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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 609-256-3 | CAS number: 365400-11-9
- 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
Additional toxicological data
Administrative data
- Endpoint:
- additional toxicological information
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 15 Mar - 28 Jul 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
- Type of study / information:
- This exploratory study was conducted primarily in order to determine the difference in development of corneal opacities between rats and mice after administration of diets containing dietary tyrosine. A secondary objective was to determine whether there was a difference in sensitivity between two strains of rats (Brown Norway and CD).
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Groups of five male and five female CD rats, Brown Norway rats and CD 1 mice were administered either basal diet or diets supplemented with 2 or 5% tyrosine for 14 days. Animals were weighed weekly, observed for clinical signs daily and subjected to ophthalmological examinations on Days 2, 3, 7, 8 and 14. At study termination, eyes were taken from selected animals for histological examination and plasma taken for free plasma tyrosine analysis of selected groups.
- GLP compliance:
- yes
Test material
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Aldrich, France, batch 68160-123
- Purity: 98%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in an air-tight, light-resistant container at approximately 5°C
- Homogeneity and stability of the test substance in the diet were analytically verified. On all occasions results for homogeneity, concentrations and stability were within the acceptable ranges. The phenylalanine and tyrosine content of basal diet was analyzed (total amino acid levels of protein origin)
and were found to be 0.77 ± 0.04% and 0.55 ± 0.03% respectively.
Results and discussion
Any other information on results incl. tables
No deaths occurred during the study. No treatment-related clinical signs were observed in CD rats of either sex at 2%, or in Brown Norway rats or CD 1 mice in either sex at 2 or 5% tyrosine. The observations in the 5% tyrosine male CD rat group were restricted to dark urine (all males during the second week of study and 3/5 females on Day 14) and one male which appeared thin and showed ptosis and piloerection from Days 10 and 13, respectively. In this animal, corneal opacity was severe and visible to the naked eye.
Body weights and food consumption were not affected by treatment.
No treatment-related corneal effects were observed in female groups of rats at 2% or 5% tyrosine. Male CD and Brown Norway rats were not affected at 2% tyrosine. No mice of either sex were affected at any dose. Slight corneal opacities were noted for 3 of 5 male CD rats at 5% tyrosine on Day 2. On the following day, these opacities had progressed to "moderate" and a fourth animal in the group showed a "slight" opacity. By Day 7, the opacities in these four animals had become "severe" and the fifth male had developed a "slight" opacity. By Day 14, two males developed a very severe opacity and showed signs of edema and vascularisation of the cornea. In three animals, congestion of the iris became evident. Only one Brown Norway rat at 5% tyrosine developed any corneal changes; in this animal the corneal opacity was slight and was only observed on Day 14.
Table 1: Individual ophthalmological findings
Group/Dietary tyrosine (%) |
Animal No. |
Sex |
Study Day |
||||
2 |
3 |
7 |
8 |
14 |
|||
CD rats |
|||||||
0 |
all |
- |
- |
- |
- |
- |
- |
2 |
all |
- |
- |
- |
- |
- |
- |
5 |
ET3M 1380 |
M |
Sl B |
M B |
SE B |
Se B Im |
Se B Im |
ET3M 1381 |
M |
Sl U |
M B If |
Se B Is |
Se B Is |
VS B Is EV |
|
ET3M 1382 |
M |
Sl B |
M B |
Se B |
Se B Im |
VS B Is EV |
|
ET3M 1383 |
M |
- |
Sl U |
Se B |
Se B |
Se B |
|
ET3M 1384 |
M |
- |
- |
Sl B |
Sl B |
Sl B |
|
all females |
F |
- |
- |
- |
- |
- |
|
Brown Norway rats |
|||||||
0 |
all |
- |
- |
- |
- |
- |
- |
2 |
all |
- |
- |
- |
- |
- |
- |
5 |
ET6M 1410 |
M |
- |
- |
- |
- |
- |
ET6M 1411 |
M |
- |
- |
- |
- |
- |
|
ET6M 1412 |
M |
- |
- |
- |
- |
Sl B |
|
ET6M 1413 |
M |
- |
- |
- |
- |
- |
|
ET6M 1414 |
M |
- |
- |
- |
- |
- |
|
all females |
F |
- |
- |
- |
- |
- |
|
CD 1 mice |
|||||||
0 |
all |
- |
- |
- |
- |
- |
- |
2 |
all |
- |
- |
- |
- |
- |
- |
5 |
all |
- |
- |
- |
- |
- |
- |
- no finding
Sl Slight opacity B Bilateral opacity
M Moderate opacity If Iris failed to dilate
Se Severe opacity Im Congestion of iris, mild
VS Very severe opacity Is Congestion of iris, severe
U Unilateral opacity EV Edema and vascularization of cormea
In male CD rats, the 2% and 5% tyrosine diets caused a 3-fold increase in plasma tyrosine to 59 mg/L and a 5-fold increase to 114 mg/L, respectively. Only the 5% group developed corneal opacity. In females the basal levels were lower than males, but the percentage increase in plasma tyrosine was similar in the 5% group for males and females.
