5-hept-6-enyloxolan-2-one

Endpoint summary

Description of key information

Not sensitising (OECD 406, GLP, K, rel.1).

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:

Between 13 December 2004 and 20 January 2005.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 406 with deviations: age at study initiation, housing and feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant. The substance is adequately identified. Therefore full validation applies.

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

17 July 1992.

Deviations:

yes

Remarks:

age at study initiation, housing and feeding conditions not reported

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

Directive 96/54/E.C.

Deviations:

yes

Remarks:

age at study initiation, housing and feeding conditions not reported.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2004-07-01 / Signed on 2004-07-11.

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

According to REACH regulation, in vivo skin sensitisation studies that were warried out or initiated before 10 May 2017 shall be considered appropriate to address this standard information requirement.

Specific details on test material used for the study:

Date received: 09 December 2004

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Centre de production Animale (F-45160 Olivet)
- Weight at study initiation: 267-361 g
- Housing: No data
- Diet: guinea-pig diet (certified 114)
- Water: No data
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-23 °C
- Humidity: 28-56 %

IN-LIFE DATES: 13 December 2004 to 20 January 2005

Route:

intradermal

Vehicle:

olive oil

Concentration / amount:

intradermic injection at 12.5%

Day(s)/duration:

Day 0

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

topical application at 100%

Day(s)/duration:

Day 7 / 24 hours

Adequacy of induction:

highest technically applicable concentration used

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

50%

Day(s)/duration:

Day 21 / 24 hours

Adequacy of challenge:

highest non-irritant concentration

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

25%

Day(s)/duration:

Day 21 / 24 hours

Adequacy of challenge:

other: 1/2 MNIC

No. of animals per dose:

Preliminary study: 7 males.
Main study: 10 (5 males and 5 females) for treated group (Group 2) and 5 (2 males and 3 females) for negative control (Group 1)

Details on study design:

PRELIMINARY TESTS:
Maximum Non Necrotizing Concentration (M.N.N.C.) determination: 2 male guinea pigs were used. The test item was injected by intradermal route at the following concentrations: 100%, diluted at 50%, 25%, 12.5%, 6.25% and 3.125% in olive oil. No necrosis has been observed, at the concentration of 12.5%, the first induction has been carried out by intradermal injection at the same concentration.

Pre-Maximum Non Irritant Concentration (Pre -M.N.I.C.) determination: 2 male guinea pigs were used. The test item was applied under an occlusive dressing during 24 hours, at the following concentrations 100%, diluted at 50%, 25% and 12.5% in paraffin oil. 24 hours after the removal of the occlusive dressings, it was only recorded a slight erythema in one animal on the treated area at 100%. In view of these results, the concentrations selected were pure (100%) for the 2nd induction of the main study and the MNIC began at the concentration of 50%

Maximum Non Irritant Concentration (M.N.I.C.) determination: 3 male guinea pigs were used. After induction by intradermal injection with olive oil and by topical application with paraffin oil and a 18-day rest phase, the challenge phase under occlusive dressing for 24 hours consists in a single topical application of the test item at the following concentrations: diluted at 50%, 25%, 12.5% and 6.25% in paraffin oil. 24 hours after removal of the occlusive dressings, no macroscopic reaction was recorded.In view of this result, the concentrations selected were 50% (MNIC) and 25% (1/2 MNIC) for the challenge phase.

MAIN STUDY
A. INDUCTION EXPOSURE (INTRADERMAL - 1st induction: Day 0)
- No. of exposures: One
- 2 intradermal injections of the test item diluted at 12.5% in olive oil.- 2 intradermal injections of Freund’s Complete Adjuvant diluted at 50% in in a physiological saline solution.- 2 intradermal injections of a mixture with equal volumes - Freund’s Complete Adjuvant at 50% and the product diluted at 25% in olive oil.
- Duration: 7 days
- Concentrations: 12.5% in olive oil

B. INDUCTION EXPOSURE (TOPICAL - 2nd induction: Day 7)
- No. of exposures: One
- Topical application, on the same zone, with the test item at 100%
- Concentrations: 100%

C. REST PHASE: 18 days

D. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Day 27
- Exposure period: 24 h
- Challenge phase (Groups 1 & 2): topical application under occlusive dressing at the following concentrations: 50% and 25%.
- Evaluation: 24 and 48 h after challenge

Challenge controls:

No. of animals for negative control group: 5 animals/tested concentrations: 25% and 50% (24h and 48h).

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazole [49-30-4] Test 8; Neomycin sulfate [1405-10-3]Tests 6 & 7.

Positive control results:

Historical data:
- NEOMYCIN SULFATE at 37.5% or 75% induced skin sensitisation in more than 30% of the treated animals indicating the validity of the study.

- 2-Mercaptobenzothiazole at 25% or 50% induced skin sensitisation in more than 30% of the treated animals indicating the validity of the study.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25% and 50%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25% and 50%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

25% and 50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

25% and 50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

25%

No. with + reactions:

4

Total no. in group:

9

Clinical observations:

None

Remarks on result:

positive indication of skin sensitisation

Remarks:

Historical data

Sensitising potential assessment:

No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test product.No cutaneous intolerance reaction was recorded in animals from the negative control group

Mortality: 

No death occurred during this study.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, test substance is not classified as sensitiser according to the criteria of the Regulation EC No. 1272/2008 (CLP) and of the GHS.

Executive summary:

In a Magnusson & Kligman maximisation study (GPMT) performed according to OECD Guideline 406 and in compliance with GLP, Guinea pigs were treated as follows:

After induction (intradermic injection at 12.5% and topical application at 100%) of 10 Guinea Pigs of treated group with the test substance and a 18 -day rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item diluted at 25% and 50 % in paraffin oil. The test concentrations for the main study were determined from a preliminary study.

 

No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item. No cutaneous intolerance reaction was recorded in animals from the negative control group.

 

The sensitivity of the guinea-pig was checked with known sensitiser i.e.,Neomycin sulfate and 2-Mercaptobenzothiazole indicating the validity of the study. 

 

Under the test conditions, the test substance is not classified as sensitiser according to the criteria of the Regulation EC No. 1272 /2008 (CLP) and of the GHS.

This study is considered as acceptable and satisfies the requirement for skin sensitisation endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

 

A key study was identified (Phycher, 2005). In this dermal sensitisation study performed according to the OECD guideline No. 406 and in compliance with GLP, Guinea pigs were treated as follows: after induction (intradermic injection at 12.5% and topical application at 100%) of 10 Guinea Pigs of treated group with the test substance and a 18 -day rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item diluted at 25% and 50% in paraffin oil. The test concentrations for the main study were determined from a preliminary study.

 

No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item. No cutaneous intolerance reaction was recorded in animals from the negative control group.

 

The sensitivity of the guinea-pig was checked with known sensitiser i.e.,Neomycin sulfate and 2-Mercaptobenzothiazole indicating the validity of the study. 

 

Under the test conditions, the test substance is not classified as sensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).

 

Self classification:

Based on the available data no additional self-classification is proposed according to the CLP and to the GHS.

 

No data was available for respiratory sensitisation. However, this substance is not a skin sensitizer, therefore according to Figure R.7.3 -4 of the Chapter R.7 (V 6 - July 2017) the chemical is not considered as a respiratory sensitiser.