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EC number: 218-080-2 | CAS number: 2050-08-0
- 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:
- not specified
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP study in accordance with OECD TG 408 with restrictions. To address toxicological endpoints as part of the REACH registration of Amyl Salicylate (Target Substance) it is proposed to read-across to Cyclohexyl Salicylate (Source Substance). The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. The Target Substance and Source Substance have been characterised using the categories and databases present in the OECD [Q]SAR Toolbox. From the profiling, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. Therefore, read across is justified.
- Justification for type of information:
- The justification for read across from Cyclohexyl Salicylate is attached in section 13.2 (Other assesment report).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- as of 12 May 1981
- Deviations:
- yes
- Remarks:
- The oral dose was only applied on five days a week
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- as of 1 March 1991, 91/325/EEC
- Deviations:
- yes
- Remarks:
- The oral dose was only applied on five days a week
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 25485-88-5
- EC Number:
- 607-733-0
- IUPAC Name:
- 25485-88-5
- Reference substance name:
- cyclohexyl salicylate
- IUPAC Name:
- cyclohexyl salicylate
- Test material form:
- other: liquid
- Details on test material:
- - Name of test material (as cited in study report): Cyclohexylsalicilate
- Physical state: colourless liquid
- Analytical purity: 100%
- Purity test date: not reported
- Lot/batch No.: 111 833 34/2
- Expiration date of the lot/batch: December 1995
- Stability under test conditions: stable in arachidis oil, DAB 10
- Storage condition of test material: at room temperature
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Hsd/Win:Wu
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: HarlanWinkelmann, Borchen, Germany
- Age at study initiation: about 5 weeks
- Weight at study initiation (at arrival): 51 to 65 g for males and 50 to 61 g for females
- Housing: two or three animals in Makrolon Type M 5 cages with standard softwood bedding
- Diet (e.g. ad libitum): pelleted Altromin Maintenance Diet 1324 ad libitum
- Water (e.g. ad libitum): community tap water ad libitum
- Acclimation period: 7 days under laboratory conditions
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 24
- Humidity (%): 39 to 65
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light (60 to 470 Lux)
IN-LIFE DATES: 109/110 days from the beginning of acclimatisation period (treatment groups) and 138 days from the beginning of acclimatisation period (recovery groups)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
The solution of the test article and vehicle was prepared daily before administration, the solution was administered to the animals within approximately 2 to 3 hours after the preparation.
VEHICLE
- Justification for use and choice of vehicle (if other than water): arachidis oil, DAB 10; no justification for vehicle provided
- Concentration in vehicle: depending on dose the concentration was 8, 24 or 72 mg/mL (i.e. between 0.8 and 7.2%)
- Amount of vehicle (if gavage): the application volume was 5 mL/kg for all dose groups - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The nominal concentrations were analysed once by HPLC. The analysed concentrations were in good agreement with nominal concentrations: the dose of 40 mg/kg contained 0.415 g/50 mL ± 0.007 [nominal 0.4 g/50 mL], the dose of 120 mg/kg contained 1.265 g/50 mL ± 0.007 [nominal 1.2 g/50 mL] and the dose of 360 mg/kg contained 3.725 g/50 mL ± 0.049 [nominal 3.6 g/50 mL]
- Duration of treatment / exposure:
- 102 to 103 days for treatment groups
131 days for recovery groups - Frequency of treatment:
- Once daily on 5 days per week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
40 mg/kg bw
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
120 mg/kg bw
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
360 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 10 females and 10 males in each dose group plus 5 females and 5 males used as recovery animals in the control and the high-dose groups
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: dose levels were derived from the already available oral 28-day study
- Post-exposure recovery period in satellite groups: After 69 applications animals of the recovery groups had a treatment-free period of 29 days - Positive control:
- not applicable
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: acclimatisation period once daily, treatment period twice daily, recovery period once daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: acclimatisation period once daily, treatment period twice daily, recovery period once daily
BODY WEIGHT: Yes
- Time schedule for examinations: arrival, once during acclimatisation, weekly during treatment and recovery period
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Frequency: weekly
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Frequency: weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: at beginning and end of treatment
- Procedure: slit lamp microscopy, after instillation of a mydriatic agent into the eyes
HAEMATOLOGY: Yes
- Time schedule for collection of blood: after six weeks of treatment and at the end of treatment period
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after six weeks of treatment and at the end of treatment period
- Animals fasted: No data
- How many animals: all
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data
OTHER: Bone marrow smears at scheduled necropsy - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
The animals of the main groups and recovery groups were sacrificed by an overdose of ether and exsanguinated by cardial heart puncture at open thorax. All animals were submitted to full necropsy procedures: external surfaces, orifices, cranial cavity, external surface of the brain, thoracic, abdominal and pelvis cavities and viscera, carcass. The following organs were weighed: brain, testes, heart, liver, spleen, adrenals, kidneys, thymus.
