Phosphoric acid, mono- and di-C11-14 (linear and branched) alkyl esters

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 21 August 2012 and 04 September 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 April 2002

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)

Test material

Test material information

Constituent 1

Reference substance name:

Phosphoric acid, mono- and di-C11-14 (linear and branched) alkyl esters

EC Number:

800-484-0

Cas Number:

154518-38-4

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance).

IUPAC Name:

Phosphoric acid, mono- and di-C11-14 (linear and branched) alkyl esters

Test material form:

liquid: viscous

Details on test material:

Sponsor's identification: Phosphoric acid, C11-14-isoalkyl C13-RICH, CAS 154518-38-4

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

One New Zealand White (Hsdlf:NZW) strain rabbit was supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animal weighed 2.39 kg and was twelve to twenty weeks old. After an acclimatisation period of at least five days the animal was given a number which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animal was housed in a suspended cage. Free access to mains drinking water and food (2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animal was provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye remained untreated and served as control

Amount / concentration applied:

A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye

Duration of treatment / exposure:

the eyes were not rinsed after treatment

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: according to OECD guideline 405

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean 24, 48, 72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean 24, 48, 72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24, 48, 72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean 24, 48, 72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Results 5

Irritation parameter:

other: discharge

Basis:

animal #1

Time point:

other: mean 24, 48, 72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Individual scores for ocular irritation are given in Table 1.
Scattered or diffuse corneal opacity was noted in the treated eye one hour after treatment with translucent corneal opacity noted at the 24, 48, 72 h and 7 d observations and opaque corneal opacity at the 14 d observation. Vascularisation, with a generalised ingrowth of vessels for up to approximately 5 mm, was noted in the treated eye at the 14 d observation. Pannus formation around approximately three quarters of the cornea and extending up to 5 mm towards the centre of the cornea was also noted in the treated eye at the 14 d observation.
Iridial inflammation was noted in the treated eye one hour after treatment and at all subsequent observations.
Severe conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48 h observations with moderate conjunctival irritation noted at the 72 h, 7 and 14 d observations.
The reactions noted in the treated eye at the 14 d observation were considered to be indicative of irreversible ocular damage.

Other effects:

Bodyweight
Individual bodyweights and bodyweight change are given in Table 2.
The animal showed expected gain in bodyweight during the study

Any other information on results incl. tables

Interpretation of Results

If evidence of irreversible ocular damage is noted, the test item will be classified as corrosive to the eye.

The results were interpreted according to the Globally Harmonised System of Classification and Labelling of Chemicals and Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.

Table 1              Individual Scoresfor Ocular Irritation

Rabbit Number and Sex	72420Male
	IPR= 2
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	7 Days	14 Days
CORNEA
Degree of Opacity	1	2	2	2	2	4VPa
Area of Cornea Involved	4	4	4	4	4	4
IRIS	1	1	1	1	1	1
CONJUNCTIVA
Redness	2	2	2	2	2	2
Chemosis	3	3	3	2	2	2
Discharge	3	3	3	2	1	1

IPR=  Initial pain reaction

V =      Vascularisation, with a generalised ingrowth of vessels for approximately up to 4 mm to 5 mm

Pa =    Pannus formation around approximately ¾ of the cornea and extending up to 5 mm towards the centre of the cornea

Table 2              Individual Bodyweights and Bodyweight Change

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 14
72420Male	2.39	2.79	0.40

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The test item produced irreversible ocular damage and was considered to be CORROSIVE to the rabbit eye.
The test item was classified as Category 1 (irreversible effects on the eye) according to the Globally Harmonised System of Classification and Labelling of Chemicals.
The test item was also classified as Irreversible effects on the eye (Category 1) according to Regulation (EC) No. 1272/2008. It is reasonable to assume that the Signal Word “Danger” and the Hazard Statement “H318: Causes serious eye damage” are therefore required.

Executive summary:

In a primary eye irritation study according to OECD Guideline 405 (Acute Eye Irritation / Corrosion), adopted 24 April 2002, and EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion), 0.1 mL of Phosphoric acid, mono- and di- C11-14 (linear and branched) alkyl esters (100% a.i.) was instilled into the conjunctival sac of the the right eye of one young adult male New Zealand White rabbit. The eye was not washed after treatment. The animal then was observed for 14 days.  Irritation was scored by the method of Draize.

Scattered or diffuse corneal opacity was noted in the treated eye one hour after treatment with translucent corneal opacity noted at the 24, 48, 72 h and 7 d observations and opaque corneal opacity at the 14 d observation. Vascularisation, with a generalised ingrowth of vessels for up to approximately 5 mm, was noted in the treated eye at the 14 d observation. Pannus formation around approximately three quarters of the cornea and extending up to 5 mm towards the centre of the cornea was also noted in the treated eye at the 14 d observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at all subsequent observations.

Severe conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48 h observations with moderate conjunctival irritation noted at the 72 h, 7 and 14 d observations. 

The reactions noted in the treated eye at the 14 d observation were considered to be indicative of irreversible ocular damage.

In this study, Phosphoric acid, mono- and di- C11-14 (linear and branched) alkyl esters is an eye irritant and produced irreversible effects on the eye (Category 1) based on the criteria of Regulation (EC) No. 1272/2008.