Reaction mass of trisodium 2-(hydroxyphosphinato)succinate and pentasodium 1-(hydroxyphosphinato)butane-1,2,3,4-tetracarboxylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 12 October 1992 To 16 October 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

Principles of method if other than guideline:

Draize test.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: tetrasodium-phosphonoethane-1,2-dicarboxylate; hexasodium-phosphonobutane-1,2,3,4-tetracarboxylate

EC Number:

410-800-5

EC Name:

A mixture of: tetrasodium-phosphonoethane-1,2-dicarboxylate; hexasodium-phosphonobutane-1,2,3,4-tetracarboxylate

Cas Number:

143239-08-1

Molecular formula:

Constituent 1 (tetrasodium phosphonoethane-1,2-dicarboxylate): Hill formula: C4H3Na4O7P CAS formula: C4 H7 O7 P .4Na Constituent 2 (hexasodium-phosphonobutane-1,2,3,4-tetracarboxylate): Hill formula: C8H5Na6O11P CAS formula: C8 H11 O7 P .6Na

IUPAC Name:

Reaction mass of tetrasodium phosphonoethane-1,2-dicarboxylate and hexasodium-phosphonobutane-1,2,3,4-tetracarboxylate

Details on test material:

- Name of test material (as cited in study report): ITC 288 (reaction mixture consisting mainly of the following components: n=1= phosphonoethane-1,2-dicarboxylic acid tetrasodium salt and n = 2= 1-phosphonobutane-1, 2, 3, 4-tetracarboxylic acid hexasodium salt)
- Physical state: white powder
- Storage condition of test material: room temperature under silica gel

Specific details on test material used for the study:

Purity of the test material is based on the phosphonate composition, with no direct measure of % sodium. ITC 288 is not the "Reaction mass of tetrasodium-phosphonoethane-1,2-dicarboxylate and hexasodium-phosphonobutane-1,2,3,4--tetracarboxylate" (EC 410-800-5) rather the substance "Reaction mass of trisodium-phosphonoethane-1,2-dicarboxylate and pentasodium-phosphonobutane-1,2,3,4--tetracarboxylate" (EC 701-079-0) as demonstrated by the manufacturing specs reported in Section 1.2, legal entity composition.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheschire, U.K.
- Age at study initiation: 12-16 weeks old
- Weight at study initiation: 2.61-3.18 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-19
- Humidity (%): 53-55
- Air changes (per hr): 15
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 12 October 1992 To: 16 October 1992

Test system

Vehicle:

not specified

Controls:

other: left eye was used for control purposes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a volume of 0.1 ml of the test material, which was found to weight approximately 93 mg was placed into the conjunctival sac of the right eye

Duration of treatment / exposure:

not rinsed

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

6 (4 males and 2 females)

Details on study design:

SCORING SYSTEM: Draize scale for scoring ocular irritation


TOOL USED TO ASSESS SCORE: examination of the eye was facilitated by use of the light source from a standard ophtalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hr

Score:

0.28

Max. score:

4

Reversibility:

fully reversible within: 72 hr

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hr

Score:

0.17

Max. score:

2

Reversibility:

fully reversible within: 24 hr

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48 and 72 hr

Score:

0.83

Max. score:

3

Reversibility:

fully reversible within: 72 hr

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24,48 and 72 hr

Score:

0.55

Max. score:

4

Reversibility:

fully reversible within: 72 hr

Irritant / corrosive response data:

A single application of the test material to a right eye of six rabbits produced diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Dulling of the normal lustre of the corneal surface was confined to one treated eye one hour after treatment. All treated eyes appeared normal 72 hours after treatment.

Other effects:

None

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

score at time point/ Reversibility	Cornea Max. score:4	Iris Max. score:2	Conjunctivae Max. score:3	Chemosis Max. score:4
1h	0/0/0/d/0/0	1/1/1/1/1/1	2/2/2/2/2/2	2/2/2/2/2/2
24h	0/0/1/1/1/0	0/0/1/1/1/0	2/1/2/1/2/1	1/1/2/1/1/1
48h	0/0/1/1/0/0	0/0/0/0/0/0	1/1/1/1/1/1	1/0/1/0/1/0
72h	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0
Average 24h, 48h, 72h	0.28	0.17	0.83	0.55
Reversibility *)	c.	c.	c.	c.

d = dulling of the normal lustre of the corneal surface

c. = completely reversible

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

according to the CLP Regulation (EC n.1272/2008)

Conclusions:

Under the conditions of this test, ITC 288 is slightly irritating to eyes. However, no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).

Executive summary:

In a primary eye irritation study (Tuffnell, 1992), six New Zealand rabbits were exposed to ITC 288. Animals were observed for 3 days. Irritation was scored by the draize scale. Dulling of the normal lustre of the cornea surface was noted in one treated eye one hour after treatment. Diffuse corneal opacity was noted in three treated eyes at the 24 -hour observation and in two treated eyes at the 48 -hour observation. No other adverse corneal effects were noted. Iridial inflammation was noted in all treated eyes one hour after treatment and in three treated eyes at the 24 -hour observation. No other adverse iridial effects were noted. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal to moderate conjunctival irritation at the 24 -hour observation and minimal conjunctival irritation at the 48 -hour observation. All treated eyes appeared normal 72 -hours after treatment. A single application of ITC 288 to the intact eye of six rabbits produced mild irritation which desappeared. Under the test conditions of this study, ITC 288 is slightly irritating to eyes but no classification is required according to the EU legislation (CLP regulation (1272/2008) and Directive 67/548/EEC).

This eye irritation study is classified as acceptable. It satisfies the guideline requirement for an eye irritation study in the rats.