Cyclohexapentylose

Endpoint summary

Description of key information

The test article showed only none to slight signs of irritation on skin and eye of New Zealand White rabbits. The observed scores are not sufficient for classification.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: SPF bred New Zealand White albino rabbits.
Supplier: Harlan/CPB, the Netherlands
Sex and age: males, young adult
Date of arrival: November 5, 1991
Body weight range at start of study: 2000-2500g
Identification: earmarking
Acclimatization period: 6/7 days
Caging: individually in suspended galvanized cages, fitted with wire-mesh floor and front
Lighting: 12 hours light/12 hours dark cycle
Temperature: 20 +/- 3 °C
Humidity: 38-72.5% (upper limit higher than 70%, because of meteorological circumstances or because of wet cleaning of the animal room)
Ventilation: ca 10 air changes/hour
Diet: standard laboratory rabbit diet and tap water, ad libitum

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes

Amount / concentration applied:

0.85 g of test mixture (0.5 g of the test substance and 0.35 g of tap water)

Duration of treatment / exposure:

4 hours

Observation period:

skin reading were made at approximately 24, 48, 72 hours after treatment

Number of animals:

3 rabbits

Details on study design:

After the acclimatization period the study was started with one rabbit, which was treated as follows:
A plastic cup with a diameter of ca 2.5 cm was loaded with 0.85 g of the test mixture (0.5 g of the test substance and 0.35 g of tap water). Next, a skin site suitable for application of the test material was selected on the shaven back and flanks of the animal. The cup was placed on the selected, intact skin and fixed to the application site by means of adhesive tape (Leukopor, BDF). The entire trunk of the rabbit was wrapped with a self-adhesive-gauze (Fixomull, art. no. 2112, BDF, W.-Germany) to maintain the cup in position and to retard evaporation of volatile substances. After an exposure period of 4 hours, the cup and the material applied were removed with a paper tissue and tap water, and ca 1 hour later, the resulting skin reactions were evaluated by the method of Draize et al.(J. Pharmacol. Exp. Ther. 82 (1944) 377-390). Since no signs of irritation were observed in this rabbit, it was decided to treat an additional two animals, using the same method as describe above. Further skin readings were made at approximately 24, 48 and72 hours after treatment.

At all observation time points, no signs of skin irritation were observed in any of the three rabbits.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

At all observation time points, no signs of skin irritation were observed in any of the three rabbits.
On the basis of the results obtained it is concluded that, under the conditions of this study and according to the EEC-standards (mentioned in
EEC-Directive 83/467/EEC and published in the Official Journal of the European Communities, L 257, Volume 26, 16 September 1983), .alpha.-cyclodextrin is not irritating or corrosive to skin.

Executive summary:

A sample of .alpha.- cyclodextrin was examined for acute dermal irritating/ corrosive properties in an experiment with three albino rabbits. The test substance, a powder, was moistened with tap water before application to ensure good skin contact and the dermal exposure period was 4 hours under semi-occlusive conditions.

The test substance did not cause signs of skin irritation in any of the three rabbits.

On the basis of the results obtained it is concluded that, under the conditions of this study and according to the EEC-standards (mentioned in EEC-Directive 83/467/EEC and published in the Official Journal of the European Communities, L 257, Volume 26, 16 September 1983), .alpha.-cyclodextrin is not irritating or corrosive to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, material from routine production

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species: SPF bred New Zealand White albino rabbits
Supplier: Harlan/CPB, The Netherlands
Sex and age: males, young adult
Date of arrival: November 5, 1991
Body weight range at start of study: 14.5%: 2000-2300 g
50%: 2250-2630 g

Acclimatization period: 14.5%: 6 days
50%: 14 days

Caging: individually in suspend galvanized cages, fitted with wire-mesh floor and front
Lighting: 12 hours light/12 hours dark cycle
Temperature: 20 +/- 3°C
Humidity:38-72.5% (upper limit higher than 70%, because of meteorological circumstanced or because of wet cleaning of the animal room)
Ventilation: ca. 10 air changes/hour
Diet: standard laboratory rabbit diet and tap water, ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.1 ml of the 14.5% or of the 50% test dilution

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 rabbits

Details on study design:

Each of the two test dilutions was tested in three rabbits. After the acclimatization period both eyes of the rabbits selected were examined just before testing. Only rabbits without observable eye defects were used. The selected rabbits were treated as follows:
An amount of 0.1 ml of the 14.5% or of the 50% test dilution was instill in the conjunctival cul-de-sac of the right eye of the rabbit. After administration, the upper and lower eye lid were carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The left eye remaining untreated, served as a control.
Ocular reactions of the test eyes were judged at circa one hour, 24, 48 and 72 hours after treatment using the scoring scale which is given in appendix at the end of this report.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 14.5 % dilution of .alpha.-CD in demineralized water

