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EC number: 843-143-1 | CAS number: 709647-81-4
- 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:
- January 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- Non-guideline study although well conducted
Data source
Reference
- Reference Type:
- publication
- Title:
- Effect of Selected Amino Acids on Toxicity of Ethanol in Rats
- Author:
- Breglia, R., Ward, C., Jarowski, C
- Year:
- 1 973
- Bibliographic source:
- Journal of Pharmaceutical Sciences, 62(1), 49-55
Materials and methods
- Principles of method if other than guideline:
- Laboratory scientific investigation
- GLP compliance:
- no
- Remarks:
- The study was performed before the implementation of GLP
- Test type:
- other: Did not follow standard acute toxicity guidelines.
- Limit test:
- no
Test material
- Reference substance name:
- (+)-L-arginine hydrochloride
- EC Number:
- 214-275-1
- EC Name:
- (+)-L-arginine hydrochloride
- Cas Number:
- 1119-34-2
- IUPAC Name:
- (+)- L-arginine hydrochloride
- Test material form:
- not specified
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sigma Chemical Co. St. Louis, Mo.
- Expiration date of the lot/batch: Not reported
- Purity test date: Not reported
RADIOLABELLING INFORMATION (if applicable): n/a
- Radiochemical purity: n/a
- Specific activity: n/a
- Locations of the label: n/a
- Expiration date of radiochemical substance: n/a
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL: Not reported
- Storage condition of test material:
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Diluted in water 6ml
- Preliminary purification step (if any): Not Reported
- Final dilution of a dissolved solid, stock liquid or gel: 140 mg/kg and 2880 mg/kg
- Final preparation of a solid: N/a
FORM AS APPLIED IN THE TEST (if different from that of starting material): n/a
OTHER SPECIFICS: No
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Not specified
- Females (if applicable) nulliparous and non-pregnant:Not specified
- Microbiological status of animals, when known: the animals were inspected for disease and diseased animals were discarded.
- Age at study initiation: 8 weeks
- Weight at study initiation: 125 to 150g
- Housing: Not reported
- Diet (e.g. ad libitum): Standard laboratory diet
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: At least 7 days
- Indication of any skin lesions: Not reported
ENVIRONMENTAL CONDITIONS: Not reported
- Temperature
- Humidity
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):
- IN-LIFE DATES:
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 10 & 20% (w/v) - Amount of vehicle (if gavage): 1.3 ml/kg - Justification for choice of vehicle: Not reported - Lot/batch no. (if required): Not reported - Purity: Not reported MAXIMUM DOSE VOLUME APPLIED: The dosages of the amino acids employed were 140 mg./kg. and 2.88 g./kg. Dose levels are equimolar to the low and high dose levels of L- lysine to which they correspond. The dose of 120 mg./kg. of L- lysine was equal to two times the minimum daily requirement for the adult rat; the dose of 2.5 g./kg. was recommended by results from previous work.
DOSAGE PREPARATION (if unusual): N/A CLASS METHOD (if applicable): N/A - Rationale for the selection of the starting dose: - Doses:
- 140 mg/kg and 2,880 mg/kg
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Remarks:
- Ethanol alone
- Details on study design:
- - Duration of observation period following administration: 14 days (or other?): 72- hours
- Frequency of observations and weighing: 30 mins and an hour
- Necropsy of survivors performed: Not stated
- Other examinations performed: clinical signs, body weight,organ weights, histopathology: Not stated
- Other: Not stated - Statistics:
- The statistical analysis (Student’s t-test) of intoxication was based on the following neurological parameters:
Ataxia - This was defined as the inability to maintain position by using four-leg motor coordination for one revolution of the modified “rotarod.” Each animal was subjected to this test individually throughout the experimental period, unless unconscious. A normal rat can maintain its equilibrium for an indefinite period, and a short training period of three to four trials was added to ensure uniform response.
Sleep time - This was defined as the total elapsed time from the initial loss of righting reflex to its return without remission. The righting reflex was said to be lost when the animal was placed on its back and did not immediately right itself fully.
