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EC number: 201-126-0 | CAS number: 78-59-1
- 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
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Endpoint summary
Administrative data
Description of key information
Among the existing valid studies following three studies were found to show the highest toxicity after oral, dermal and inhalation application of isophorone: The acute toxicity in laboratory animals is low to moderate with an oral LD50 (rat) of 1500 mg/kg bw (Günzel and Richter, Schering AG, 1968), a dermal LD50 (rabbit) of 1200 mg/kg bw (Dutertre-Catella, 1976) and an inhalative LC50 (rat, aerosol) of 7000 mg/m3 air (Esso Research, 1965).
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:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
- Principles of method if other than guideline:
- Method: Acute oral toxicity study in rats - single administration
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Breeder Voss
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Study performed with animals of relatively low body weight: Weight at study initiation: 80-115 g.
- Route of administration:
- oral: unspecified
- Vehicle:
- other: Emulsion 0.5 g carboxymethyl cellulose in 100 ml dist. water
- Doses:
- Doses: 0.5; 1.0; 1.25; 1.50; 1.75; 2.0; 2.5 g/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- Post dose observation period: 13 days;
EXAMINATIONS: gross examination of: coat of fur, skin, eye and conjunctiva, nose, mouth, ear, anus, preputial opening, vulva, subcutaneous
connective tissue, abdominal cavity, pelvic cavity, peritoneum, esophagus, stomach, small intestine, large intestine, mesenteric lymph nodes, liver,
pancreas, spleen, kidneys, urinary bladder, seminal vesicle, prostate, testicles, epididymis, ovary, uterus, vagina, thoracic cavity, pleura, heart, lungs,trachea, thymus gland, cerebrum, middle ear, application sites - Statistics:
- STATISTICAL METHODS: Probit analysis
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 1 500 mg/kg bw
- Remarks on result:
- other: LD50 confidence limits: 1400-1800 mg/kg
- Mortality:
- MORTALITY:
- Time of death: 1 hour to 3 days after dosing
- Number of deaths at each dose: 500 mg/kg: 0/10; 1000 mg/kg: 1/10; 1250 mg/kg: 1/10; 1500 mg/kg: 5/10; 1750 mg/kg: 7/10; 2000 mg/kg: 10/10; 2500 mg/kg: 8/10;
LD50 confidence limits: 1400-1800 mg/kg - Clinical signs:
- other: > 1,000 mg/kg: general apathy, lateral position, irregular respiration
- Gross pathology:
- NECROPSY FINDINGS: Results of animals that died: - increased secretion in stomach and small intestine , - thickening and hermorrhagic erosions of
proventiculus lining, - urine retention, - hyperemia of liver, - pulmonary emphysema, edema or hyperemia and - splenic enlargement - Other findings:
- no data
- Conclusions:
- The LD50 value of isophorone in female and male rats was estimated to be 1500 mg/kg bw. Clinical signs like general apathy, lateral position and
irregular respiration occured at doses > 1000 mg/kg bw. The test animals died 1 hour to 3 days after feeding. - Executive summary:
The acute oral toxicity to rats was evaluated by standard acute method. The test item was administered to five female and five male rats orally. The animals were observed for mortality and any sub-lethal effects for 13 days after dosing. Isophorone was orally of moderate acute toxicity: The LD50 value in rats was estimated to be 1500 mg/kg bw. Clinical signs like general apathy, lateral position and irregular respiration occured at doses > 1000 mg/kg bw. Increased secretion in stomach and small intensine, thickening and hermorrhagic erosions of proventiculus lining, urine retention, hyperemia of liver, pulmonary emphysema, edema or hyperemia and splenic enlargement were found at necrospy.
