Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 265-025-3 | CAS number: 64704-23-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2011-07-13 to 2012-01-10
- 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:
- 2 012
- Report date:
- 2012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- Adopted 22 July 2010
- Deviations:
- yes
- Remarks:
- The relative humidity in the animal room was between approx 45 - 78 % instead of 45 - 65 % for several hours
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- 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
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Purity test date: > 98.5 %
RADIOLABELLING INFORMATION
- Substance: ³H-Methyl thymidine (Hartman Analytic MT6032, aqueous solution)
- Radiochemical purity: not specified
- Specific activity: 74 GBq/mmol (2 Ci/mmol), 37 MBq/mL (1 mCi/mL)
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: not reported
- Solubility and stability of the test substance in the solvent/vehicle: Not indicated by the sponsor
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not reported
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test item was placed into a mortar on a tared balance and propylene glycol was added to achieve the required test item concentration. The different test item concentrations were prepared individually and made freshly before each dosing occasion. Homogeneity of the test item in vehicle was maintained during treatment using a magnetic stirrer.
- Preliminary purification step (if any): not reported
- Final dilution of a dissolved solid, stock liquid or gel: 5, 10, and 25% (w/w) in propylene glycol
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA/Ca
- Remarks:
- OlaHsd
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst / The Netherlands
- Females (if applicable) nulliparous and non-pregnant: yes
- Microbiological status of animals, when known: not specified
- Age at study initiation: 10-11 weeks (pre-test); 8 weeks (main study)
- Weight at study initiation: within the range commonly recorded for animals of this strain and age
- Housing: all animals belonging to the same experimental group were kept in one cage: Makrolon Type II / III, with wire mesh top (EHRET GmbH)
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum (Harlan Laboratories B.V.)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days prior to the start of dosing under test conditions after health examination.
- Indication of any skin lesions: Not specified; only animals without any visible signs of illness were used for the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 45-78 %
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): artificial light 6 am to 6 pm
Study design: in vivo (LLNA)
- Vehicle:
- propylene glycol
- Concentration:
- 5, 10, 25% (w/w) test item in vehicle
- No. of animals per dose:
- 5
- Details on study design:
- PRE-SCREEN TESTS:
- Compound solubility: A solubility experiment was performed according to the recommendations given by OECD 429. The highest test item concentration, which could be technically used was a 25 % (w/w) suspension in propylene glycol
- Irritation: To determine the highest non-irritant test concentration that did at the same time not induce signs of systemic toxicity, a pre-test was performed in two animals. Two mice were treated by (epidermal) topical application to the dorsal surface of each ear with test item concentrations of 10 and 25%, once daily, each on three consecutive days. Prior to the first application of the test item and before sacrifice the body weight was determined. Clinical signs were recorded at least once daily. Eventual signs of local skin irritation were documented and a score was used to grade a possible reddening of the ear skin. Eventual ear irritation was considered to be excessive if reddening of the ear skin of a score value ≥3 was observed at any observation time and/or if an increase in ear thickness of ≥25% was recorded on day 3 or day 6. At the tested concentrations the animals did not show any signs of local skin irritation.
- Ear thickness measurements: Prior to the first application of the test item (day 1), on day 3 and before sacrifice (day 6) the ear thickness was determined using a micrometer. Additionally, for both animals, the ears were punched after sacrifice (day 6) at the apical area using a biopsy punch and were immediately pooled per animal and weighed using an analytical balance.
- Erythema scores: No visible erythema on either tested animal at any day of observation.
- Systemic toxicity: At the tested concentrations the animals did not show any signs of systemic toxicity.
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response:
1) Exposure to at least one concentration of the test item resulted in an incorporation of ³HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the Stimulation Index
2) Data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression
- In additon to the sensitising reactions observations of mortality/viability, body weight, ear thickness, ear weights, and clinical signs (local and systemic) were recorded during the test and observation period
TREATMENT PREPARATION AND ADMINISTRATION:
- Topical application: Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear with different test item concentrations of 5, 10, and 25% (w/w) in propylene glycol. The application volume, 25 µL/ear/day, was spread over the entire dorsal surface (Ø ~ 8 mm) of each ear once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
- Administration of ³H-Methyl Thymidine: Five days after the first topical application (day 6) 250 µL of phosphate-buffered saline (PBS) containing 20.1 µCi of ³HTdR (equivalent to ³HTdR 80.5 µCi/mL) were injected into each test and control mouse via the tail vein.
