5H-Dicyclopropa[6,7:15,16]cyclopenta[a]phenanthrene-3,5,17-triol, octadecahydro-17-(3-hydroxypropyl)-10,13-dimethyl-, (3S,5R,6R,7R,8R,9S,10R,13S,14S,15S,16S,17S)-

Endpoint summary

Description of key information

Skin irritation (Rat, GLP): not skin irritating
[Nihon Schering K.K., Report No. A06723, 2004-06-18]
Eye irritation (Rabbit, GLP, OECD TG 405): not eye irritating
[Nihon Schering K.K., Report No. A06710, 2004-06-18]

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:

September to October 2001

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 dermal irritation/corrosion study; single dermal application of test substance (2000 mg/kg; application volume 1.0 ml) to male and female rats; occlusive conditions; exposure for 24 hours; values for reddening, scab formation and swelling of the skin obtained 1, 24, 48 and 72 h after removal of the bandage and the substance determined according to the grading system (OECD TG 404)

GLP compliance:

yes

Species:

rat

Strain:

Sprague-Dawley

Type of coverage:

occlusive

Preparation of test site:

shaved

Controls:

no

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3/sex

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema 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

Executive summary:

The single dermal administration of Dimethylenpropanol 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. No local intolerance reactions at the application sites were observed. The mean value grades across the time points (24, 48 and 72 h after removal of the pad) were 0 both for reddening/scab formation and for swelling.

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:

December 2001

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:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

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)	0	0	0	0.0
	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

Slight reactions of the conjunctivae and iris were observed on the day of application. The cornea was not affected. However, all animals were without findings 24 hours after application.

Conclusions:

The test item did not cause eye irritation.

Executive summary:

The single administration of Dimethylenpropanol into the right eye of male and female rabbits with a volume of 0.1 ml/eye (corresponding to 34.3 -38.7 mg) results in slight reactions of the conjunctivae and iris on administration day. From day 2 (24 h after administration) 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, conjunctival reddening and conjuntival swelling. Therefore, according to EU classification criteria the test substance is not eye irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The single dermal administration of Dimethylenpropanol 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. No local intolerance reactions at the application sites were observed. The mean value grades across the time points (24, 48 and 72 h after removal of the pad) were 0 both for reddening/scab formation and for swelling.

Although the study was with respect to skin irritation / corrosion not conducted according to current guidelines and with the most sensitive species rabbit Dimethylenpropanol 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 semi-occlusive conditions) was tolerated by 6 rats (instead of 3 animals) without any local skin reactions.

The single administration of Dimethylenepropanol into the right eye of male and female rabbits with a volume of 0.1 ml/eye (corresponding to 34.3 -38.7 mg) results in slight reactions of the conjunctivae and iris on administration day. From day 2 (24 h after administration) 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, conjunctival reddening and conjuntival swelling. 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.