Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 908-998-8 | CAS number: -
- 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

Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1991
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: publication with acceptable reporting
Data source
Reference
- Reference Type:
- publication
- Title:
- Isopropanol 13-week vapor inhalation study in rats and mice with neurotoxicity evaluation in rats
- Author:
- Burleigh-Flayer HD, Gill MW, Strother DE, Masten LW, McKee RH, Tyler TR, Gardiner T
- Year:
- 1 994
- Bibliographic source:
- Fundam. Appl. Toxicol. 23:421-428
- Report date:
- 1994
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- no
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Propan-2-ol
- EC Number:
- 200-661-7
- EC Name:
- Propan-2-ol
- Cas Number:
- 67-63-0
- Molecular formula:
- C3H8O
- IUPAC Name:
- propan-2-ol
- Details on test material:
- The substance was identified by chemical name and CAS number.
Constituent 1
Test animals
- Species:
- other: rat and mouse
- Strain:
- other: Fischer 344 rats and CD®-1 mice
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Source: Fischer 344 rats from Harlan Sprague-Dawley, Inc. (Indianapolis, IN); CD®-1 mice from Charles River Breeding Laboratories, Inc. (Portage, MI).
- Age at study initiation: rats: 8-12 weeks; mice: 8-10 weeks
- Weight at study initiation: male rats: 140-165 g; female rats: 112-130 g; male mice: 25-37 g; female mice: 19-26 g
- Fasting period before study: not reported
- Housing: individually in stainless steel, wire-mesh cages (15 cm x 22 cm x 18 cm for rats; 22.5 cm x 9.5 cm x 12.5 cm for mice); during exposure, animals were individually housed, separated by sex and exposure group, in stainless steel, wire-mesh cages (14.5 cm x 9.5 cm x 17.5 cm or 17.5 cm x 12 cm x 18 cm for rats, and 7.5 cm x 9.5 cm x 17.5 cm for mice).
- Diet (e.g. ad libitum): powdered food (Certified Rodent Chow 5002, Ralston Purina Co., St. Louis, MO) ad libitum
- Water (e.g. ad libitum): water (Municipal Authority of Westmoreland County, Greensburg, PA) ad libitum
- Acclimation period: animals were acclimated to the exposure chambers (air-only exposure) on 2 days prior to the initiation of the exposure regimen
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24 °C
- Humidity (%): 52-56 %
- Air changes (per hr): 13.5 per hr (in inhalation chamber)
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: no vehicle
- Details on inhalation exposure:
- The volume of each chamber was approximately 1330 liters, and the airflow was approximately 300 liters/minute (13.5 air changes per hour).
Temperature and relative humidity measurements were recorded at least 12 times per exposure.
Animals were acclimated to the exposure chambers (air-only exposure) for 2 days prior to the initiation of the exposure regimen. Target isopropanol vapor concentrations of 0 (control), 100, 500, 1500, and 5000 ppm were selected for this study. The rats (55 days of age) and mice (56 days of age) were exposed for 6 hours per day, 5 days per week for 13 weeks. During the 14th week, male and female rats (excluding those animals designated for neuroanatomic pathology evaluation) received 2 and 3 consecutive days of exposure, respectively. The 10 female rats of the 500, 1500, and 5000 ppm group designated for neuroanatomic pathology evaluation were exposed for 1 day during the 14th week; the male rats of the 500, 1500, and 5000 ppm group designated for neuroanatomic pathology evaluation were not exposed during the 14th week. Male and female mice received 4 and 5 consecutive days of exposure during the 14th week, respectively. Control (air-only exposure) animals were handled in an identical manner as the isopropanol-exposed animals.
Liquid isopropanol was metered from a piston pump (Fluid Metering, Inc., Oyster Bay, NY) into a glass evaporator similar in design to that described by Snellings and Dodd (1990). Piston pumps were equipped with a 1/8'' piston (G-6 FMI pump), 1/4" piston (C-6 FMI pump), 3/8" piston (C-6 FMI pump) and 1/4" piston (G-20 FMI pump) for the 100, 500, 1500 and 5000 ppm exposure chambers, respectively. The temperature in the evaporator was maintained at a level sufficient to vaporize the test substance - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Chamber concentrations of isopropanol vapor were analyzed by flame ionization gas chromatography. At least 2 samples per hour were obtained from each exposure chamber and also the control chamber.
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hours per day, 5 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 ppm (nominal)
- Dose / conc.:
- 500 ppm (nominal)
- Dose / conc.:
- 1 500 ppm (nominal)
- Dose / conc.:
- 5 000 ppm (nominal)
- No. of animals per sex per dose:
- All exposure groups (except for the 100 ppm group) consisted of 10 rats/sex. An additional 15 rats/sex were assigned to the 0, 500, 1500, and 5000 ppm groups for assessment of neurobehavioral function.
- Control animals:
- yes, sham-exposed
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: during exposures, observations were recorded on a group basis. Preceding and following each exposure, animals were examined individually, and observations were recorded for each animal exhibiting overt clinical signs
BODY WEIGHT: Yes
- Time schedule for examinations: All rats and mice were weighed on Week 0 (prior to the start of exposures). These values were used as the preexposure reference weights and were subtracted from each subsequent weight to determine the change in body weight. Animals were weighed weekly during the study, at neurobehavioral evaluations, and immediately preceding sacrifice.
