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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 222-158-1 | CAS number: 3373-59-9
- 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 irritation / corrosion
Administrative data
- Endpoint:
- skin irritation: in vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Based on read across to L-TEE, L-TME is considered not to be a skin irritant.The toxicokinetic properties of L-TEE and L-TME are evaluated to be different. Read across to L-TEE is possible for endpoints in which hydrolysis of the ester bond does not take place, e.g. skin irritation and sensitisation. For endpoints in which hydrolysis takes place, thereby liberating the alcohols, i.e. methanol in the case of L-TME and ethanol in the case of L-TEE, the toxicities of the hydrolysis products must be taken into account. In general, no interaction of toxicological relevance between L-threonine and the alcohol parts is expected. Based on structural similarity and the similarity in physico-chemical properties determining skin irritation, read across to L-TEE using the analogue approach is concidered a valid approach. Further information on read across to L-TEE using the analogue approach can be found in the data matrix table attached as background material and in section 13.
- Justification for type of information:
- Data on target substance is not available. Thus, read-across has been applied using data from the source substance L-Threonine Ethyl Ester (L-TEE). See further read-across justification in attached background material and in section 13.
Cross-reference
- Reason / purpose for cross-reference:
- read-across source
Reference
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- April 10, 2000 - April 28, 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- Minor deviations in humidity were observed during the study period but these deviations did not affect the integrity of the study.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Version / remarks:
- EC method B4
- Deviations:
- yes
- Remarks:
- humidity
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- humidity
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- Deviations:
- yes
- Remarks:
- humidity
- Principles of method if other than guideline:
- NA
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: 142-576-6
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: < 10 °C when not in use
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: 50% m/v dispersion
OTHER SPECIFICS
- measurement of pH, osmolality, and precipitate in the culture medium to which the test chemical is added: pH of 9.16 - Species:
- rabbit
- Strain:
- New Zealand White
- Remarks:
- Crl:NZW/Kbl.BR
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River UK Ltd, Margate
- Age at study initiation: 11 to 13 weeks old
- Weight at study initiation: 2.03 to 2,37 kg
- Housing: floor-pens, single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 22 °C
- Humidity (%): 40 to 80% RH (on the first eleven days of the study, humidity fell below range by up to 15% RH)
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours with fluorescent strip-lights
IN-LIFE DATES: From 4 April 2000 To 28 April 2000 - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- water
- Remarks:
- moistening with approx. 0.1 mL of water
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500mg
VEHICLE
- Amount(s) applied (volume or weight with unit): moistening with approx. 0.1 mL of water - Duration of treatment / exposure:
- 4 h
- Observation period:
- 3 days
- Number of animals:
- 3 animals (1 male, 2 females)
- Details on study design:
- TEST SITE
- Area of exposure: 30 x 20 mm
- % coverage: No data
- Type of wrap if used: semi-occlusive gauze patch and an open weave, elasticated adhesive bandage wrapped firmly around the torso
REMOVAL OF TEST SUBSTANCE
- Washing (if done): lightly brushed clean of any solid residues and swabbed with moist cotton wool
- Time after start of exposure: 4 hours
SCORING SYSTEM:
Erythema and eschar (Grade):
- No erythema (0)
- Very slight erythema (1)
- Well-defined erythema (2)
- Moderate erythema (3)
- Severe erythema (beet redness) or eschar preventing reading of erythema (4)
Oedema (Grade):
- No oedema (0)
- Very slight oedema (barely perceptible) (1)
- Slight oedema (edges of area well-defined by definite raising) (2)
- Moderate oedema (edges raised approximately 1 mm) (3)
- Severe oedema (raised >1 mm and extending beyond area of exposure) (4) - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritant / corrosive response data:
- No dermal response to treatment or signs of toxicity or ill health were observed in any animal throughout the observation period
- Other effects:
- None
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The skin irritation/corrosion of L-TEE was evaluated using a single semi-occluded application to intact rabbit skin for four hours. The study was perforned in compliance with the testing guidelines OECD (404) and EC (method B4). L-TEE did not elicit any dermal reactions. Based on these data, L-TEE is not classified.
- Executive summary:
This study was conducted to determine the irritation or corrosion caused to intact rabbit skin. L-TEE (500 mg) was applied to a 30 x 20 mm area on the clipped dorsum of each of three New Zealand White rabbits on Day 1. The treated area of skin was covered by a semi-occlusive bandage for four hours. Dermal reactions to treatment were assessed for three days after removal of the dressings.
No reactions were observed following a single semi-occluded, topical application of L-TEE to the intact skin of three rabbits for four hours.
Based on these data, L-TEE is not classified.
