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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation, other
Remarks:
In vivo: Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 30 July 2012 and 04 September 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of GLP inspection: Date of Signature on GLP certificate: 26/11/2009

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Sponsor's identification : trisodium hydrogen diphosphate
Description: white powder
Batch number: 147/12
Purity: 95%
Date received: 07 March 2012
Expiry date: 01 February 2012
Storage conditions: 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 UK Limited, Bicester, Oxon, UK

- Age at study initiation: Twelve to twenty weeks old

- Weight at study initiation: 2.37 or 2.69 kg

- Housing: The animals were individually housed in suspended cages. The animals were 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.

- Diet (e.g. ad libitum): ad libitum (2030C Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK)

- Water (e.g. ad libitum): ad libitum.

- Acclimation period: At least five days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 17 to 23°C

- Humidity (%): 30 to 70%

- Air changes (per hr): At least fifteen changes per hour

- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (06:00 to 18:00) and twelve hours darkness


IN-LIFE DATES:
From: day 1 To:day 3

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit): A volume of 0.1 ml (96 mg) of the test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.

- Concentration (if solution): Undiluted and used as supplied

VEHICLE

- Amount(s) applied (volume or weight with unit):Not applicable

- Concentration (if solution):Not applicable

- Lot/batch no. (if required):Not applicable

- Purity: Not applicable
Duration of treatment / exposure:
Up to 21 days (test item was not removed from the eyes).
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular effects.
Number of animals or in vitro replicates:
2 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, one additional animals was treated).

Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): Not applicable

- Time after start of exposure: Not applicable


SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given in Appendix 2, (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).


TOOL USED TO ASSESS SCORE:

Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
72293 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
72394 Male
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
72293 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effect observed
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
72394 Male
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Remarks:
72293 Male
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Remarks:
72394 Male
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Haemorrhage on the lower and nictating conjunctival membranes was observed
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
72293 Male
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
72394 Male
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritant / corrosive response data:
Individual scores for ocular irritation are given in Table 1.

Scattered or diffuse corneal opacity was noted in one treated eye one hour after treatment and at the 24, 48, 72-Hour, 7, 14 and 21-Day observations.
Iridial inflammation was noted in one treated eye one hour after treatment and at the 24, 48, 72-Hour and 7-Day observations.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Severe conjunctival irritation was noted in one treated eye and moderate conjunctival irritation was noted in the other treated eye at the 24-Hour observation. Moderate conjunctival irritation was noted in both treated eyes at the 48 and 72-Hour observations. Moderate conjunctival irritation was noted in one treated eye and minimal conjunctival irritation was noted in the other treated eye at the 7-day observation. Minimal conjuctival irritation was noted in one treated eye at the 14-day observation.
Petechial haemorrhage of the nictitating and lower conjunctival membranes was noted in one treated eye one hour after treatment and at the 24, 48 and 72-Hour observations. A small area of haemorrhage, approximately 3 mm x 3 mm in size, on the lower eyelid was noted in this treated eye at the 7-Day observation. A small dark brown/black coloured scab, possibly due to rabbit scratching, was noted on the lower eyelid of this animal at the 14-Day observation. One treated eye appeared normal at the 14-Day observation.

The persistence of reactions in one treated eye at the 21-Day observation was considered to be indicative of irreversible ocular damage.
Other effects:
BODYWEIGHT: Individual bodyweights and bodyweight changes are given in Table 2.
Both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1. Individual Score and Individual Total Scores for Ocular Irritation

 

Rabbit Number and Sex

72293 Male

72394 Male

IPR= 3

IPR = 0+

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

7
Days

14

Days   

1
Hour

24
Hours

48
Hours

72
Hours

1

Day

14

Days

21

Days

CORNEA

 

 

 

 

 

 

 

 

 

 

 

 

 

Degree of Opacity

0

0

0

0

0

0

1

1

1

1

1

1

1

Area of Cornea Involved

0

0

0

0

0

0

1

4

4

3

2

1

1

IRIS

0

0

0

0

0

0

1

1

1

1

1

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

Redness

2

2

2

2

1

0

3Pt

3Pt

3Pt

3Pt

2H

1

Chemosis

2

2

2

1

1

0

2

2

2

2

2

1

0

Discharge

2

1

1

1

0

0

2

3

2

2

1

0

0

 

IPR=  Initial pain reaction

+ = One drop of local anaesthetic instilled into both eyes 1 to 2 minutes before treatment

Pt = Petechial haemorrhage on the nictitating and lower conjunctival membranes

H = Small area of haemorrhage, approximately 3 mm x 3 mm in size, on lower eyelid

¤ = Small dark brown/black coloured scab on lower eyelid , possibly due to rabbit scratching

Table 2. Individual bodyweights and bodyweight changes

Rabbit number and sex

Individual bodyweight (kg)

Bodyweight change (kg)

72293 Male

Day 0

Day 14

0.24

2.69

2.93

72394 Male

Day 0

Day 21

0.43

2.37

2.80

 

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test item produced irreversible ocular damage and was considered to be corrosive to the rabbit eye and classified as Irreversible effects on the eye (Category 1) according to Regulation (EC) No. 1272/2008 (EU CLP).

This study is conducted according to the appropriate guidelines (OECD 405) and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for REACH (Regulation (EC) No.1907/2006) as a key study for this endpoint. Study is sufficient for classification and labelling purposes, in accordance with Regulation (EC) No. 1272/2008 (EU CLP).