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EC number: 203-536-5 | CAS number: 107-95-9
- 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
Neurotoxicity
Administrative data
- Endpoint:
- neurotoxicity: sub-chronic oral
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Inconsistent result
Data source
Reference
- Reference Type:
- publication
- Title:
- Dietary beta-alanine results in taurine depletion and cerebellar damage in adult cats.
- Author:
- Lu P.; Xu W., Sturman J.A.
- Year:
- 1 996
- Bibliographic source:
- Journal of Neuroscience Research 43:112-119
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Female domestic cats were fed a completely defined, taurine-free purified diet alone or containing 0.05% taurine for at least 2 years before being assigned to this study. 5 cats in each group were caged individually and fed the same diets and provided with 5% beta-alanine in the drinking water for 20 weeks.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- β-alanine
- EC Number:
- 203-536-5
- EC Name:
- β-alanine
- Cas Number:
- 107-95-9
- Molecular formula:
- C3H7NO2
- IUPAC Name:
- β-alanine
- Details on test material:
- - Name of test material (as cited in study report): beta-alanine
- Analytical purity: no data
Constituent 1
Test animals
- Species:
- cat
- Strain:
- not specified
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: domestic cats raised in the colony of the Institute for Basic Research in Developmental, NY, USA
- Housing: cats were housed individually
- Diet (e.g. ad libitum): animals were fed a completely defined, taurine-free purified diet (Bioserve, Frenchtown, NJ, USA) alone or containing 0.05% taurine for at least 2 years before being assigned to this study.
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on exposure:
- No further data
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 20 weeks
- Frequency of treatment:
- during the entire study period
Doses / concentrations
- Remarks:
- Doses / Concentrations:
5% of beta-alanine in drinking water
Basis:
nominal in water
- No. of animals per sex per dose:
- 5 (female cats)
- Control animals:
- yes, concurrent no treatment
Examinations
- Observations and clinical examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: No
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
OPHTHALMOSCOPIC EXAMINATION: No
OTHER: From each cat the brain was removed and the right half immersed in cold fixative (1% paraformaldehyde and 2.5% gluteraldehyde in 0.1 M Sorensen´s phosphate buffer, pH 7.4) for several days prior to processing for routine histology and immunohistochemistry.
The left halves of brain were rapidly dissected and frozen on dry ice prior to extraction for determination of taurine and beta-alanine concentrations. Tissues were homogenized in 10 vols 20% trifluoroacetic acid (TFA) and centrifuged at 20000 for 30 min.
The clear supernatants were passed through a 0.45 µm µStar filter and stored at -70 °C until used for taurine and beta-alanine measurements. Analysis was accomplished by derivatizing with phenylisothiocynate and the taurine and beta-alanine derivatives separated by reverse-phase high performance liquid chromatography (HPLC).
- Neurobehavioural examinations performed and frequency:
- No
- Sacrifice and (histo)pathology:
- - Time point of sacrifice: at the end of the 20-week exposure period
- Number of animals sacrificed: 5 per experimental group
- Tissues evaluated: brain.
- Type of staining: immunohistochemistry and histology staining. Sections were deparaffined and hydrated by warming at 60 °C for 65 minutes in a histoclear bath, followed by graded ethanol washes. Staining with the antisera (1: 2000 dilution) was carried out at 4°C overnight and visualized using the peroxidise-conjugated avidin/DAB method (Dako Corporation, Carpintera, CA, USA). Control sections were included in every batch, those in which the antisera were preadsorbed with the immunogen prior to processing, and others replacing the primary antiserum with preimmune serum at similar dilutions. Control slides showed no visible staining after processing, whereas slides prepared with the antisera showed brown reaction products. Counterstaining, when employed, was with hematoxylin. Other histological stains employed were cresyl violet, toluidine blue, hematoxylin and eosin, and Luxol fast blue. Photomicrographs were taken on a Zeiss Axiophot using Kodak 40 color reversal film and Kodak Panatomic X film.
- Methodology of preparation of sections: Tissue was embedded in paraffin and serial 6 µm coronal sections cut and mounted on glass slides.