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Weekly. For rats, food consumption was determined over a 7-day period. For mice, food consumption was measured over a 6-day period rather than a 7-day period due to excessive food spillage during the first 24 hours after the containers were filled with fresh food
WATER CONSUMPTION: Yes
- Time schedule for examinations: Weekly.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: During the 6th week of the study in 10 rats/sex/group. At sacrifice in 10 rats/sex/group and 10 mice/sex/group.
- Anaesthetic used for blood collection: Yes (methoxyflurane)
- Animals fasted: Yes
- How many animals: 10 rats/sex/group during the 6th week; 10 rats/sex/group and 10 mice/sex/group at sacrifice
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at sacrifice
- Animals fasted: Yes
- How many animals: 10 rats/sex/group and 10 mice/sex/group
NEUROBEHAVIOURAL EXAMINATION: Yes (rats only)
- Time schedule for examinations: 10/15 rats selected were evaluated with the functional observational battery (FOB) prior to the first exposure and on the weekend following Weeks 1, 2, 4, 9, and 13. Motor activity evaluations were conducted on all 15 rats per sex selected from the 0, 500, 1500, and 5000 ppm groups prior to the first exposure and on the weekend following Weeks 4, 9, and 13.
- Dose groups that were examined: 15 rats per sex from each group - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Organ Weights: The brain, liver, lungs, kidneys, adrenals, testes (males), and ovaries (females) from all surviving animals (except animals designated for neuroanatomic pathology evaluation) were weighed at sacrifice. - Statistics:
- The data for continuous, parametric variables were intercompared for the exposure and control groups by use of Levene's test for homogeneity of variances, by analysis of variance, and by t-tests. The t-tests were used, if the analysis of variance was significant, to delineate which groups differed from the control group. If Levene's test indicated homogeneous variances, the groups were compared by an analysis of variance for equal variances followed, when appropriate, by pooled variance t-tests. If Levene's test indicated heterogeneous variances, the groups were compared by an analysis of variance for unequal variance followed, when appropriate, by separate variance t-tests. Frequency data, such as microscopic diagnoses, were compared using Fisher's exact test. All statistical tests, except the frequency comparisons, were performed using BMDP Statistical Software (Dixon, 1985). The frequency data tests are described in Biometry (Sokal and Rohlf, 1969). The probability value of p < 0.05 (two-tailed) was used as the critical level of significance for all tests.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Ophthalmological findings:
- effects observed, treatment-related
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
Effect levels
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 5 000 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- organ weights and organ / body weight ratios
- Remarks on result:
- other: Based on elevated liver weight and hyaline droplets in kidneys. However, these effects are unspecific and a clear NOAEC is not derivable
Target system / organ toxicity
- Key result
- Critical effects observed:
- not specified
- Organ:
- kidney
- liver
Any other information on results incl. tables
- Clinical signs:
In rats, clinical signs observed following exposures included swollen periocular tissue (females) at the highest dose and perinasal encrustation (males) at 500 ppm and above.
- Behaviour:
Narcosis was observed in a few animals of both species during exposure to 5000 ppm and possibly 1500 ppm as well. However, the animals became tolerant to the narcotic effects of isopropanol after week 2. No neurobehavioral changes were observed in any parameters of the functional observational battery. However, increased motor activity was noted at week 9 of exposure in female rats of the 5000 ppm group.
- Body weight/body weight gain:
After an initial drop in body weight gain in the first week of exposure at the high dose (5000 ppm), rats in the 1500 and 5000 ppm groups had significant increases in body weight gain and/or body weight throughout most of the exposure period. But only the 5000 ppm group had greater than 10% body weight gain compared to controls. Increases in body weight and body weight gain greater than 10% were also noted in female mice in the 5000 ppm group.
- Haematology/clinical chemistry:
Consistent clinical pathology changes included an increase in mean corpuscular volume (rats; female mice) and mean corpuscular hemoglobin (male rats; female mice) at the 5000 ppm exposure level. Other changes noted include a slight anemia in rats at week 6 only and a slight dehydration in female mice at the end of the study.
- Organ weight:
Relative liver weight in rats was elevated no more than 8% in the 5000 ppm groups. However, a 10 and 21% increase in relative liver weight was observed in female mice at 1500 and 5000 ppm, respectively.
Macroscopy:
No gross lesions were observed in any organs.
- Histopathology:
The only microscopic change observed was hyaline droplets within kidneys of all male rats. This change was not clearly concentration related, although it was most pronounced in the 5000 ppm group.
Applicant's summary and conclusion
- Conclusions:
- Based on the observed effects after inhalation exposure to 110, 500, 1500 or 5000 ppm isopropanol for 13 weeks no clear NOAEC is derivable. However, since effects on liver and kidneys of unclear relevance are reported the NOAEC might be set at 5000 ppm.
- Executive summary:
Repeated exposure to isopropanol for 13 weeks produced effects at the highest concentration (5000 ppm) and a kidney change of unknown biological signifiance. Clinical signs of toxicity on the central nervous system (including ataxia, narcosis, ) are acute effects and not relevant for limit value determination for repeated dose systemic effects. Increases in absolute body weight and body weight gain, and changes in hematology parameters in animals exposed to 1500 and 5000 ppm of isopropanol, increased relative liver weight in rats exposed to 5000 ppm, as well as increased motor activity for female rats in the 5000 ppm group have been observed.
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.

EU Privacy Disclaimer
This website uses cookies to ensure you get the best experience on our websites.