Phosphonic acid, P-phenyl-, zinc salt (1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17th December 2013 to 14th February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study undertaken to GLP and internationally accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Eye Irritation (2-1-5), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Phenylphosphonic acid, zinc salt:

IUPAC Name:

Phenylphosphonic acid, zinc salt:

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Phenylphosphonic acid, zinc salt
- Substance type: Inorganic
- Physical state: White powder
- Analytical purity: > 99%
- Purity test date:
- Lot/batch No.: 1408
- Expiration date of the lot/batch: March 2014
- Stability under test conditions: Nop data
- Storage condition of test material: Room temperature, dark, desiccated

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Commercial laboratory animal supplier
- Age at study initiation: 47 to 52 weeks
- Weight at study initiation: 3.55 to 3.71 kg
- Housing: The rabbits were housed individually in plastic cages with perforated floors.
- Diet: Each rabbit was offered 125 g of a standard laboratory rabbit diet per day. The animals were given a dietary supplement of hay during acclimatisation until two days prior to dose instillation. Wholemeal bread was offered for the remainder of acclimatisation and throughout the study observation period..
- Water: ad libitum
- Acclimation period: 27 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 16 to 20°C
- Humidity: 40 to 70%
- Air changes (per hr): no data
- Photoperiod: 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): as supplied

Duration of treatment / exposure:

1, 24, 48 and 72 h

Observation period (in vivo):

8 d

Number of animals or in vitro replicates:

3

Details on study design:

Animal management
Naïve animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain. They were in the weight range of 3.55 to 3.71 kg and 47 to 52 weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the
experimental environment for a period of 27 weeks prior to the start of the study. Each animal was housed individually in a plastic cage with perforated floors and was offered 125 g of a standard laboratory rabbit diet per day; drinking water was provided ad libitum.
The batch of diet used for the study is analysed for nutrients, possible contaminants and micro-organisms likely to be present in the diet and which, if in excess of specified amounts, might have an undesirable effect on the test system. A dietary supplement of hay was offered
during acclimatisation until two days prior to dose instillation, for the remainder of acclimatisation and throughout the study observation period wholemeal bread was offered. During the acclimatisation and study period the animals were given small soft white untreated wood blocks for environmental enrichment. Results of routine physical and chemical examination of drinking water, as conducted by the supplier are made available to Huntingdon Life Sciences.
Animal room environmental controls were set to maintain temperature within the range 16 to 20°C, and relative humidity within 40 to 70%. These environmental parameters were recorded and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to give 12 hours of artificial light (06:00 to 18:00 GMT) in each 24 hour period.
Each animal was identified by a numbered tag placed through the edge of one ear. This identification was unique within the Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study number and animal number. 3.2 Test substance preparation
Phenylphosphonic acid, zinc salt was administered as supplied by the Sponsor. The absorption of Phenylphosphonic acid, zinc salt was not determined.
The identity, strength and purity of the test substance received, its stability under the storage conditions and the conditions of administration were the responsibility of the Sponsor.
Treatment procedure
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation. Each animal was gently restrained. The dose was instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped. The eyelids were then gently held together for one second before releasing; the left eye remained untreated. A single animal (Number 99) was treated in advance; in the absence of a severe effect in this animal two further animals were committed to the study. Huntingdon Life Sciences: ONE0198 12
Topical anaesthetics and systemic analgesia
The following topical anaesthetic and systemic analgesia regime was employed: 60 minutes before administration: 0.01 mg/kg buprenorphine was administered subcutaneously. 15 minutes before administration topical anaesthesia was administered: one/two drops of topical ocular anaesthesia were applied to each eye; the procedure was repeated 10 minutes later. The test material was administered approximately 5 minutes after the last administration of anaesthesia. Eight hours after test material administration: 0.01 mg/kg buprenorphine and 0.5 mg/kg meloxicam were administered subcutaneously.
Following completion of the observation period the animals were humanely killed by an intravenous injection of sodium pentobarbital.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

0

Reversibility:

other: no effect

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

7

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Clinical signs
There was no sign of toxicity or ill health in any rabbit during the observation period.
Ocular responses
A crimson-red conjunctival appearance was evident in all treated eyes one hour after instillation; conjunctival injection was evident in one animal 24 and 48 hours after instillation.
The treated eye of each animal was overtly normal 72 hours after instillation.
Instillation of the test material gave rise to no initial pain response.

Any other information on results incl. tables

The means of scores for the ocular reactions at approximately 24, 48 and 72 hours after administration, calculated separately for each animal, are summarised below:

Animal number	Corneal opacity	Iridial lesions	Conjunctival
			Redness	Chemosis
97	0.0	0.0	0.0	0.0
98	0.0	0.0	0.0	0.0
99	0.0	0.0	0.7	0.0
EC Category 1 trigger values*	≥3	≥1.5
EC Category 2 trigger values*	≥1	≥1	≥2	≥2

*Classification triggered if any value is attained by two or more animals.

Phenylphosphonic acid, zinc salt did not require labelling in accordance with European Commission regulation 1272/2008.

Mean values for ocular lesions for Kay and Calandra classification

Mean irritation scores after instillation of Phenylphosphonic acid, zinc salt

Area of eye	1 hour	24 hours	48 hours	72 hours
Cornea	0.0	0.0	0.0	0.0
Iritis	0.0	0.0	0.0	0.0
Conjunctiva	4.0	0.7	0.7	0.0
Total mean score	4.0	0.7	0.7	0.0

Mean values for ocular lesions for EC (Regulation 1272/2008) and GHS classification

24, 48 and 72 hours after instillation of Phenylphosphonic acid, zinc salt)

Animal number and sex	Corneal Opacity	Iridial Lesions	Redness of Conjunctiva	Chemosis
97F	0.0	0.0	0.0	0.0
98F	0.0	0.0	0.0	0.0
99F	0.0	0.0	0.7	0.0

F: Female

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The highest total mean score was 4.0 occurring at the 1 hour observation; accordingly under the criteria Kay and Calandra (1962) Phenylphosphonic acid, zincsalt was classified as “minimally irritating” to the eye.
Phenylphosphonic acid, zinc salt did not require labelling in accordance with European Commission regulation 1272/2008.

Executive summary:

.