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Diss Factsheets
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EC number: - | CAS number: -
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- 13-week repeated dose toxicity study of L-tyrosine in rats by daily oral administration
- Author:
- Shibui Y., Manabe Y., Kodama T., Gonsho A.
- Year:
- 2 016
- Bibliographic source:
- Food Chem Toxicol. 87:55-64
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Tyrosine
- EC Number:
- 200-460-4
- EC Name:
- Tyrosine
- Cas Number:
- 60-18-4
- Molecular formula:
- C9H11NO3
- IUPAC Name:
- tyrosine
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc.
- Age at study initiation: 6 weeks old
- Weight at study initiation: males 176 - 200 g, females 151 - 173 g
- Housing: individually in suspended, stainless-steel cages
- Diet (e.g. ad libitum): free acces to certified rodent diet sterilized by gamma irradiation (CRF-1; Oriental Yeast Co., Ltd., Tokyo, Japan).
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: 5 - 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 h a day (from 7 a.m. to 7 p.m.)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
L-tyrosine suspensions of 20, 60 and 200 mg/mL were prepared once a day and mixed just prior to each administration.
Dose volume: 10 mL/kg
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2 000 mg/kg bw/day (nominal)
- Dose / conc.:
- 600 spores/kg bw/day (nominal)
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 90 days
- Frequency of observations and weighing: day 1 and 2 and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, heamatology, clinical chemistry, ophthalmology, food and water consumption
Examinations
- Statistics:
- Body weight, food consumption, water consumption, urinalysis (expect qualitative analysis), hematology, blood chemistry, and organ weight data were recorded using a MiTOX RDT system. Numerical data obtained during the study were used to calculate group mean values and standard deviations. Group variances for the appropriate parameters were compared using Bartlett's method (significant at p < 0.01 in two-tailed test). When the differences between group variances were not significant, Dunnett's multiple comparison method was applied to determine the significance of differences between the control group and each L-tyrosine-treated group (significant at p < 0.05 in two-tailed test) (Dunnett, 1955). If the Bartlett's test indicated significant differences between group variances for a given parameter, that parameter was compared among groups using the Steel's multiple comparison method for mean ranking (significant at p < 0.05 in two-tailed test).
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Crust formation was seen in the neck in a few animals in all groups including the control group, and was not considered to be treatment-related because a similar finding was also seen in the control group and its incidence did not increase in a dose-dependend
- Mortality:
- no mortality observed
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Endocrine findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Significant increases, or a tendency thereof, were found in absolute and relative weights of liver and kidneys in males and females at 2000 mg/kg bw/day. Decreased absolute adrenal weight (right side) was noted in females at 600 and 2000 mg/kg bw/day, but was considered to be incidental because it was seen unilaterally, was not associated with a changes in relative adrenal weight, and individual weight was within the range of variation in the control group.
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- - Stomach: Edema of the cornified layer at the limiting ridge (minimal to slight) was seen in 2 females at 600 mg/kg bw/day and in 3 males and 4 females at 2000 mg/kg bw/day. Edema of the cornified layer at the forestomach (minimal) was seen in 1 female at 2000 mg/kg bw/day.
- Liver: Centrilobular hypertrophy of hepatocytes (minimal) was seen in 2 males and 2 females at 2000 mg/kg bw/day.
- Kidney: Diffusely increased hyaline droplets were seen in the proximal tubules (minimal to moderate) in 9 males at 2000 mg/kg bw/day with higher grade and incidence than in the control.
Effect levels
- Key result
- Dose descriptor:
- other: LD50
- Effect level:
- > 2 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- mortality
Applicant's summary and conclusion
- Conclusions:
- We can assume that the LD50 for males and females will be > 2000 mg/kg bw/d because after 90 days of dosing no animal died.
- Executive summary:
O-phospho-L-tyrosine dissociates in aqueous solutions. As according to REACH regulation only publicly available data has to be provided with the Registration dossier for on-site isolated intermediates in a tonnage band of < 1,000 t/a. Thus, information on the paren compound L-tyrosin is considered relevant and will be used for the registration dossier of O-phospho-L-tyrosine.
In this current study the potential toxicity of L-tyrosine was evaluated in a 13-week repeated-dose oral toxicity study in rats according to OECD 408. The study was not GLP. L- tyrosine was administered by gavage to 4 groups each consisting of 10 males and 10 females. The doses were 0 (vehicle: water), 200, 600 or 2000 mg/kg bw/day.
No deaths occured during the administration period in any of the study groups. No L-tyrosine-related changes were observed in clinical signs, body weight, food and water consumption, ophthalmology or necropsy.
Some L-tyrosine-related changes were observed in the stomach, the liver and kidneys.
Additionally, significant changes were seen in biochemical parameters.
Cataract formation was not observed in this study at any dose level.
Even though this study is not an acute toxicity study, based on the above results, we can assume that the LD50 for males and females will be > 2000 mg/kg bw/d because after 90 days of dosing no animal died.
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.
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