Various organis were preserved for histopathology and fixated in 10% neutral formalin (except for eyes fixated in Davidson's fluid): adrenals aorta, bone marrow, brain, caecum, colon, duodenum, epididymis, eyes, heart, ileum, jejunum, kidneys, liver, lungs, lymph node (submandibularis), lymp node (mesenteric), lymph node (inguinalis), mammary gland, oesophagus, ovaries, pancreas, parathyroids, prostate, rectum, salivary glands, skeleta muscle, skin, spinal cord (lumbal region), spleen, stomach (fundus, pylorus), testes, thymus, thyroids, trachea, urinary bladder, uterus (horn, carvix), lumbal vertebrates, all gross lesions.
HISTOPATHOLOGY: Yes
Histopathology was performed on all fixated organs in the control group and the high-dose group. - Statistics:
- T-test for determination of significant differences between the groups for body weight gains (L Sachs, Statistische Auswertungsmethoden, 3rd edition, Springer-Verlag, Berlin 1971); t-test for determination of significant differences between the groups for haematological and clinical chemistry results (CW Dunnett 1955, Journal of the American Statistical Association 372, 1096-1120 and 1964, Biometrics 1964, 482-490); Steel test for determination of significant differences between the groups for organ weights (RGD Steel 1959, Biometrics 15, 560-572)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Water consumption was increased in the high dose group.
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- Females, high dose group: significant, slight increase of the polymorphnuclear neutrophils in the differential white blood cell count, but within normal range of historical controls
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Males, high dose group: significant, slight decrease of bilirubin, but within normal range of historical controls
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- Incidental, slight increase in liver weight
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- Small areas of necrosis in the livers of 4 males in the high dose group, but similar findings also in male animals of other groups; therefore considered not treatment-related
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 360 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: overall effects
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
To address toxicological endpoints as part of the REACH registration of Amyl Salicylate (Target Substance) it is proposed to read-across to Cyclohexyl Salicylate (Source Substance).
The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible.
The Target Substance and Source Substance have been characterised using the categories and databases present in the OECD [Q]SAR Toolbox. From the profiling , it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific.
See Section 13, document Read across justification_Cyclohexyl salicylate.
Applicant's summary and conclusion
- Conclusions:
- Repeated oral administration by gavage of the substance to female and male rats at doses ranging from 40 to 360 mg/kg bw/day on 5 days a week over a period of 90 days did not reveal adverse systemic effects. The NOEL in this oral repeated dose toxicity study was 360 mg/kg bw/day.
- Executive summary:
The oral repeated dose toxicity of the test substance Cyclohexyl salicylate over a period of 90 days was studied under GLP in accordance with OECD TG 408 with some restrictions. The test substance dissolved in arachidis oil was administered to male and female rats by oral gavage on 5 days per week for a period of 90 days. Rats were about five weeks old at the initiation of the study and weighed between 50 and 65 g. The nominal test concentrations were 0 (vehicle control), 40, 120 and 360 mg/kg bw/day. The total volume of administered formulation was 5 mL/kg in all dose groups. In addition to the ten male and female rats per study group that were sacrificed at the end of the 90 -day treatment period, additional five male and female animals were used for investigation during a 29-day recovery period without oral treatment. The administration of test substance by oral gavage to male and female rats at doses of 40, 120 and 360 mg/kg body weight over a period of 90 days did not produce adverse systemic effects in this study.
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.
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