Cycloheptapentylose

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: GLP compliant OECD Guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: albino (no further details reported)

Details on test animals or test system and environmental conditions:

Species: rabbit
Strain: albino
Origin: VASSEUR, PROUZEL. FRANCE
Sex: males
Weight: 2.0 kg - 3.0 kg
Number :6/group

Housing: individual stainless steel cage. wire-floor size 61 x 48 x 37 cm
Feed: SANDERS / LAPIPLUS - ROBENZ
Beverage: drinking water, automatic drinking bowl
Environment:
temperature 20° C +/- 1
hygrometry 50 %+/- 10
artificial lighting 12 hrs/day
air renewal 12 times/hr

The animals were housed for at least one week before the beginning of the experiment.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: yes, untreated area of animal

Amount / concentration applied:

0.5 g of solid substance, on each flank

Duration of treatment / exposure:

23 hr

Observation period:

up to 14 days

Number of animals:

6

Details on study design:

About 24 hrs prior to the study, the six rabbits were clipped with a fine-tooth electric clipper to bare a skin surface of 14 cm x 14 cm (cutting
height = 1/20th mm); thus a precise cut can be achieved without irritating the skin mechanically. The animals were left to rest for 24 hours; then only those with a perfectly healthy skin were chosen for the test.
Three incisions of about 2 cm long, 0.5 cm apart, were made into the right flank of each rabbit, parallel to the vertebral axis, by means of a sterile
vaccinostyle. The incisions were made so as to attack the epidermis without reaching the dermis. Any bleeding has to be avoided, and in any case, the
underlying muscle must not appear.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Remarks on result:

other: none

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0.5

Reversibility:

fully reversible

Remarks on result:

other: none

Irritant / corrosive response data:

The figures for erythema and oedema obtained 1 hr. 24 and 48 hrs after removal of the dressings on both flanks were added for the 6 rabbits; then the index of primary cutaneous irritation (Pci) was calculated by dividing the total by the number of data
The results were interpreted according to the following scale:

less than 0.5 non irritant
from 0.5 up to 2 slightly irritant
from 2 up to 5 moderately irritant
from 5 up to 8 severely irritant

Other effects:

none reported

Interpretation of results:

GHS criteria not met

Conclusions:

Beta-Cyclodextrine showed practically no irritating potential when applied to the skin of rabbits.

Executive summary:

In a skin irrtation assay with beta-Cyclodextrin (purity 100%) according to OECD Guideline 404 on 6 albino rabbits 0.5 g of the substance was administered to the clipped and shaved skin. A primary cutaneous irritation scheme ranging from 0 to 8 was used. The substance was left under occlusive conditions for 23 h. The skin was then observed after 1, 24 and 48 hr, showing an edema score of 0 and also an erythema score of 0 for all animals at all observation times. Only one animal exhibited a erythema score of 0.5 at the 24 h observation interval. The erythema score of this animal returned to 0 after 48 hr and showed full reversibility. Under the conditions used beta Cyclodextrin has to be clssified as not irritant to the skin of rabbits.

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: GLP Compliant OECD Guideline study report

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: albino (no further details reported)

Details on test animals or tissues and environmental conditions:

Species: rabbit
Strain: albino
Origin: VASSEUR, PROUZEL. FRANCE
Sex: males
Weight: 2.0 kg - 3.0 kg
Number :6/group

Housing: individual stainless steel cage. wire-floor size 61 x 48 x 37 cm
Feed: SANDERS / LAPIPLUS - ROBENZ
Beverage: drinking water, automatic drinking bowl
Environment:
temperature 20° C +/- 1
hygrometry 50 %+/- 10
artificial lighting 12 hrs/day
air renewal 12 times/hr

The animals were housed for at least one week before the beginning of the experiment.

Vehicle:

unchanged (no vehicle)

Controls:

other: other eye served as control

Amount / concentration applied:

0,1 ml of the substance

Duration of treatment / exposure:

The animals were placed in restraining devices (type IFFA CREDO les Oncins). The test substance was introduced into the conjonctival sac of the right eye of each rabbit. the left eye serving as a control; the instillation was unique. The eye was kept shut for one minute to avoid any loss of substance.
The animals were kept in the restraining devices for one hour, after which the
first reading was taken.

Observation period (in vivo):

1 hour, then 1, 2, 3, 4 and 7 days after the instilllation of the substance

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
According to the AFNOR NF T03-264 standard we determined:
- IIOI Individual Index of Ocular Irritation.
- MIOI Mean Index of Ocular Irritation
- IAOI The greatest Mean Index of Ocular Irritation (MIOI)
obtained from these readings is the Index of Acute Ocular Irritation.

