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EC number: 204-435-9 | CAS number: 120-92-3
- 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
Endpoint summary
Administrative data
Description of key information
Based on the oral chronic toxicity study performed on cyclohexanone
(rats) and considered as a key study (Lijinsky W, 1986) a NOAEL of 723
mg/kg b.w./day was identified in rats for cyclopentanone and for body
weight decrease.
For inhalation, based on a study performed on cyclohexanone and on
rabbits a NOAEC of 773 ppm (3040 mg/m3) was identified for systemic
effects (lethargy, distention of the ear veins)
and a NOAEC of 190 ppm (750 mg/m3) for local effects (eye irritation) (Treon, 1943 - considered as a key study)for cyclopentanone.
Several studies both performed on cyclopentanone and cyclohexanone showed that the two substances induce similar effects and that cyclohexanone is more toxic than cyclopentanone (see justification for read-across).
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- 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:
- other: The study was well conducted. The protocol and the results were detailed. The cyclohexanone purity was known and confirmed by analysis. The GLP were not mentioned.
- Principles of method if other than guideline:
- Sub-chronic toxicity study in drinking water
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- * TEST ANIMALS:
- Source: Animal Production Facility of the NCI-Frederick Cancer Reasearch Facility
- Age at study initiation: 7 to 8 weeks old
- Weight at study initiation: the weight of the male rats averaged 162 g (139-180 g), that of the female rats 126 g (107-143 g)
- Fasting period before study: data not available
- Housing: 5 to a cage
- Diet: Wayne Sterilizable Lab Meal, ad libitum
- Water: data not available
Acclimation period: data not available
* ENVIRONMENTAL CONDITIONS:
- Temperature: 22 to 24 °C
- Air changes: 15 times per hour
- Humidity, photoperiod: data not available
IN-LIFE DATES: data not available - Route of administration:
- oral: drinking water
- Vehicle:
- other: acidified water
- Details on oral exposure:
- * PREPARATION OF DOSING SOLUTIONS: cyclohexanone was dissolved in acidified water (pH 2.5) and stored at 5 °C. The solution was prepared every 2 weeks, stored at 5 °C.
* VEHICLE:
Justification for use and choice of vehicle: water was acidified to suppress bacterial growth - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analysis of the solution at intervals and after 28 days showed that there was no detectable decomposition during this time. Cyclohexanone was also
completely stable at room temperature for at least 4 days. - Duration of treatment / exposure:
- For 25 weeks
- Frequency of treatment:
- daily
- Remarks:
- Doses / Concentrations:
190 ppm (29 mg/kg bw), 400 ppm (61 mg/kg bw), 800 ppm (122 mg/kg bw), 1600 ppm (246 mg/kg bw), 3300 ppm (508 mg/kg bw), 4700 ppm (723 mg/kg bw), 6500 ppm (1000 mg/kg bw). The ppm doses would provide approximately mg/kg bw/day doses.
Basis: - No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- * Dose selection rationale: based on a LD50 at 1.6 g/kg bw
* Rationale for animal assignment: data not available - Positive control:
- no
- Observations and examinations performed and frequency:
- * CAGE SIDE OBSERVATIONS: No data
* DETAILED CLINICAL OBSERVATIONS: No data
* BODY WEIGHT: Yes
Time schedule for examinations: once a week and at the end of the study
* WATER CONSUMPTION AND COMPOUND INTAKE: No data
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: No data
* CLINICAL CHEMISTRY: No data
* URINALYSIS: No data
* NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Other examinations:
- no data
- Statistics:
- no data
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Details on results:
- - Clinical signs and mortality: no effects
Up to the termination study at 25 weeks, cyclohexanone did not affect survival, even in the rats exposed to 6500 ppm concentration.
There was moderate chronic respiratory disease in all animals, cyclohexanone-treated and control rats.
- Body weight and weight gain: yes: a depression of body weight gain (10% less than controls) was noted in both male and female rats exposed to
cyclohexanone at 6500 ppm for the 25 weeks exposure.