Reference
no remarks
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 1 500 mg/kg bw
- Quality of whole database:
- The study is well documented, meets generally accepted scientific principles, and is acceptable for assessment. Klimisch score 2 (reliable with restrictions)
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1964-12-02 - 1965-01-15
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
- Principles of method if other than guideline:
- Method: Acute Inhalation Toxicity: Whole body exposure; described in reference
- GLP compliance:
- no
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS:
- Weight at study initiation: 200-225 grams
- Number of animals: 10
- Controls: yes - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- - Type of exposure: inhalation, aerosol
- Analytical verification of test atmosphere concentrations:
- not specified
- Duration of exposure:
- 4 h
- Concentrations:
- - Concentrations: 5; 7; 10; 17.8 mg/l
- No. of animals per sex per dose:
- 10 males
- Control animals:
- yes
- Details on study design:
- EXAMINATIONS:
- Observations for deaths and toxic signs: 30 min intervals
- post observation: 14 days, daily
- gross pathology: at end of post observation period: all surviving animals - Statistics:
- no data
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- 7 mg/L air
- Exp. duration:
- 4 h
- Remarks on result:
- other: aerosol
- Mortality:
- - Number of deaths at each dose, time of death:
5000 mg/m3: 4 hours = 0; 14 days = 1 death
7000 mg/m3: 4 hours = 0; 14 days = 4 deaths
>= 10000 mg/m3: 4 hours = 10 deaths
LD50 confidence intervals: 5700-8600 mg/m3; slope function 1.27 - Clinical signs:
- other: 5000 mg/m3: none; higher doses: ataxia and coma, dyspnea, piloerection, depression, decreased activity
- Body weight:
- no data
- Gross pathology:
- >= 10000 mg/m3:
- pulmonary congestion - Other findings:
- no other findings
- Conclusions:
- Under the conditions of this study, the acute toxicity of isophorone after inhalative exposure in male rats is very low : the LC50 value was determined to be 7 mg/l.
- Executive summary:
Groups of 10 male rats were exposed to isophorone for 4 hours by whole body exposure. The observation period was 2 weeks. At a concentration of 5000 mg/m3 one animal died after the observation period of 14 days. At a concentration of 7000 mg/m3 40 % of the rats died . At very high concentrations of 10000 and 17800 mg/m3 all animals died within 4 hours. Clinical signs were ataxia and coma, dyspnea, piloerection, depression and decreased activity at doses >= 5000 mg/m3. At necropsy of the high exposure concentrations, congestion of the lungs were observed.
The LC50 value was determined to be 7 mg/l. Therefore, under the conditions of this study the acute toxicity of isophorone after inhalative exposure in rats is very low.
Reference
no remarks
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 7 000 mg/m³ air
- Quality of whole database:
- The study is well documented, meets generally accepted scientific principles, and is acceptable for assessment. Klimisch score 2 (reliable with restrictions)
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1975 - 1976-06-24
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Principles of method if other than guideline:
- Method: based on Draize, modified method
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rabbit
- Strain:
- not specified
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ORGANISMS:
- Weight at study initiation: ca. 2.5 kg
- Controls: yes - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- ADMINISTRATION:
- Occlusion: yes
- Vehicle: none
- Doses: 9.2; 13.85; 23; 23; 32.3 g
absorbed: see Results
- Removal of test substance: after 24 hours, unresorbed quantity determined - Duration of exposure:
- 24 hours
- Doses:
- 600 mg/kg, 750 mg/kg, 1700 mg/kg, 2500 mg/kg and 2850 mg/kg
- No. of animals per sex per dose:
- 6
- Control animals:
- yes
- Details on study design:
- EXAMINATIONS: mortality, clinical signs, skin reaction,
14 days postexposure observation, autopsy - Statistics:
- no data
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 1 200 mg/kg bw
- Mortality:
- - Number of deaths and time at each dose:
9.2 g dose(0.6 +/- 0.4 g/kg absorbed): none
13.85 g dose (0.75 +/- 0.5 g/kg): 2 after 6 and 12 hours, resp.
23 g dose (1.7 +/- 0.9 g/kg): 3 after 3, 4, and 5 hours, resp.
23 g dose (2.85 +/- 1.3 g/kg): 3 after 4, 6, and 48 hours, resp.
