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EC number: 272-823-5 | CAS number: 68916-18-7
- 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:
- key 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:
- The effect of brewed and instant coffee on reproduction and teratogenesis in the rat.
- Author:
- Nolen GA
- Year:
- 1 981
- Bibliographic source:
- Toxicology and Applied Pharmacology, 58, 171-183
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- 90-day subchronic study (growth to sexual maturity)
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- not applicable - High molecular weight constituents (Mwt > 719 g mol-1) such as polysaccharides, proteins and melanoidin polymers
- Molecular formula:
- not applicable - High molecular weight constituents (Mwt > 719 g mol-1) such as polysaccharides, proteins and melanoidin polymers
- IUPAC Name:
- not applicable - High molecular weight constituents (Mwt > 719 g mol-1) such as polysaccharides, proteins and melanoidin polymers
- Reference substance name:
- not applicable - Inorganic constituents (including K, Mg and Ca) of Coffee, bean, roasted, ext.
- Molecular formula:
- not applicable - Inorganic constituents (including K, Mg and Ca) of Coffee, bean, roasted, ext.
- IUPAC Name:
- not applicable - Inorganic constituents (including K, Mg and Ca) of Coffee, bean, roasted, ext.
- 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
- Reference substance name:
- 1-methylpyridinio-3-carboxylate
- EC Number:
- 208-620-5
- EC Name:
- 1-methylpyridinio-3-carboxylate
- Cas Number:
- 535-83-1
- Molecular formula:
- C7H7NO2
- IUPAC Name:
- 1-methylpyridinium-3-carboxylate
- Reference substance name:
- 5-O-(3,4-dihydroxycinnamoyl)-L-quinic acid
- EC Number:
- 206-325-6
- EC Name:
- 5-O-(3,4-dihydroxycinnamoyl)-L-quinic acid
- Cas Number:
- 327-97-9
- Molecular formula:
- C16H18O9
- IUPAC Name:
- 3-{[3-(3,4-dihydroxyphenyl)acryloyl]oxy}-1,4,5-trihydroxycyclohexanecarboxylic acid
Constituent 1
Constituent 2
Constituent 3
Constituent 4
Constituent 5
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Folgers instant coffee and ground vacuum coffee
- Expiration date of the lot/batch: not available
- Purity test date: not available
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not available
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble in water
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the brewed coffee was prepared freshly each day of the study by brewing 648 g of ground coffee in 16’244 ml of water for 47 min. The instant coffee solutions were made by dissolving 14 g of instant coffee crystals in 1000 ml of water heated up to 150ºF (65.5ºC).
- Preliminary purification step (if any): none
- Final dilution of a dissolved solid, stock liquid or gel: not available
- Final preparation of a solid: not applicable
OTHER SPECIFICS: none
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: ARS/Sprague-Dawley, Inc. Madison, Wisconsin.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: (P) 21-23 days
- Weight at study initiation: not available
- Fasting period before study: no
- Housing: individually in stainless-steel suspended wire cages with raised floors.
- Diet (e.g. ad libitum): Purina Laboratory Chow ad libitum
- Water (e.g. ad libitum): ad libitum during acclimation period
- Acclimation period: 3 days
ENVIRONMENTAL CONDITIONS
- Temperature: 23 ± 2°C
- Humidity: 50 ±10 %
- Air changes (per hr): not available
- Photoperiod (hrs dark / hrs light): 12-hour light and 12-hour dark cycle
IN-LIFE DATES: From: To: not available
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on oral exposure:
- The appropriate fluid was dispensed in clean calibrated bottles daily at about 10 AM and the consumption measured.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The brew solids were determined daily for each brew with Fuchs hydrometer and biweekly on a composite sample by reftactive index measurements.
These composite samples were also analyzed for pH, titratable acidity, and caffeine. Typical analyses showed brew solids of 0.90%, a caffeine level of 0.057%, pH 5.23 and titratable acidity of 13.65 ex-
pressed as milliliters of 0.1 N NaOH required to neu-tralize 1.5% solids in 100 ml of the coffee brew. - Duration of treatment / exposure:
- Rats were exposed to coffee solutions during growth to maturity phase (91 days)
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 25 other: %
- Remarks:
- brewed and instant coffee
- Dose / conc.:
- 50 other: %
- Remarks:
- brewed and instant coffee
- Dose / conc.:
- 100 other: %
- Remarks:
- brewed and instant coffee
- No. of animals per sex per dose:
- 20 males and 30 females per group
- Control animals:
- yes
- yes, concurrent vehicle
- Details on study design:
- Groups of animals were randomly assigned to the following treatments:
1) Distilled water
2) 100% brewed coffee
3) 50% brewed coffee
4) 25% brewed coffee
5) 100% instant coffee
6) 50% instant coffee
7) 25% instant coffee - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: no data
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: weekly food consumption and daily fluid consumption records
OTHER: During first 12 weeks of the study, 10 randomly selected rats of each sex per group were transferred to stainless-steel metabolism cages, where they stayed for 48 hours without feed. Their urine was collected for two consecutive 12-hour period. The total volume for 24 hours was measured and the second 12-hour collection was measured with Ames “Clinitest” strips for pH, sugar, ketones and total protein. Afterward the animals were returned to their regular cages.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 91 day
- Anaesthetic used for blood collection: animals were sacrificed
- Animals fasted: Not specified
- How many animals: 10 rats of each sex par testing group
- Parameters examined: WBC, RBC, hemoglobin, hematocrit, lymphocyte differencial count
CLINICAL CHEMISTRY: Not specified
URINALYSIS: Yes
IMMUNOLOGY: No
OTHER: none - Sacrifice and pathology:
- After the end of the 91-day growth phase, 10 rats of each sex per group were randomly selected and sacrificed by excessive ether. The heart, liver, kidneys and gonads were removed and weighted; these and the following organs were removed, fixed in 10% neutral, buffered formalin, mounted in paraffin, sectioned, and stained with haematoxylin-eosin: lung, stomach, pancreas, jejunum, colon, mesenteric lymph node, urinary bladder, spleen, and brain. The slides were examined for histopathology.