- Determination of incorporated ³HTdR: Approximately five hours after treatment with 3HTdR all mice were euthanised by intraperitoneal injection of Pentobarbital-Natrium. The draining lymph nodes were rapidly excised and pooled per animal (2 nodes per animal). Single cell suspensions (in phosphate buffered saline) of pooled lymph node cells were prepared by gentle mechanical disaggregation through stainless steel gauze (200 um mesh size). After washing two times with phosphate buffered saline (approx. 10 mL) the lymph node cells were resuspended in 5 % trichloroacetic acid (approx. 3 mL) and incubated at approximately +4 °C for at least 18 hours for precipitation of macromolecules. The precipitates were then resuspended in 5 % trichloroacetic acid (1 mL) and transferred to plastic scintillation vials with 10 mL of ‘Ultima Gold’ scintillation liquid (Perkin Elmer (LAS) GmbH) and thoroughly mixed. The level of 3HTdR incorporation was then measured on a β-scintillation counter (Tricarb 2900 TR, Perkin Elmer (LAS) GmbH). Similarly, background 3HTdR levels were also measured in two 1ml-aliquots of 5 % trichloroacetic acid. The β-scintillation counter expresses 3HTdR incorporation as the number of radioactive disintegrations per minute (DPM). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The mean values and standard deviations were calculated in the body weight tables and for the DPM values (group mean DPM ± standard deviation).
Results and discussion
- Positive control results:
- valid
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 1
- Variability:
- SD: 272.0
- Test group / Remarks:
- Vehicle control
- Key result
- Parameter:
- SI
- Value:
- 0.98
- Variability:
- SD: 251.3
- Test group / Remarks:
- 5% L-Cystine
- Key result
- Parameter:
- SI
- Value:
- 1.24
- Variability:
- SD: 188.1
- Test group / Remarks:
- 10% L-Cystine
- Key result
- Parameter:
- SI
- Value:
- 1.02
- Variability:
- SD: 250.4
- Test group / Remarks:
- 25% L-Cystine
- Cellular proliferation data / Observations:
- CELLULAR PROLIFERATION DATA
: The proliferative response of the lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph nodes of each animal (DPM/animal). Before DPM/animal values were determined, mean scintillation-background DPM was subtracted from test and control raw data.
DETAILS ON STIMULATION INDEX CALCULATION : The ratio of ³HTdR incorporated into lymph node cells of lymph nodes of test animals relative to that recorded for lymph nodes of control animals
EC3 CALCULATION : The EC3 value could not be calculated, since all S.I.'s are below the threshold value of 3.
CLINICAL OBSERVATIONS: No symptoms of local toxicity at the ears of teh animals and no systemic findings were observed during study period.
BODY WEIGHTS: Body weight of the animals recorded prior to first application and prior to treatment with ³HTdR, was within the range commonly recorded for animals of this strain and age.
Any other information on results incl. tables
No death occurred during the study period
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Based on OECD guideline test 429 Local Lymph Node Assay with mice, the test item L-Cystine was not a skin sensitiser under the test conditions of this study.
- Executive summary:
In order to study a possible skin sensitising potential of L-Cystine following OECD guideline 429, three groups each of five female mice were treated once daily with the test item at concentrations of 5, 10, and 25% (w/w) in propylene glycol by topical application to the dorsum of each ear for three consecutive days. A control group was treated with the vehicle only. Five days after the first topical application the mice were injected intravenously into a tail vein with radio-labelled thymidine (3H-methyl thymidine). Single cell suspension of lymph node cells were prepared from pooled auricular lymph nodes and the proliferative capacity of the lymph node cells was determined.
In this study Stimulation Indices of 0.98, 1.24, 1.02 were determined with the test item at concentrations of 5, 10, and 25% (w/w) in propylene glycol, respectively. The EC3 value could not be calculated, since none of the tested concentrations induced a S.I. greater than the threshold value of 3. The test item, L-Cystine, was not a skin sensitiser under the test conditions of this study.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.