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 is Maximization test with Gyrane in guinea pigs from TNO Central institute for nutrition and food research, dated on July 1979 and performed accoring to an equivalent method of OECD guideline 406.

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:

01 June, 1979 - 24 June, 1979

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 406 (Skin Sensitisation)

Principles of method if other than guideline:

The test was mainly conducted according to the method described by Magnusson and Kligman, "Allergic contact dermatitis in the guinea pig", Ed. Ch.C. Thomas, Springfield, Illinois, USA (1970).

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

This available in vivo studies (non LLNA) was sufficient to allow us to filled this endpoint and determined the classification.

Specific details on test material used for the study:

Material Identification (as stated in the report) : Gyrane T 05315
Appearance: Clear colorless liquid
Sample received on 4th, May 1979

Species:

guinea pig

Strain:

other: Albino SPF

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Central Institute for the breeding of laboratory animals TNO, Zeist, The Netherlands
- Age at study initiation: young male animals
- Weight at study initiation: 368 - 562 g
- Housing: Individually housed in suspended stainless steel cages, fitted with wire mesh floors and fronts
- Diet: Stock diet enriched with vitamin C ad libitum
- Water: Tap water ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 1
- Humidity (%): 50 ± 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

other: Freund's adjuvant with propylene glycol

Concentration / amount:

a concentration of 50% Gyrane was chosen for the induction

Adequacy of induction:

other: this concentration induced only moderate irritation reactions in preliminary observations

Route:

other: topical application

Vehicle:

unchanged (no vehicle)

Concentration / amount:

100% of Gyrane

Day(s)/duration:

48 hours

No.:

#1

Route:

other: topical application

Vehicle:

other: vaseline

Concentration / amount:

a concentration of 20% which proved to be non-irritating in a preliminary test was used for the challenge

No. of animals per dose:

Test animals: 10 males
Control animals: 5 males

Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1

1) Intradermal injections on day 1:
- Site: shoulder region shaved with electric clippers
Three pairs of intradermal injections in an area of 2x4 cm:
1) 0.05 mL: Freund's Adjuvant
2) 0.05 mL: test substance at a 50% concentration in vehicle (control animals: propylene glycol)
3) 0.05 mL: 1:1 mixture of 50% concentration of the test substance in Freund's Adjuvant (control animals: propylene glycol in Freund's Adjuvant)

2) Topical application on day 8:
- Site: shoulder region shaved with electric clippers
- Amount: 100% test substance
- Area: approximately 8 cm^2
- Exposure period: 48 hours (occlusive)

B. CHALLENGE EXPOSURE
- Day of challenge: day 21, all animals, with the 20% test substance mixed with vaseline
- Exposure period: 24 hours (occlusive)
- Site: right flank, shaven
- Readings: 24 hours after patch removal

OBSERVATIONS
Skin reactions were judged by the method of Draize, as described in J. Pharmacol. 82 (1944) 377-390

Challenge controls:

Not applicable.

Positive control substance(s):

no

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

20%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

20%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

no indication of skin sensitisation

Preliminary test:

A concentration of 50% was chosen for intradermal induction, because this concentration induced only moderate irritation.

A concentration of 20%, which proved to be non-irritating in the topical induction, was used for the challenge.

Main test:

The intradermal injections given in the induction phase resulted in:

- FCA: abscesses

- 50% test substance in propylene glycol: abscesses;

- 50% test substance in propylene glycol + FCA: abscesses

The 100% concentration test substance induced neither erythema nor edema upon topical application in the induction phase. No sodium lauryl sulphate (SLS) has been used, in order to create a local irritation.

In the challenge, the 20% concentration provoked no erythema or edema in any of the animals in the test group. The control animals showed no reaction.

Interpretation of results:

GHS criteria not met

Conclusions:

Gyrane was examined for possible sensitization properties in a maximisation test with guinea pigs. From the reaction to the challenge dose it was concluded that the test material induced no sensitization.

Executive summary:

In a guinea pig maximisation test method the potential of Gyrane for skin sensitisation was tested similar to OECD 406 guideline.

The intradermal injections (50% test substance concentration) given in the induction phase resulted in abscesses.

The 100% concentration test substance induced neither erythema nor edema upon topical application in the induction phase. Sodium lauryl sulphate (SLS) should have been used, in order to create a local irritation.

In the challenge, the 20% concentration provoked no erythema or edema in any of the animals in the test group. A higher concentration should have been used for challenge (see induction). The control animals showed no reaction. Therefore, the test material does not meet the critera to be classified for skin sensitisation 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 sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In a guinea pig maximisation test method the potential of Gyrane for skin sensitisation was tested similar to OECD 406 guideline.

The intradermal injections (50% test substance concentration) given in the induction phase resulted in abscesses.

The 100% concentration test substance induced neither erythema nor edema upon topical application in the induction phase. Sodium lauryl sulphate (SLS) should have been used, in order to create a local irritation.

In the challenge, the 20% concentration provoked no erythema or edema in any of the animals in the test group. A higher concentration should have been used for challenge (see induction). The control animals showed no reaction. Therefore, 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.