- Statistics:
- The continuous data were analyzed by the analysis of variance, least significant difference test, Bartlett’s test for homogeneity, Wilcoxon’s rank sum test and t test for unequal variance. The discrete data were analyzed by X2.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Four rats died and four moribund were sacrificed during the study (thee males and five females). Five had severe pulmonary disease; one female given 25% brewed coffee died during parturition; one female given 25% instant coffee was sacrificed because of a mammary carcinoma and one male given 100% brewed coffee because of a nephroblastoma. These deaths and/or conditions were scattered through the test and control groups and were not related to the coffee treatments.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- During 91-day period, rats given either brewed or instant coffee solutions gained as much as or more weight than control rats given water. In fact, the three groups of female rats given brewed coffee solutions and the two groups of females given either the 100 or 50% instant coffee solutions, gained significantly more body weight than controls. All of the female rats given coffee more feed than the controls, while only the males given 50% brewed coffee or 50 and 25% instant coffee ate significantly more. The male rats fed 100% and 25% brewed coffee and 100% instant coffee solutions also ate more than controls although the difference was not statistically significant. Thus, in general, the rats that ate more, gained more weight, resulting in no significant differences in the feed efficiencies among groups of either sex.
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- The rats given either brewed or instant coffees at full strength (100%) drank significantly less than controls from the very beginning of the study. However, the rats given 50 or 25% solutions drank more than controls. Among the males, the difference was statistically significant only for the group fed the 25% dilution of brewed coffee, but among the females the differences were significant for the groups fed the two dilutions (50 and 25%) of both coffees.
The male rats ingested less caffeine per unit body weight than the females because of their larger size and of course, the rats given the instant coffee ingested less caffeine than those given brewed coffee. - Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- Hematological characteristics did not exhibit patterns indicative of a treatment-related effect.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The dicreased fluid intake of the rats given full-strength coffees resulted in a decreased urnary output with s concomitant increase in urinary protein. Otherwise the urinary characteristics measured were within the normal range of the rat and did not exhibit a dose-resonse relationship.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- At the end of 91-day growth period, among the males, the kidneys of the rats given both full-strength coffees were enlarged (based on both absolute and relative weights). The only other statistical difference among males was in the weight of the hearts of rats given 50% instant coffee, but this appeared to be without biological significance. Among the females, both the liver and the kidneys were heavier in all rats given brewed coffee, although the relative weights (ratios) were significantly higher only in the rats given the full-strength solution. Both the absolute and relative weights of these two organs were increased in the females given either 100 or 50% solutions of instant coffee. However, there were no clear patterns of dose-responses.
Significant differences also occurred in the heart weights of females given 50% brewed coffee and 100 or 50% instant coffee, as well as in the ovary/body weight ratio of rats given 25% instant coffee. These differences can be dismissed, since there is no dose-response, and they appear to be within normal limits.
Although there was liver and kidney enlargement in the females and kidney enlargement in males, no histopathology related to the ingestion of the coffees was discerned in any of the tissues examined in either males of females. The liver and kidney enlargement appeared to be adaptive hyperthophy. - Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No histopathology associated with the coffee treatments was observed in either sex.
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 25 other: %
- Based on:
- test mat.
- Remarks:
- Brewed/instant coffee
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 20 mg/kg bw/day (nominal)
- Based on:
- other: caffeine
- Sex:
- male/female
- Basis for effect level:
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In a 91-day study in rats receiving high doses of brewed and instant coffee, the NOAEL for both male and female rats was 25% brewed and instant coffee dilutions, which was equivalent to 20 mg/kg body weight per day of caffeine.
- Executive summary:
In a 91-day study, female and male rats received brewed or instant coffee as 100, 50, or 25% solutions instead of their drinking water. For the brewed coffee, this represented approximately 80, 40 or 20 mg/kg body weight per day of caffeine with slightly lower doses for the 3 solutions of instant coffee. Control animals received water.
The replacement of the rats’ drinking water with the coffee solutions exposed animals to very high doses of coffee and caffeine, albeit distributed throughout most of the day in small increments. This consumption was equivalent to up to 50-60 cups per day in the human.
At the end of 91-day period, male rats receiving both full-strength coffees had enlarged kidneys.
The only other statistical difference among males was in the weight of the hearts of rats given 50% instant coffee, but this appeared to be without biological significance. In females receiving either 100 or 50% solutions of instant coffee, the absolute and relative weights of liver and kidneys were increased; however, there were no clear patterns of dose-responses.
Although there was liver and kidney enlargement in the females and kidney enlargement in males receiving higher doses of coffees, no histopathology related to the ingestion of the coffees was discerned in any of the tissues examined in either males of females. The liver and kidney enlargement appeared to be adaptive hyperthophy.
The NOAEL for both male and female rats was 25% brewed and instant coffee dilutions, which was equivalent to 20 mg/kg body weight per day of caffeine.
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