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EC number: 212-480-0 | CAS number: 821-55-6
- 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
Repeated dose toxicity- Oral:
In a repeated dose toxicity study, CD, COBS male rats treated with Methyl heptyl ketone ( IUPAC name: nonan-2-one) in the concentration of 0, 1000, 2000 and 4000 mg/kg/day orally by gavage for 3 weeks. Following two to four doses of 4000 mg/kg/day animals withsevear depressionwere died and significant decrease in body weight gain were observed in treated rats as compared to control. Slitdecrease in body weight gain in in 2000 mg/kg/day and significant increase in absolute and relative liver and relative kidney weight were observed in 1000 and 2000 mg/kg/day treated rats as compared to control. Increased mean absolute kidney weights were considered to be not statistically significantfor 1000 mg/kg/day dose group.In addition, Vascular congestion and hemorrhage in major organ andModerate hepatocyte hypertrophy with minimal focal hepatic necrosis and enlarged hepatocytes impinged on sinusoidal spaces reducing their volume and severe central nervous system depression and consequent failure to maintain normal pulmonary ventilation and perfusion were observed at 4000 mg/kg/day treated ratsandminorto moderate hepatocyte hypertrophy were observed at 2000 mg/kg/day treated rats as compared to control. Therefore, No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day when CD, COBS male rats treated with Methyl heptyl ketone.
Repeated dose toxicity: Inhalation
In Combined repeated dose repro-devp. Screen test, Sprague Dawley male and female rats were exposed to 2 -Nonanone by inhalation in the concentration of 0, 80, 400 and 1000 ppm (0, 80, 400 or 1000 mg/L). Actual exposure concentrations is 0, 78.6, 405.8 or 1022.6 ppm (0, 78.6, 405.8 or 1022.6 mg/L) for 6 hours/day, 7 days/week for 50 days. No effect on survival, body weight and weight gain were observed in treated rats as compared to control. Minimal reductions in activity level were observed in 40 and 100 mg/kg/day dose group andreduction in food consumption during days 0 -7 in 100 mg/kg/day dose group were observed as compared to control. In addition, no effects were observed on organ weight, gross pathology, sperm parameter and histopathology of treated rats as compared to control. Therefore, the No Observed Adverse effect concentration (NOAEC) was considered to be 80 ppm (80 mg/L) (actual dose 78.6 mg/L) when Sprague-Dawley male and female rats treated with 2-Nonanone
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from peer reviewed publication
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- To evaluate the acute toxicity of Methyl heptyl ketone in COBS, CD (SD) BR male rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material: Methyl heptyl ketone
- IUPAC name: nonan-2-one
- Molecular formula: C9H18O
- Molecular weight: 142.24g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): 27.7 % - Species:
- rat
- Strain:
- other: CD, COBS
- Details on species / strain selection:
- No data
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Lab; Wilmington, Mass
- Age at study initiation: No data available.
- Weight at study initiation: No data available.
- Fasting period before study: No data available.
- Housing: They were singly housed in solid floor cages covered by Ab-Sorb-Dri bedding to reduce the likelihood of wire mesh-induced pressure neuropathy.
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow 5001 was available ad libitum.
- Water (e.g. ad libitum): Water was available ad libitum.
- Acclimation period: No data available.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available.
- Humidity (%): No data available.
- Air changes (per hr): No data available.
- Photoperiod (hrs dark / hrs light): No data available.
IN-LIFE DATES: From: To: No data available. - Route of administration:
- oral: gavage
- Details on route of administration:
- No data
- Vehicle:
- water
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Methyl heptyl ketone was dissolved in water to give a dose level of 0, 1000, 2000 or 4000 mg/kg
DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Water
- Concentration in vehicle: 0, 1000, 2000 and 4000 mg/kg
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 3 Weeks
- Frequency of treatment:
- Once a day, 5 days per week
- Remarks:
- 0, 1000, 2000 or 4000 mg/kg
- No. of animals per sex per dose:
- Total animals -18 male rats
0 mg/kg: 9 male rats
1000 mg/kg: 3 male rats
2000 mg/kg :3 male rats
4000 mg/kg :3 male rats - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data available.
