Cyclooctapentylose

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:

Himalayan

Details on test animals or test system and environmental conditions:

Species / strain: rabbit / Himalayan, an albino rabbit
Breeder: LPT Laboratory of Pharmacology and Toxicology KG; branch Löhndorf; D-24601 Löhndorf/Post Wankendorf
Selection of species: the rabbit is a commonly used non-rodent species for acute skin irritation tests (patch Test)
Sex: female animals
Number of animals: 3
Initial age: approx. 10 months
Initial body weight: 2.4-2.9 kg
Identification of animals: by tattooed number assigned by the Löhndorf breeding station
Duration of study: at least 20 adaptation days, 1 test day and a follow-up period of 72 hours

Diet:
ssniff K-H (ssniff Spezialdiäten GmbH, 0-59494 Soest) served as food. The food was available ad libitum before and after the exposure period.
At regular intervals (at least twice a year), the food is analysed for contaminants. Certificates of analysis of the composition and for contaminants were supplied by the manufacturer.

Drinking Water:
Drinking water was offered ad libitum before and after the exposure period. Samples of the drinking water are examined according to the 'Deutsche Trinkwasserverordnung, Bundesgesetzblatt, Jahrgang 1990' [German Regulations on drinking water, public notice of the law, 1990] by the Wasserbeschaffungsverband Harburg, D-21220 Seevetal twice a year.
In addition, drinking water samples taken at LPT are analysed by LUFA-ITL once a year for means of bacteriological investigations according to the German 'Deutsche Trinkwasserverordnung, Bundesgesetzblatt, Jahrgang 1990, Anlage 4' [German Regulations on drinking water, public notice of the law, 1990, Addendum 4].

Housing:
Before and after the 4-hour exposure period, the animals were kept singly in cages measuring 425 mm x 600 mm x 380 mm (manufacturer: Dipl. Ing. W. EHRET GmbH, D-16352 Schönwalde) at a room temperature of 20°C ± 3°C (maximum range) and relative humidity of 55% ± 15% (maximum range). Deviations from the maximum range caused for example during cleaning procedures are dealt with in SOPs.
During the exposure period, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn. The cages excluded irritation of the skin by excrements and urine.
The rooms were lit (150 lux at approx. 1.5 m room height) and darkened on a 12-hour light/12-hour dark cycle.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

500 mg/6 cm² moistured with water

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

Route of administration: dermal application to the shaved, intact dorsal skin
Selection of route of administration: according to OECD/EC guidelines
Exposure period: 4 hours
Frequency of administration: single administration
Dose level: 500 mg/patch and animal
Approximately 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animals. Care was taken to avoid abrading the skin. Only animals with healthy intact skin were used. A dose of 500 mg was moistured sufficiently with water, to ensure good contact with the skin and applied to the test site (area: approx. 6 cm2). The test substance was applied to the test site and then covered with a gauze patch.
The patch was held in contact with the skin by means of a semi-occlusive dressing (non-irritating tape) for the duration of the exposure period. The surrounding untreated skin served as a control. Exposure time was four hours. During the exposure the animals were kept in comfortable restrainers.
Protective clothing:
All personnel handling the animals met the requirements for strict cleanliness. All experimental manipulations were performed by the designated personnel wearing a sterile cap, mask, gown and gloves.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

Under the present test conditions three rabbits were exposed for 4 hours to 500 mg .gamma.-cyclodextrin/patch and animal (semi-occlusive condition). An erythema (grade 1) was noted in animal nos. 1 and 3 from 60 minutes up to 24 hours after patch removal. Animal no. 2 showed no substance related changes at the examination time-points 60 minutes, 24, 48 and 72 hours.
There were no systemic intolerance reactions.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

There were no systemic intolerance reactions.

Executive summary:

Test system: acute skin irritation test (patch test) in rabbits according to EC guideline B.4. and OECD guideline 404

Test substance: .gamma.-cyclodextrin

Under the present test conditions three rabbits were exposed for 4 hours to 500 mg .gamma.-cyclodextrin/patch and animal (semi-occlusive condition). An erythema (grade 1) was noted in animal nos. 1 and 3 from 60 minutes up to 24 hours after patch removal. Animal no. 2 showed no substance related changes at the examination time-points 60 minutes, 24, 48 and 72 hours.

There were no systemic intolerance reactions.

According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions .gamma.-cyclodextrin was non – irritating to skin, hence, no labelling is required.

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species: conventionally bred New Zealand White albino rabbits
Supplier: ENKI-Konijnenfarm, Someren, the Netherlands
Sex and age: males, young adult
Date of arrival: October 23, 1990
Body weight range at start of study: 2992-3129 g
Identification: earmarking: 5451-5453
Acclimatization period: 27 days
Caging: individually in suspended galvanized cages, fitted with wire-mesh floor and front
Lighting: 12 hours light/12 hours dark cycle
Temperature: 16-19 °C
Humidity: 62.5% - 80% (but higher for short periods of time after 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:

other: Untreated eye served as a control

Amount / concentration applied:

An amount of 0.1 ml (0.063 g) of the test substance was instilled in the conjunctival cul-de-sac of the right eye of the rabbit.

Duration of treatment / exposure:

according to guideline

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3 males

Details on study design:

The study was started with one rabbit. After the acclimatization period both eyes of the rabbit selected were examined just before testing. Only rabbits without observable eye defects were to be used. The selected rabbit was treated as follows:
An amount of 0.1 ml (0.063 g) of the test substance was instilled 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.
At one hour after treatment, only a slight eye effect was observed in this rabbit. Therefore, it was decided to complete the study with another two rabbits.
Ocular reactions of the test eye were judged at circa one hour, 24, 48, and 72 hours after treatment using the scoring scale.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

other: ocular discharge

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

At 1 hour after treatment, the eye effects observed in the three rabbits consisted of very slight redness with or without very swelling of the conjunctivae.
At 24 hours after treatment, the eye effects observed in the three rabbits consisted of very slight redness of the conjunctivae only.
At 48 hours after treatment, all eye effects had cleared completely.
At 72 hours after treatment again, no signs of eye irritation were observed in any of the three rabbits.

Other effects:

none

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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), .gamma.-cyclodextrin is not irritating or corrosive to eyes.

Executive summary:

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

The test substance caused slight redness with or without slight swelling of the conjunctivae. At 48 hours after treatment, all eye effects had cleared completely.

On the basis of the results obtained it was concluded that, under the conditions of this study and according to the EU standards, gamma.-cyclodextrin is not irritating or corrosive to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN .gamma.-cyclodextrin was tested in an acute skin irritation test (patch test) in rabbits according to OECD guideline 404.

Under the test conditions three rabbits were exposed for 4 hours to 500 mg .gamma.-cyclodextrin/patch and animal (semi-occlusive condition). Erythema (grade 1) was noted in animal no. 1 and 3 from 60 minutes up to 24 hours after patch removal. Animal no. 2 showed no substance related changes at the examination time-points 60 minutes, 24, 48 and 72 hours. There were no systemic intolerance reactions. According to the results obtained under the present test conditions .gamma.-cyclodextrin is non–irritating to skin.

 

EYE A sample of .gamma.-cyclodextrin was examined for acute eye irritating/corrosive properties in an experiment with three albino rabbits according to OECD Guideline 405.

The test substance caused slight redness with or without slight swelling of the conjunctivae. At 48 hours after treatment, all eye effects had cleared completely. On the basis of the results obtained it was concluded that, under the conditions of this study and according to the EU standards, gamma.-cyclodextrin is not irritating to eyes.

 

 

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 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.