2-Hydroxypropyl-β-cyclodextrine ethers

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

characterisation of test item lacking

Justification for type of information:

read-across, structural analogue

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

see principles

Principles of method if other than guideline:

1. Animals will be weighed prior to initiation of the study.
2. Prior to dosing. the eyes of each animal will be examined using sodium fluorescein and ultraviolet light. Any animals with pre-existing irritation or defects will not be used.
3. The test article will be instilled into one eye of each animal; the other eye will serve as the untreated control.
4. The treated eyes of the animals will be held closed for one second following instillation and will not be irrigated.
5. Observations for eye irritation will be made at 24,48 and 72 hours and again at 7 days (if irritation is noted at 72 hours) after application of the test article. Sodium fluorescein and ultraviolet light will be used for examinations.
6. Eye irritation will be graded and recorded according to the numerical scoring system of Draize. 1959 . The cornea will be scored on the basis of the density and extensive-ness of any opacities (if present). The iris will be scored on the intensity or degree of inflammation exhibited. The palpebral and bulbar mucosae will be scored on: the extent of chemosis, hyperemia, and discharge.
7. Any unusual observations and mortality will be recorded. Animals which die on test will be given a gross necropsy

No. of Animals 3
Test Article Level: 0.1 ml if liquid; 0.1 g if solid; if spray, 2 second exposure at a distance of 4 in

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cycloheptapentylose

EC Number:

231-493-2

EC Name:

Cycloheptapentylose

Cas Number:

7585-39-9

Molecular formula:

C42H70O35

IUPAC Name:

CYCLOHEPTAAMYLOSE

Test material form:

solid: particulate/powder

Details on test material:

Name: Beta Cyclodextrin
purity and impurities as well as analysis and expiry date not mentioned in report

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals and Animal Husbandry - All housing and care shall conform to the standards established in "Guide for the Care and Use of Laboratory Animals" DREW publication No. (NIH) 78-23.
1. Species/Strain: New Zealand White rabbits
2. Source: approved rabbit supplier LaCrosse Industries, Inc. Schenectady, New York, USA
3. Age at Initiation: Young adult.
4. Number: 3 males, 2.37 - 2.77 kg
5. Identification: Ear tag. cage tag.
6. Housing: Individually housed in wire mesh bottom cages.
7. Food: NIH 09 rabbit ration certified feed, ad libitum supplied fresh daily.
8. Water: Tap water ad libitum. Water was monitored for contaminants at periodic intervals according to FDRL Standard Operating Procedures.
9. Environment: All animals were housed in environment controlled rooms. A 12 hour light-dark cycle was maintained.
10. Quarantine:5 days. During this conditioning period, the rabbits were observed for any clinical signs of disease. All rabbits with any evidence of disease or physical abnormalities will be discarded.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated eye

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

no washing performed

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

Prior to test initiation, the eyes of each rabbit were examined with sodium fluorescein and an ultraviolet lamp. Only those rabbits whose eyes were free of irritation and cor-neal lesions were used. On the day of dosing, an amount of 0.1 g of the test article was instilled in one eye of each rabbit. The test article was instilled into the eye by gently pulling the lower lid away from the eyeball to form a cup into which the test article was deposited. The other eye served as the untreated control. The eyes were examined with fluorescein and the grade of ocular reaction for each animal was recorded at 24, 48 and 72 hours post-instillation using the Draize Scale for Scoring Ocular Lesions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Eye irritation was graded and recorded according to the numerical scoring system of Draize. 1959
CORNEA
(A) Opacity - degree of density (area most dense taken for reading)
No opacity 0
Scattered or diffuse areas. details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescenc areas, no details of iris visible, size of pupil barely discernible 3
Opaque. iris invisible 4

(B) Area of cornea involved
One quarter (or less) but not zero 1
Greater than one quarter, but less than half 2
Greater than half, but less than three quarters 3
Greater than three quarters, up to whole area. 4
Score = A x B x 5 Total Maximum = 80


IRIS
(A) Values
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris is still reacting to light (sluggish reaction is positive). 1
No reaction to light, hemorrhage, gross destruction (any or all of these). 2
Score = A x 5 Total Maximurn = 10

CONJUNCTIVAE
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal 0
Vessels definitely injected above normal (slight erythema) 1
Nore diffuse, deeper crimson red. individual vessels not easily discernible (moderate erythema) 2
Diffuse beefy red (marked erythema) 3

(B) Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane. slightly swollen) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids about half closed to completely closed 4

(C) -Discharge
No discharge o
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs and considerable area around the eye 3
Score = (A + B + C) x 2 Total Maximum = 20

The maximum total score is the sum of all scores obtained from the cornea, iris, and conjunctivae. Total maximum possible score = 110.

Non-Irritating  0.0 - 0.5         To maintain this rating, all scores at the 48-hour reading must be zero; otherwise, increase rating one level.
Practically Non-Irritating   Greater than 0.5 - 2.5        To maintain this rating, all scores at the 48-hour reading must be zero; otherwise, increase rating one level.
Minimally Irritating     Greater than 2.5 - 15.0       To maintain this rating, all scores at the 72-hour reading must be zero; otherwise, increase rating one level.
Mildly Irritating           Greater than 15.0 - 25.0     To maintain this rating, the 7-day reading must be wise, increase rating one all scores at zero; otherwise increase rating one level.
Moderately Irritating Greater than 25.0 - 50.0 To maintain this rating, scores at 7 days must be less than or equal to 10 for 60% or more of the animals. Also, mean 7-day score must be less than or equal to 20. If 7-day mean score is less than or equal to 20 and more than 60% of animals show scores less than 10, then no animal among those showing scores greater than 10 can exceed a score of 30 if rating is to be maintained; otherwise, increase rating one level.
Severely Irritating      Greater than 50.0 - 80.0     To maintain this rating, scores at 7 days must be less than or equal to 30 for 60% or more of the animals. Also, mean 7day score must be less .than or equal to 4~. If 7-day mean score is less than or equal to 40 and more than 60% of the animals show scores less than or equal to· 30, then no animal among those showing scores greater than 30 can exceed a score of 60 if rating is to be maintained, otherwise, increase rating one level.
 Extremely Irritating   Greater than 80.0 - 110.0

Other effects:

none reported

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Substance is slightly irritating to eyes, need no classification on this endpoint.

Executive summary:

.Beta.-Cyclodextrin was evaluated in an acute eye irritation study on three adult New Zealand White Rabbits according to a guideline equivalent to OECD 405. 0.1 g of the test article was be instilled into one eye of each animal; the other eye served as the untreated control. The test article was instilled into the eye by gently pulling the lower lid away from the eyeball to form a cup into which the test article was deposited. Observation was performed after 24, 48 and 72 hours, the eyes were examined with fluorescein. Eye irritation was graded and recorded according to the numerical scoring system of Draize 1959. The maximum total score was the sum of all scores obtained from the cornea (opacity and area of cornea involved), iris, and conjunctivae (redness, chemosis and discharge). Total maximum possible score = 110. Only minimal effects were seen on cornea and iris score whereas the conjunctivae score showed a mild irritation at 24 hours. The overall mean irritation score for each time period was 18.7 +/- 8.1 at 24 hours, 5.7 +/- 5.5 at 48 hours and 0 at 72 hours. Therefore all effects were reversible within 72 hours. The substance caused slight irritation which was not sufficient for classification.