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations checked in table [No.?] were included: Clinical conditions were observed.
DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: Twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: On 0, 3,7,14 and 21 day of treatment.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes ,
Time schedule: 0, 3,7,14 and 21 day of treatment.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available.
FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water studies): No data available.
OPHTHALMOSCOPIC EXAMINATION: No data available.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the termination of study
- Anaesthetic used for blood collection: Yes, carbon dioxide were used
- Animals fasted: No data available.
- How many animals: All 18 rats were examined.
- Parameters checked in table [No.?] were examined: Hemoglobin concentration, haematocrits, and total and relative white blood cell counts were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the termination of study
- Anaesthetic used for blood collection: Yes, carbon dioxide were used
- Animals fasted: No data available.
- How many animals: All 18 rats were examined.
- Parameters checked in table [No.?] were examined.-
Glutamic-oxaloacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (AP), and lactic dehydrogenase (LDH), Urea nitrogen and glucose were examined.
URINALYSIS: No data available.
NEUROBEHAVIOURAL EXAMINATION: No data available.
OTHER: Liver and kidney weights were recorded prior to fixation. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Gross abnormalities were examined.
Tissues were fixed in 10% buffered formalin (pH 7.0), embedded in paraffin, sectioned at 5 pm, stained with hematoxylin-eosin, and examined by light microscopy.
Eyes were fixed in a modified Zenker’s (Russell’s) fixative.
HISTOPATHOLOGY: Yes,
Organ examined:
Trachea, lungs, thymus, heart, tongue, salivary glands, esophagus, stomach, small intestine, large intestine, kidneys, urinary bladder, adrenal glands, pituitary, thyroids, parathyroids, pancreas, testes, epididymides, accessory sex glands, spleen, mesenteric lymph nodes, bone marrow, medulla oblongata, pons, cerebellum, cerebral cortex, thalamus, basal ganglia and eyes were examined. - Other examinations:
- No data
- Statistics:
- Statistical analyses included Bartlett’s test, one-way analysis of variance (ANOVA), and Duncan’s multiple range test as a significance level of 5%.
- 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):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality:
Mortality:
When treated with 4000 mg/kg/day, following two to four doses animals were died as compared to control.
Clinical signs:
When treated with 4000 mg/kg/day, sevear depression was observed in treated rats as compared to control.
Body weight and weight gain: When treated with 4000 mg/kg/day, significant decrease in body weight gain was observed in treated rats as compared to control.
When treated with 2000 mg/kg/day, slit decrease in body weight gain was observed in treated rats as compared to control.
Food consumption and compound intake: No significant change was observed in 1000 and 2000 mg/kg/day treated group compare to control group.
Food efficiency: No data
Water consumption and compound intake: No data
Opthalmoscopic examination: No data
Haematology: No significant change was observed in 1000 and 2000 mg/kg/day treated group compare to control group.
Clinical chemistry: No significant change was observed in 1000 and 2000 mg/kg/day treated group compare to control group.
Urinanalysis: No data
Neurobehaviour: No data
Organ weights: When treated with 1000 and 2000 mg/kg/day, significant increase in absolute and relative liver and relative kidney weight were observed in treated rats as compared to control.
Increased mean absolute kidney weights were considered to be not statistically significant.
Gross pathology: Vascular congestion and hemorrhage in major organ in 4000 mg/kg/day treated rats.
Histopathology: Moderate hepatocyte hypertrophy with minimal focal hepatic necrosis and enlarged hepatocytes impinged on sinusoidal spaces reducing their volume and severe central nervous system depression and consequent failure to maintain normal pulmonary ventilation and perfusion were observed at 4000 mg/kg/day treated rats as compared to control.
Minor to moderate hepatocyte hypertrophy were observed at 2000 mg/kg/day treated rats as compared to control. - Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No adverse effect on survival, body weight and body weight gain, food consumption, haematology, clinical chemistry, organ weight, gross pathology and histopathology.
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day when CD, COBS male rats treated with Methyl heptyl ketone.
