Ethyl 3-[[bis(1-methylethoxy)phosphinothioyl]thio]propionate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

non GLP, body weight development not recorded, no clinical signs recorded, observation period only 3 days (effects were reversible within two days)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: "Hazardous Substances Regulations" under the U.S.A. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965)

Principles of method if other than guideline:

0.1 ml of the test compound were instilled into the conjunctival sac of the left eye of six rabbits. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml. of warm water. The rabbits were examined 1, 24, 48 and 72 hours after application.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 3-[[bis(1-methylethoxy)phosphinothioyl]thio]propionate

EC Number:

275-965-6

EC Name:

Ethyl 3-[[bis(1-methylethoxy)phosphinothioyl]thio]propionate

Cas Number:

71735-74-5

Molecular formula:

C11H23O4PS2

IUPAC Name:

ethyl 3-{[bis(propan-2-yloxy)(sulfanylidene)-λ⁵-phosphanyl]sulfanyl}propanoate

Details on test material:

- Physical state: liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12-14 weeks
- Weight at study initiation: males: 2.32 kg; females: 2.57
- Housing: individually
- Diet: commercial irradiated diet (Styles-Oxoid) ad libitum
- Water: Sterile filtered water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1
- Humidity (%): 50-70
- Photoperiod (hrs dark / hrs light): 14 / 10

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Left eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

In three rabbits, the eyes were rinsed after 30 seconds. The test eye of the other three rabbits remained unwashed.

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

6 (3 male and 3 female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml of warm water.

SCORING SYSTEM: method described in "Appraisal of the Safety of Chemicals in Food, Drugs, and Cosmetics" page 51, published by the Association of Food and Drug Officials of the U.S.A. (see appendix 1)

TOOL USED TO ASSESS SCORE: Corneal damage was assessed after staining with fluorescein.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

unwashed eyes

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: minimal effects observed in one rinsed eye

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

unwashed eyes

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: no effects

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

unwashed eyes

Time point:

24/48/72 h

Score:

0.2

Max. score:

3

Reversibility:

fully reversible within: 48 h

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

unwashed eyes

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: minimal chemosis observed after 1 h

Irritant / corrosive response data:

Minimal conjunctival redness was observed in both rinsed and unrinsed eyes at the 1h and 24 h timepoint. In addition, in on rinsed eye minimal corneal opacity was observed. All effects were reversible within 48 hours the latest.

Any other information on results incl. tables

EXPERIMENTAL RESULT

Animal Number	11				13				15 (rinsed)				12				14 (rinsed)				16 (rinsed)
Timepoint (hrs)	1	24	48	72	1	24	48	72	1	24	48	72	1	24	48	72	1	24	48	72	1	24	48	72
Cornea
Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Area	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivae
Redness	1	1	0	0	1	0	0	0	2	0	0	0	2	1	0	0	1	1	0	0	1	0	0	0
Chemosis	0	0	0	0	1	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Discharge	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Mean values after 24, 48 and 72 hours for animals with non-rinsed eyes are:

Iris: 0

Corneal Opacity: 0

Conjunctival Redness: 0.2

Chemosis: 0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance caused minimal conjunctival effects in all animals and minimal corneal opacity in one animal; all effects were reversible within 48 hours.

Executive summary:

The occular irritation potential of the test substance was assessed in an in vivo study performed with six New Zealand White rabbits. The eyes of the experimental animals were examined and found normal prior to the test. 0.1 mL of the test compound were instilled into the conjunctival sac of the left eye. The eyelids were then held closed for 1 second. The right eye served as a control. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits with approximately 200 ml of warm water. The rabbits were examined 1, 24, 48 and 72 hours after application of the test compound and for any further period that was considered necessary. The ocular reactions were scored by the method described in "Appraisal of the Safety of Chemicals in Food Drugs and Cosmetics" page 51, published by the Association of Food and Drug Officials of the USA. Corneal damage was assessed after staining with fluorescein. A very slight to slight conjunctival reaction was seen in all treated eyes one hour after application of the compound. This was still present in three eyes (2 unwashed, 1 washed) at 24 hours. Damage to the surface epithelium of the cornea with slight opacity was seen at 24 hours only in one washed eye. After 48 hours, all occular effects had reversed. Therefore, the substance was considered to be not irritating to eyes.