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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: dermal
Administrative data
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- no data
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: This study is limited in design and in reporting detail. Few animals were used, at very high dose levels
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:
- Toxicol Appl Pharmacol 5: 576-687
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- Rabbits were treated on their backs with four dose levels of methyl salicylate for approximately 6.5 hours daily for up to 96 days. Since the compound was absorbed, the backs of the rabbits were not wiped before they were replaced in their individual cages. Microscopic examinations were made of the major organs
- GLP compliance:
- no
- 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:
- rabbit
- Strain:
- not specified
- Sex:
- male/female
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- unchanged (no vehicle)
- Duration of treatment / exposure:
- up to 96 days
- Frequency of treatment:
- daily on five days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.5, 1.0, 2.0 and 4.0 ml/kg/day (590, 1180, 2360, and 4720 mg/kg body weight/day)
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 3 per dose level (mixed sexes)
- Control animals:
- no
Examinations
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- Local dermal effects
Results and discussion
Results of examinations
- Dermal irritation:
- effects observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Details on results:
- CLINICAL SIGNS AND MORTALITY
The three rabbits on 4.0 ml/kg died after 6, 8, and 28 days and exhibited anorexia, weight loss, and depression.
BODY WEIGHT AND WEIGHT GAIN
Several of the survivors had subnormal weight gains
HISTOPATHOLOGY:
Microscopically: one high-dose animal had "several distinct lesions" including dilatation, desquamation, and formation of new atypical epithelium of the renal tubules; a moderate number of small foci of superficial necrosis and sloughing of the skin; foci of moderate necrosis and slight calcification of voluntary muscles; marked vacuolation of pancreatic acinar cells, slight myeloid hyperplasia and shift to the left of bone marrow, and slight hepatitis. These effects were not seen in the other examined high-dose animals, but an effect on the distal portion of the nephrons was indicated.The incidence of spontaneous nephritis and mild hepatitis in the nine surviving rabbits was increased over that in rabbits in other experiments.
OTHER FINDINGS: A slight sloughing of epidermal scales occurred in two of the three rabbits on 2.0 ml/kg/day. The remaining animals showed no skin abnormalities.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- Local effects
- Effect level:
- 1 180 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: slight to very slight dermatitis (sloughing of epidermal scales) at 2.0 ml/kg bw/day (2360 mg/kg bw/day)
- Dose descriptor:
- LOAEL
- Remarks:
- Systemic effects
- Effect level:
- 590 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Increased spontaneous nephritis and mild hepatitis.
- Dose descriptor:
- LOAEL
- Remarks:
- Systemic effects
- Effect level:
- 1 015 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
Any other information on results incl. tables
One high dose decedent was not necropsied due to extreme autolysis. Of the two high dose animals examined, one showed local dermal effects (small foci of superficial necrosis and sloughing of the skin) as well as lesions in several organs (kidney, voluntary muscle, pancreas, bone marrow, liver). The only effect reported in the other high dose animal examined was a suggestion of an effect on the distal portion of nephrons. At 2.0 ml/kg (2360 mg/kg), slight sloughing of epidermal scales was observed in 2/3 rabbits. No dermal effects were noted in rabbits exposed to 0.5 or 1.0 ml/kg (590 and 1180 mg/kg body weight/day).The NOAEL for local effects was 1.0 ml/kg/day (1180 mg/kg bw/day).
No clear NOAEL was determined for systemic effects due to the reported increased incidence in spontaneous nephritis and mild hepatitis over that in rabbits in other experiments.
Applicant's summary and conclusion
- Conclusions:
- Under the test conditions, the NOAEL value for local dermal effects of methyl salicylate was 1.0 ml/kg/day (1180 mg/kg bw/day). The LOAEL for systemic effects was 0.5 ml/kg/day (590 mg/kg bw/day) for methyl salicylate, which corresponds to 1015 mg/kg bw/day of homosalate.
- Executive summary:
In a study by Webb and Hansen (1963), groups of three rabbits of both sexes were administered methyl salicylate of 99% purity to sites on the back clipped free of hair. Dermal exposures of 0.5, 1.0, 2.0 and 4.0 ml/kg/day (590, 1180, 2360, and 4720 mg/kg body weight/day) were administered 5 days/week for up to 96 days. The animals were restrained in holders for 6.5 h, but due to absorption the test substance was not wiped from the test sites after the exposure period. Following termination, the major organs from all rabbits except one severely autolysed animal were subjected to histological examination.
All the 3 high-dose animals had died by day 28 of exposure, following weight loss and depressed activity. In one of these animals, local effects on the skin (small foci of superficial necrosis and sloughing of the skin) and lesions in a number of organs (skin, kidney, voluntary muscle, pancreas, bone marrow, liver) were reported. The only effect reported in the other high dose animal examined was a suggestion of an effect on the distal portion of nephrons. At 2.0 ml/kg (2360 mg/kg), slight sloughing of epidermal scales was observed in 2/3 rabbits. No dermal effects were noted in rabbits exposed to 0.5 or 1.0 ml/kg (590 and 1180 mg/kg body weight/day).The NOAEL for local effects was 1.0 ml/kg/day (1180 mg/kg bw/day), however the lower pH of SA predicts a higher potential for irritation for the acid than for the ester. No clear NOAEL for local effects for SA could therefore be determined.
No clear NOAEL was determined for systemic effects due to the reported increased incidence in spontaneous nephritis and mild hepatitis over that in rabbits in other experiments.
This dermal study at very high doses was limited in design and in reporting detail and is not useful for the purposes of risk assessment for systemic toxicity.. It is not possible to determine whether the effects reported on kidney and other organs in one high dose animal represent systemic toxicity or a secondary effect due to skin and muscle damage.
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