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EC number: 225-582-5 | CAS number: 4940-11-8
- 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:
- chronic toxicity: oral
- Remarks:
- Combined Chronic Toxicity / Carcinogenicity Study
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1968
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Not all the raw study results have been published in the publication, limited information available on methods (no guideline followed, no info regarding dosing preparation). The study was reviewed by the JECFA (2006) as part of their safety evaluation (JECFA (2006). Safety evaluation of certain food additives. Who Food Additives Series:56. Prepared by the sixty fifth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). World Health Organization, Geneva).The study was also considered valid by the EFSA expert panel (EFSA Journal 2015;13(9):4244).
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 969
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Version / remarks:
- 1981, EFSA assignment
- GLP compliance:
- no
- Remarks:
- pre-GLP
- Limit test:
- no
Test material
- Reference substance name:
- 2-ethyl-3-hydroxy-4-pyrone
- EC Number:
- 225-582-5
- EC Name:
- 2-ethyl-3-hydroxy-4-pyrone
- Cas Number:
- 4940-11-8
- Molecular formula:
- C7H8O3
- IUPAC Name:
- 2-ethyl-3-hydroxy-4H-pyran-4-one
- Test material form:
- solid
1
Test animals
- Species:
- rat
- Strain:
- other: Charles River weanling albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River
- Age at study initiation: weanling
- Housing: Individual
- Diet: Ground rat food mixed with the test substance
- Water (e.g. ad libitum): ad libitum
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Mixing appropriate amounts with (Type of food): Rockland Ground Rat Food - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- None
- Duration of treatment / exposure:
- 2 years
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 200 mg/kg bw/day (nominal)
- Dose / conc.:
- 100 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- 10 males and 10 females were mated to produce two separate litters, in order to test reproductive toxicity (described in the endpoint on reproductive toxicity)
- Positive control:
- not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 0, 3, 6, 9, 12, 18 and 24 months
- Anaesthetic used for blood collection: Not specified
- Animals fasted: No
- How many animals: 5 males and 5 females per group
- Parameters checked: Hemoglobin, hematocrit, red blood cells, white blood cells, differential count
URINALYSIS: Yes
- Time schedule for collection of urine: 0, 3, 6, 9, 12, 18 and 24 months
- Metabolism cages used for collection of urine: Yes
- Animals fasted: overnight water deprivation, not fasted.
- Parameters checked: color, volume, specific gravity, pH, blood, albumin, glucose, and microscopic examination of the sediment after centrifugation
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
The following organs were evaluated: heart, lung, liver, kidney, pancreas, spleen, thymus, mesenteric lymph node, adrenals, thyroid, brain, hypophysis, uterus and ovary;
HISTOPATHOLOGY: Yes
The following tissues were evaluated: brain (sectioned at the optic chiasm, mammillary body, cerebellum, pons, and medulla oblongata), cervical spinal cord, hypophysis, eye, parotid gland, thyroid and parathyroid, thymus, heart, lung, sternum, rib, aorta, liver, spleen, pancreas, kidneys, adrenals, stomach (fore and hind), small and large intestine (four levels), mesenteric lymph node, reproductive tract (all levels), urinary bladder, skeletal muscle, femoral nerve, femoral bone marrow, skin and mammary gland - Statistics:
- No data
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- All parameters were considered normal.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The body weight of test and control animals evolved in a comparable manner over the 2 year exposure period
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- All parameters were considered normal.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- One control rat developed anemia (RBC, 1.8 x 10^3 /mm3; hemoglobin, 8.0 % and hematocrit,18.5 %) of unknown etiology.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- All parameters were considered normal.
- Urinalysis findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All rats showed a tendency toward albuminuria; All other parameters were considered normal.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- All parameters were considered normal.
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Pathologic changes consistent with aged rats were observed primarily in the pulmonary, endocrine, urinary, and cardiovascular systems.
- Neuropathological findings:
- not examined
- Description (incidence and severity):
- No specific neurotoxicity examination was performed.
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Pathologic changes consistent with aged rats were observed primarily in the pulmonary, endocrine, urinary, and cardiovascular systems.
- Histopathological findings: neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Neoplasia occurred in a random manner with no apparent relationship between number, location, or type of tumors and treatment. This was due presumably to the advanced age of the animals.
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Ethyl maltol had no effect on fertility, gestation, parturition, lactation, or fetal development. A fall in fertility was noted in test and control groups at the second mating. This was due presumably to the advanced age of the animals.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: highest dose tested
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Refer to Tables 4 -6 in publication attached.
Applicant's summary and conclusion
- Conclusions:
- This chronic oral toxicity study (feeding) in rats (similar to OECDTG 453) did not report any treatment-related effects. Based on these findings, a NOAEL of >=200 mg/kg bw/day was established.
- Executive summary:
In a combined chronic toxicity/carcinogenicity study (Gralla et al., 1969), Ethyl Maltol was administered to 4 groups of Charles River weanling albino male and female rats (25/sex/group) in the diet at dose levels of 0, 50, 100 and 200 mg/kg bw/day daily for 2 years.
There were no effects observed on clinical signs, mortality, body weights, food consumption, clinical biochemistry and organ weight. There was a non-treatment-related effect observed on urinalysis; all rats showed a tendency toward albuminuria, with other parameters normal. There were non-treatment-related effects observed on gross pathology and (non)-neoplastic histopathology, due to the advanced age of the animals; changes were consistent with aged rats or there was no apparent relationship between effect and treatment.
The NOAEL (male/female) was >=200 mg/kg bw/day.
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