Androsta-1,4-diene-3,17-dione

Endpoint summary

Description of key information

Androstadiendion is not irritating to the skin of rats (Kurth, 1995) or to the eyes of rabbits (Treher, 1995).

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:

Feb to Mar 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable to guideline study with acceptable restrictions: A combined study on acute dermal toxicity and on local tolerance was used to assess skin irritation/corrosion. The study design and reporting deviates from the current OECD TG 404, however, the study is considered sufficient for assessment of this endpoint.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

- exposure time 24 hrs instead of 4 hrs, 6 animals instead of 3, few details in test description and reporting

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Species:

rat

Strain:

Wistar

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

physiological saline

Controls:

other: the untreated skin served as control

Amount / concentration applied:

208-226 mg/male animal or 178-196 mg/female animal

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Executive summary:

A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg (208 -226 mg/male and 178 -196 mg/female applied as a paste) was tolerated without any local irritations. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours 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:

Mar 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

- 4 instead of 3 animals

GLP compliance:

yes

Remarks:

- but a QA check was not performed

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye, which remained untreated, served as control.

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

test substance remained in the eye (eye was not rinsed)

Observation period (in vivo):

5 days

Number of animals or in vitro replicates:

4 females

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Table 1: Results of the study

		Irritant effects (score)
Animal no. (sex)	Irritation parameter	24 h	48 h	72 h	Mean scores
1 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
2 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0

The control eyes were without findings.

The single application of 0.1 ml ZK 4947 (corresponding to 70.6 - 76.4 mg) into the conjunctival sac of the right eye led to slight to moderate, transient irritations mainly on the application day. Only one animal showed severe secretion 30 minutes after application. From day 2 onwards, all animals were without findings

Executive summary:

In a local tolerance test on the rabbit eye similar to OECD TG 405 a single application of the test substance into the conjunctival sac provoked transient slight to moderate irritations mainly on the application day. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea, iris, conjunctival reddening and conjunctival swelling. According to EU classification criteria ZK 4947 (androstadiendion) need not be labelled as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A combined study on acute dermal toxicity and on local tolerance was conducted (Kurth, 1995). The study design and reporting deviates from the current OECD TG 404, however, the study was considered sufficient for assessment of skin irritation/corrosion. In this study a single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg (208 -226 mg/male and 178-196 mg/female applied as a paste) was tolerated without any local irritations. The mean values of findings relevant for classification (reddening, scab formation and swelling of the skin) at the time-points 24, 48 and 72 hours after the end of administration were 0 according to the system recommended in Directive 67/548/EEC.

In a local tolerance test on the rabbit eye similar to OECD TG 405 a single application of the test substance into the conjunctival sac provoked transient slight to moderate irritations mainly on the application day (Treher, 1995). The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameters cornea, iris, conjunctival reddening and conjunctival swelling. According to EU classification criteria androstadiendion need not be labelled as an eye irritant.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Justification for classification or non-classification

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