Cyclohexapentylose

Eye irritation

Administrative data

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

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cyclohexapentylose

EC Number:

233-007-4

EC Name:

Cyclohexapentylose

Cas Number:

10016-20-3

Molecular formula:

C36H60O30

IUPAC Name:

(1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31R,32R,33R,34R,35R,36R,37R,38R,39R,40R,41R,42R)-5,10,15,20,25,30-Hexakis(hydroxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29-dodecaoxahe ptacyclo[26.2.2.23,6.28,11.213,16.218,21.223,26]dotetracontane-31,32,33,34,35,36,37,38,39,40,41,42-dodecol

Details on test material:

Date of receipt: February 11, 1991
Designation: .alpha.-cyclodextrin
General appearance: white powder
Batch no.: 8708644
CAS. Reg. no.: 10016-20-3
Storage conditions: ambient (circa 20°C)

Just prior to testing, a 14.5% test dilution of the test substance was prepared by dissolving 1.45 g of .alpha.-cyclodextrin in 10 ml demi-water, and a 50% test dilutions were prepared by mixing equal amounts (g) of .alpha.-cyclodextrin with demi-water. For this study sample 5 (see above) was used.
The 14.5% test dilution appeared to be a clear, colourless solution, whereas the 50% test dilution appeared to be a white suspension.

Test animals / tissue source

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Applicant's summary and conclusion

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.