- Histopathology: non-neoplastic: yes: the only histopathological change observed was a mild degenerative change in the thyroid gland of 2/5 male
rats exposed to 4700 ppm but not seen in other animals. - Dose descriptor:
- NOAEL
- Effect level:
- 4 700 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Depression of body weight gain / 4700 ppm correspond to 723 mg/kg b.w./day.
- Dose descriptor:
- LOAEL
- Effect level:
- 6 500 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Depression of body weight gain / 6500 ppm correspond to 1000 mg/kg b.w./day.
- Critical effects observed:
- not specified
- Executive summary:
In a sub-chronic toxicity study (Lijinsky W, 1986) Cyclohexanone (96% purity) was administered to 5 F344 rat/sex/dose in water at dose levels of 0, 190, 400, 800, 1600, 3300, 4700, 6500 ppm (equiv. to ca. 29, 61, 122, 246, 508, 723, 1000 mg/kg bw/day).
Up to the end of the study at 25 weeks, cyclohexanone did not affect survival, even in the rats exposed to 6500 ppm concentration. However, the body weight gain was 10% lower than controls in both male and female rats at the highest dose. It was concluded that in absence of significant histopathologic findings, the MTD was 6500 ppm, dose also considered as the LOAEL in Fisher 344 rats. The NOAEL was 4700 ppm (723 mg/kg bw).- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- see below attached justification for read-across
- Reason / purpose for cross-reference:
- read-across source
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Route of administration:
- oral: drinking water
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Dose descriptor:
- NOAEL
- Effect level:
- 4 700 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Depression of body weight gain / 4700 ppm correspond to 723 mg/kg b.w./day.
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Dose descriptor:
- LOAEL
- Effect level:
- 6 500 ppm
- Sex:
- male/female
- Basis for effect level:
- other: Depression of body weight gain / 6500 ppm correspond to 1000 mg/kg b.w./day.
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Critical effects observed:
- not specified
- Executive summary:
Read accross with Cyclohexanone was used for repeated dose toxicity.
Summary of the study by oral route:
In a sub-chronic toxicity study (Lijinsky W, 1986) Cyclohexanone (96% purity) was administered to 5 F344 rat/sex/dose in water at dose levels of 0, 190, 400, 800, 1600, 3300, 4700, 6500 ppm (equiv. to ca. 29, 61, 122, 246, 508, 723, 1000 mg/kg bw/day).
Up to the end of the study at 25 weeks, cyclohexanone did not affect survival, even in the rats exposed to 6500 ppm concentration. However, the body weight gain was 10% lower than controls in both male and female rats at the highest dose. It was concluded that in absence of significant histopathologic findings, the MTD was 6500 ppm, dose also considered as the LOAEL in Fisher 344 rats. The NOAEL was 4700 ppm (723 mg/kg bw).Based on this data and by analogy, Cyclopentanone is not classified for repeated dose toxicity and orale route.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 723 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was very old and performed before the GLP standard was established. However, the inhalation protocol and the results were well described.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Subchronic inhalation study
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rabbit
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
- Acclimation period: 2 to 6 weeks
- Source, age at study initiation, weight at study initiation, fasting period before study, housing, diet, water: data not available
ENVIRONMENTAL CONDITIONS
- Temperature: 24 °C
- Humidity: controlled not to exceed 45%
- Air changes: 30-60 per hour
- Photoperiod (hrs dark / hrs light): data not available
IN-LIFE DATES: data not available - Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- other: no data
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The prolonged inhalation of lower concentration was effected by the use of a battery of nine insulated plywood cages, each having a capacity of 600 litres and equipped with a front glass door. The rate of flow into the cage ranged from 350 to 800 L per minute. The equipment for conditioning the air in these cages has been described by Moore (1941). A special apparatus was used for constant vaporization of liquid with low vapour pressures and slow rates of evaporation such as cyclohexanone.
