Estr-5(10)-en-17-one, 3,3-dimethoxy-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Apr 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

3,3-Dimethoxyestr-5(10)-en-17-one

EC Number:

606-278-5

Cas Number:

19257-34-2

Molecular formula:

C20 H30 O3

IUPAC Name:

3,3-Dimethoxyestr-5(10)-en-17-one

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kisslegg, Germany
- Weight at study initiation: males: 3.2 - 3.9 kg; females: 3.4 - 3.6 kg
- Housing: individually, in conventional metal cages
- Diet (e.g. ad libitum): pell. Altromin® K, ad libitum
- Water (e.g. ad libitum): demineralized water, ad libitum
- Acclimation period: ≥ 14 days; du ring this period the animals were vaccinated against rabbit hemorrhagic disease (Arvilap®)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 64-66
- 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):

4 days

Number of animals or in vitro replicates:

2 males and 2 females

Details on study design:

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

SCORING SYSTEM: Evaluation of the local tolerance on the conjunctiva of the rabbits was performed according to the score system recommended for the EU

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

no swelling of the eye lids or the nictating membranes was reported but swelling of the conjuntivae was reported

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 3

Irritation parameter:

iris score

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 4

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 5

Irritation parameter:

conjunctivae score

Remarks:

reddening

Basis:

animal: #1, #2, #4

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Results 6

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

animal: #1 - #4

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

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)	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)	1	0	0	0.33
	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 of the test item into the conjunctival sac of the right eye provoked slight conjunctival reddening in one out of four animals only 24 hours after administration.

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 slight conjunctival reddening in one out of four animals only 24 hours after administration.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 as well as 0.08 for conjunctival reddening. According to EU classification criteria the test item need not be labelled as an eye irritant.

Executive summary:

In a primary eye irritation study similar to OECD TG 405, 0.1 mL corresponding to 50.9-56.9 mg of Dimethoxyketal was instilled into the conjunctival sac of the right eye of young adult female and male 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.

The single application of 0.1 mL of the test item into the conjunctival sac of the right eye provoked slight conjunctival reddening in one out of four animals only 24 hours after administration. 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 as well as 0.08 for conjunctival reddening. In this study, the test item is not an eye irritant.