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Diss Factsheets
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EC number: 200-362-1 | CAS number: 58-08-2
- 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
![](https://poisoncentres.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: guideline study (NTP)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 983
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: NTP protocol
- Principles of method if other than guideline:
- NTP Protocol
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Caffeine
- EC Number:
- 200-362-1
- EC Name:
- Caffeine
- Cas Number:
- 58-08-2
- Molecular formula:
- C8H10N4O2
- IUPAC Name:
- 1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione
- Details on test material:
- - Name of test material (as cited in study report): Caffeine
- Analytical purity: 99.9%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- continuously in the drinking water
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
19.7, 41.8, 85.4, 151.0, 271.9 mg/kg/d (males); 23.1, 51.0, 104.2, 174.2, 287.0 mg/kg/d (females)
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
188, 375, 750, 1500, 3000 ppm
Basis:
nominal in water
- No. of animals per sex per dose:
- 12 males and 12 females per group
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Post-exposure period: none
Results and discussion
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 1 500 ppm
- Sex:
- male/female
- Basis for effect level:
- other: The daily dose was calculated to be 151.0 mg/kg for males and 174.2 mg/kg for females.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
The aim of this study was to determine the dose levels for a 2-year chronic bioassay. Groups of 12 rats/sex were given the test substance in the drinking water at concentrations of 0 (control), 188, 375, 750, 1500, and 3000 ppm. According to the authors, based on data of body weights and water consumption, the daily doses were calculated to be 0, 19.7, 41.8, 85.4, 151.0, and 271.9 mg/kg for males and 0, 23.1,
51.0, 104.2, 174.2, and 287.0 mg/kg for females. All animals were sacrificed at the end of the treatment period; body and organ weights were recorded. Clinical chemical examinations were performed on animals from the 188, 750, and 3000 ppm and control groups. Microscopic pathology was performed on all lesions appearing grossly and routinely in all major systems in the high dose and control groups.
The body weight gains of all treated groups were decreased. The effect was significant in the highest dose only (reduction of 26%, males, 20%, females). Both food and water consumption was decreased by ca. 10% in this group in both sexes. However, water consumption was increased at 750 ppm (both sexes) and at 375 ppm (females). No significant clinical symptoms were recorded in any group.
Clinical chemistry indicated some significantly increased and/or decreased serum aspartate aminotransferase and alanine aminotransferase values and significantly decreased
serum amylase values in treated rats; however, no dose-related patterns were established.
There were no significant treatment-related gross lesions.
Microscopic examination revealed alterations (cell enlargement) of the salivary gland which were most marked in the high dose group, diminishing with decreasing dose.
The observed effect in salivary gland was dose dependent in rats and mice in the highest dose group only, the authors gave no description about adverse effect. These is a functional adaptive and reversible effect of salivary glands to well known pharmacological effect of caffeine (sympathicomimetic). The morphological changes correlate to this function are so fare not considered to be an adverse effect of the substance.
According to the authors, these results indicated that the maximum tolerated dose to be used for a 2-year chronic bioassay should be 2000 ppm; doses of 0, 500, 1000, and 2000
ppm were recommended for this study.
Applicant's summary and conclusion
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.
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