Registration Dossier
Registration Dossier
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EC number: 209-665-3 | CAS number: 589-92-4
Endpoint summary
Administrative data
Description of key information
Acute Oral Toxicity
Four existing studies are available which report acute oral toxicity information. Eastman(1959) reported LD50=400 -3200mg/kg bw in rats, Eastman(1960) reported LD50=800 -1600mg/kg bw in rats, and LD50=1600 -3200mg/kg bw in mice. Treon(1943) reported lethal effects in white rabbits with LDlow=1250mg/kg bw (an LD50 was not determined). Although none of the studies can be considered to be reliable, primarily due to the extremely limited details documented in the reports, the values are considered to be sufficiently consistent for the purposes of classification. As a worst case, the lowest reported LD50 of 400mg/kg bw has been taken for the purposes of classification and risk assessment.
Acute Dermal Toxicity
No reliable studies following standard guideline methods for acute dermal toxicity were available. The study by Treon (1943) was not considered reliable due to methodological issues.
Both in-vitro skin corrosion studies according to OECD 430 and 431 gave positive results. As a result, and in accordance with REACH, Annex VIII, 8.5.3, column 2, due to skin corrosiveness of the test substance the study on acute dermal toxicity does not have to be performed.
Acute Inhalation Toxicity
No adequate or reliable studies following standard guideline methods for acute inhalation toxicity were available.
Both in-vitro skin corrosion studies according to OECD 430 and 431 gave positive results. As a result, and in accordance with o Regulation (EC) No 1907/2006 (REACH) Annex VIII Item 8.5.3 column 2, due to skin corrosiveness of the test substance the study on acute dermal toxicity does not have to be performed.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1959
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No information on a guideline was reported, but assumed to be standard acute method.
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
Not reported.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Not reported.
- Test material: undiluted - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
Not reported.
ENVIRONMENTAL CONDITIONS
Not reported. - Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Details on oral exposure:
- VEHICLE:
Not reported.
MAXIMUM DOSE VOLUME APPLIED:
Not reported. - Doses:
- 50, 400 and 3200 mg/kg
- No. of animals per sex per dose:
- 3 rats reported (assumed to be total, with one per dose)
- Control animals:
- not specified
- Details on study design:
- Not reported.
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- >= 400 - <= 3 200 mg/kg bw
- Based on:
- test mat.
- Mortality:
- time to death: 1 hour
- Clinical signs:
- other: Symptoms slight to very weak.
- Gross pathology:
- Not reported.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The reported LD50 was 400 to 3200 mg/kg for rats.
- Executive summary:
Undiluted test substance was applied orally to rats at doses of 50, 400 and 3200 mg/kg. The resulting LD50 is 400 to 3200 mg/kg.
There were only slight to very weak symptoms observed. Time until death was 1 hour.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1960
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Qualifier:
- no guideline followed
- Version / remarks:
- None reported.
- Principles of method if other than guideline:
- No information on a guideline was reported, but assumed to be standard acute method.
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL:
Not Reported.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING:
Not reported. - Species:
- mouse
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
Not reported.
ENVIRONMENTAL CONDITIONS:
Not reported. - Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Details on oral exposure:
- VEHICLE:
Not reported. - Doses:
- Dose range from 200 to 3200 mg/kg
- No. of animals per sex per dose:
- 10 mice in total (animals per dose not reported).
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: ambiguous.
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- >= 1 600 - <= 3 200 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Time to death 10min to 1 day.
- Clinical signs:
- other: Symptoms in mice: Slight to very weak, ataxia, vasodilation, prostration, labored respiration, kicking, loss of reflex action.
- Gross pathology:
- Not reported.
- Other findings:
- Not reported.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The reported LD50 was 1600 to 3200 mg/kg.
- Executive summary:
The results origin from laboratory data received by testing the effects of 4 -methylcyclohexanone by undiluted oral adminitration to mice.
Dose range for the rats: 200 to 3200 mg/kg; LD50 dose: 1600 to 3200 mg/kg; Time until death: 10min to 1 day.
Symptoms in rats: Slight to very weak, ataxia, vasodilation, prostration, labored respiration, kicking, loss of reflex action.- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1960
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- documentation insufficient for assessment
- Qualifier:
- no guideline followed
- Version / remarks:
- None reported.
- Principles of method if other than guideline:
- No information on a guideline was reported, but assumed to be standard acute method.
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL:
Not Reported.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING:
Not reported. - Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS:
Not reported.
ENVIRONMENTAL CONDITIONS:
Not reported. - Route of administration:
- oral: unspecified
- Vehicle:
- not specified
- Details on oral exposure:
- VEHICLE:
Not reported. - Doses:
- Dose range from 800 to 3200 mg/kg
- No. of animals per sex per dose:
- 6 rats in total (animals per dose not reported).
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: ambiguous.
