2-Butenoic acid, 4-(diethoxyphosphinyl)-2-methyl-, ethyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP guideline study, available as unpublished report, minor restrictions in design and/or reporting, but otherwise adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-(diethoxyphosphinyl)-2-methyl-2-butenoic acid ethyl ester

EC Number:

601-818-6

Cas Number:

122009-11-4

Molecular formula:

C11 H21 O5 P

IUPAC Name:

4-(diethoxyphosphinyl)-2-methyl-2-butenoic acid ethyl ester

Details on test material:

- Name of test material (as cited in study report): C-5-Ester-phosphonat Techn.

Test animals / tissue source

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler, D-6050 Offenbach/Main, FRG
- Weight at study initiation: 3.13 kg for the males and 3.39 kg for the female
- Housing: single housed in stainless steel cages with wire mesh walk floors; floor area: 40 cm x 51 cm; no bedding in cages, saw-dust in the waste trays
- Diet: Kliba 341, 4MM; Firma Klingentalmuehle AG, CH-4303 Kaiseraugst; ad libitum (about 130 g per animal per day)
- Water: about 250 mL tap water per animal per day
- Acclimation period: at least 8 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL of the test substance was applied to the conjunctival sac of the right eye of each animal

Duration of treatment / exposure:

Single application

Observation period (in vivo):

- Total observation period: 21 days

Number of animals or in vitro replicates:

3 (2 males and 1 female)

Details on study design:

REMOVAL OF TEST SUBSTANCE:
- The substance was not washed out

SCORING SYSTEM:
- Mean score was calculated in accordance with 83/467/EEC criteria, 29 Jul 1983. For calculation of the means of opacity, iris, redness, and swelling only the readings of 24, 48, and 72 hours were used.
- Readings: 1, 24, 48, and 72 hours and 8, 15, and 21 days after application.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24 - 72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24 - 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24 - 72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 - 72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24 - 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24 - 72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24 - 72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 9

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24 - 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 10

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24 - 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Loss of corneal tissue, marginal vascularization of the cornea, small retractions in the eyelids or suppuration were observed (see Table 1) and, for 2 animals, were still observable at the end of the observation period.

Any other information on results incl. tables

Table 1: Draize scores and symptoms

Readingtime	Test animal	Cornea		Iris	Conjunctiva			Symptoms
		Opacity	Area		erythema	Edema	secretion
After 1 hours	First male	1	2	0	2	2	2	LC
	Second male	1	3	0	2	2	2	LC
	Female	1	2	0	2	2	2	LC
After 24 hours	First male	1	2	0	2	1	1	LC
	Second male	1	2	0	2	1	1	LC
	Female	1	4	0	2	1	1	LC
After 48 hours	First male	1	4	0	2	1	1	PC
	Second male	1	2	0	2	0	1	LC
	Female	1	4	0	2	0	1	PC
After 72 hours	First male	1	4	0	2	1	2	PC/S
	Second male	1	2	0	2	0	1	LC
	Female	1	4	0	2	0	1	PC
After 8 days	First male	1	2	1	1	1	2	LC/PC
	Second male	0	0	0	0	0	0
	Female	1	2	0	2	0	1	LC/PC/MV/RE
After 15 days	First male	2	2	0	2	1	3	LC/PC/MV/RE
	Second male	0	0	0	0	0	0
	Female	1	2	0	2	0	2	LC/PC/MV/RE
After 21 days	First male	2	2	0	2	1	3	LC/PC/MV/RE
	Second male	0	0	0	0	0	0
	Female	1	2	0	2	0	1	LC/PC/MV/RE
mean 24, 48 and 72 hours	First male	1.0		0.0	2.0	1.0
	Second male	1.0		0.0	2.0	0.3
	Female	1.0		0.0	2.0	0.3
	3-animals mean	1.0		0.0	2.0	0.6
LC: loss of corneal tissue; MV: marginal vascularization of the cornea; RE. small retractions in the eyelids; S: suppuration

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information

Conclusions:

Under the conditions of the test, the substance was considered to cause irreversable damage to the eye.

Executive summary:

The potential to cause damage to the eye was assessed in an OECD 405 guideline study (in compliance with GLP) in which 3 Vienna white rabbits were subjected to a single ocular application of 0.1 mL of the undiluted test substance. Effects on conjunctiva and cornea were observed. The mean score (24 to 72 hours) for irritation was calculated to be 1, 1 and 1 for corneal opacity, 0, 0 and 0 for iritis, 2, 2 and 2 for conjunctivae redness, and 1, 0.3 and 0.3 for chemosis, for animal 1, 2 and 3 respectively. Findings for animal 1 and 3 were not reversible within 21 days. It was therefore concluded that the test substance causes severe eye damage.