- Executive summary:
In a repeated dose toxicity study, CD, COBS male rats treated with Methyl heptyl ketone in the concentration of 0, 1000, 2000 and 4000 mg/kg/day orally by gavage for 3 weeks. Following two to four doses of 4000 mg/kg/day animals withsevear depressionwere died and significant decrease in body weight gain were observed in treated rats as compared to control. Slitdecrease in body weight gain in in 2000 mg/kg/day and significant increase in absolute and relative liver and relative kidney weight were observed in 1000 and 2000 mg/kg/day treated rats as compared to control. Increased mean absolute kidney weights were considered to be not statistically significantfor 1000 mg/kg/day dose group.In addition, Vascular congestion and hemorrhage in major organ andModerate hepatocyte hypertrophy with minimal focal hepatic necrosis and enlarged hepatocytes impinged on sinusoidal spaces reducing their volume and severe central nervous system depression and consequent failure to maintain normal pulmonary ventilation and perfusion were observed at 4000 mg/kg/day treated ratsandminorto moderate hepatocyte hypertrophy were observed at 2000 mg/kg/day treated rats as compared to control. Therefore, No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day when CD, COBS male rats treated with Methyl heptyl ketone.
Reference
Table: TERMINAL BODY AND ORGAN WEIGHTS FOR RATS DOSED WITH COMMERCIAL-GRADE METHYL HEPTYL KETONE
Range finding study |
Terminal body weight (g) |
Liver |
Kidneys |
||
g |
% body weight |
g |
% body weight |
||
2000 mg/Kg |
302 a |
13.80b |
4.51b |
2.82 |
0.93b |
n: 3 |
23.2 |
0.770 |
0.178 |
0.412 |
0.064 |
1000 mg/Kg |
311 |
11.98b |
3.86b |
2.90 |
o.94b |
n: 3 |
26.0 |
0.805 |
0.064 |
0.189 |
0.087 |
Control |
320 |
9.79 |
3.06 |
2.51 |
0.78 |
n: 9 |
15.8 |
0.652 |
0.147 |
0.283 |
0.057 |
a Values are listed as X + SD.
b Indicates a statistically significant difference from control p Y 0.05, one-way ANOVA.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Data is from K2 peer reviewed publication
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from NTRL report
- Qualifier:
- according to guideline
- Guideline:
- other: OECD:TG- 421
- Principles of method if other than guideline:
- Combined repeated dose repro-devp. Screen of 2-Nonanone was performed usins Sprague-Dawley rats
- GLP compliance:
- no
- Limit test:
- no
- Specific details on test material used for the study:
- - Name of test material: 2-Nonanone
- IUPAC name: nonan-2 -one
- Molecular formula: C9H18O
- Molecular weight: 142.24g/mol
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): 99% pure - Species:
- rat
- Strain:
- Sprague-Dawley
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available.
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- air
- Remarks:
- Fileterd room air
- Remarks on MMAD:
- MMAD / GSD: No data available
- Details on inhalation exposure:
- No data available.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 50 days
- Frequency of treatment:
- 6 hours/day, 7 days/week
- Remarks:
- 0, 80, 400 or 1000 ppm. (0, 80, 400 or 1000 mg/L)
Actual exposure concentrations: 0, 78.6, 405.8 or 1022.6 ppm (0, 78.6, 405.8 or 1022.6 mg/L) - No. of animals per sex per dose:
- No data available
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- No data available
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included: Survival was observed.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: No data available
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available
FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER:
The testes and epididymis were also weighed - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, The ovaries, vagina, uterus, Fallopian tubes, and testes, epididymis, and male accessory sex organs were examined histologically. - Other examinations:
- No data
- Statistics:
- Homogeneity of data were evaluated by Bartlett's test (p, 0.01), analysis of variance (ANOVA, <0.05), and Dunnett's test (p, 0.05). When the variances of the means were not considered equal by Bartlett's test, the data were evaluated by Kruskal-Wallis H-test (p, 0.05) followed by Mann-Whitney U-test (p<0.05). The reproductive performance of dams and fertility and fecundity indices were evaluated in contingency tables, using Chi-square test (p,0.05). The total number of pups per litter (live and dead) and the total number of live pups per litter were evaluated by a linear regression model.
