Disodium L-cystinate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-05-09 to 2012-11-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study from supporting substance (structural analogue)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Adopted 24 April 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Cystine

EC Number:

200-296-3

EC Name:

Cystine

Cas Number:

56-89-3

Molecular formula:

C6H12N2O4S2

IUPAC Name:

cystine

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Name: L-Cystine
CAS No.: 56-89-3
Physical State: solid powder
Colour: white or off-white
Decomposition: 260-261 °C
Purity: 99%
Storage Conditions: at room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: 16-17 weeks old
- Weight at study initiation: >2 kg
- Housing: Semi barrier in an air-conditioned room, housed in ABS - plastic rabbit cages, floor 4200 cm2
- Diet (e.g. ad libitum): Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 1013), rich in crude fibre
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: adequate acclimatisation period (at least 5 days) under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature 18 ± 3 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): at least 10x/hour
- Photoperiod (hrs dark / hrs light): articifical light, sequence being 12 hours light, 12 hours dark

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 g
- Concentration (if solution): not applicable

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

72 hours (24 and 48 hours also recorded)

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was not rinsed 24 hours after the application.

SCORING SYSTEM: Annex VI to Commission Directive 2001/59EC; Annex B.5 to Commission Regulation (EC) No. 440/2008, L 142, Annex I of Regulation (EC) 1272/2008, GHS - Globally Harmonized System of Classification and Labelling of Chemicals, third revised edition, July 2009.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
At the end of the observation period the treated eyes were examined with the aid of a fluorescein solution. The eyes were rinsed with physiological saline 0.9% NaCl after the examination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 12

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

The test item produced irritant but not corrosive effects in all animals

Other effects:

- Lesions and clinical observations: no mortalities nor significant clinical signs of toxicity were observed
- Ophthalmoscopic findings: upon fluorescien examinations at the end of the observation period of 72 hours, no corneal lesions were found in any animal
- Histopathological findings: not specified
- Effects of rinsing or washing: The eyes were not rinsed after the application
- Other observations: conjunctival redness and discharge were observed in all animals. Iris lesion was observed in animal #1.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A single ocular application of the test item L-Cystine to rabbits at a dose of 0.1 g produced irritant effects, which were fully reversible within 72 hours. Neither mortalities nor significant clinical signs of toxicity were observed.

Executive summary:

A single ocular application of the test item L-Cystine to rabbits at a dose of 0.1 g produced irritant effects, which were fully reversible within 72 hours. Neither mortalities nor significant clinical signs of toxicity were observed. The test item under the conditions of the present study does not meet the GHS criteria for eye irritation.