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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
between 1997-06-02 to 1997-07-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
1996-21-02

Test material

Constituent 1
Chemical structure
Reference substance name:
Potassium dibenzyl phosphate
EC Number:
616-628-9
Cas Number:
78543-37-0
Molecular formula:
C14-H14-O4-P.K
IUPAC Name:
Potassium dibenzyl phosphate
Test material form:
other: Solid

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, Cheshire, UK
- Age at study initiation: 16 weeks
- Weight at study initiation: 3.32 kg
- Housing: suspended metal cage
- Diet (e.g. ad libitum): ad libitum (STANRAB SQC Rabbit diet, special diets services, Witham, Essex, UK)
- Water (e.g. ad libitum):ad libitum
- Acclimation period: yes, at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 21 °C
- Humidity (%): 51 to 70%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: To: 2 June 1997 to 23 June 1997

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (Approximately 20 mg)
Duration of treatment / exposure:
Only one treatment
Observation period (in vivo):
just after the administration of the test item, 1h, 24h, 48h, 72h (according to the numerical evaluation from Draize J H 1977 "Dermal and Eye Toxicity test")
Additional observation were made on Days 7, 14 and 21 to assess the reversibility of the ocular test.
Number of animals or in vitro replicates:
1 animal
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing

SCORING SYSTEM: according to the numerical evaluation from Draize J H 1977 "Dermal and Eye Toxicity test" in: Principles and Procedures for evaluating the toxicity of Household Substances, National Academy of sciences, Washington DC p 48-49

TOOL USED TO ASSESS SCORE: standard ophtalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
55
Reversibility:
fully reversible within: 21d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
5
Reversibility:
fully reversible within: 14d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 21d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible within: 14d
Irritant / corrosive response data:
Individual and total scores for ocular irritation are given in table 1.

Areas of translucent corneal opacity were noted in the treated eye one hour after treatment with area of diffuse corneal opacity at the 24 and 48-hour observations, areas of translucent corneal opacity at 72-hour observation and diffuse corneal opacity at the 7 and 14-day observations. Sloughing of the cornea was noted in the treated eye at the 72-hour observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour and 7-day observations. No other iridial affect were noted

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24, 48 72-hour and 7-day observation with minimal conjunctival irritation at the 14 and 21-day observations. Pale green discolouration of the nictitating and conjunctival membranes was noted in the treated eye one hour after treatment. An off white appearance of the nictitating membrane and approximately half of the lower conjunctival membrane was noted in the treated eye at the 24, 48 and 72-hour and 7-day observations. An area of haemorrhage approximately 3 mm² in size on the conjunctival membrane of the lower eyelid was noted in the treated eye at 48 and 72-hour and 7-day observations. An abnormally shaped nictitating membrane was noted in the treated eye at the 14 and 21 day observations.

Any other information on results incl. tables

Table 1: Acute irritation test in the rabbit: Individual Scores and total Scores for Ocular Irritation

 

Rabbit Number and Sex

(Bodyweight kg)

IPR = 3

63 Female (3.32)

Time after Treatment

1 hour

24 hours

48 hours

72 hours

7 days

14 days

21 days

CORNEA

 

E = Degree of Opacity

2

1

1

2 SI

1

1

0

F = Area of opacity

4

4

4

3

3

1

 

Score (E x F) x 5

40

20

20

30

15

5

0

IRIS

 

D

1

1

1

1

1

0

0

Score (D x 5)

5

5

5

5

5

0

0

CONJUNCTIVAE

 

A = redness

2G

2W

2WH

2WH

2WH

1AB

1AB

B = Chemosis

2

2

2

2

2

1

0

C = discharge

2

3

3

1

1

0

0

Score (A +B + C) x 2

12

14

14

10

10

4

2

Total Score

57

39

39

45

30

9

2

 

IPR = Initial Pain Reaction

AB = Abnormally shaped nictitating membrane

G = Pale green discolouration of the nictating and conjunctival membrane of lower eyelid

H = Area of haemorrhage approximately 3 mm² located on conjuntival membrane of lower eyelid

W = off white appearance of nictating membrane and approximately half of the lower conjunctival membrane

SI = sloughing of corneal membrane

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test material produced a maximum total of 57 and was considered to be at least a SEVERE IRRITANT (Class 6 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on the rabbit only).

Under the test conditions, test item is irritating to the eye rabbit and required the classification as Eye Dam. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP).
Executive summary:

In an eye irritation study performed similarly to the OECD No. 405 guideline, 0.1 mL of undiluted test item was instilled into the right eye of 1 female New Zealand White Rabbits. The animal was then observed for 21 days for eye oedema and erythema of the conjunctivae, corneal opacity and iris lesion.

Eye irritation was assessed and scored according to the Draize scale at 24, 48 and 72 hrs after the instillation of the substance and then at days 7, 14 and 21.

The highest score was observed 1 hour after treatment. The effects was not fully reversible during the 21 days of observation, with still effect on conjonctivae ( redness and abnormally shaped nictitating membrane)

 

Under the test conditions, test item is considered as highly irritating to the eye rabbit and is therefore classified as Eye Dam. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

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