None
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Version / remarks:
- EC method B4
- Deviations:
- yes
- Remarks:
- humidity
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- humidity
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- Deviations:
- yes
- Remarks:
- humidity
- Principles of method if other than guideline:
- NA
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Methyl L-threoninate
- EC Number:
- 222-158-1
- EC Name:
- Methyl L-threoninate
- Cas Number:
- 3373-59-9
- Molecular formula:
- C5H11NO3
- IUPAC Name:
- Methyl (2S,3R)-2-amino-3-hydroxy-butanoate
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Name of test material (as cited in study report): L-threonine methyl ester
- Physical state: white crystalline powder
- Analytical purity: 99.8%
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- other: New Zealand White Crl:NZW/Kbl.BR
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River UK Ltd, Margate
- Age at study initiation: 11 to 13 weeks old
- Weight at study initiation: 2.03 to 2,37 kg
- Housing: floor-pens
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 22 °C
- Humidity (%): 40 to 80% RH (on the first eleven days of the study, humidity fell below rge range by up to 15% RH)
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours with fluorescent strip-lights
IN-LIFE DATES: From 4 April 2000 To 28 April 2000
Test system
- Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- water
- Remarks:
- moistening with approx. 0.1 mL of water
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500mg
VEHICLE
- Amount(s) applied (volume or weight with unit): moistening with approx. 0.1 mL of water - Duration of treatment / exposure:
- 4 h
- Observation period:
- 3 days
- Number of animals:
- 3 animals (1 male, 2 females)
- Details on study design:
- TEST SITE
- Area of exposure: 30 x 20 mm
- % coverage: No data
- Type of wrap if used: open weave, elasticated adhesive bandage wrapped firmly around the torso
REMOVAL OF TEST SUBSTANCE
- Washing (if done): lightly brushed clean of any solid residues and swabbed with moist cotton wool
- Time after start of exposure: 4 hours
SCORING SYSTEM:
Erythema and eschar (Grade):
- No erythema (0)
- Very slight erythema (1)
- Well-defined erythema (2)
- Moderate erythema (3)
- Severe erythema (beet redness) or eschar preventing reading of erythema (4)
Oedema (Grade):
- No oedema (0)
- Very slight oedema (barely perceptible) (1)
- Slight oedema (edges of area well-defined by definite raising) (2)
- Moderate oedema (edges raised approximately 1 mm) (3)
- Severe oedema (raised >1 mm and extending beyond area of exposure) (4)
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Irritant / corrosive response data:
- No dermal response to treatment or signs of toxicity or ill health were observed in any animal throughout the observation period
- Other effects:
- None
Any other information on results incl. tables
The toxicokinetic properties of L-TEE and L-TME are evaluated to be different. Read across to L-TEE is possible for endpoints in which hydrolysis of the ester bond does not take place, e.g. skin irritation and sensitisation. For endpoints in which hydrolysis takes place, thereby liberating the alcohols, i.e. methanol in the case of L-TME and ethanol in the case of L-TEE, the toxicities of the hydrolysis products must be taken into account. In general, no interaction of toxicological relevance between L-threonine and the alcohol parts is expected.
L-TME holds the same structure as L-TEE except that L-TME contains a methyl alkyl-side group to the ester bond and L-TEE an ethyl alkyl-side group. Both substances are characterized by a high water solubility, a low log Pow and low vapour pressure. Hydrolysis is evaluated not to be relevant for skin irritation.
Further information on the analogue approach can be found in the data matrix attached as background material (see section below).
Applicant's summary and conclusion
- Interpretation of results:
- not classified
- Conclusions:
- The skin irritation/corrosion of L-TEE was evaluated using a single semi-occluded application to intact rabbit skin for four hours. The study was perforned in compliance with the testing guidelines OECD (404) and EC (method B4). L-TEE did not elicit any dermal reactions. Based on these data, L-TEE is not classified.
Due to the structural and physico-chemical similarity to L-TEE read cross can be made from skin irritation data on L-TEE. These data do not indicate concern for eye irritation of L-TME, hence L-TME is considered not to be a skin irritant. - Executive summary:
The skin irritation/corrosion of L-TEE was evaluated using a single semi-occluded application to intact rabbit skin for four hours. The study was perforned in compliance with the testing guidelines OECD (404) and EC (method B4). L-TEE did not elicit any dermal reactions. Based on these data, L-TEE is not classified.
L-TME holds the same structure as L-TEE except that L-TME contains a methyl alkyl-side group to the ester bond and L-TEE an ethyl alkyl-side group. The toxicokinetic profile of L-TME and L-TEE is different in terms of the alcohol part (methanol and ethanol). However, read across to L-TEE is possible for endpoints in which hydrolysis of the ester bond does not take place, e.g. skin irritation and sensitisation.
Due to the structural and physico-chemical similarity to L-TEE read cross can be made from skin irritation data on L-TEE. These data do not indicate concern for skin irritation of L-TME.
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.