TEST ATMOSPHERE
The concentrations of cyclohexanone in air were determined colorimetrically by measuring in the air alcoholic extract compound the intensity of the pink colour produced by a reaction of the Zimmerman type, with m-dinitrobenzene. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Period of 10 weeks
- Frequency of treatment:
- 5 days a week, 6 hours daily
- Remarks:
- Doses / Concentrations:
190 ppm (0.75 mg/L), 309 ppm (1.21 mg/L), 773 ppm (3.04 mg/L), 1414 ppm (5.56 mg/L)
Basis:
no data - No. of animals per sex per dose:
- 4 per dose group
- Control animals:
- yes
- Details on study design:
- Post-exposure period: Observation for 2 months after the end of exposure
- Observations and examinations performed and frequency:
- * CAGE SIDE OBSERVATIONS: No data
* DETAILED CLINICAL OBSERVATIONS: No data
* BODY WEIGHT: Yes
- Time schedule for examinations: daily
* FOOD CONSUMPTION: No data
* WATER CONSUMPTION: No data
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: Yes
- Time schedule for collection of blood: weekly
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: data not available
- Parameters: blood cell analysis (erythrocytes and leucocytes) and
hemoglobin concentration
* CLINICAL CHEMISTRY: No data
* URINALYSIS: Yes
- Time schedule for collection of urine: weekly
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters: urine of rabbits exposed to 190 ppm, 309 ppm and 1414 ppm cyclohexanone were analysed for the excretion of organic and inorganic sulfates using a turbidimetric method. Urine of rabbits exposed to the lowest concentration ( 190 ppm = 0.75 mg/L) were analysed for their glucuronic-acid content using a naphthoresorcinol method.
* NEUROBEHAVIOURAL EXAMINATION: No data
* OTHER: rectal temperature was determined daily - Sacrifice and pathology:
- * GROSS PATHOLOGY: Yes
* HISTOPATHOLOGY: Yes - Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Haematological findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Details on results:
- - CLINICAL SIGNS AND MORTALITY:
At the lowest concentration (190 ppm = 0.75 mg/L) no abnormality in the behaviour of the animals was noted but degenerative changes in the liver and kidney were barely
demonstrated. These changes, not significative, were observed only at the lowest concentration and can not be considered as an effect of the test substance.
At the highest concentration (1414 ppm), slight lethargy, distention of the ear veins, salivation and conjunctival irritation manifested by congestion, lacrimation, and secretion of mucus were noted throughout the daily periods of exposure.
A lesser degree of ocular irritation resulted from exposure to the concentrations at 309 ppm and 773 ppm while slight salivation was observed under the latter conditions (773 ppm).
No mortality was observed.
- BODY WEIGHT AND WEIGHT GAIN: The rabbits gained in weight during exposure at the different concentrations.
- HAEMATOLOGY: No specific or general toxic effects upon the cellular elements of the peripheral blood were observed.
- URINALYSIS: The weekly variations in the percentage of inorganic sulfates (in relation to the total urinary sulfates) were normal before and immediately after the termination of exposures. However, some conjugation occurred during exposure to all but the lowest concentration (190 ppm = 0.75 mg/L), the mean value for this period being within normal limits (84.5%).
At this lowest concentration, there was an average daily out-put of 61 mg of glucuronic acid per rabbit during the period before exposure, with an increase to 222 mg per rabbit during exposure, and a decrease to 39 mg per rabbit after exposure had been terminated.
The changes in body temperature of the exposed animals were comparable to those observed in control animals. - Dose descriptor:
- NOAEC
- Effect level:
- 190 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 190 ppm correspond to 750 mg/m3.
- Dose descriptor:
- LOAEC
- Effect level:
- 309 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 309 ppm correspond to 3040 mg/m3.
- Dose descriptor:
- NOAEC
- Effect level:
- 773 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 773 ppm correspond to 3040 mg/m3
- Dose descriptor:
- LOAEC
- Effect level:
- 1 414 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 1414 ppm correspond to 5560 mg/m3.
- Critical effects observed:
- not specified
- Conclusions:
- The LOAEL was 309 ppm since only ocular irritation was observed at this concentration.
- Executive summary:
In a subchronic inhalation toxicity study (Treon, 1943) cyclohexanone (purity unknown) was administered to rabbits (4/group), by exposure at concentrations of 0.75, 1.21, 3.04, 5.56 mg/L (190, 309, 773 and 1414 ppm) for 6 hours per day, 5 days/week for a total of 10 weeks.
At the lowest concentration (190 ppm), no depression in body weight gain, no changes in body temperature, no abnormality in the behavior of the animals and no specific or general toxic effects upon cellular elements of the peripheral blood were noted. However, barely demonstrated degenerative changes in the liver and kidney were observed in the rabbits exposed to 190 ppm. However, these changes were not significant and were not observed at higher doses. At the highest concentration (1414 ppm), slight lethargy, distention of the ear veins, salivation and conjunctival irritation manifested by congestion, lacrimation, and secretion of mucus were noted throughout the daily periods of exposure. A lesser degree of ocular irritation resulted from exposure to the concentrations at 309 ppm and 773 ppm while slight salivation was observed under the latter conditions (773 ppm). Based on this study, a NOAEC of 773 ppm (3.04 mg/L) can be identified for systemic effects (lethargy, distention of the ear veins) and a NOAEC of 190 ppm (0.75 mg/L) for local effect (eye irritation).- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- see below attached justification for read-across
- Reason / purpose for cross-reference:
- read-across source
- Species:
- rabbit
- Route of administration:
- inhalation
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Haematological findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Dose descriptor:
- NOAEC
- Effect level:
- 190 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 190 ppm correspond to 750 mg/m3.
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Dose descriptor:
- LOAEC
- Effect level:
- 309 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 309 ppm correspond to 3040 mg/m3.
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Dose descriptor:
- NOAEC
- Effect level:
- 773 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 773 ppm correspond to 340 mg/m3
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Dose descriptor:
- LOAEC
- Effect level:
- 1 414 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 1414 ppm correspond to 5560 mg/m3
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Critical effects observed:
- not specified
- Executive summary:
Read accross with Cyclohexanone was used for repeated dose toxicity.
Summary of the study by inhalation route:
In a subchronic inhalation toxicity study (Treon, 1943) cyclohexanone (purity unknown) was administered to rabbits (4/group), by exposure at concentrations of 0.75, 1.21, 3.04, 5.56 mg/L(190, 309, 773 and 1414 ppm)for 6 hours per day, 5 days/week for a total of 10 weeks.
At the lowest concentration (190 ppm), no depression in body weight gain, no changes in body temperature, no abnormality in the behavior of the animals and no specific or general toxic effects upon cellular elements of the peripheral blood were noted. However, barely demonstrated degenerative changes in the liver and kidney were observed in the rabbits exposed to 190 ppm.However, these changes were not significant and were not observed at higher doses. At the highest concentration (1414 ppm), slight lethargy, distention of the ear veins, salivation and conjunctival irritation manifested by congestion, lacrimation, and secretion of mucus were noted throughout the daily periods of exposure. A lesser degree of ocular irritation resulted from exposure to the concentrations at 309 ppm and 773 ppm while slight salivation was observed under the latter conditions (773 ppm). Based on this study, a NOAEC of 773 ppm (3.04 mg/L) can be identified for systemic effects (lethargy, distention of the ear veins) and a NOAEC of 190 ppm (0.75 mg/L) for local effect (eye irritation).Based on this study and by analogy, Cyclopentanone is not classified for repeated dose toxicity by inhalation.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 3 040 mg/m³
- Study duration:
- subchronic
- Species:
- rabbit
- System:
- other: Systemic effect
Repeated dose toxicity: inhalation - local effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was very old and performed before the GLP standard was established. However, the inhalation protocol and the results were well described.
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Subchronic inhalation study
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rabbit
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
- Acclimation period: 2 to 6 weeks
- Source, age at study initiation, weight at study initiation, fasting period before study, housing, diet, water: data not available
ENVIRONMENTAL CONDITIONS
- Temperature: 24 °C
- Humidity: controlled not to exceed 45%
- Air changes: 30-60 per hour
- Photoperiod (hrs dark / hrs light): data not available
IN-LIFE DATES: data not available - Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- other: no data
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The prolonged inhalation of lower concentration was effected by the use of a battery of nine insulated plywood cages, each having a capacity of 600 litres and equipped with a front glass door. The rate of flow into the cage ranged from 350 to 800 L per minute. The equipment for conditioning the air in these cages has been described by Moore (1941). A special apparatus was used for constant vaporization of liquid with low vapour pressures and slow rates of evaporation such as cyclohexanone.
TEST ATMOSPHERE
The concentrations of cyclohexanone in air were determined colorimetrically by measuring in the air alcoholic extract compound the intensity of the pink colour produced by a reaction of the Zimmerman type, with m-dinitrobenzene. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Period of 10 weeks
- Frequency of treatment:
- 5 days a week, 6 hours daily
- Remarks:
- Doses / Concentrations:
190 ppm (0.75 mg/L), 309 ppm (1.21 mg/L), 773 ppm (3.04 mg/L), 1414 ppm (5.56 mg/L)
Basis:
no data - No. of animals per sex per dose:
- 4 per dose group
- Control animals:
- yes
- Details on study design:
- Post-exposure period: Observation for 2 months after the end of exposure
- Observations and examinations performed and frequency:
- * CAGE SIDE OBSERVATIONS: No data
* DETAILED CLINICAL OBSERVATIONS: No data
* BODY WEIGHT: Yes
- Time schedule for examinations: daily
* FOOD CONSUMPTION: No data
* WATER CONSUMPTION: No data
* OPHTHALMOSCOPIC EXAMINATION: No data
* HAEMATOLOGY: Yes
- Time schedule for collection of blood: weekly
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: data not available
- Parameters: blood cell analysis (erythrocytes and leucocytes) and
hemoglobin concentration
* CLINICAL CHEMISTRY: No data
* URINALYSIS: Yes
- Time schedule for collection of urine: weekly
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters: urine of rabbits exposed to 190 ppm, 309 ppm and 1414 ppm cyclohexanone were analysed for the excretion of organic and inorganic sulfates using a turbidimetric method. Urine of rabbits exposed to the lowest concentration ( 190 ppm = 0.75 mg/L) were analysed for their glucuronic-acid content using a naphthoresorcinol method.
* NEUROBEHAVIOURAL EXAMINATION: No data
* OTHER: rectal temperature was determined daily - Sacrifice and pathology:
- * GROSS PATHOLOGY: Yes
* HISTOPATHOLOGY: Yes - Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Haematological findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Details on results:
- - CLINICAL SIGNS AND MORTALITY:
At the lowest concentration (190 ppm = 0.75 mg/L) no abnormality in the behaviour of the animals was noted but degenerative changes in the liver and kidney were barely
demonstrated. These changes, not significative, were observed only at the lowest concentration and can not be considered as an effect of the test substance.
At the highest concentration (1414 ppm), slight lethargy, distention of the ear veins, salivation and conjunctival irritation manifested by congestion, lacrimation, and secretion of mucus were noted throughout the daily periods of exposure.
A lesser degree of ocular irritation resulted from exposure to the concentrations at 309 ppm and 773 ppm while slight salivation was observed under the latter conditions (773 ppm).
No mortality was observed.
- BODY WEIGHT AND WEIGHT GAIN: The rabbits gained in weight during exposure at the different concentrations.
- HAEMATOLOGY: No specific or general toxic effects upon the cellular elements of the peripheral blood were observed.
- URINALYSIS: The weekly variations in the percentage of inorganic sulfates (in relation to the total urinary sulfates) were normal before and immediately after the termination of exposures. However, some conjugation occurred during exposure to all but the lowest concentration (190 ppm = 0.75 mg/L), the mean value for this period being within normal limits (84.5%).
At this lowest concentration, there was an average daily out-put of 61 mg of glucuronic acid per rabbit during the period before exposure, with an increase to 222 mg per rabbit during exposure, and a decrease to 39 mg per rabbit after exposure had been terminated.