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 14.5 % dilution of .alpha.-CD in demineralized water

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 14.5 % dilution of .alpha.-CD in demineralized water

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 50 % dilution of .alpha.-CD in demineralized water

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 48

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 50 % dilution of .alpha.-CD in demineralized water

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 50 % dilution of .alpha.-CD in demineralized water

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

On the basis of the results obtained it was concluded that, under the conditions of this study, a 14.5% and a 50% dilution of .alpha.-cyclodextrin in demi-water are, respectively, not irritating or only minimally irritating for the eyes of rabbits. According to the EEC-standarts (mentioned in EEC-Directive 83/467/EEC and published in the Official Journal of the European Communities, L 257, Volume 26, 16 September 1983), both a 14.5% and a 50% dilution of .alpha.-cyclodextrin in demi-water are not irritating or corrosive to eyes.
Furthermore, it can be concluded that the result of the ex vivo CEET (see annex) are fully in agreement with the results of the conventional in vivo rabbit test.

Executive summary:

Executive summary of the in vivo and ex vivo part of the study (see also the cross reference):

A sample of .alpha.-cyclodextrin was examined as a 14.5% and a 50% dilution in demineralized water (demi-water) for acute eye irritating/corrosive properties in an experiment with two groups of three albino rabbits each. Prior to the vivo testing, both dilutions were also examined in an alternative ex vivo bioassay, namely the chicken enucleated-eye-test (CEET), which uses the eyes from slaughter animals.

Material is crystalline (not pulverized) from routine production. Mechanical effects can be excluded as suspensions in water have been used for testing.

 

Ex vivo testing clearly showed that both concentrations of the test substance were non-irritating.

 

In the in vivo test, the 14.5% test dilution caused slight redness of the conjunctivae in one out of the three rabbits only, while the 50% test dilution caused slight redness and slight swelling of the conjunctivae and moderate ocular discharge in the other three rabbits. In both cases, all eye effects had cleared completely at 24 hours after treatment.

 

On the basis of the results obtained it was concluded that, under the sonditions of the studies, a 14.5% and a 50% dilution of .alpha.-cyclodextrin in demi-water are, respectively, not irritating or only minimally irritating for the eyes of rabbits. According to the EEC-standards (mentioned in EEC-Directive 83/467/EEC and published in the Official Journal of the European Communities, L 257, Volume 26, 16 September 1983), both a 14.5% and a 50% dilution of a .alpha.-cyclodextrin in demi-water are not irritating or corrosive to eyes.

Furthermore, it could be concluded that the result of the ex vivo CEET were fully in agreement with the results of the conventional in vivo rabbit test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN A sample of .alpha.-cyclodextrin was examined for acute dermal irritating/ corrosive properties in an experiment with three albino rabbits. The test substance, a powder, was moistened with tap water before application to ensure good skin contact and the dermal exposure period was 4 hours under semi-occlusive conditions. The test substance did not cause any signs of skin irritation.

 

EYE A sample of .alpha.-cyclodextrin was examined for acute eye irritating/corrosive properties in an experiment with three albino rabbits.

The test substance was crude material taken from non-routine production (non-pulverized) and caused slight to severe corneal opacity, slight iritis, ischemic necrosis of the nictitating membrane, slight or moderate redness and moderate or severe swelling of the conjunctivae, and severe ocular discharge. At 14 days after treatment, all eye effects had cleared completely.

To exclude any mechanical effects caused by the crystal form of .alpha.-cyclodextrin an additional study using solutions of .alpha.-cyclodextrin in water was performed; using crude material from routine production (non-pulverized). On the basis of the results obtained it was concluded that, under the conditions of this study, a 14.5% and a 50% dilution of .alpha.-cyclodextrin in demineralized water are not irritating for the eyes of rabbits. According to the EEC-standarts (mentioned in EEC-Directive 83/467/EEC and published in the Official Journal of the European Communities, L 257, Volume 26, 16 September 1983), both a 14.5% and a 50% dilution of .alpha.-cyclodextrin in water are not irritating or corrosive to eyes. Furthermore, it can be concluded that the result of the ex vivo CEET are fully in agreement with the results of the conventional in vivo rabbit test.

 

 

Justification for selection of skin irritation / corrosion endpoint:
Guideline Study

Justification for selection of eye irritation endpoint:
Guideline Study

Justification for classification or non-classification

The substance caused no irritation to the skin but was slightly irritating to eyes in an OECD 405 guideline study. Some of the effects were not fully reversible within 7 days, but all eye effects had cleared completely at 14 days after treatment. An additional study using a 50% water solution of the test substance showed no irritating properties. The effects observed in the first study has probably been caused by mechanical effects; especially as material from non-routine production has been used in the first test and the crystallin substance has not been pulverized prior to application.