Estr-4-ene-3,17-dione

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Nov 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 26 Feb. 1987

Deviations:

yes

Remarks:

4 instead of 3 animals

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Estr-4-ene-3,17-dione

EC Number:

211-995-8

EC Name:

Estr-4-ene-3,17-dione

Cas Number:

734-32-7

Molecular formula:

C18H24O2

IUPAC Name:

estr-4-ene-3,17-dione

Test material form:

other: solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Schriever
- Weight at study initiation: males: 3.0 kg, females: 2.8 - 3.1 kg
- Housing: 1/cage
- Diet (e.g. ad libitum): pell. Altromin® K, ad libitum
- Water (e.g. ad libitum): demineralized water, ad libitum
- Acclimation period: > 14 days; during this period a diet containing 0.03% sulfaquinoxaline was offered for 7 consecutive days as coccidiosis prophylaxis; the animals received Jacutin® emulsion into the meatus acusticus exterilljg for prophylaxis
against mite infection of the ear and were vaccinated against rabbit haemorrhagic disease (Arvilap®)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22°C
- Humidity (%): 66 - 70%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

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):

6 days

Number of animals or in vitro replicates:

2 males, 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
Draize scale

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.4

Max. score:

3

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

Animal no. 605F was sacrificed on day 3 of the study for humane reasons since it suffered from a paresis of the hind legs due to dislocation of sacral vertebra. This animal was without findings from day 2 onwards.

Any other information on results incl. tables

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)	0	0	0	0.0
	Conjunctiva (swelling)	0	0	0	0.0
2 (M)	Cornea	0	0	0	0.0
	Iris	0	0	0	0.0
	Conjunctiva (reddening)	2	0	0	0.7
	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)	2	0	0	0.7
	Conjunctiva (swelling)	0	0	0	0

 

 

The control eyes were without findings.

 

Findings after treatment with the test substance were slight to severe secretion, slight to moderate reddening and swelling of the outer eye lids and eye lid closure on the application day. Furthermore, slight to mainly moderate reddening and swelling of the conjunctivae and slight to moderate injection of blood vessels were observed. Additionally, in one animal moderate reddening of the iris was noted 1 and 2 hours after application. On day 2, 2 animals still showed slight to moderate reddening and vascular injection of the conjunctivae. From day 2 or 3 onwards, all animals were without findings.

Applicant's summary and conclusion

Conclusions:

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 transient mainly moderate signs of irritation. The findings were fully reversible by day 3 after administration. According to EU classification criteria need not be labelled as an eye irritant.

Executive summary:

In an eye irritation study according to OECD Guideline 405, four New Zealand White rabbits (2M, 2F) each received a volume of 0.1 ml Norandrostenedione (corresponding to 60.1 - 64.0 mg substance) into the conjunctival sac of the right eye. The left eye remained untreated and served as control.

During application and observation on the application day (first day of the test) the animals were kept in restraining cages for approximately 2.5 hours. No food or water was available during this time. Conjunctivae, eyelids, cornea and iris were evaluated before application, 0.5, 1 and 2 hours thereafter, and then once daily until termination of the study on day 4.

Findings after treatment with the test substance were slight to severe secretion, slight to moderate reddening and swelling of the outer eye lids and eye lid closure on the application day. Furthermore, slight to mainly moderate reddening and swelling of the conjunctivae and slight to moderate injection of blood vessels were observed. Additionally, in one animal moderate reddening of the iris was noted 1 and 2 hours after application. On day 2, 2 animals still showed slight to moderate reddening and vascular injection of the conjunctivae. From day 2 or 3 onwards, all animals were without findings.

According to EU classification criteria need not be labelled as an eye irritant.