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Description of key information

L-Cysteine was found to be non-irritating in in-vivo skin and eye irritation tests.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 14-15 weeks old
- Weight at study initiation: >2kg
- Housing: ABS - plastic rabbit cages, floor 4200 cm2
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Adequate , at least 5 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 55± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12:12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: aqua ad injectionem
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g per test site

VEHICLE
- Concentration (if solution): test item was moistened with vehicle to ensure good skin contact
- Lot/batch no. (if required): 10952_1
Duration of treatment / exposure:
4-h period
Observation period:
72h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: left side of the dorsal area
- % coverage: approx. 6 cm²
- Type of wrap if used: gauze was held in place withnon-irritating tape; patch was fixed with a semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the residual test item was removed with aqua ad injectionem
- Time after start of exposure: 4h
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72h
Score:
0
Max. score:
4
Other effects:
Neither mortalities nor significant clinical signs of toxicity were observed.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, the single dermal application of the test item L-Cysteine to three rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects.
Neither mortalities nor significant clinical signs of toxicity were observed.
The test item L-Cysteine does not have to be classified and has no obligatory labelling requirement for skin irritation.
Executive summary:

L-Cysteine was tested in an Acute dermal Irritation/Corrosion test in rabbits according to OECD Guideline 404.

On the basis of the test results, the substance should be assigned the following risk phrase:no phrase

On the basis of the test results, the substance should be: Not classified

On the basis of the test results, the substance should be: not classified

 

Species/strain: New Zealand White Rabbits Crl: KBL (NZW)

Number of animals: 3

Duration of exposure: 4h

Amount of substance: 0.5 g per test site

Type of dressing: semi-occlusive

Vehicle (moistening): aqua ad injectionem

First time of effects: no effects observed

Last time of effects: no effects observed

Reversibility of the observed effects: no effects observed

Method: OECD 404 [3]; EC 440/2008, Method B.4 [4]; OPPTS 870.2500 [5]

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guidline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species/strain: healthy New Zealand White Rabbits, Crl: KBL (NZW)
Source: Charles River Deutschland, 97633 Sulzfeld, Germany
Sex: female
Body weight at the beginning of the study: > 2 kg
Age at the beginning of the study: approximately 19 weeks old
Number of animals: 3

Semi barrier in an air-conditioned room
Temperature: 18 ± 3 °C
Relative humidity: 55 ± 10%
Artificial light, sequence being 12 hours light, 12 hours dark
Air change: at least 10 x I hour
Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 0650), rich in crude fibre. Free access to tap water (drinking water, municipal residue control, microbi-ological controls at regular intervals)
Housed in ABS - plastic rabbit cages, floor 4200 cm2
Adequate acclimatisation period (at least 5 days) under laboratory conditions
Vehicle:
unchanged (no vehicle)
Controls:
other: other eye served as a control
Amount / concentration applied:
The test item (0.1 g) was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second in order to prevent loss of the material. The untreated contralateral eye served as control.
Duration of treatment / exposure:
The treated eye was not rinsed 24 hours after the application.
Observation period (in vivo):
The animals were observed for 72 hours after dosing.
Number of animals or in vitro replicates:
3
Details on study design:
Approximately 24 hours before the test and immediately prior to the application both eyes of each animal were examined. A health inspection was performed to ensure the good state ofhealth ofthe animals. Approximately 24 hours before the application the eyes were also examined with the aid
of a fluorescein solution (Fluoreszein SE Thilo®). The eyes were rinsed with physiological saline 0.9% NaCl (AlleMan Pharma, lot no. 111214, expiry date: 11/2014) after the examination. None of the animals showed eye irritation, ocular defects, or pre-existing corneal injury.
One hour before the application of the test item, 0.01 mg/kg of buprenorphine (Reckitt Benckiser, lot no.: 5230, expiry date: 02/2016) was administered subcutaneously in order to achieve a therapeutic level of systemic analgesia. Approximately 5 minutes prior to the application ofthe test item, 2-3 drops of an ocular anaesthetic (proparacaine hydrochloride ophtalmic 0.5% solution, Ursapharma, were administered in both the treated and the
control eye of each animal. The test item was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 second in order to prevent loss of the material. The untreated
contralateral eye served as control. The eyes were examined for signs of irritation throughout the observation period. At the end of the observation period the treated eyes were examined with the aid of a fluorescein solution (Fluoreszein SE Thilo®). The eyes were rinsed with physiological saline 0.9% NaCl after the examination.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: all
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: any
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: an
Score:
0
Max. score:
4
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not irritating to eyes under the conditions of this study.
Executive summary:

An eye irritation study according to OECD Guideline 405 was performed with L-Cysteine. 0.1 g of the pure test substance was administered into the conjunctival sac of the eye of three New Zealand White rabbits. The eyes were not rinsed after the application.

After the application into the eyes of three female NZW rabbits the test item produced slight irritant but no corrosive ocular effects.

Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal.

Conjunctival redness was observed in all animals, discharge in one animal. There were no significant body weight changes during the observation period. Under the conditions of the present study, a single ocular application of the test item LCysteine

to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours. Neither mortalities nor significant clinical signs of toxicity were observed.

In conformity with the EC criteria for classification and labelling requirements the test item L-Cysteine has no obligatory labelling requirement for eye irritation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Under the conditions of an OECD 404 study, the single dermal application of the test item L-Cysteine to three rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects. Neither mortalities nor significant clinical signs of toxicity were observed.

Under the conditions of an OECD 405 study, a single ocular application of the test item L-Cysteine 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.


Justification for selection of skin irritation / corrosion endpoint:
In vivo guideline study according OECD 404.

Justification for selection of eye irritation endpoint:
In vivo guideline study according OECD 405.

Justification for classification or non-classification

L-Cysteine has no obligatory labelling requirement for skin irritation.

L-Cysteine has no obligatory labelling requirement for eye irritation.