Reaction mass of 6-butyl-3,6-dihydro-2,4-dimethyl-2H-pyran and 2-butyl-3,6-dihydro-4,6-dimethyl-2H-pyran and 2-butyltetrahydro-6-methyl-4-methylene-2H-pyran

Endpoint summary

Description of key information

Key study_Primary skin irritation test with Gyrane in albino rabbits dated on February 1986 performed according to a similar guidance to OECD guideline 404.

Key study_ Eye irritation test with Gyrane in albino rabbits dated on June 1983 performed according to a similar guidance to OECD guideline 405.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion, other

Remarks:

Available In vivo studies were sufficient to allow us to filled this endpoint and determined the classification.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 17, 1985 - December 30, 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study has been performed equivalent to OECD 404 guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

other: EEC Directive 79-831, Annex V, Part B: Methods for the determination of toxicity, B.4. Acute toxicity, skin irritation, dated December 1983.

GLP compliance:

yes

Specific details on test material used for the study:

Material Identification (as stated in the report) : Gyrane ST 2
Appearance: Clear yellow slightly viscous liquid
Sample received on: November 25, 1985

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ENKI-Konijnenfarm, Someren, The Netherlands
- Weight at study initiation: 2500 - 3500 g
- Housing: Individually in suspended, galvanized cages, fitted with wire-mesh floor and front.
- Diet and water: provided ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 40 - 70
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

The skin reactions were assessed directly, 24, 48 and 72 hours and 7 and 13 days after the removal of the dressings and test substance.

Number of animals:

6 male adults

Details on study design:

STUDY DESIGN
The test substance is brought on the intact and abraded skin under a surgical patch measuring 1 inch x 1 inch. The patch were fixed to the application site by means of adhesive tape and the entire trunk of each rabbit was wrapped with an impervious material to maintain the test patches in position and to retard the evaporation of the test material.

TEST SITE
Twenty four hours prior to applying the material, the hair is removed from the back and flanks of the animals with an electric clipper in such a way as to avoid abrasions.
Six rabbits are treated on the intact skin and on the abraded skin. The abrasions are minor incisions of the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing and test substance was removed.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Irritation parameter:

erythema score

Basis:

animal: 3452 and 3455

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 13 days

Irritation parameter:

erythema score

Basis:

animal: 3453 and 3454

Time point:

24/48/72 h

Score:

1.6

Max. score:

2

Reversibility:

fully reversible within: 13 days

Irritation parameter:

erythema score

Basis:

animal: 3456 and 3457

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 13 days

Irritation parameter:

edema score

Basis:

animal: 3452, 3453, 3454, 3456 and 3457

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 13 days

Irritation parameter:

edema score

Basis:

animal: 3455

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

After 4 to 76 hours after exposure, the dermal effects observed in all six animals consisted of very slight or well-defined erythema with or without very slight oedema. After seven days, very slight erythema with or without very slight oedema was observed in five out of six animals. There were no significant differences between the effects of the intact skin and the effects of the abraded skin. After 13 days, all skin effects had cleared completely.

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

In an skin irritation study with rabbits, performed equivalent to OECD 404 test guidelines and GLP principles, slight irritation was observed but no sufficient to classify according the CLP Regulation (EC) No. 1272/2008.

Executive summary:

Gyrane St 2 was tested in a skin irritation study with rabbits, performed equivalent to OECD 404 test guideline and GLP principles.

After 4 to 76 hours after exposure, the dermal effects observed in all six animals consisted of very slight or well-defined erythema with or without very slight oedema. After seven days, very slight erythema with or without very slight oedema was observed in five out of six animals. There were no significant differences between the effects of the intact skin and the effects of the abraded skin. After 13 days, all skin effects had cleared completely.

Based on the results, slight irritation was observed but no sufficient to classify according the CLP Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation, other

Remarks:

An available In vivo study were sufficient to allow us to filled this endpoint and determined the classification.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The techniques of tests as published by the FDA of the US (Fed. Reg. 28 (119), 5582, 1963) and Draize and Kelley (Drug Cosmet. Industr. 71 (1952) 36) are followed.

GLP compliance:

no

Specific details on test material used for the study:

Material Identification (as stated in the report) : Gyrane U 05315
Appearance: Clear colorless liquid
Sample received on 8th, March 1983

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: individually housed

Vehicle:

unchanged (no vehicle)

Remarks:

The test material was examined pure and undiluted in six rabbits.

Controls:

other: the other eye remaining intreated, serves as control

Amount / concentration applied:

TEST MATERIAL- Amount applied: 0.1 mL

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 7 days after instillation of the test substance.

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

STUDY DESIGN
0.1 mL of the test substance is allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material.

REMOVAL OF TEST SUBSTANCE
The eyes are not washed following instillation and the animals are released immediately.

OBSERVATIONS
The eyes of each animal were examined approximately 24, 48 and 72 hours and 7 days after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.

Irritation parameter:

cornea opacity score

Basis:

animal: 1, 2, 3, 4, 5, and 6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: score 0

Irritation parameter:

iris score

Basis:

animal: 1, 2, 3, 4, 5, and 6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: score 0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: 4, 5 and 6

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: 2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: score 0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal: 1 and 2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal: 1, 3 and 4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible within: score 0

Irritation parameter:

chemosis score

Basis:

animal: 2

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal: 5 and 6

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

After 24 hours the eye effects caused by the test substance consisted of slight redness of the conjunctivae in five out of six animals and slight swelling of the conjunctivae in three out of six animals. Up to day 7 some of these effects cleared up completely. However, after 7 days slight redness of the conjuctivae was still seen in three out of six animals.

Interpretation of results:

GHS criteria not met

Conclusions:

In an eye irritation study with rabbits, performed equivalent to OECD 405 test guideline, Gyrane caused slight redness and slight swelling of the conjunctivae in the animals. Nevertheless the test results do not meet the critera to be classified for skin irritation according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances.

Executive summary:

Gyrane was tested in an eye irritation study with rabbits, performed equivalent to OECD 405 test guideline.

Eye effects caused by the test substance consisted of slight redness of the conjunctivae in five out of six animals and slight swelling of the conjunctivae in three out of six animals. Up to day 7 some of these effects cleared up completely. However, after 7 days slight redness of the conjuctivae was still seen in three out of six animals.

Although the observation period was not extended it is assumed that after 21 days the effects observed (only redness of the conjunctivae) will be reversible. The test material does not meet the critera to be classified for skin irritation according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances according to this test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Skin irritation_ Key study

Gyrane St 2 was tested in a skin irritation study with rabbits, performed equivalent to OECD 404 test guideline and GLP principles.

After 4 to 76 hours after exposure, the dermal effects observed in all six animals consisted of very slight or well-defined erythema with or without very slight oedema. After seven days, very slight erythema with or without very slight oedema was observed in five out of six animals. There were no significant differences between the effects of the intact skin and the effects of the abraded skin. After 13 days, all skin effects had cleared completely.

Based on the results, slight irritation was observed but no sufficient to classify according the CLP Regulation (EC) No. 1272/2008.

Eye irritation:

Gyrane was tested in an eye irritation study with rabbits, performed equivalent to OECD 405 test guideline.

Eye effects caused by the test substance consisted of slight redness of the conjunctivae in five out of six animals and slight swelling of the conjunctivae in three out of six animals. Up to day 7 some of these effects cleared up completely. However, after 7 days slight redness of the conjuctivae was still seen in three out of six animals.

Although the observation period was not extended it is assumed that after 21 days the effects observed (only redness of the conjunctivae) will be reversible. The test results do not meet the critera to be classified for skin irritation according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances.