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Diss Factsheets
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EC number: 204-260-8 | CAS number: 118-56-9
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: This is an old study (1963), predating GLP however the protocol and results were reported in adequate detail and included hematological studies, gross pathology, and limited histopathological examinations of key organs and tissues.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Chronic and subacute toxicology and pathology of methyl salicylate in dogs, rats and rabbits
- Author:
- Webb WK, Hansen WH
- Year:
- 1 963
- Bibliographic source:
- Toxicology and Applied Pharmacology 5: 576-687
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- MeS was administered in dogs orally in capsule daily for a period of 2 years.
- Limit test:
- no
Test material
- Reference substance name:
- Methyl salicylate
- EC Number:
- 204-317-7
- EC Name:
- Methyl salicylate
- Cas Number:
- 119-36-8
- Molecular formula:
- C8H8O3
- IUPAC Name:
- Methyl 2-hydroxybenzoate
Constituent 1
Test animals
- Species:
- dog
- Strain:
- Beagle
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
IN-LIFE DATES: no data
Administration / exposure
- Route of administration:
- oral: capsule
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): no data
- Storage temperature of food: no data
VEHICLE: none - Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- none
- Duration of treatment / exposure:
- 2 years
- Frequency of treatment:
- daily for 6 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 50, 150 and 350 mg/kg/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 2/sex/dose
- Control animals:
- yes
- Details on study design:
- no data are available
- Dose selection rationale: the data reported in the subchronic study in dogs by the same authors (methyl salicylate/ 59 days/oral (capsule)/dogs). - Positive control:
- none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: the animals were weighed weekly
FOOD EFFICIENCY: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY:
it made at 2 weeks, 1, 3, and 6 months and 1 and 2 years
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- no data
- Statistics:
- no data available
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- 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
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
- No clinical signs were observed.
- Two dogs dying of unrelated disease: one high-dose female died of infectious canine hepatitis after 33 days on the experiment.
Her replacement died of canine distemper after 19 weeks on the experiment.
BODY WEIGHT AND WEIGHT GAIN
The administration of 350 and 150 mg/kg/day retarded the growth of the dogs:
- The dogs on the highest level lost an average of 1.90 kg while the control dogs gained an average of 1.85 kg.
- The dogs on 150 mg/kg/day gained an average of only 0.5 kg.
HAEMATOLOGY
Hematological analyses at 1, 3, 6, 12 and 24 months were normal.
ORGAN WEIGHTS
Enlarged livers were seen at necropsy of the dogs on the 150 and 350 mg/kg/day levels. The heavier livers plus reduced bodyweight gain produced higher ratios of liver weight to body weight.
GROSS PATHOLOGY
At necropsy, the dogs treated at 150 and 350 mg/kg body weight/day had enlarged livers.
HISTOPATHOLOGY:
Microscopically, these livers had larger hepatic cells than those seen in the control dogs.
Fatty metamorphosis was not greater in the livers of the treated dogs than the very small amounts seen in the livers of the control dogs.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: for methyl salicylate
- Dose descriptor:
- NOAEL
- Effect level:
- 86 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: read-across value for homosalate
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Under these test conditions, animals of the 150 and 350 mg/kg groups had retarded growth and enlarged livers were observed in these animals. No effects were reported at 50 mg/kg bw/day. Based on this study, the NOAEL /oral/dogs is 50 mg/kg body weight/day for methyl salicylate. This corresponds to 86 mg/kg bw/day of homosalate.
- Executive summary:
Webb and Hansen (1963) studied groups of two male and two female purebred beagles fed methyl salicylate in capsule form at doses of 0, 50, 150, or 350 mg/kg body weight/day, 6 days/week for 2 years.
One high-dose animal died of hepatitis apparently unrelated to methyl salicylate. Hematological analyses at 1, 3, 6, 12 and 24 months and complete necropsy examination were normal, except that dogs treated at 150 and 350 mg/kg body weight/day had enlarged livers, seen microscopically as enlarged hepatic cells. No other pathology was reported in any of the animals. Reduced body weight was reported in the 350 and 150 mg/kg body weight/day groups.
Based on this chronic oral study, the NOAEL value is 50 mg/kg body weight/day.
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