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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001-01-18 to 2001-01-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium dicyanoamide
EC Number:
217-703-5
EC Name:
Sodium dicyanoamide
Cas Number:
1934-75-4
Molecular formula:
C2HN3.Na
IUPAC Name:
sodium dicyanamide
Test material form:
solid
Specific details on test material used for the study:
The pH of a 10% w/w aqueous preparation of the test material was determined prior to
commencement of the study and found to be 9.7.

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: 12 - 16 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: suspended metal cage
- Diet (e.g. ad libitum): ad libitum
- 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): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 2001-01-18 - 2001-01-21

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (approx. 78 mg)


Duration of treatment / exposure:
single application, no washing
Observation period (in vivo):
72 hours (study was terminated after 72 hours)
Number of animals or in vitro replicates:
single male animal
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM:
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: standard ophthalmoscope

Interpretation of Results:
Using the numerical data obtained originally a modified version of the system described by Kay J H and Calandra J C, J. Soc. Cosmet. Chem., 1962 13 281-289 was used to classify the ocular irritancy potential of the test material.

Using the raw data, a re-interpretation according to recend standards was performed.

Judgment is based on cornea, iris, conjunctiva and chemosis calculated as mean scores for each animal following grading at 24, 48 and 72 hours after application of the test material, in consideration of reversibility.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
Areas of diffuse corneal opacity were noted in the treated eye one and 24 hours after treatment with areas of translucent corneal opacity at the 48-hour observation and areas of opalescent comeal opacity at the 72-hour observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48 and 72-hour observation.

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observations with severe conjunctival irritation at the 72-hour observation. The nictitating membrane of this eye appeared pale throughout the study. Petechial haemorrhage scattered over the nictitating membrane was noted in the treated eye at the 24-hour observation.
Three areas of haemorrhage (approximately 2 mm x 2 mm in size:) on the nictitating membrane were noted in the treated eye at the 48 and 72-hour observation.
Other effects:
- Lesions and clinical observations:
the animal was showing initial signs of moderate pain and was killed for humane reasons immediately after the 72-hour observation. No further animals were treated.

- Ophthalmoscopic findings:
Areas of diffuse corneal opacity were noted in the treated eye one and 24 hours after treatment with areas of translucent corneal opacity at the 48-hour observation and areas of opalescent comeal opacity at the 72-hour observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48 and 72-hour observation.

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observations with severe conjunctival irritation at the 72-hour observation. The nictitating membrane of this eye appeared pale throughout the study. Petechial haemorrhage scattered over the nictitating membrane was noted in the treated eye at the 24-hour observation.
Three areas of haemorrhage (approximately 2 mm x 2 mm in size:) on the nictitating membrane were noted in the treated eye at the 48 and 72-hour observation.


- Histopathological findings: no histopathology was performed
- Effects of rinsing or washing: no

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

1

1

2

2

24 h

1

1

2

2

48 h

2

1

2

2

72 h

3

1

3

3

Average 24h, 48h, 72h

2

1

2.3

2.3

Area effected

3

 

 

 

Reversibility*)

 n.

 n.

 n.

 n.

Average time (unit) for reversion

 

 

 

 

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test (original table from study report)

Rabbit Number and Sex

IPR= 3

148 Male

Time After Treatment

1 hour

24 hours

48 hours

72 K hours

CORNEA

E= Degree of Opacity

F = Area of Opacity

 

1

3

 

1

3

 

2

3

 

3

3

Score (E x F) x 5

15

15

30

45

IRIS
D

 

1

 

1

 

1

 

1

Score (0 x 5)

5

5

5

5

CONJUNCTIVAE
A = Redness

B = Chemosis

C = Discharge

 

2P

2

2

 

2P

2PT

3

 

2H

2P

3

 

3H

2P

3

Score (A + B + C) x 2

12

14

14

16

Total Score

32

34

49

66

IPR = initial pain reaction

K = animal humanely killed immediately after observation

P = pale appearance of nictitating membrane

H = three areas of haemorrhage (approximately 2 mm x 2 mm) on the nictitating membrane

Pt = petechial haemorrhage scattered over nictitating membrane

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In this study, Sodium dicyanoamide has irreversible effects on the eyes (Category 1).
Executive summary:

In a primary eye irritation study according to OECD guideline 405, adopted 24 February 1987 and EU method B.5, 78 mg (approximately 0.1 mL) of Sodium dicyanoamide was instilled into the conjunctival sac of an eye of a male young adult New Zealand White rabbit. The eye was not rinsed after application. The animal was observed for 72 h.  Irritation was scored by the method of Draize.

Instillation of the test substance into the eye resulted in severe effects on the eyes, necessitating intermediate sacrifice of the animal for ethical reasons approximately 72 hours after dosing.

 

Areas of diffuse corneal opacity were noted in the treated eye one and 24 hours after treatment with areas of translucent corneal opacity at the 48-hour observation and areas of opalescent corneal opacity at the 72-hour observation.

 

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48 and 72-hour observation.

 

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48-hour observations with severe conjunctival irritation at the 72-hour observation. The nictitating membrane of this eye appeared pale throughout the study. Petechial haemorrhage scattered over the nictitating membrane was noted in the treated eye at the 24-hour observation.

Three areas of haemorrhage (approximately 2 mm x 2 mm in size:) on the nictitating membrane were noted in the treated eye at the 48 and 72-hour observation.

Due to the severity of effects in this animal, no further animals were treated.

 

In this study, Sodium dicyanoamide has irreversible effects on the eyes (Category 1).

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