- Key result
- Sex:
- not specified
- Dose descriptor:
- LD50
- Effect level:
- >= 800 - <= 1 600 mg/kg bw
- Based on:
- test mat.
- Mortality:
- Time to death 1 to 2.5 hours.
- Clinical signs:
- other: Symptoms in rats: Prostration within one hour in all animals; a low labored respiration; loss of reflexes; vasodilatation; dark eyes and cyanosis.
- Gross pathology:
- Not reported.
- Other findings:
- Not reported.
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The reported LD50 was 800 to 1600 mg/kg.
- Executive summary:
The results origin from laboratory data received by testing the effects of 4 -methylcyclohexanone by undiluted oral adminitration to rats.
Dose range for the rats: 800 to 3200 mg/kg; LD50 dose: 800 to 1600 mg/kg; Time until death: 1 to 2.5h.
Symptoms in rats: Prostration within one hour in all animals; a low labored respiration; loss of reflexes; vasodilatation; dark eyes and cyanosis.- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1943
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Qualifier:
- no guideline followed
- Version / remarks:
- No guideline reported.
- Principles of method if other than guideline:
- The study reported toxicity following oral and dermal exposure to methylcyclohexanone isomers, and several other structurally related compounds.
For the oral toxicity investigations, the test material was administered in a single oral dose using a syringe and rubber tube. After admnistration, the animal was released, behaviour and physiological parameters recorded until death or regain of original body weight. - GLP compliance:
- no
- Test type:
- other: study did not explicitly determine LD50.
- Limit test:
- no
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL:
Barrett Division of Allied Chemical and Dye Corporation.
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
Not reported. - Species:
- rabbit
- Strain:
- other: White
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: local breeders
- Age at study initiation: young
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: until observed to be healthy.
ENVIRONMENTAL CONDITIONS:
Not reported. - Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on oral exposure:
- VEHICLE:
Not reported.
MAXIMUM DOSE VOLUME APPLIED:
Not reported. - Doses:
- 0.56, 1.0, and 1.25 to 5.0 g/kg bw
- No. of animals per sex per dose:
- Assumed to be one animal per dose. Five animals in the range 1.25 to 5.0g/kg bw.
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: daily
- Other examinations performed: clinical signs, body weight, pathology, hematology, metabolites. - Key result
- Sex:
- not specified
- Dose descriptor:
- LDLo
- Effect level:
- 1 250 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: Lowest reported lethal dose
- Mortality:
- Mortality was reported for five rabbits with doses in the range 1.25 to 5.0 g/kg bw, within 14 to 90min of administration.
- Clinical signs:
- other: Rapid onset of narcosis, tremors, cyanosis. Lethal doses were followed by convulsive movements within 10-15min, followed by coma and death. Sublethal doses resulted in prostration within 30 and 60min, and remained so for 2.5 and 7.25 hours.
- Gross pathology:
- Widespread vascular damage was observed, with gibrinocellular thrombi in capillaries and venules, and coagulation necrosis in organs (heart, liver, spleen, kidneys).
Cerebal edema and congestion were noted in some animals at lethal doses. Superficially eroded and edematous gastric mucosa were also observed in some animals.
At sublethal doses, one animal displayed treatment related effects in heart, lung, liver and kidney. - Other findings:
- - Organ weights: not reported
- Histopathology: at sublethal dose, marked parenchyatours degeneration of central and midzonal cords, associated with inflammation in cells and sinusoids. Glomerulo tubular degeneration was seen in the kidney, associated with vascular degeneration and sclerosis of the glomerular tufts. - Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- The test material was administered to white rabbits by oral gavage for doses at 0.56, 1.0, and 1.25 to 5.0 g/kg bw. Mortality was observed for all animals within the range 1.25 to 5.0 g/kg bw, with two animals surviving at 0.56 and 1.0 g/kg bw. The LD50 is estimated to fall in the range relevant for classification under GHS, as acute Category 4.
- Executive summary:
The test material was administered to white rabbits by oral gavage for doses at 0.56, 1.0, and 1.25 to 5.0 g/kg bw. Mortality was observed for all animals within the range 1.25 to 5.0 g/kg bw. Rapid onset of narcosis, followed by convulsive movements was observed. Widespread vascular damage was observed, with gibrinocellular thrombi in capillaries and venules, and coagulation necrosis in organs (heart, liver, spleen, kidneys).
Referenceopen allclose all
92% of methylcyclohexanone was excreted conjugated with glucuronic acid.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 400 mg/kg bw
- Quality of whole database:
- None of the available studies are considered to be reliable individually. However, the effects observed occure at consistent dose levels across four independent studies, including three different species.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Justification for classification or non-classification
From the available existing studies, the lowest reported acute oral toxicity was an LD=400mg/kg bw (Eastman, 1959). As a result, and in accordance with the criteria set out in CLP, Annex I, Part 3, 3.1.2.1, Table 3.1.1, the substance is classified for acute oral toxicity, Category 4 - H302: Harmful if swallowed.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
