on Day 1.
- Site: 6 different sites (2 x 4 cm) on shoulder region
- Duration: Days 1-7

B. INDUCTION EXPOSURE: TOPICAL
- No. of exposures: One
- Exposure period: 48 h
- Test groups: Six days after the intradermal injections, the injections sites were clipped and treated with 10 % sodium lauryl sulphate in petrolatum. On Day 8, filter paper patches (2 x 4 cm) loaded with the undiluted test substance were topically applied over the shoulder injection sites via occlusive patch.
- Treated control group: Filter paper patches saturated with vehicle alone were topically applied on Day 8 via occlusive patch.
- Site: Shoulder region
- Frequency of applications: Single application
- Duration: Days 8-21

C. CHALLENGE EXPOSURE: TOPICAL
- No. of exposures: One
- Days of challenge: Days 22
- Exposure period: 24 h
- Test group: Filter paper patch (2 x 2 cm) was loaded with the undiluted test material and then topically applied to the clipped flank on Day 22 via occlusive patch.
- Site: Flank
- Evaluation (h after application of challenge patch): 48 and 72 h

Challenge controls:

- Control groups: Filter paper patches were loaded with the test material at the concentrations of 100 % (undiluted) and 50 % in petrolatum and then topically applied to the clipped flank on Day 22 via occlusive patches.

Positive control substance(s):

no

Positive control results:

Not applicable

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

12

Clinical observations:

no data

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 12.0. Clinical observations: no data.

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

12

Clinical observations:

no data

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 12.0. Clinical observations: no data.

Preliminary test:

- At 7 days following intradermal injections: Slightly raised reaction

Main test:

- At 7 days following intradermal injections: Slight inflammatory response at sites injected with test material; marked inflammatory reactions at sites injected with Freund’s Adjuvant mixed with or without test material;

- At 24 h following topical induction: Mild to moderate inflammatory response

- At 48 and 72 h following challenge application: No skin reactions

Interpretation of results:

not sensitising

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

Executive summary:

In a Magnusson and Kligman maximisation study (GPMT) performed similarly to OECD guideline 406, 12 male guinea pigs were intradermally induced with two injections each of 0.1 mL of Freund’s adjuvant alone, 5 % (v/v) Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran 9.6.1980 in vehicle (water for injections B.P.) and 5 % (v/v) test item emulsified in adjuvant on Day 1 on six different sites on shoulder region. Treated control group of 10 male guinea pigs was intradermally induced with FCA, vehicle and a mixture of FCA in vehicle. After 6 days of injection, the same sites were clipped and treated with 10 % sodium lauryl sulphate in petrolatum. On next day (Day 8), filter paper patches (2 x 4 cm) loaded with the undiluted test substance were topically applied over the sites via occlusive patch. Animals in the control group were patched with the filter paper saturated with vehicle alone. After 2 weeks of rest period, a challenge filter paper patch of undiluted test material was applied to the shaved flank of all animals in treatment and control groups. After 24 h, the patches were removed and skin reactions were observed at 48 and 72 h after challenge. The test concentrations for the main study were determined from a sighting study using male guinea pigs which received intradermal injections of test material at concentrations of 1 and 5 % (v/v) in liquid paraffin B.P. and evaluated for local reactions at 7 days after injection.

No skin reactions were noted at the challenge sites in treatment and control group animals at the 48 or 72-h post-challenge observations. Test item didn't produce any sensitisation (0 animal out of 12) after challenge exposure and was considered not to be a sensitizer to guinea pig skin.

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a Magnusson and Kligman maximisation study (GPMT) performed similarly to OECD guideline 406, 12 male guinea pigs were intradermally induced with two injections each of 0.1 mL of Freund’s adjuvant alone, 5 % (v/v) Reaction mass of 3,6-dihydro-4-methyl-2-phenyl-2H-pyran and tetrahydro-4-methylene-2-phenyl-2H-pyran in vehicle (water for injections B.P.) and 5 % (v/v) test item emulsified in adjuvant on Day 1 on six different sites on shoulder region. Treated control group of 10 male guinea pigs was intradermally induced with FCA, vehicle and a mixture of FCA in vehicle. After 6 days of injection, the same sites were clipped and treated with 10 % sodium lauryl sulphate in petrolatum. On next day (Day 8), filter paper patches (2 x 4 cm) loaded with the undiluted test substance were topically applied over the sites via occlusive patch. Animals in the control group were patched with the filter paper saturated with vehicle alone. After 2 weeks of rest period, a challenge filter paper patch of undiluted test material was applied to the shaved flank of all animals in treatment and control groups. After 24 h, the patches were removed and skin reactions were observed at 48 and 72 h after challenge. The test concentrations for the main study were determined from a sighting study using male guinea pigs which received intradermal injections of test material at concentrations of 1 and 5 % (v/v) in liquid paraffin B.P. and evaluated for local reactions at 7 days after injection.

Migrated from Short description of key information:
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 a skin sensitiser to guinea pigs and therefore is not classified according to the Directive 67/548/EEC and the CLP Regulation.

Justification for selection of skin sensitisation endpoint:
Reliable in vivo study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Migrated from Short description of key information:
No respiratory sensitisation study available. However, such effects are unlikely as Rosyrane is not a skin sensitiser to guinea pigs and its low volatility indicates that significant inhalation is unlikely under anticipated conditions of use.

Justification for classification or non-classification

Based on a negative result in the reliable in vivo skin sensitisation study, classification under the EU DSD or CLP regulations is not required.