3'H-Cycloprop[15,16]androsta-6,15-dien-17-one, 15,16-dihydro-3,5-dihydroxy-, (3.beta.,5.beta.,15.alpha.,16.alpha.)-

Endpoint summary

Description of key information

Skin irritation (Rat, GLP, OECD TG 404): not skin irritating

Eye irritation (Rabbit, GLP, OECD TG 405): not eye irritating

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

Study period:

July 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Principles of method if other than guideline:

combined acute dermal toxicity and local irritation study; single dermal application of test substance (application volume 0.5 ml) to male and female rats; exposure for 24 hours; values for reddening, scab formation and swelling of the skin obtained 1 h after removal of the bandage and the substance and 24, 48 and 72 h after the end of administration.

GLP compliance:

yes

Species:

rat

Strain:

Wistar

Type of coverage:

occlusive

Preparation of test site:

not specified

Controls:

no

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3/sex

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

No compound-related findings were observed in neither clinical observation nor body weight gain nor autopsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not cause local skin irritation.

Executive summary:

The single dermal administration of Endiol to male and female rats at the dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs. The test substance was tolerated without any local skin irritations.

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

Study period:

January 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987-02-24

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Controls:

other: left eye served as control

Duration of treatment / exposure:

test substance remained in the eye and eye was not rinsed

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2 males and 2 females

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

mean

Time point:

24/48/72 h

Score:

0.08

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Remarks:

swelling

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

The treatment did not result in any effect on body weight.

Results of the study

		Irritant Effects (Score)
Animal		24 h	48 h	72 h	Mean scores
1 (male)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddening)	1	0	0	0.3
	Conjunctivae (swelling)	0	0	0	0.0
2 (male)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddening)	0	0	0	0.0
	Conjunctivae (swelling)	0	0	0	0.0
3 (female)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddening)	0	0	0	0.0
	Conjunctivae (swelling)	0	0	0	0.0
4 (female)	Corneal Opacity	0	0	0	0.0
	Iris (redness, swelling, reaction of pupillary reflex etc.)	0	0	0	0.0
	Conjunctivae (reddening)	0	0	0	0.0
	Conjunctivae (swelling)	0	0	0	0.0

A slight reddening of the conjunctivae were seen in all animals and a slight swelling of the conjunctivae in three out of four animals on administration day.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not irritant to eye.

Executive summary:

The single administration of Endiol into the right eye of male and female rabbits with a volume of 0.1 ml/eye (corresponding to 59.1 -71.0 mg) results in a slight reddening of the conjunctivae in all animals and a slight swelling of the conjunctivae in three out of four animals on administration day. On day 2 (24 h after administration) only slight conjunctival reddening was seen in one out of four animals and from day 3 onwards, all animals were without findings. According to the system of evaluation recommended for EU, the mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after administration were 0 for the cornea, iris and conjuntival swelling and 0.08 for conjunctival reddening. Therefore, according to EU classification criteria the test substance is not eye irritating.

.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The single dermal administration of Endiol to male and female rats at the dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs.

Although the study was with respect to skin irritation / corrosion not conducted according to current guidelines and with the most sensitive species rabbit Endiol can be regarded as not irritating to the skin since 24 h exposure to the test substance (instead of 4 h) was tolerated by 6 rats (instead of 3 animals) without any local skin reactions.

The single administration of Endiol into the right eye of male and female rabbits with a volume of 0.1 ml/eye (corresponding to 59.1 -71.0 mg) results in a slight reddening of the conjunctivae in all animals and a slight swelling of the conjunctivae in three out of four animals on administration day. On day 2 (24 h after administration) only slight conjunctival reddening was seen in one out of four animals and from day 3 onwards, all animals were without findings. According to the system of evaluation recommended for EU, the mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after administration were 0 for the cornea, iris and conjuntival swelling and 0.08 for conjunctival reddening. Therefore, according to EU classification criteria the test substance is not eye irritating.

Justification for classification or non-classification

Based on the study results a classification according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008 (CLP) is not required.