Cyclooctapentylose

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

other:

Sex:

male/female

Details on test animals and environmental conditions:

Species: SPF-bred albino guinea pigs (Crl:(HA)BR)
Supplier: Charles River Wiga GmbH, Germany
Sex and age: males and females, young adult
Identification: earmarking, males even nos. 870-898; females odd nos. 755-783
Date of arrival: September 15, 1992
Start date of study: September 29, 1992
Termination date of study: October 23, 1992
Body weight range prior to start of study: males 345-403g; females 314-383 g
Caging: individually in suspended, stainless steel cages, fitted with wire mesh floor and front
Lighting: 12 hours light/12 hours dark cycle
Temperature: 22 +/- 3 °C
Humidity: 42.5% - 90% (upper limit higher than the intended 70%, because of meteorological circumstances or because of wet cleaning of the animal room)
Ventilation: ca 10 air changes/hour
Diet: pelleted, natural ingredient diet for guinea pigs (Hope Farms, Woerden, The Netherlands) and tap water, ad libitum

Route:

intradermal

Vehicle:

other: vaseline

Concentration / amount:

10 % and 30%

Route:

epicutaneous, semiocclusive

Vehicle:

other: vaseline

Concentration / amount:

10 % and 30%

No. of animals per dose:

15 males and 15 females

Details on study design:

Main study
Fifteen male and 15 female guinea pigs were randomly divided into two groups, viz. a test group of 10 males and 10 females and a control group
of 5 males and 5 females. The animals were weighed one day before the study was initiated and at the completion of the study.

Induction
Induction was effected in two different ways, firstly by intradermal injections and secondly, one week later, by topical application over the injection sites.

a. Intradermal injections
For this purpose an area of about 24 cm2 of dorsal skin in the scapular region was clipped free from hair with electric clippers.
Pairs of intradermal injections (0.1 ml each) were made simultaneously in the clipped area. The following preparations were injected:
test animals
- two injections with Freund's Complete Adjuvant (FCA) and demi-water (1:1),
- two injections with a 3% dilution of the test substance in demi-water,
- two injections with a 3% dilution of the test substance in demi-water and FCA (1:1),
control animals
- two injections with FCA and demi-water (1:1),
- two injections with demi-water,
- two injections with FCA and demi-water (1:1).
Skin readings were made at 24 hours after the treatment.

b. Topical application
One week after the intradermal injections, the dorsal skin in the scapular region of the test and control animals was closely shaved again. The induction by topical application was made in this region. The test animals were treated as follows:
A circa 2 x 4 cm patch of Whatman No. 3 MM filter paper was loaded with a 30% dilution of the test substance in vaseline. The loaded patch was placed over the sites of the intradermal injections and was secured. The dressing was left in place for 48 hours. The control animals were similarly treated with patches loaded with vaseline only. Skin readings were made directly after removal of the patches.

c. Challenge
The topical challenge was carried out two weeks after the topical induction as follows:
An area of circa 5 x 5 cm on both flanks of each test and control animal was clipped free from hair. Patches were loaded with a 30% or a 10% test dilution in vaseline, or with vaseline only. One patch loaded with the 10% test dilution was placed on the clipped area of the left flank of each test and control animal. The right flank was treated with the 30% test dilution in vaseline and with vaseline alone. The patches were covered with Leukopor bandage, and held in place by Tensoplast for 24 hours. Skin readings were made at 24 and 48 hours after removal of the patches.

Challenge controls:

5 males and 5 females

Positive control substance(s):

yes

Remarks:

DNCB

Statistics:

The results were evaluated according to the EEC-standards (EEC-Directive 91/325/EC as published in the Official Journal of the European Communities, L 180, Volume 34, 8 July 1991), which state that a substance is considered a sensitizer if 30% or more of the test animals show a positive reaction.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The challenge treatment with the 30% test dilution, the 10% test dilution, and with vaseline alone produced a similar skin response in animals of the test and control group. Therefore, the skin effects observed after the challenge treatment were attributed to skin irritation, rather than sensitization. Because none of the test animals showed positive signs of sensitization, it was concluded that under the conditions of this study and according to the EEC-standards .gamma.-cyclodextrin is not a sensitizer.

Executive summary:

The test substance .gamma.-cyclodextrin was examined for possible sensitizing properties by a maximization test in guinea pigs using 20 test animals and 10 controls.

The test comprised:

test animals

 - induction treatment by intradermal injections of Freund's Complete Adjuvant (FCA) 1:1 diluted with demineralized water (demi-water), a 3% dilution of the test substance in demi-water, and a 3% dilution of the test substance in a 1:1 mixture of FCA and demi-water, followed one week later by topical application of a 30% dilution in vaseline,

- challenge treatment, 14 days after the last induction, by topical application of a 30% and a 10% dilution in vaseline, and of vaseline alone, controls

controls

- induction treatment by intradermal injections of FCA 1:1 diluted with demi-water, demi-water alone, and a 1:1 mixture of FCA and demiwater, followed one week later by topical application of vaseline alone, and

- challenge treatment, 14 days after the last induction, by topical application of a 30% and a 10% dilution of the test substance in vaseline, and of vaseline alone.

The challenge treatment with .gamma.-cyclodextrin did not induce signs of sensitization in the test animals. On the basis of the results, it was concluded that under the conditions of this study and according to the EEC-standards , the test substance.gamma.-cyc1odextrin is not a sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The sensitization potential of .gamma.-cyclodextrin was examined in a guinea pig maximization test according to OECD guideline 406. The challenge treatment with the 30% test dilution, the 10% test dilution, and with vaseline alone produced a similar skin response in animals of the test and control group. Therefore, the skin effects observed after the challenge treatment were attributed to skin irritation, rather than sensitization. Because none of the test animals showed positive signs of sensitization, it was concluded that under the conditions of this study and according to the EEC-standards .gamma.-cyclodextrin is not a sensitizer.

Migrated from Short description of key information:
The substance .gamma.-cyclodextrin did not exhibit any signs of allergic skin reaction when applied on the skin of guinea pigs in a maximization test.

Justification for selection of skin sensitisation endpoint:
Guideline Study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The substance .gamma.-cyclodextrin did not exhibit any signs of allergic skin reaction when applied on the skin of guinea pigs in a maximization test.