Oestr-5(10)-ene-3,17-dione

Endpoint summary

Description of key information

Skin irritation (rat): not irritating [Ihara 2004]
Eye irritation (rabbit): not irritating [Takashima 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:

key study

Study period:

from March to April 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 July 1992

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

Principles of method if other than guideline:

A combined study on acute dermal toxicity and on local tolerance was used to assess skin irritation/corrosion (comparable to OECD TG 402 and 404). The study design and reporting deviates from the current OECD TG 404, however, the study is considered sufficient for assessment of this endpoint. As described in ATP 96/54/EC ANNEX IV A, PART B: METHODS FOR THE DETERMINATION OF TOXICITY AND OTHER HEALTH EFFECTS, a strategy of testing for irritancy allows the non-performance of a test if an acute toxicity study by the dermal route has been conducted at the limit test dose with the substance (method B.3), and no skin irritation was observed, further testing for skin irritation (method B.4) may be unnecessary.

GLP compliance:

yes

Species:

rat

Strain:

other: Jcl:SD

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CLEA Japan, Inc.
- Age at study initiation: 7 weeks (male), 10-11 weeks (female)
- Weight at study initiation: 257-288 g (male), 264-272 g (female)
- Housing: 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7-22.8
- Humidity (%): 42-57
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

other: shorn

Vehicle:

other: liquid paraffin

Controls:

other: the untreated skin served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 514 - 576 mg/male; 528 - 544 mg/female

VEHICLE
- Amount(s) applied (volume or weight with unit): 1mL
- Lot No. 2Y28

Duration of treatment / exposure:

24 hours

Observation period:

14 days

Number of animals:

3 males and 3 females

Details on study design:

TEST SITE
- Area of exposure: 4 x 9 cm
- % coverage: 10% of body surface
- Type of wrap: gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing: rinsed out with lukewarm water
- Time after start of exposure: 24 hours

Scoring system: according to OECD404

Irritation parameter:

erythema score

Basis:

animal: #1 to #6

Time point:

24/48/72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal: #1 to #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One male and one female revealed very slight reddenings at only 24 hours after removal of the pad (day 3). The mean values of grades across 3 time-points (24, 48 and 72 hours after removal of the pad) and across all 6 animals were 0.1 for reddenings/scab formation and 0 for swelling, and these findings were temporarily observed.

Other effects:

No systemic intolerance reactions were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

A combined study on acute dermal toxicity and on local tolerance was conducted . The study design and reporting deviates from the current OECD TG 404, however, the study was considered sufficient for assessment of skin irritation/corrosion. A single dermal administration of the test substance for 24 hours to male and female rats at a dose of 2000 mg/kg provoked very slight reddenings at only 24 hours after removal of the pad (day 3) which was fully reversible on day 4 (48 hours after removal of the pad) after administration.

Executive summary:

In a primary dermal irritation study similar to OECD TG 404, (young adult) Jcl:SD rats, female and male (3/sex) were dermally exposed to 514-576 mg/male animal or 528-544 mg/female animal of Delta-5-Norandrostendion in liquid paraffin for 24 hours. Animals then were observed for 14 days. Irritation was scored by the method according to the system recommended in OECD Test Guideline 404.

No local irritations were observed. In this study, the test item is not a dermal irritant.

 

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 2003

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:

24 February 1987

Deviations:

yes

Remarks:

- 4 instead of 3 animals

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kbl:NZW

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kitayama Labes Co., Ltd.
- Age at study initiation: 14 weeks
- Weight at study initiation: 2.93 - 3.18 kg (male), 2.80 - 2.85 kg (female)
- Housing: 1 animal/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7 - 22.8
- Humidity (%): 45 - 63 %
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

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

Amount / concentration applied:

0.1 mL (corresponded to 39-41.8 mg substance)

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:

chemosis score

Time point:

24/48/72 h

Reversibility:

other: not applicable

Remarks on result:

other: Chemosis refers to reddening of the eye lids and nictating membranes, only reddening of the conjunctivae was measured.

Irritation parameter:

cornea opacity score

Basis:

animal: #1 to #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1 to #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal: #1 to #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal: #1 to #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The single application of 0.1 mL ZK 67026 into the conjunctival sac of the right eye led to predominantly slight reactions observed within 2 hours after application. The data reveal that conjunctiva was only transiently affected. However, cornea and iris were not affected. Moreover, all animals were without findings 2 hours after application.

Interpretation of results:

GHS criteria not met

Remarks:

only slight irritation of the conjuntivae which were fully reversible within 2h after application

Conclusions:

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 slight transient irritation (only 0.5 to 1 hours after application).

Executive summary:

In a primary eye irritation study similar to OECD TG 405, 0.1 mL corresponding to 39-41.8 mg of Delta-5-Norandrostendion was instilled into the conjunctival sac of the right eye of young adult female and male Kbl:New Zealand White rabbits (2/sex) and the animals were observed for 4 days. The eyes were not washed. Irritation was scored by the method described in the guideline.

A single application of the test substance into the conjunctival sac provoked on the whole slight irritation which lasted up to 2 h after application. 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 and conjunctival swelling and reddening. In this study, the test item is not an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a primary dermal irritation study similar to OECD TG 404, (young adult) Jcl:SD rats, female and male (3/sex) were dermally exposed to 514-576 mg/male animal or 528-544 mg/female animal of Delta-5-Norandrostendion in liquid paraffin for 24 hours. Animals then were observed for 14 days. Irritation was scored by the method according to the system recommended in OECD Test Guideline 404.

No local irritations were observed. In this study, the test item is not a dermal irritant.

 

In a primary eye irritation study similar to OECD TG 405, 0.1 mL corresponding to 39-41.8 mg of Delta-5-Norandrostendion was instilled into the conjunctival sac of the right eye of young adult female and male Kbl:New Zealand White rabbits (2/sex) and the animals were observed for 4 days. The eyes were not washed. Irritation was scored by the method described in the guideline.

A single application of the test substance into the conjunctival sac provoked on the whole slight irritation which lasted up to 2 h after application. 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 and conjunctival swelling and reddening. In this study, the test item is not an eye irritant.

 

Justification for classification or non-classification

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