Pregn-4-ene-3,20-dione, 21-(acetyloxy)-6-fluoro-16-methyl-, (6.alpha.,16.alpha.)-

Endpoint summary

Description of key information

Skin irritation (rat): not irritating [Draft report, Stark 1996b]
Eye irritation (rabbit): not irritating [Draft report, Schauer 1997]

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:

other information

Study period:

Sep to Oct 1996

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

Species:

rat

Strain:

Wistar

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

physiological saline

Controls:

other: the untreated skin served as control

Amount / concentration applied:

202-214 mg/male animal or 210-216 mg/female animal

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

A single dermal administration (occlusive conditions, exposure for 24 hours) of 210.1-216.0 mg ZK 4841/female rat and 202.1-214.0 mg ZK 4841/male rat as a paste was tolerated without any local irritation. According to the system of evaluation recommended for the EU, this compound showed no irritating potential.

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 (202 -214 mg/male and 210 -216 mg/female applied as a paste) was tolerated without any local 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:

other information

Study period:

Apr 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

- 4 instead of 3 animals

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):

8 days

Number of animals or in vitro replicates:

2 males and 2 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:

0.5

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.25

Max. score:

4

Reversibility:

fully reversible within: 2 days

Table 1: Results of the study

		Irritant effects (score)
Animal no. (sex)	Irritation parameter	24 h	48 h	72 h	Mean scores
1 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	0	0	0.3
	Conjunctiva (swelling)	0	0	0	0.0
2 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	0	0	0.3
	Conjunctiva (swelling)	0	0	0	0.0
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	1	1.0
	Conjunctiva (swelling)	3	0	0	1.0
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	0	0	0.3
	Conjunctiva (swelling)	0	0	0	0.0

The control eyes were without findings.

The single application of 0.1 mL ZK 4841 (corresponding to 67.6 -74.9 mg) into the conjunctival sac of the right eye provoked slight irritation which lasted for 7 days after application.

Executive summary:

In a local tolerance test on the rabbit eye according to OECD TG 405 a single application of the test substance into the conjunctival sac provoked slight irritation which were fully reversible within 8 days. The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameter cornea and iris, 0.5 for conjunctival reddening as well as 0.25 for conjunctival swelling. According to EU classification criteria ZK 4841 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 (Stark, 1996b). 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 (202-214 mg/male and 210-216 mg/female

applied as a paste) was tolerated without any local irritations.

In a local tolerance test on the rabbit eye according to OECD TG 405 a single application of the test substance into the conjunctival sac provoked slight irritation which were fully reversible within 8 days (Schauer, 1997). The mean values of findings relevant for classification at the time-points 24, 48 and 72 hours after application were 0 for the parameter cornea and iris, 0.5 for conjunctival reddening as well as 0.25 for conjunctival swelling. According to EU classification criteria ZK 4841 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 Directive 67/548/EEC or Regulation (EC) No. 1272/2008 (CLP) is not required.