3'H-Cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione, 1,2-dihydro-17-hydroxy-, (1.alpha.,2.alpha.)-

Endpoint summary

Description of key information

Skin irritation in vivo (Rabbit-NZW, GLP, comparable to OECD TG 404): no evaluation possible [Schering AG, Report -draft-, 1994-04-27]

Skin irritation in vivo (Rat, GLP): not irritating to the skin [Schering AG, Report No. X110 -draft-, 1996-08-06]

Eye irritation in vivo (Rabbit-NZW, GLP, OECD TG 405): not irritating to the eye [Schering AG, Report No. X136 -draft-, 1996-08-23]

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:

November to December 1995

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 0.3 ml) to male and female rats; occlusive exposure for 24 hours; values for reddening, scab formation and swelling of the skin obtained immediately 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

Controls:

no

Duration of treatment / exposure:

24 hours

Observation period:

for local effects 72 hours, whole study 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 mortalities occurred and 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 revealed no skin irritating properties

Executive summary:

The single dermal administration of the test substance (ZK 12126) to male and female rats at a dose of 2000 mg/kg was tolerated without any mortality or compound-related clinical or macroscopic pathological signs. Moreover, no local intolerance reactions at the application sites were observed. The mean values of findings relevant for dermal classification (reddening, scab formation and swelling of the skin) at the time-points immediately after removal of the bandage and the substance, 24, 48 and 72 h after the end of administration were 0.

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:

February 1996

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, eye was not rinsed

Observation period (in vivo):

5 d

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:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

2

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results of the study after 24, 48 and 72 h:

		Irritant Effects (Score)
Animal		24 h	48 h	72 h			Mean scores
1 (M)	Cornea	0	0	0			0.0
	Iris	0	0	0			0.0
	Conjunctivae (reddening)	1	0	0			0.33
	Conjunctivae (swelling)	0	0	0			0.0
2 (M)	Cornea	0	0	0
	Iris	0	0	0			0.0
	Conjunctivae (reddening)	2	1	1			1.33
	Conjunctivae (swelling)	2	1	0			1.0
1 (F)	Cornea	0	0	0			0.0
	Iris	0	0	0			0.0
	Conjunctivae (reddening)	2	1	0			1.0
	Conjunctivae (swelling)	0	0	0			0.0
2 (F)	Cornea	0	0	0			0.0
	Iris	0	0	0			0.0
	Conjunctivae (reddening)	1	0	0			0.33
	Conjunctivae (swelling)	0	0	0			0.0

A single application of 0.1 ml ZK 12126 into the conjunctival sac of the rabbit eye led to slight secretion, swelling and reddening of the outer eye lids as weil as eye lid closure and to moderate to severe reddening, swelling and blood vessel injection of the conjunctivae mainly on the application day. These effects gradually subsided and from day 3 (2 animals), 4 or 5 onwards, all animals were without findings.

Interpretation of results:

GHS criteria not met

Executive summary:

The single administration of 1,2 -Methylen-4,6 -dien into the right eye of 2 male and 2 female rabbits with a volume of 0.1 ml/eye (corresponding to 50.3 -56.4 mg) resulted in slight secretion, swelling and reddening of the outer eye lids as weil as eye lid closure and to moderate to severe reddening, swelling and blood vessel injection of the conjunctivae mainly on the application day. These effects gradually subsided and from day 3 (2 animals), 4 or 5 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 and iris, 0.3 for conjuntival swelling and 0.8 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

In a dermal study in rats a single dermal administration of 1,2 -Methylene-4,6 -dien 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 1,2 -Methylene-4,6 -dien can be regarded as not irritating to the skin since 24 h exposure to the test substance (instead of 4 h) under occlusive conditions (instead of semiocclusive conditions) was tolerated by 6 rats (instead of 3 animals) without any local skin reactions.

 

The single administration of 1,2 -Methylen-4,6 -dien into the right eye of 2 male and 2 female rabbits with a volume of 0.1 ml/eye (corresponding to 50.3 -56.4 mg) resulted in slight secretion, swelling and reddening of the outer eye lids as weil as eye lid closure and to moderate to severe reddening, swelling and blood vessel injection of the conjunctivae mainly on the application day. These effects gradually subsided and from day 3 (2 animals), 4 or 5 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 and iris, 0.3 for conjuntival swelling and 0.8 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 Regulation (EC) No. 1272/2008 (CLP) is not required.