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EC number: 207-975-3 | CAS number: 503-74-2
- 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
Isovaleric acid is a relatively strong acid (pKa=4.7; cf. section 4.21) wich is corrosive to the skin. The acute toxicity is, however moderate (oral LD50, rat approx. 2500 mg/kg bw; dermal LD50, rabbit >2000 mg/kg bw; inhalation, rat LC50 >2060 mg/m³).
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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Basic data given: comparable to guideline studies
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: males 184 g ; females 162 g (means)
- Fasting period before study: 15-20 hr - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.5% and 1-2 drops of Chremophore El.
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle:6.8 - 50%
- Amount of vehicle (if gavage): dose volume: 10 mL/kg bw
- Justification for choice of vehicle: aqueous solution of 0.5% CMC
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw - Doses:
- 681, 1000, 1470, 2150, 2610, 3160, 3830, and 5000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- other: not needed
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: daily; weighing: on days 0, 2-4, 7, and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- ca. 2 500 mg/kg bw
- Based on:
- test mat.
- Mortality:
- see table below
- Clinical signs:
- other: Dyspnea, apathy, unkempt fur, and poor condition was seen at 1000 mg/kg bw and above. Cyanosis, atony, unsteady gait was seen at 1470 mg/kg bw and above; narcosis, impaired pain reflexes, trembling, exsiccation and exophthalmia was seen at 2610 mg/kg bw a
- Gross pathology:
- Dead animals: heart: hyperaemic congesting; glandular stomach: haemorrhage, gastritis; intestine: reddened mucosa, injected vessels.
Surviving animals: forestomach: button formation (in groups 1470-3160 mg/kg bw; wall thickened in animals at 215ß-3160 mg/kg bw. No changes in animals at 681-1000 mg/kg bw - Interpretation of results:
- not classified
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The LD50 of isovaleric acid was approx. 2500 mg/kg bw in male and female rats
- Executive summary:
The acute oral toxicity of isovaleric acid was determined in male and female Sprague-Dawley similar to OECD 401 (5 rats/sex; oral gavage; test substance at 681, 1000, 1470, 2150, 2610, 3160, 3830, and 5000 mg/kg bw in 0.5% CMC; observation period 14 days). Signs of toxicity were seen at 1000 mg/kg bw and above in a dose-dependent manner. No deaths occurred at doses up to and including 2150 mg/kg bw, with a steep increase of mortality at higher doses. The LD50was ca. 2500 mg/kg bw for male and female rats. Necropsy revealed lesions in the stomach and intestine that are attributable to the irritating property of the isovaleric acid (BASF, 1980).
The study is considered to be valid and suitable for assessment.
Reference
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 500 mg/kg bw
- Quality of whole database:
- suitable for assessment
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Similar to guideline study. Documentation scarce, but raw data are available upon request
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Principles of method if other than guideline:
- Inhalation risk test
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- not specified
- Vehicle:
- air
- Details on inhalation exposure:
- Air was guided through a 5-cm layer of test material contained in a wash bottle to generate a saturated vapour atmosphere
- Analytical verification of test atmosphere concentrations:
- not specified
- Duration of exposure:
- 7 h
- Concentrations:
- saturated atmosphere
- No. of animals per sex per dose:
- 12 animals
- Dose descriptor:
- LC0
- Effect level:
- 2 060 mg/m³ air
- Exp. duration:
- 7 h
- Remarks on result:
- other: Exposure to saturated atmosphere in Inhalation Risk Test. Effect level (2060 mg/m³) calculated.
- Mortality:
- rats survived inhalation exposure at saturation, exposure period 7 hours
- Conclusions:
- The LC0 was 2060 mg/m³ in this study. All rats (n=12) survived inhalation exposure at saturation, exposure period 7 hours. Slight respiratory tract irritation was noted.