Results and discussion
Effect levels
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 2 880 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No effect observed
- Clinical signs:
- other: No effect observed
- Gross pathology:
- No effect observed
- Other findings:
- No effect observed
Any other information on results incl. tables
Table 2. Effect of Simultaneous Administration of Amino Acid-Ethanol Solution on Acute Ethanol Toxicity
Drug treatment | Doses of amino acid mg/kg. | LD50 of Ethanolag/kg |
L-Arginine hydrochloride | 140 | 10.05 ± 1.32 |
a = Dead animals per group counted at 72 hr. after drug administration. No difference in mortality between males and females was noted.
Table 3. Onset of Ataxia
Treatment | Doses of amino acid mg/kg. | Onset of Ataxia with Amino Acid Pre-treatment before Single-Dose Administration of Ethanol | Onset of Ataxia with Amino Acid Pre-treatment before Serial Administration of Ethanol | Onset of Ataxia with After Single-Dose Administration of Amino Acid-Ethanol | Onset of Ataxia with After Serial Administration of Amino Acid-Ethanol | ||||
Mean Onsetaof Ataxia, min | pValueb | Mean Onsetaof Ataxia, min | pValueb | Mean Onsetaof Ataxia, min | pValueb | Mean Onsetaof Ataxia, min | pValueb | ||
L-Arginine hydrochloride | 140 | 8.32 ± 3.27 | 0.2 | 26.76 ± 1.70 | 0.001 | 23.16±7.60 | 0.02 | 52.63±7.21 | 0.001 |
L-Arginine hydrochloride | 2,880 | 30.98 ± 5.29 | 0.0001 | 66.32 ± 9.46 | 0.001 | - | - | - | - |
a=Onset of ataxia values (min.) ±SE. b= p value < 0.05 was significant. - = Not investigated
Table 4. Effect of treatment on sleeping time
Amino acid | Dose mg/kg | Sleeping Time with Amino Acid Pre-treatment before Single-Dose Administration of Ethanol | Effect of Amino Acid Pre-treatment on Sleeping Times Produced by Serial Administration of Ethanol | Sleeping Time after Single-Dose Administration of Amino Acid-Ethanol Solution | Sleeping Time after Serial Administration of Amino Acid-Ethanol Solution
| ||||||||
Mean sleeping timeamin | PValueb | Percentage of rat responding | Mean sleeping timeamin | PValueb | Percentage of rat responding | Mean sleeping timeamin | PValueb | Percentage of rat responding | Mean sleeping timeamin | PValueb | Percentage of rat responding | ||
L- Arginine hydrochloride | 140 | 116.56±48.8 | 0.001 | 70 | 293.39±30.9 | 0.6 | 100 | 315.79±58.1 | 0.9 | 90 | 203.92±35.2 | 0.01 | 100 |
L- Arginine hydrochloride | 2,880 | 224.10± 50.3 | 0.05 | 50 | 167.89± 51.6 | 0.01 | 80 | - | - | - | - | - | - |
a.Sleeping time values (min), ± SE, b = p value <0.05 was significant, - = not investigated
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- No mortality was reported in the study up to 2,880 mg/kg bw, the highest tested dose which is established as the LD50. Based on this information the substance does not meet the criteria for acute oral toxicity in accordance with Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.
- Executive summary:
Breglia et al 1973: The amino acid solutions in distilled water (dosage of 10 and 20% (w/v)) were administered orally to rats at two dose levels of 140 mg/kg and 2.88 g./kg L-arginine hydrochloride. The rats were subject to neurological tests for signs of pharmacological effects. Saline (volume) controls were used as the basis for comparison for amino acid treatment.
All rats treated with L-arginine hydrochloride were found to be without pharmacological effect at the doses employed for treatment. At the high dose, some signs of toxicity such as ataxia, dyspnea, decreased muscle tonus and loss of righting reflex.
The amino acid controls for each amino acid administered demonstrated that no acute toxicological effects in this experimentation were due to the administration of amino acids alone.
It can be concluded that the acute exposure to L-arginine hydrochloride does not pose any significant toxicity via acute oral toxicity and the LD50 is considered at 2,880 mg/kg bw/day.
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