The changes in body temperature of the exposed animals were comparable to those observed in control animals. - Dose descriptor:
- NOAEC
- Effect level:
- 190 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 190 ppm correspond to 750 mg/m3.
- Dose descriptor:
- LOAEC
- Effect level:
- 309 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 309 ppm correspond to 3040 mg/m3.
- Dose descriptor:
- NOAEC
- Effect level:
- 773 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 773 ppm correspond to 3040 mg/m3
- Dose descriptor:
- LOAEC
- Effect level:
- 1 414 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 1414 ppm correspond to 5560 mg/m3.
- Critical effects observed:
- not specified
- Conclusions:
- The LOAEL was 309 ppm since only ocular irritation was observed at this concentration.
- Executive summary:
In a subchronic inhalation toxicity study (Treon, 1943) cyclohexanone (purity unknown) was administered to rabbits (4/group), by exposure at concentrations of 0.75, 1.21, 3.04, 5.56 mg/L (190, 309, 773 and 1414 ppm) for 6 hours per day, 5 days/week for a total of 10 weeks.
At the lowest concentration (190 ppm), no depression in body weight gain, no changes in body temperature, no abnormality in the behavior of the animals and no specific or general toxic effects upon cellular elements of the peripheral blood were noted. However, barely demonstrated degenerative changes in the liver and kidney were observed in the rabbits exposed to 190 ppm. However, these changes were not significant and were not observed at higher doses. At the highest concentration (1414 ppm), slight lethargy, distention of the ear veins, salivation and conjunctival irritation manifested by congestion, lacrimation, and secretion of mucus were noted throughout the daily periods of exposure. A lesser degree of ocular irritation resulted from exposure to the concentrations at 309 ppm and 773 ppm while slight salivation was observed under the latter conditions (773 ppm). Based on this study, a NOAEC of 773 ppm (3.04 mg/L) can be identified for systemic effects (lethargy, distention of the ear veins) and a NOAEC of 190 ppm (0.75 mg/L) for local effect (eye irritation).- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- see below attached justification for read-across
- Reason / purpose for cross-reference:
- read-across source
- Species:
- rabbit
- Route of administration:
- inhalation
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Haematological findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Dose descriptor:
- NOAEC
- Effect level:
- 190 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 190 ppm correspond to 750 mg/m3.
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Dose descriptor:
- LOAEC
- Effect level:
- 309 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Local effects (ocular irritation) / 309 ppm correspond to 3040 mg/m3.
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Dose descriptor:
- NOAEC
- Effect level:
- 773 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 773 ppm correspond to 340 mg/m3
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Dose descriptor:
- LOAEC
- Effect level:
- 1 414 ppm
- Sex:
- not specified
- Basis for effect level:
- other: Systemic effects / 1414 ppm correspond to 5560 mg/m3
- Remarks on result:
- other: results on an analogous (cyclohexanone)
- Critical effects observed:
- not specified
- Executive summary:
Read accross with Cyclohexanone was used for repeated dose toxicity.
Summary of the study by inhalation route:
In a subchronic inhalation toxicity study (Treon, 1943) cyclohexanone (purity unknown) was administered to rabbits (4/group), by exposure at concentrations of 0.75, 1.21, 3.04, 5.56 mg/L(190, 309, 773 and 1414 ppm)for 6 hours per day, 5 days/week for a total of 10 weeks.
At the lowest concentration (190 ppm), no depression in body weight gain, no changes in body temperature, no abnormality in the behavior of the animals and no specific or general toxic effects upon cellular elements of the peripheral blood were noted. However, barely demonstrated degenerative changes in the liver and kidney were observed in the rabbits exposed to 190 ppm.However, these changes were not significant and were not observed at higher doses. At the highest concentration (1414 ppm), slight lethargy, distention of the ear veins, salivation and conjunctival irritation manifested by congestion, lacrimation, and secretion of mucus were noted throughout the daily periods of exposure. A lesser degree of ocular irritation resulted from exposure to the concentrations at 309 ppm and 773 ppm while slight salivation was observed under the latter conditions (773 ppm). Based on this study, a NOAEC of 773 ppm (3.04 mg/L) can be identified for systemic effects (lethargy, distention of the ear veins) and a NOAEC of 190 ppm (0.75 mg/L) for local effect (eye irritation).Based on this study and by analogy, Cyclopentanone is not classified for repeated dose toxicity by inhalation.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 750 mg/m³
- Species:
- rabbit
Additional information
Read accross with Cyclohexanone was used for repeated dose toxicity.