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- no mortality observed
- Description (incidence):
- No effects were observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not specified
- 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
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality:
Mortality:
No effect on survival of treated rats was observed as compared to control.
Clinical sign:
Minimal reductions in activity level were observed in 40 and 100 mg/kg/day dose group.
No other abnormalities were observed in treated rats as compared to control.
Body weight and weight gain :No effect were observed on body weight and weight gain of treated rats as compared to control
Food consumption and compound intake:
Food consumption:
In male rats, reduction in food consumption during days 0-7 hen treated with 100 mg/kg/day as compared to control.
Compound intake:
No data available
Food efficiency: No data available
Water consumption and compound intake: No data available
Opthalmoscopic examination: No data available
Haematology: No data available
Clinical chemistry: No data available
Urinanalysis: No data available
Neurobehaviour: No data available
Organ weights: No effect was observed on organ weight of treated rats as compared to control.
Gross pathology: No gross pathological changes were observed in treated rats as compared to control.
Histopathology: No histopathological changes in organs were observed in treated rats as compared to control.
Other: Sperm parameter:
No change in Mean sperm motility and mean epididymal spermatozoan and testicular spermatid counts were observed in treated male rats as compared to control. - Dose descriptor:
- NOAEC
- Remarks:
- F0
- Effect level:
- 80 mg/L air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No advarse effect on survival clinical sign, body weight and body weight gain, food consumption, sperm parameter, gross pathology and histopathology
- Dose descriptor:
- NOAEC
- Remarks:
- F1
- Effect level:
- 1 000 mg/L air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effect on clinical signs, weight gain and gross pthology
- Critical effects observed:
- not specified
- Conclusions:
- The No Observed Adverse effect concentration (NOAEC) was considered to be 80 ppm (80 mg/L) (actual dose 78.6 mg/L) when Sprague-Dawley male and female rats treated with 2-Nonanone
- Executive summary:
In Combined repeated dose repro-devp. Screen test, Sprague Dawley male and female rats were exposed to 2 -Nonanone by inhalation in the concentration of 0, 80, 400 and 1000 ppm (0, 80, 400 or 1000 mg/L). Actual exposure concentrations is 0, 78.6, 405.8 or 1022.6 ppm (0, 78.6, 405.8 or 1022.6 mg/L) for 6 hours/day, 7 days/week for 50 days. No effect on survival, body weight and weight gain were observed in treated rats as compared to control. Minimal reductions in activity level were observed in 40 and 100 mg/kg/day dose group andreduction in food consumption during days 0 -7 in 100 mg/kg/day dose group were observed as compared to control. In addition, no effects were observed on organ weight, gross pathology, sperm parameter and histopathology of treated rats as compared to control. Therefore, the No Observed Adverse effect concentration (NOAEC) was considered to be 80 ppm (80 mg/L) (actual dose 78.6 mg/L) when Sprague-Dawley male and female rats treated with 2-Nonanone
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 80 mg/m³
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is from K4 company report
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity- Oral:
Various peer reviewed publications were removed to determine the toxic nature of 2 -Nonanone ( IUPAC name: nonan-2-one) upon repeated application by oral route of exposure.
In a repeated dose toxicity study by Donoghue et al (Toxicology and applied pharmacology, 1982), CD, COBS male rats treated with Methyl heptyl ketone ( IUPAC name: nonan-2-one) in the concentration of 0, 1000, 2000 and 4000 mg/kg/day orally by gavage for 3 weeks. Following two to four doses of 4000 mg/kg/day animals withsevear depressionwere died and significant decrease in body weight gain were observed in treated rats as compared to control. Slitdecrease in body weight gain in in 2000 mg/kg/day and significant increase in absolute and relative liver and relative kidney weight were observed in 1000 and 2000 mg/kg/day treated rats as compared to control. Increased mean absolute kidney weights were considered to be not statistically significantfor 1000 mg/kg/day dose group.In addition, Vascular congestion and hemorrhage in major organ andModerate hepatocyte hypertrophy with minimal focal hepatic necrosis and enlarged hepatocytes impinged on sinusoidal spaces reducing their volume and severe central nervous system depression and consequent failure to maintain normal pulmonary ventilation and perfusion were observed at 4000 mg/kg/day treated ratsandminorto moderate hepatocyte hypertrophy were observed at 2000 mg/kg/day treated rats as compared to control. Therefore, No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day when CD, COBS male rats treated with Methyl heptyl ketone.
