Phosphinic acid, P-[3-(acetyloxy)-3-cyanopropyl]-P-methyl-, butyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 04, 1995 to April 11, 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

February 24, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Phosphinic acid, P-[3-(acetyloxy)-3-cyanopropyl]-P-methyl-, butyl ester

EC Number:

605-460-1

Cas Number:

167004-78-6

Molecular formula:

C11 H20 N O4 P

IUPAC Name:

Phosphinic acid, P-[3-(acetyloxy)-3-cyanopropyl]-P-methyl-, butyl ester

Details on test material:

Molecular weight: 261 g/mol
Molecular formular: C11H2ONO4P

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material: Test substance: Hoe 125869; Identification No.: C00083/001
- Purity, including information on contaminants, isomers, etc.: 88.4%(w/w)
- Appearance: yellow-viscous fluid
- Storage stability: 6 months at -10°C +-5°C
- Expiration date: June 15, 1995

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: darkness, -20°C

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Chemical pharmaceutical factory Dr. K. Thomae, 88400 Biberach
- Age at study initiation: approx. 3 - 5 months
- Weight at study initiation: 3.41 - 3.98 kg
- Housing: in fully air-conditioned rooms, separate cages (arranged in a battery)
- Diet (e.g. ad libitum): ssniff® K-H (V2333), ad libitum
- Water (e.g. ad libitum): tap water from automatic water dispensers, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs light): 12 hours per day

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Duration of treatment / exposure:

24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution took place, the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C.

Observation period (in vivo):

The eyes were examined 1, 24, 48 and 72 hours after application of the test substance. At 24 and 72 hours as well as after 7 days the eyes were also examined for corneal lesions under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 24 hours after application and at all other designated examination times at which the treated eyes still showed discharge or at which a corneal examination with fluorescein sodium solution took place, the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C.
- Time after start of exposure: 24 hours after

SCORING SYSTEM: Based on the system of evaluation defined by the EEC


TOOL USED TO ASSESS SCORE: Under UV light after instillation of one drop of 0.01 % fluorescein-sodium solution.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: conjunctiva chemosis

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

other: conjunctiva chemosis

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 3

Irritation parameter:

other: conjunctiva chemosis

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

other: conjunctiva redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

other: conjunctiva redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

other: conjunctiva redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 8

Irritation parameter:

iris score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 h

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 11

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.88

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.88

Max. score:

4

Reversibility:

fully reversible within: 7 days

Other effects:

One hour after application contracted pupil (miosis) was observed in all animals.
No clinical signs of systemic toxicity were observed.

Any other information on results incl. tables

Observations:

Animal	Time point	Cornea opacity	Iris	Conjunctiva redness	Conjunctiva chemosis	Conjunctiva discharge
#1	24 h	0	0	2	1	0
	48 h	0	0	1	0	0
	72 h	0	0	1	0	0
	7 days	0	0	0	0	0
#2	24 h	0	1	3	3	2
	48 h	0	0	3	2	0
	72 h	0	0	1	0	0
	7 days	0	0	0	0	0
#3	24 h	1	1	3	1	0
	48 h	0	0	2	1	0
	72 h	0	0	1	0	0
	7 days	0	0	0	0	0

All effects wee fully reversible within 7 days. 

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Executive summary:

0.1 mL of the test item was applied once to the conjunctival sac of the left eye of three female New Zealand White rabbits. The treated eyes were washed out 24 hours after application of the test substance.
The test substance caused minor up to moderate effects in the eyes of most animals in the form of conjunctival reddening, chemosis and discharge, and inflammation of the iris, ranging in degree from slight to moderate. 24 hours after application the cornea of one animal showed diffuse opacity areas. All signs of irritation were reversible within 7 days. One hour after application contracted pupil (miosis) was observed in all animals.
No clinical signs of systemic toxicity were observed.

Slight irritation was observed.

Conjunctiva reddening in 2 of 3 animals with a score (24/48/72 h mean/animal) of ≥2 warrants classification according to CLP 1272/2008 as eye irritating Cat. 2.