- Executive summary:
Inhalation risk test; similar to guideline (saturation exposure without analytical measurement). The saturation concentration can be calculated (using data from GESTIS: molecular weight 102.13; vapour pressure 0.5 mbar at 20°C; 1 ppm = 3.53 mg/m³). Result: the saturation concentration is 2060 mg/m³, i.e. 584 ppm. All rats (n=12) survived a 7-hr exposure period at the maximum attainable concentration, i.e. the LC0 -value was 2060 mg/m³.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 2 060 mg/m³ air
- Quality of whole database:
- suitable for assessment
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Equivalent to guideline study.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- Vienna White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Gauckler. D-6050 Offebach
- Weight at study initiation: 2-3 kg
- Fasting period before study: no data
- Housing: in stainles steel cages
- Diet: approx. 130 g/animal and day
- Water: approx. 250 mL/animal and day
- Acclimation period: at least 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- semiocclusive
- Vehicle:
- vegetable oil
- Details on dermal exposure:
- TEST SITE
- Area of exposure: 300 cm²
- Type of wrap if used: semiocclusive
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water
- Time after start of exposure: 24 hours
TEST MATERIAL
- Amount(s) applied: 5 mL/kg bw
- Concentration (if solution): 40%
- Constant volume or concentration used: yes
VEHICLE
- Amount(s) applied (volume or weight with unit): 5 mL/kg bw
- Concentration (if solution): 60%
- Purity: olive oil, DAB 9 - Duration of exposure:
- 24 hrs
- Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 3
- Control animals:
- not required
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: at least once per day; weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology of treated skin - Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Remarks on result:
- other: 1/6 animals died within 24 hours
- Mortality:
- One male died during day 1. Necropsy revealed dilatation of the heart and moderate lung edema
- Clinical signs:
- other: none
- Other findings:
- One male died during day 1. Necropsy revealed dilatation of the heart and moderate lung edema.
Sacrificed animals: skin: full thickness necrosis; organs: no pathological findings - Conclusions:
- The dermal LD50 was >2000 mg/kg bw in male and female rabbits.
- Executive summary:
The acute dermal toxicity of isovaleric acid was determined in White Vienna rabbits (3 per sex; semi-occlusive dressing, exposure period 24 hours; dose 2000 mg/kg bw; vehicle: olive oil) using a protocol that was equivalent to OECD 402. The observation period was 14 days. One male died on day 1, all other animals survived without clinical signs of toxicity. At termination, histopathology revealed full thickness necrosis at all treated sites, moderate lung oedema and heart dilatation in the animal that died, no findings in animals that were sacrificed. Hence, the dermal LD50 was >2000 mg/kg bw in rabbits (BASF, 1990).
The study is considered to be valid and suitable for assessment.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- suitable for assessment. Local effects on skin described.
Additional information
The acute oral toxicity of isovaleric acid was determined in male and female Sprague-Dawley similar to OECD 401 (5 rats/sex; oral gavage; test substance at 681, 1000, 1470, 2150, 2610, 3160, 3830, and 5000 mg/kg bw in 0.5% CMC; observation period 14 days). Signs of toxicity were seen at 1000 mg/kg bw and above in a dose-dependent manner. No deaths occurred at doses up to and including 2150 mg/kg bw, with a steep increase of mortality at higher doses. The LD50was ca. 2500 mg/kg bw for male and female rats. Necropsy revealed lesions in the stomach and intestine that are attributable to the irritating property of the isovaleric acid (BASF, 1980).
Rats survived inhalation a 7-hour exposure period at saturation (calculated: 2060 mg/m³ or 584 ppm), indicating a low inhalation hazard. A slight respiratory tract irritation was noted (BASF, 1980).
The acute dermal toxicity of isovaleric acid was determined in White Vienna rabbits (3 per sex; semi-occlusive dressing, exposure period 24 hours; dose 2000 mg/kg bw; vehicle: olive oil) using a protocol that was equivalent to OECD 402. The observation period was 14 days. One male died on day 1, all other animals survived without clinical signs of toxicity. At termination, histopathology revealed full thickness necrosis at all treated sites, moderate lung oedema and heart dilatation in the animal that died, no findings in animals that were sacrificed. Hence, the dermal LD50 was >2000 mg/kg bw in rabbits (BASF, 1990).
Justification for selection of acute toxicity – oral endpoint
Rat study similar to guideline; vehicle: water
Justification for selection of acute toxicity – inhalation endpoint
Inhalation risk test; similar to guideline (saturation exposure without analytical measurement). The saturation concentration can be calculated (using data from GESTIS: molecular weight 102.13; vapour pressure 0.5 mbar at 20°C; 1 ppm = 3.53 mg/m³). Result: the saturation concentration is 2060 mg/m³, i.e. 584 ppm. All rats (n=12) survived a 7-hr exposure period the maximum attainable concentration, i.e. LC0 was 2060 mg/m³.
Justification for selection of acute toxicity – dermal endpoint
Rabbit study similar to guideline. Limit dose: 2000 mg/kg bw
Justification for classification or non-classification
According to regulation EC/1272/2008 no classification is required for the acute oral, inhalation, or dermal toxicity.
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