In the same study by Donoghue et al (1982), Chronic repeated dose toxicity study particularly the neurotoxic potential was performed, CD, COBS male rats were treated with Methyl heptyl ketone ( IUPAC name: nonan-2-one) in the concentration of 0 and 2000 mg/kg/dayorally by gavage for 90 days.Peripheral neuropathy, Hind limb weakness, reduction in extension of the hind limbs and a tendency toward a base-wide stance and low or droop tail, dragging of at least one hindpawwere observed.Observed sign were considered to be neurotoxic signs. Minor differences in mean weekly body weight were observed in treated rats during the first 3 weeks of exposure, but the differences did not reach statistical significance until the fourth week as compared to control.Similarly,Minor decreases in food consumption, total white blood cell count anddecrease in glucose level were observed in treated rats.In addition, Depression, weakness, numbness and clinical neuropathywere observed.Significant increase in absolute and relative liver weight and absolute brain, adrenal and testes weight and relative kidney weight and decrease in relative heart weight,generalized adipose tissue and hindlimb musculature atrophy evident in affected muscles by flaccidity, pallor, and reduction in total muscle mass and Hepatocyte hypertrophy and increased hyalin droplet formation in the proximal renal tubular epithelium, higher degree of regenerating renal tubular epithelium and tubular dilation with casts, muscle fiber atrophy of tongue, quadriceps femoris, calf and hindpaw interosseous muscles were observed in treated rats. Atrophic changes were characterized by increased numbers of central myofiber nuclei, increased angular myofibers, foci of small myofibers, and coalescence of atrophic foci into large areas. “Giant” axons and degenerating axons were located in intramuscular nerves. Therefore, No Observed Adverse Effect Level (NOAEL) was considered to be > 2000 mg /kg for Methyl heptyl ketone (MHK) in Charles River CD, COBS male rats for 90 days study.
Another repeated dose oral toxicity study was reviewed. In a 90-Days Repeated dose toxicity study (Eastman Kodak Company, 1994), Charles River CD, COBS male rats treated with Methyl heptyl ketone (MHK; IUPAC name: nonan-2-one)orally by gavage in the concentration of 0 and 2000 mg/kg. Peripheral neuropathy, Hind limb weakness, reduction in extension of the hind limbs and a tendency toward a base-wide stance and low or droop tail were observed in treated rats.The observed sign were considered to be neurotoxic signs.Feed consumption was significantly reduced for the first week and then was comparable to control values except during weeks 10 and 12 when it was significantly lower. Body weight was the lowest from the fourth week and by the sixth week was significantly lower than all other groups.Significantly reduced total white cell count and glucose level. Statistically significant decreased in absolute and increased in relative liver weight, statistically significantly increased relative kidney, adrenal gland and testes weight and decreased absolute brain and heart weight and decreased relative spleen weights were observed as compared to control. In addition, Flaccidity, pallor and reduction in total muscle mass, generalized decrease in adipose tissue and atrophy of the hind limb musculature and Hyperkeratosis with pseudoepitheliomatous hyperplasia of the non-glandular mucosa of the stomach, hepatocyte hypertrophy, and increased hyalin droplet formation in the proximal renal tubular epithelium. Regenerating renal tubular epithelium and tubular dilation with casts. Muscle atrophy of tongues,quadriceps femoris muscle, calf musculature and hind limb interosseous muscles. Increased numbers of central myofiber nuclei, increased angular myofibers, and foci of atrophic myofibers and coalesence of atrophic myofibers into large areas of atrophy were observed in treated rats. "Giant" axons and degenerating axons were located in some intramuscular nerves. "Giant" axonal lesions in cerebellum, medulla oblongata, spinal cord and peripheral nerves were observed in treated rats characterized by multifocal axonal swelling with thinning of myelin sheath and paranodal myelin retraction. More severely affected axons showed fragmentation and myelin degeneration in the form of ovoids were observedas compared to control. Therefore, The No-observed-adverse-effect-level (NOAEL) was found to be >2000 mg /kg for Methyl heptyl ketone (MHK) in Charles River CD, COBS male rats for 90 days study.
