Oxaceprol

Endpoint summary

Description of key information

Oxaceprol produced a 0 % (0/10) sensitisation rate and is classified as a non-sensitiser to guinea pig skin under the conditions of the test.

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:

2001-03-09 to 2001-11-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992-07-17

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study perforemd in 2001.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Kyowa Hakko Kogyo Co., Ltd. / lot 000703

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Solubility and stability of the test substance in the solvent/vehicle: highly soluble

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: none
For the purpose of the intradermnal phase of the study the test material was freshly prepared in distilled water and for the topical phase of the study the test material was freshly prepared in 90 % aqueous ethanol.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Ltd., Burton-on-Trent, Staffordshire, UK
- Age at study initiation: ca. 8 - 12 weeks
- Weight at study initiation: 300 - 450 g
- Housing:singly or in pairs in soild-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 d
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route:

intradermal

Vehicle:

water

Concentration / amount:

0.1 ml of 1 % (w/w) formulation

Day(s)/duration:

21 d

Adequacy of induction:

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

Route:

epicutaneous, occlusive

Vehicle:

other: 90 % aqueous ethanol

Concentration / amount:

a square filtre paper 20 mm x 20 mm , saturated with the test material formulation, 25 % (w/w)

Day(s)/duration:

2 d

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10, 5 for control

Details on study design:

RANGE FINDING TESTS:
The concentration of test materia to b eused at each stage of the main study was determined by 'sighting tests' in which gropus of guinea pigs were treated with various concentrations of test material.

Selection of concentration for intradermal induction: Intradermal injections (o.1 ml/injection site) in concnetrations of 1 5 and 5 % in distilled water. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systematically, was selected for the intradermnal indusction stage of the study.

Selection of concentration for topical induction: 2 guinea pigs (intradermally injected with Freund's Complete Adjuvant 14 d earlier) were treated with 4 preparations of the test material (25 %, 10 %, 5 % and 2 % in 90 % aqueous ethanol). The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.

Selection of concentration for topical challenge: 4 preparations of the test material (25 %, 10 %, 5 % and 2 % in 90 % aqueous ethanol) were applied to 2 guinea pigs for an exposure period of 24 h. The highest non-irritant concentration and one lower concentration were selected for the topical challenge of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
A row of 3 injections (0.1 ml each) was made on each side of the mid-line into a 20 mm x 40 mm area. The injections were:
1. Freund's Complete Adjuvant plus distilled water 1 : 1
2. 1 % formulation of the test material in distilled water
3. 1 % formulation of the test material in distilled water plus reund's Complete Adjuvant in distilled water, ration 1 : 1.
24 and 48 h after intradermal injection the degree of erythema at the test material sites was evaluated.
On day 7 the same area on the shoulder region used previously for intradermal injections was clipped again and treated with a topical application of the test material formulation. A filtre paper saturated with the test material formulation ( 25 % in 90 % aqueous ethanol) was applied and held in place The occlusive dressing was kept in place for 48 h. The degree of erythema and odeema was quantified 1 h and 24 h after remioval of the test patches.


B. CHALLENGE EXPOSURE
Treatment was on day 21. A filtre paper saturated with the test material formulation ( 25 % in 90 % aqueous ethanol) was applied to the right shorn flank of each animal. To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 10 % in 90 % aqueous ethanol was similarily applied to a skin site on the left shorn flank. All patches were held in place.
After 24 h, the dressing was carefulyl removed and discarded. The challenge sites were swabbed with cotton wool soaked in diethyl ether to remove residual material.
The degree of erythema and odeema was quantified 24 h and 48 h after remioval of the challenge dressing.


OTHER:
Any other reactions were also recorded.

Challenge controls:

10 % in 90 % aqueous ethanol

Positive control substance(s):

yes

Remarks:

Historical positive control data with 2-Mercaptobenzothiazole and alpha-Hexylcinnamaldehyde

Positive control results:

Valid

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25 % (w/w) in 90 % aqueous ethanol

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25 % (w/w) in 90 % aqueous ethanol

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10 % (w/w) in 90 % aqueous ethanol

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10 % (w/w) in 90 % aqueous ethanol

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

Oxaceprol produced a 0 % (0/10) senistiation rate and is classified as a non-sensitiser to guinea pig skin under the conditions of the test.

Executive summary:

The skin sensitiastion potential of oxaceprol was assessed in a test according to OECD 406 (guinea pig maxiisation test of Magnussen and Kligman) in 2001. Oxaceprol produced a 0 % (0/10) sensitisation rate and is clasified as a non-sensitiser to guinea pig skin under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Justification for classification or non-classification

Oxaceprol produced a 0 % (0/10) sensitisation rate and is classified as a non-sensitiser to guinea pig skin under the conditions of the test.