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EC number: 205-181-1 | CAS number: 135-16-0
- 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
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017-12-18 to 2018-03-22
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 018
- Report date:
- 2018
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
- Version / remarks:
- adopted 17 December, 2001
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
- Version / remarks:
- 30 May, 2008
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1100 (Acute Oral Toxicity)
- Version / remarks:
- December 2002
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- yes
Test material
- Reference substance name:
- N-[4-[[(2-amino-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid
- EC Number:
- 205-181-1
- EC Name:
- N-[4-[[(2-amino-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid
- Cas Number:
- 135-16-0
- Molecular formula:
- C19H23N7O6
- IUPAC Name:
- (2S)-2-[(4-{[(2-amino-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
- Test material form:
- solid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Step 1: animals no. 1-3: 148 – 164 g; Step 2: animals no. 4-6: 153 – 166 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted).
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Ad libitum, Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): Ad libitum, tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: It is the principle of the acute toxic class method that, based on a stepwise procedure with the use of a minimum number of animals per step, sufficient information is obtained on the acute toxicity of the test item to enable its classification. The item is tested using a stepwise procedure with up to four fixed doses. Absence or presence of compound-related mortality of the animals dosed at one step will determine the next step - Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 3 per step
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.
- Other examinations performed: clinical signs, body weight
Results and discussion
Effect levelsopen allclose all
- Key result
- Sex:
- female
- Dose descriptor:
- LD50 cut-off
- Effect level:
- 5 000 mg/kg bw
- Based on:
- test mat.
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Remarks:
- experimental
- Effect level:
- > 2 000
- Based on:
- test mat.
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Mortality:
- no mortality occurred
- Clinical signs:
- other: The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, piloerection, hunched posture and half eyelid-closure. All symptoms recovered within up to 2 days post-dose.
- Gross pathology:
- At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.
Any other information on results incl. tables
Table 1: Clinical signs - Individual data (Step 1)
Step |
Animal No. / Sex |
Starting Dose (mg/kg bw) |
Timepoint |
Observations |
1 |
1 / Female |
2000 |
0 – 30 min |
nsf |
30 – 60 min |
Slightly reduced spontaneous activity, slight piloerection, half eyelid-closure |
|||
60 – 240 min |
Slightly reduced spontaneous activity, slight piloerection, hunched posture |
|||
240 min - d 2 |
Slightly reduced spontaneous activity, slight piloerection |
|||
d 2 – d 15 |
nsf |
|||
0 – 30 min |
nsf |
|||
2 / Female |
30 – 60 min |
Slightly reduced spontaneous activity, slight piloerection, half eyelid-closure |
||
60 – 240 min |
Slightly reduced spontaneous activity, slight piloerection, hunched posture |
|||
240 min - d 2 |
Slightly reduced spontaneous activity, slight piloerection |
|||
d 2 – d 15 |
nsf |
|||
0 – 30 min |
nsf |
|||
3 / Female |
30 – 60 min |
Slightly reduced spontaneous activity, moderate piloerection, half eyelid-closure |
||
60 – 120 min |
Slightly reduced spontaneous activity, hunched posture, moderate piloerection, half eyelid-closure |
|||
120 – 240 min |
Slightly reduced spontaneous activity, hunched posture, slight piloerection |
|||
240 min – d 2 |
Slightly reduced spontaneous activity, slight piloerection |
|||
d 2 – d 15 |
nsf |
Table 2: Clinical signs - Individual data (Step 2)
Step |
Animal No. / Sex |
Starting Dose (mg/kg bw) |
Timepoint |
Observations |
2 |
4 / Female |
2000 |
0 – 60 min |
nsf |
60 – 180 min |
Slightly reduced spontaneous activity, hunched posture, slight piloerection |
|||
180 - 240 min |
Slight piloerection, hunched posture |
|||
240 min - d 2 |
Slightly reduced spontaneous activity, hunched posture, slight piloerection |
|||
d 2 – d 15 |
nsf |
|||
5 / Female |
0 – 60 min |
nsf |
||
60 – 180 min |
Slightly reduced spontaneous activity, hunched posture, slight piloerection |
|||
180 – 240 min |
Hunched posture, slight piloerection |
|||
240 min - d 2 |
Slightly reduced spontaneous activity, hunched posture, slight piloerection |
|||
d 2 – d 15 |
nsf |
|||
6 / Female |
0 – 60 min |
nsf |
||
60 – 180 min |
Slightly reduced spontaneous activity, hunched posture, slight piloerection |
|||
180 – 240 min |
Hunched posture, slight piloerection |
|||
240 min - d 2 |
Slightly reduced spontaneous activity, hunched posture, slight piloerection |
|||
d 2 – d 15 |
nsf |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the conditions of the present study, a single oral application of the test item Tetrahydrofolic acid (THFA) to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity but no mortality.
The median lethal dose of Tetrahydrofolic acid (THFA) after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 5000 mg/ kg bw
Thus, the substance does not need to be classified according to Regulation (EC) No 1272/2008 (CLP) and the Globally Harmonized System for Calssification and Labelling of Chemicals (GHS).
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