Polyphosphoric acids, ammonium salts

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 09 March 2015 to 30 March 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conclusive, performed to a valid guideline (OECD TG 405, adopted 2 October 2012) and was conducted under GLP conditions. No deviations from the test methods were noted.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of GLP inspection: 12 to 14 March 2015 Date of Signature on Certificate: 12 May 2015

Test material

Test material information

Constituent 1

Reference substance name:

Polyphosphoric acids, ammonium salts

EC Number:

269-789-9

EC Name:

Polyphosphoric acids, ammonium salts

Cas Number:

68333-79-9

Molecular formula:

[NH4PO3]n

IUPAC Name:

undecaammonium bis(phosphonatooxy)phosphinate dihydrogen phosphate hydrogen (phosphonatooxy)phosphonate hydrogen phosphate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Polyphosphoric acids, ammonium salts (solid)
- Physical state: white powder
- Analytical purity: 100%
- Lot/batch No.: MD141010
- Expiration date of the lot/batch: 14 October 2015
- Storage condition of test material: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratoires UK Ltd., Leicestershire, UK
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.95 or 3.12 kg
- Housing: Individually in suspended cages
- Diet (e.g. ad libitum): 2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK was supplied ad libitum
- Water (e.g. ad libitum): Mains drinking water provided ad libitum.
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): At least fifteen per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye of each animal remained untreated and was used for control purposes.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL, approx 84 mg (as measured by gently compacting the required volume into an adapted syringe)

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

Two - after consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated.

Details on study design:

ANALGESIA
A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre-dose anesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.

Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.

TEST PROCEDURE
The test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM: Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment according to the Draize scale (Appendix 2).

TOOL USED TO ASSESS SCORE: Standard opthalmascope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 74927 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 75004

Time point:

other: Mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 3

Irritation parameter:

iris score

Basis:

animal: 74927 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

iris score

Basis:

animal: 75004 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

other: redness

Basis:

animal: 74927 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

other: redness

Basis:

animal: 75004 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

chemosis score

Basis:

animal: 74927 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal: 75004 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Individual scores for ocular irritation are given in Table 1. Individual and Mean Scores for Cornea, Iris and Conjunctivae required for classification and labelling are given in Table 2.
No corneal effects were noted during the study.
Iridial inflammation was noted in both treated eyes 1 and 24 hours after treatment.
Moderate conjunctival irritation was noted in all treated eyes 1 hour after treatment and at the 24 and 48-Hour observations with minimal conjunctival irritation noted at the 72-Hour observation.
Both treated eyes appeared normal at the 7-Day observation.

Other effects:

Individual body weights and body weight change are given in Table 3.
Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 1: Individual Scores for Ocular Irritation

Rabbit Number and Sex	74927Male					75004 Male
	Initial Pain Response = 0					Initial Pain Response = 0
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	7 Days	1 Hour	24 Hours	48 Hours	72 Hours	7 days
CORNEA
Degree of Opacity	0	0	0	0	0	0	0	0	0	0
Area of Cornea Involved	0	0	0	0	0	0	0	0	0	0
IRIS	1	1	0	0	0	1	1	0	0	0
CONJUNCTIVAE
Redness	2	2	2	2	0	2	2	2	2	0
Chemosis	2	2	2	1	0	2	2	2	1	0
Discharge	1	1	0	0	0	2	2	1	0	0

Table 2 Individual and Mean Scores for Cornea, Iris and Conjunctivae

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iridial Inflammation	Conjuctival Redness	Conjunctival Chemosis
74927 Male	24 Hours	0	1	2	2
	48 Hours	0	0	2	2
	72 Hours	0	0	2	1
Mean		0.0	0.3	2.0	1.7
75004 Male	24 Hours	0	1	2	2
	48 Hours	0	0	2	2
	72 Hours	0	0	2	1
Mean		0.0	0.3	2.0	1.7

Table 3 Individual Bodyweights and Bodyweight Change

Table 3 Individual Bodyweights and Bodyweight Change

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 7
74927 Male	3.12	3.18	0.06
75004 Male	2.95	3.00	0.05

 

Applicant's summary and conclusion

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced individual scores of 0.0 for corneal opacity, 0.3 for iritis, 2.0 for conjunctival redness and 1.7 for chemosis, calculated as the mean scores following grading at 24, 48 and 72 hours after instillation. Observed effects were fully reversible within the observation period.

The test item was classified as Category 2B (mildly irritating to eyes) according to the Globally Harmonized System of Classification and Labelling of Chemicals.

The test item was also classified as Irritating to eyes (Category 2) according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

Results

A single application of the test item to the non-irrigated eye of two rabbits produced iridial inflammation and moderate conjunctival irritation. Both treated eyes appeared normal at the 7-Day observation.

Conclusion

The test item produced individual scores of 0.0 for corneal opacity, 0.3 for iritis, 2.0 for conjunctival redness and 1.7 for chemosis, calculated as the mean scores following grading at 24, 48 and 72 hours after instillation. Observed effects were fully reversible within the observation period. The test item was classified as Category 2B (mildly irritating to eyes) according to the Globally Harmonized System of Classification and Labelling of Chemicals.

The test item was also classified as Irritating to eyes (Category 2) according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures. It is reasonable to assume that the Signal Word “Warning” and the Hazard Statement “H319: Causes serious eye irritation” are therefore required