32.3 g dose (2.5 +/- 1 g/kg): 6 after 2.5, 4x4, 5 hours, resp. - Clinical signs:
- other: CLINICAL SIGNS: accelerated breathing, prostration, narcosis, death (mostly within 6 hours) or recovery. The intensity of the erythema varied between animals. Recovery of the skin was not always complete within the postexposure period. Doses at which c
- Gross pathology:
- no data
- Other findings:
- - POTENTIAL TARGET ORGANS: none identified (except skin)
- SEX-SPECIFIC DIFFERENCES: none identified - Conclusions:
- Under the conditions of this study, the acute toxicity of isophorone after dermal application to male and female rabbits is moderate: the LD50 value
was determined to be 1200 mg/kg bw. - Executive summary:
The acute dermal toxicity was evaluated by standard acute method. A single application of test item to the intact skin of six female and six male rabbits was made at dosage levels of 600 mg/kg bw to 2850 mg/kg bw for 24 hours.The animals were observed for mortality and any sub-lethal effects for 14 days after application. Isophorone was dermally of moderate acute toxicity. The LD50 value in rabbits was estimated to be 1200 mg/kg bw. Clinical signs were accelerated breathing, prostration and narcosis.
Reference
no remarks
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 1 200 mg/kg bw
- Quality of whole database:
- Test procedure of the study is in accordance with generally accepted scientific standards and described in sufficient detail. Klimisch score 1 (reliable without restriction).
Additional information
Oral
LD50 values of isophorone in rats were 1500 mg/kg bw (Günzel and Richter, Schering AG, 1968), 2100 mg/kg bw (Dutertre-Catella, 1976) and 3450 mg/kg (Esso Research, 1964). The LD50 in mice is 2200 mg/kg bw (Dutertre-Catella, 1976). Clinical signs like general apathy, depression, wearness (leading to coma) ptosis, lacrimation and laboured respiration occured at doses of >= 1450 mg/kg bw (Günzel and Richter, 1968; Dutertre-Catella, 1976; Esso Redearch 1965). At doses of >= 5000 mg/kg bw congestion of lungs, kidneys and pancreas (Esso Research, 1964) and liver lesions (Dutertre-Catella, 1976) were found at necropsy.
Inhalation
In acute inhalation studies isophorone showed very low acute toxicity with LC50 values sometimes exceeding the maximum tested concentrations (LC0 > 3500 mg/m3 and LC50 = 7000 mg/m3; both aerosol) in rats, mice and guinea pigs (Esso Reserach 1964; Esso Research, 1965). Mortality was observed in another study with rats but not guinea pigs at concentrations > 10570 mg/m3 (Smyth and Seaton, 1940). Clincal signs were nose and eye irritation, accelerated, laboured respiration, intestinal peristalsis and coma at dose
>= 5000 mg/m3 (Smyth and Seaton, 1940; Esso Research, 1965). At necropsy of the high exposure concentrations, congestion of the lungs and occasionally observed liver and stomach congestion was found (Esso Research 1965; Smyth and Seaton, 1940).
Dermal
In rats, the LD50 after dermal application was 1700 mg/kg bw (Günzel and Richter, Schering AG, 1968). For rabbits the LD50 values were 1200 mg/kg bw (Dutertre-Catella, 1976) and > 3160 mg/kg bw (Esso Research, 1964). Clinical signs were general apathy, later on occasionally coma, cachexia, tremor, lacrimation (Günzel and Richter, 1968) and depression, accelerated/laboured respiration, sprawling, prostration and narcosis at doses of 3160 mg/kg bw at least. At necropsy uniform thickening of the cutaneous stomach mucosa and pulmonary emphysema, edema or hyperemia was observed.
Justification for selection of acute toxicity – oral endpoint
Among the excisting valid studies the selected study was found to
show the highest toxicity after oral application of isophorone.
Justification for selection of acute toxicity – inhalation endpoint
Among the excisting valid studies the selected study was found to
show the highest toxicity after inhalative application of isophorone.
Justification for selection of acute toxicity – dermal endpoint
Among the excisting valid studies the selected study was found to
show the highest toxicity after dermal application of isophorone.
Justification for classification or non-classification
According to the criteria of CLP Regulation 1272/2008 isophorone is classified as harmful if swallowed (Acute Tox. 4; H302) as well as harmful in contact with skin (Acute Tox. 4; H312).
Based on the result of the acute inhalation studies (Esso Research, 1965; Esso Research; 1964) isophorone has a low acute toxicity if inhaled. Therefore, the test substance must not be classified.
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.
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