Gona-1,3,5(10)-trien-17-ol, 13-ethyl-3-methoxy-, (17.beta.)-

Endpoint summary

Description of key information

Skin irritation (rat): not irritating [report No. 11076, Döhr 2004]
Eye irritation (rabbit): transient irritation [report No. A12127, Amir 2004]

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:

August 2002

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, rats instead of rabbits, few details in test description and reporting

GLP compliance:

yes

Species:

rat

Strain:

other: Shoe: WST (SPF)

Type of coverage:

occlusive

Preparation of test site:

other: The backs of the animals were shom one day before compound administration.

Vehicle:

physiological saline

Controls:

other: the untreated skin served as control

Amount / concentration applied:

(705 - 831 mg/mL in male animals and 900 - 925 mg/mL in female animals) and 0.9% (w/v) sodium chloride (0.7 - 0.8 mL in male
animals and 0.4 mL in female animals)

Duration of treatment / exposure:

24 hours

Observation period:

up to 72 hours after removal of the patches

Number of animals:

3 males and 3 females

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.

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 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:

other information

Study period:

August 2002

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

GLP compliance:

yes

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 (corresponded to 61.6 - 62.9 mg test material)

Duration of treatment / exposure:

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

Observation period (in vivo):

4 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:

0.08

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.59

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.42

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

Local findings after single administration of ZK 46060 into the conjunctival sac of the rabbit eye were slight to moderate reddening of the conjunctivae observed in all animals on administration day up to day 3 (except animal no. 359M only until day 2). Slight to moderate swelling of the conjunctivae was observed in all animals on administration day up to day 2 or 3. In addition, one male and one female animal showed vessel injection of the iris on administration day. The same finding was also observed in the other male animal but only on day 2. All animals were without findings on day 4.

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	1	0	0	0.33
	Conjunctiva (reddening)	1	1	0	0.67
	Conjunctiva (swelling)	1	0	0	0.33
2 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	0	0.67
	Conjunctiva (swelling)	2	0	0	0.67
3 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	0	0.67
	Conjunctiva (swelling)	1	1	0	0.67
4 (F)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	1	1	0	0.67
	Conjunctiva (swelling)	0	0	0	0.0

The control eyes were without findings.

Local findings after single administration of ZK 46060 into the conjunctival sac of the rabbit eye were slight to moderate reddening of the conjunctivae observed in all animals on administration day up to day 3 (except animal no. 359M only until day 2). Slight to moderate swelling of the conjunctivae was observed in all animals on administration day up to day 2 or 3. In addition, one male and one female animal showed vessel injection of the iris on administration day. The same finding was also observed in the other male animal but only on day 2. All animals were without findings on day 4.

Executive summary:

A single conjunctival administration into the conjunctival sac of the rabbit eye (OECD TG 405) provoked slight to moderate irritation which was fully reversible on day 4 after administration.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg was tolerated without any local irritations. Consequently 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.

A single conjunctival administration into the eonjunctival sac of the rabbit eye (OECD TG 405) provoked slight to moderate irritation which was fully reversible on day 4 after administration.

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.