Summary of the selected key studies by oral and inhalation route:
Oral route:
In a chronic toxicity study (Lijinsky W, 1986) Cyclohexanone (96% purity) was administered to 5 F344 rat/sex/dose in water at dose levels of 0, 190, 400, 800, 1600, 3300, 4700, 6500 ppm (equiv. to ca. 29, 61, 122, 246, 508, 723, 1000 mg/kg bw/day). Up to the end of the study at 25 weeks, cyclohexanone did not affect survival, even in the rats exposed to 6500 ppm concentration. However, the body weight gain was 10% lower than controls in both male and female rats at the highest dose. It was concluded that in absence of significant histopathologic findings, the MTD was 6500 ppm (1000 mg/kg bw), dose also considered as the LOAEL in Fisher 344 rats. The NOAEL was 4700 ppm (723 mg/kg bw) based on body weight gain decrease.
In the same study (Lijinsky 1989) cyclohexanone (96% purity) was administered to 10 B6C3F1 mice/sex/dose in water at dose levels of 400, 2300, 6500,13000,25000,34000,47000ppm (equiv. to 100, 575, 1625, 3250, 6250, 8500,11750 mg/kg bw/day) for 13 weeks. Based on the body weight depression data and on the absence of histopathological findings, the authors considered that the MTD was 25000ppm (6250 mg/kg bw) in female and 13000ppm (3250 mg/kg bw) in male mice. For males a NOAEL of 13000ppm (3250 mg/kg) can be identified based on body weight gain decrease. For females the NOAEL was considered as 25000ppm (6250 mg/kg) based on the same effect.
Inhalation route:
In a
subchronic inhalation toxicity study (Treon, 1943) cyclohexanone (purity
unknown) was administered to rabbits (4/group), by exposure at
concentrations of 0.75,1.21,3.04
and 5.56 mg/L
(190, 309, 773 and 1414 ppm) for 6 hours per day, 5 days/week for a
total of 10 weeks.
At the lowest concentration (0.75 mg/L), no depression in body weight
gain, no changes in body temperature, no abnormality in the behaviour of
the animals and no specific or general toxic effects upon cellular
elements of the peripheral blood were noted. Barely demonstrated
degenerative changes in the liver and kidney were observed in the
rabbits exposed to 0.75 mg/L. However,
these changes were not significant and were not observed at higher
doses. At the highest concentration (1414 ppm), slight lethargy,
distention of the ear veins, salivation and conjunctival irritation
manifested by congestion, lacrimation, and secretion of mucus were noted
throughout the daily periods of exposure. A lesser degree of ocular
irritation resulted from exposure to the concentrations at 309 ppm and
773 ppm while slight salivation was observed under the latter conditions
(773 ppm). Based on this study, a NOAEC of 773 ppm (3.04 mg/L) can be
identified for systemic effects (lethargy, distention of the ear veins)
and a NOAEC of 190 ppm (0.75 mg/L) for local effect (eye irritation).
Repeated dose toxicity: inhalation - systemic effects (target
organ) neurologic: behaviour
Justification for classification or non-classification
Based on cyclohexanone data:
- NOAEL = 723 mg/kg bw/day in rats for body weight gain decrease after oral route exposure (25 weeks)
- NOAEC = 773 ppm (3040 mg/m3) in rabbits for systemic effects (lethargy, distention of the ear veins) (10 weeks of exposure by inhalation)
- NOAEC = 190 ppm (775 mg/m3) in rabbits for local effects (eye irritation) (10 weeks of exposure by inhalation)
Cyclopentanone, by analogy, is not classified for repeated dose toxicity.
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