In male Brown Norway rats, the basal plasma tyrosine levels were similar to female CD rats, as were the levels with 5% diets (68 mg/L). The levels for the 2% and 5% dietary male groups were about 3 fold and 5 fold the basal level, respectively. One male in the 5% group had a very high plasma tyrosine level (nearly 10 times that of the other four rats in the group), and was the only Brown Norway rat with a corneal lesion.
In CD 1 mice, the basal levels were similar to female CD rats and male Brown Norway rats but with a 5% tyrosine diet, there was no significant increase in plasma tyrosine levels.
Table 2: Mean plasma tyrosine concentrations
Animal strain |
Dietary tyrosine (%) |
Mean plasma tyrosine (mg/L) |
|||
Males |
Females |
||||
Mean |
S.D. |
Mean |
S.D. |
||
CD rat |
0 |
21 |
4.2 |
13 |
2.0 |
2 |
59 |
4.8 |
- |
- |
|
5 |
114 |
39.9 |
62 |
29.8 |
|
Brown Norway rat |
0 |
12 |
0.6 |
- |
- |
2 |
32 |
15.0 |
- |
- |
|
5 |
68* |
13.0 |
- |
- |
|
CD 1 mouse |
0 |
13 |
1.8 |
- |
- |
5 |
18 |
7.1 |
- |
- |
- not determined * excluding one high outlier
At necropsy, no significant gross changes attributable to treatment were observed except for the corneal opacities described below.
Histopathology
No treatment-related changes were seen in female CD rats at any dose level or in males at 2% tyrosine. The two male rats examined at 5% tyrosine presented qualitatively and quantitatively similar lesions. They were characterized by the following changes:
- diffuse corneal epithelial intracytoplasmic vacuolation
- severe interstitial edema of the basal epithelial layer of the cornea
- edematous and/or swollen nuclear changes in the corneal epithelial cells
- inflammatory reaction involving the whole cornea: diffuse polymorphonuclear (PMNs) cell infiltration of the corneal stroma and epithelium, focal infiltration of the corneal epithelium and ciliary processes.
These changes were correlated to the corneal opacities (superficial keratitis) observed for almost two weeks at the ophthalmologic examinations.
No treatment-related changes were seen in male Brown Norway rats at 2% tyrosine. One of the examined eyes from the 5% male group was from the only animal in the group of five to show changes visible at ophthalmoscopy. The histological changes in this eye were characterized by:
- focal accumulation of PMNs in the anterior chamber
- mild diffuse infiltration of the corneal stroma by PMNs lining up at the base of the epithelium
- solitary focus of superficial epithelial desquamation of non-keratinized cells in central portion of cornea.
These changes were correlated with the observation of a slight corneal opacity which was first detected shortly before necropsy.
No treatment-related changes were observed for any group of male mice.
Applicant's summary and conclusion
- Conclusions:
- This study demonstrates that a high dietary intake of free L-tyrosine leads to increased plasma tyrosine in rats, but not in mice. Furthermore, there was a strong correlation between the presence of corneal opacities and high plasma tyrosine. The same dietary treatment in mice did not result in corneal opacities.
CD rats were more susceptible to the corneal effects of dietary tyrosine than the other strain of rat tested. The higher basal plasma tyrosine levels in male CD rats in comparison with female CD rats or male Brown Norway rats, may be important in explaining different responses to elevated tyrosine intake between rat strains. However, this is not true for the inter species-comparison. Mice appear to be resistant to high tyrosine intake with no significant increase in plasma tyrosine and no corneal lesions.
The typical corneal lesion seen in the different strains of rat treated with tyrosine and those observed in regulatory studies have common characteristics. The lesions all have a "snow-flake" appearance and are variously described as keratitis or focal or multifocal opacities of the cornea. Following high tyrosine diets, the lesion appears rapidly (often 2-3 days) and is multifocal. The lesion in the single Brown Norway rat appeared late in the study (Day 14) but had the same appearance as lesions in the CD rat at Day 2 at ophthalmoscopy.
Most histological findings indicate an inflammatory reaction suggestive of a keratitis, in various corneal layers, sometimes with involvement of associated structures (eg. ciliary processes).
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.
Although ECHA is providing a lot of online material in your language, part of this page is only in English. More about ECHA’s multilingual practice.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
the-echa-website-uses-cookies
find-out-more-on how-we-use-cookies