Sodium dicyanoamide

Eye irritation

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

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:

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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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).