IAOI MIOI (*) IIOl (*)
0 - 5 = 0 after 2 days non irritant
5 - 15 < 5 after 2 days slightly irritant
15 - 30 < 5 after 4 days irritant
30 - 60 < 20 after 7 days after 7 days very irritant
< 30 in 6 rabbits out of 6
and
< 15 in at least
4 rabbits out of 6

60- 80 < 40 after 7 days after 7 days severely irritant
< 60 in 6 rabbits out of 6
and
< 30 in at least
4 rabbits out of 6
80 - 110 extremely irritant


TOOL USED TO ASSESS SCORE: biomicroscope

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

given in tables

Other effects:

not reported

Reading Time	Rabbit	Conjunctiva			IRIS		Cornea Opacticity		IIOI	MIOI
		Chemosis A	Lachrynation B	Enanthena C	Reflex	Congest ions D	Degree E	Surface F
1 hr	1 2 3 4 5 6	4 1 1 1 1 1	2 2 2 2 2 2	1 1 1 1 1 1	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	- - - - - -	14 8 8 8 8 8	9.0
1 d	1 2 3 4 5 6	1 0 1 0.5 1 1	0 0 0 0 0 0	1 1 1 1 1 1	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	- - - - - -	4 2 4 3 4 4	3.5
2 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	- - - - - -	0 0 0 0 0 0	0
3 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	- - - - - -	0 0 0 0 0 0	0
4 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	- - - - - -	0 0 0 0 0 0	0
7 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	- - - - - -	0 0 0 0 0 0	0

 

x =2 (A + B + C)

y=5 x (D)

z= 5 x E x F

x+y+z = IIOI

Reading Time	Rabbit	Conjunctiva		Iris	Cornea
		Redness	Swelling
1 hr	1 2 3 4 5 6	1 1 1 1 1 1	4 1 1 1 1 1	0 0 0 0 0 0	0 0 0 0 0 0
1 d	1 2 3 4 5 6	1 1 1 1 1 1	1 0 1 0.5 1 1	0 0 0 0 0 0	0 0 0 0 0 0
2 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0
3 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0
4 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0
7 d	1 2 3 4 5 6	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0	0 0 0 0 0 0

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is only slightly irritating to eyes when administered to rabbits.

Executive summary:

In an eye irrtation assay with beta-Cyclodextrin (purity 100%) according to OECD Guideline 405 on 6 albino rabbits received 0.1 ml of the substance. The substance was administered to the conjonctival sac of the right eye of each rabbit. the left eye serving as a control; the instillation was unique. The substance was left in the sack and reading was performed after 1 h and 1, 2, 3, 4 and 7 days after administration. The scoring scheme used was that given by kay and Calanora. Only slight effects were seen in the conjunctiva score (especially chemosis, lachrynation and enanthena) which were fully reversible within 2 days. Under the conditions used beta Cyclodextrin can be clssified as only slightly irritant to the eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

.Beta.-Cyclodextrin was evaluated in an acute skin irritation study on three adult New Zealand White Rabbits according to a guideline equivalent to OECD 404. An amount of 0.5g of the test article moistened with 0.5 ml of physiological saline was applied to the back of each rabbit. Following application, the test site was occluded with a one-inch square gauze patch. The trunk of each animal was then wrapped with an occlusive binder.

A scaling system 0-4 is used. A total for erythema and eschar formation was added to a total for edema then divided by 4 to yield the individual aniumal score. The mean of the three scores was calculated and this score represents the mean primary irritation score.

24 hours post application, the occlusive binders and patches were removed. The exposure sites were gently wiped with clean gauze to remove as much non-abraded test article as possible. Half an hour after unwrapping the exposure sites were examined and scored separately for both erythema and and edema. The exposure sites were again examined and scored at 72 hours post-application. The mean primary irritation score of 0.5 was caused by barely perceptible erythema in the three rabbits at the 24 h interval. No eschar or edema was observed at any interval. All treated sites were completely normal be 24 hours post-application. The substance caused minimal irritation which was not sufficient for classification. 

In another skin irrtation assay with beta-Cyclodextrin (purity 100%) according to OECD Guideline 404 on 6 albino rabbits 0.5 g of the substance was administered to the clipped and shaved skin. The substance was left under occlusive conditions for 23 h. The skin was then observed after 1, 24 and 48 hr, showing an edema score of 0 and also an erythema score of 0 for all animals at all observation times. Only one animal exhibited a erythema score of 0.5 at the 24 h observation interval. The erythema score of this animal returned to 0 after 48 hr and showed full reversibility. Under the conditions used beta Cyclodextrin has to be clssified as not irritant to the skin of rabbits.

 

.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.

In another eye irrtation assay with beta-Cyclodextrin (purity 100%) according to OECD Guideline 405 on 6 albino rabbits received 0.1 ml of the substance. The substance was administered to the conjonctival sac of the right eye of each rabbit. the left eye serving as a control; the instillation was unique. The substance was left in the sack and reading was performed after 1 h and 1, 2, 3, 4 and 7 days after administration. The scoring scheme used was that given by kay and Calanora. Only slight effects were seen in the conjunctiva score (especially chemosis, lachrynation and enanthena) which were fully reversible within 2 days. Under the conditions used beta Cyclodextrin is only slightly irritant to the eyes of rabbits, not relevant for classification according to European legislation.

 

 

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The substance caused none or only slight irritation which was not sufficient for classification accoring CLP.