In the same study mentioned above, Subacute repeated dose toxicity study (Eastman Kodak Company, 1994) was also performed. CD, COBS male rats were treated with Methyl heptyl ketone ( IUPAC name: nonan-2-one) in the concentration of 0, 1000, 2000 or 4000 mg/kg orally by gavage for 3 weeks. 3 rats died within 24 to 28 hours and depression and prostration were observed in 4000 mg/kg treated rats as compared to control. No effects were observed on Body weight and weight gain,food consumption and haematology of treated rats as compared to control. Significant increase in absolute and relative liver weight and slightly increased absolute and relative kidney weight were observed in 1000 and 2000 mg/kg. in addition, serosal hemorrhage in the jejunum, porphyrin stained tears, congestion of the liver and a small contracted spleen and minor acute bronchitis and severe congestion, edema and atelectasis, moderate congestion and interstitial pneumonia in lung, moderate hyperplasia of the epithelium of the non-glandular mucosa of the stomach, moderate hepatocyte hypertrophy, characterized by an increase in the absolute volume of the cytoplasm, a decrease in basophilic grandular cytoplasm and enlarged, vesicular nuclei with prominent nucleoli and Enlarged hepatocytes impinged on the sinusoidal space reducing its volume in liver, dilatation of the lumena of the renal tubules and multiple hemorrhages into the lamina propria and submocosa of the urinary bladder, congested and cells of the zona fasiculata were hypertrophied in adrenal gland, congestion in Bone marrow and brain, Atrophy of the mesenteric adipose tissue were observed in 4000 mg/kg dose group. Minor to severe degree of hyperplasia of the epithelium of the nonglandular mucosa was observed in stomach and minor to moderate degree of hepatocyte hypertrophy were observed in 2000 mg/kg treated rats as compared to control. Therefore, No-observed-adverse-effect-level (NOAEL) was considered to be 1000 mg/kg when CD, COBS male rats treated with Methyl heptyl ketone
Repeated dose toxicity: Inhalation
Data for repeated inhalation toxicity was reviewed to determine the toxic nature of 2 -Nonanone ( IUPAC name: nonan-2-one) upon repeated exposure by inhalation route. The summary is as mentioned below:
In Combined repeated dose repro-devp. Screen test (Eastman Kodak Company, 1994), Sprague Dawley male and female rats were exposed to 2 -Nonanone by inhalation in the concentration of 0, 80, 400 and 1000 ppm (0, 80, 400 or 1000 mg/L). Actual exposure concentrations is 0, 78.6, 405.8 or 1022.6 ppm (0, 78.6, 405.8 or 1022.6 mg/L) for 6 hours/day, 7 days/week for 50 days. No effect on survival, body weight and weight gain were observed in treated rats as compared to control. Minimal reductions in activity level were observed in 40 and 100 mg/kg/day dose group andreduction in food consumption during days 0 -7 in 100 mg/kg/day dose group were observed as compared to control. In addition, no effects were observed on organ weight, gross pathology, sperm parameter and histopathology of treated rats as compared to control. Therefore, the No Observed Adverse effect concentration (NOAEC) was considered to be 80 ppm (80 mg/L) (actual dose 78.6 mg/L) when Sprague-Dawley male and female rats treated with 2-Nonanone
Based on the information observed for the target chemical, it is summarized that 2 -Nonanone does not exhibit repeated oral and inhalation toxicity. Thus, the chemical is not likely to classify as a toxicant upon repeated exposure by oral and inhalation route of exposure.
Justification for classification or non-classification
Based on the information observed for the target chemical, it is summarized that 2 -Nonanone does not exhibit repeated oral and inhalation toxicity. Thus, the chemical is not likely to classify as a toxicant upon repeated exposure by oral and inhalation route of exposure.
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