- Thickness: 6 µm
- Embedding media: paraffin
- Number of animals evaluated from each sex and treatment group: 5 - Positive control:
- No
- Statistics:
- Standard deviations and significance of difference between groups were calculated using the Student´s t test using a standard computer program (STATA, Computer Resource Center, Santa Monica, CA)
Results and discussion
Results of examinations
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Behaviour (functional findings):
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- effects observed, treatment-related
- Details on results:
- During the 20-week period of study, each cat consumed approximately 500 g of beta-alanine. The concentrations of taurine in the three regions of the brain investigated in this study, cerebellum, occipital lobe, and hippocampus, were significantly reduced in both taurine-supplemented and taurine-deprived cats. A major difference was the accumulation of small amounts of beta-alanine in these regions of taurine-supplemented cats compared with large amounts accumulated in taurine-deprived cats.
Microscopic examination of the cerebellum of cats treated with beta-alanine showed a reduced number of granule cells compared to the cerebellum of cats treated only with water and many of those remaining were pyknotic. There was also a clear reduction in the number of Purkinje cells and many of those still remaining were dead or dying. The cerebellar white matter contained numerous long and swollen fibers which resemble the Rosenthal fibers described in several human disease states of the cerebellum, generally accompanied by reactive or neoplastic astrocytosis. As with Rosenthal fibers, these fibers in the cerebellar white matter also stained on the periphery with an antibody to ubiquitin. Such fibers are not seen in taurine-supplemented or taurine-deprived cats not treated with beta-alanine. There was also prominent gliosis in the cerebellum of cats treated with beta-alanine, shown by GFAP staining, compared to cats treated only with water. Morphological changes in beta-alanine-treated cats were greater in taurine-deprived than in taurine-supplemented cats. This gliosis was much more severe than has been noted in taurine-deprived kittens.
Immunohistochemical staining of cerebellum of cats treated with beta-alanine with an antibody to beta-alanine showed prominent localization in Purkinje cells and their dendrites.
Golgi II cells also contained beta-alanine. Some granule cells contained beta-alanine, especially in taurine-deprived cats treated with beta-alanine while others were devoid. None of the granule cells with pyknotic appearance were stained by antibody with beta-alanine (or taurine).
Cerebellum of cats treated only with water was negative to this antibody. Using an antibody to taurine, this compound appears to have been virtually eliminated from cerebellar Purkinje cell and granular cells of cats treated with beta-alanine and concentrated in Golgi II and glial cells of the hippocampus, and in the visual cortex, suggesting that beta-alanine accumulation with neurons is global. Beta-alanine and taurine have been shown repeatedly to be transported by a single carrier in neuronal cells, so it is not surprising that the prolonged treatment with beta-alanine in this study resulted in displacement of taurine from many neural components.
The authors concluded that although dietary treatment with beta-alanine results in great reductions in the concentration of taurine in cerebellum (and other brain regions) of taurine–supplemented cats treated with beta-alanine, yet taurine-deprived cats do not show the unusual pathology described here. Taurine has an influence on many cellular processes, including calcium concentrations which, in turn, regulated extra- and intracellular glutamate.
Beta-alanine may lack this ability and allow more gluatemate to penetrate the cells and thus cause cell death.
However, the quality of histochemical and immuno-histochemical stainings as presented in the publication is low (contrast quality and magnification scales of the shown cerebellar slides differ between treated and untreated groups). This makes it difficult to interpret the observed effects. Moreover, GFAP-stainings showed also gliosis in the animal group, which was taurine-deprived (0% taurine), but not treated with beta-alanine.
Therefore, the conclusion of the authors, that beta-alanine itself caused the pathologic changes in cerebellum could be wrong.
Taurine is an essential component of cat diets. In contrast to other species including humans, dogs, horses, cattle and rodents, cats cannot synthesize taurine from cysteine due to the lack of the required decarboxylating enzymes. It is well known, that insufficient dietary taurine -supplementation in feline food leads to central retinal atrophy and dilated cardiomyopathy in cats. Beta-alanine is a taurine analogue, which uses the same cellular transport system (carrier). Thus, prolonged exposure to beta-alanine will increase the serum levels of beta-alanine and finally lead to a displacement of intracellular taurine.
In conclusion, the observed neuropathological changes in feline cerebellum could be due to the taurine-deficiency, which was induced through dietary beta-alanine, rather than through beta-alanine treatment itself.
Effect levels
- Dose descriptor:
- NOAEL
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
Applicant's summary and conclusion
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