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EC number: 500-687-1 | CAS number: 162303-51-7
- 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
Developmental toxicity / teratogenicity
Some information in this page has been claimed confidential.
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- A robust study summary including evaluation of all possible parameters for developmental toxicity study. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- A robust study summary including evaluation of all possible parameters for developmental toxicity study. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the hazardous degradation product (alcohol) released from the target substance. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance, which might change the hazardous properties of the target substance compared to the properties of the pure alcohol. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across data from the degradation product (relevant alcohol) to evaluate irritation, sensitization and the short term and long-term toxicological effects and mutagenicity of the target substance.
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- Groups of approximately 15 Sprague-Dawley rats were exposed at 8000, 6000, 3500, or 0 ppm n-butanol, for 7 hr/day on Gestation Days 1- 19 (sperm = 0). The highest concentration was selected to produce maternal toxicity. Dams were sacrificed on Gestation Day 20, and fetuses were individually weighed, tagged, and examined for external malformations. One-half of the fetuses were stained and examined for skeletal abnormalities, and the other half were examined for visceral defects using the Wilson technique
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Charles River breeding laboratories, Wilmington, MA
- Weight at study initiation: Female (176-200) and male (300 g)
- Housing: 32×41×18 cm stainless steel wire mesh cages for all animals except female with sperm placed in 30×34×17 cm poly carbonate cages having autoclavable polyester filter covers.
- Water (e.g. ad libitum): Purina or NIH-07 Lab chow
- Acclimation period: 1-2 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2
- Humidity (%): 50 ± 10
- Photoperiod (hrs dark / hrs light): 12 hr - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Hinners type exposure chamber
- Method of holding animals in test chamber:
- Source and rate of air: heated compressed air was introduced through the second inlet of the three way valve.
- Air change rate: one change per min.
- System of generating particulates/aerosols: vapor generation equipement were housed above the exposure chamber in glove boxes which were maintain under negetive pressure
TEST ATMOSPHERE
- Brief description of analytical method used: Concentration with in the chamber was monitored by Infra red analyzer which was calibrated with in the range.
-Sample of bulk chemical were analyzed by Gas chromatography for purity.
-For independent verification of chamber concentration sample were collected by charcoal tube from chamber atmoshphere
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration within the chamber was monitored continuously with a Miran 1 A general-purpose infrared analyzer
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage:1
- Proof of pregnancy:vaginal plug and/or sperm in vaginal smear referred to as [day 0] of pregnancy
: - Duration of treatment / exposure:
- 7 hrs/day exposure were given to pregnant females from gestation days 1 to 19
- Frequency of treatment:
- 7 h/d
- Duration of test:
- until day 20 of gestation
- No. of animals per sex per dose:
- 15-18 females per group
- Control animals:
- yes
- Details on study design:
- Dose selection rationale: The doses were selected based on the results of an initial pilot study. For the teratology phase, the high concentration was selected to be maternally toxic, but not lethal, and two lower concentrations were included.
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: not specified
- Cage side observations: not specified
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: not specified
BODY WEIGHT: Yes
- Time schedule for examinations: Maternal weights were measured on Gestation Days 0, 7, 14, and 20. Females were also weighed each morning for the first week of exposure.
FOOD CONSUMPTION: Yes
Weekly food intake was measured on Gestation Days 0, 7, 14, and 20.
WATER CONSUMPTION: Yes
- Time schedule for examinations: Water intake was measured on Gestation Days 0, 7, 14, and 20.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: uterus with ovaries attached, no futher organs specified - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [half per litter]
- Head examinations: No data - Statistics:
- For maternal data multivariate analysis was used for weight comparisions across groups. A kruskal wallis test for group comaparision of corpora lutea per animal. for fetal data, analysis of variance (ANOVA) was used to compare fetal weight and fisher's exact test used for variables including skeletal variations and visceral malformation
- Indices:
- no data
- Historical control data:
- no data
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
The highest concentration of 1 butanol (8000 ppm) produced mortality in 2 of 18 rats. Food consuption was reduced in both at 6000 and 8000 ppm. The number of corpora leutea was not affected (shown in picture attched below). - Dose descriptor:
- NOAEL
- Effect level:
- 10 800 mg/m³ air
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Reduction in fetal weights at 6000 and 8000 ppm and a slight increase in skeletal malformations at 8,000 ppm were observed in offspring. - Dose descriptor:
- NOAEL
- Effect level:
- 10 800 mg/m³ air
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Groups of approximately 15 pregnant Sprague-Dawley rats were exposed via inhalation to 0, 3500, 6000 or 8000 ppm (0, 10 800, 18 500, 24 700 mg/m3) of n-butanol for 7 hours/ day from gestation Day 1 - 19. The NOAEL for maternal animals was 10 800 mg/m3 and the NOAEL for offspring was 10 800 mg/m3.
- Executive summary:
n-Butanol concentration of 24 700 mg/m3 produced narcosis in approximately one-half of the dams. No behavioral effects were noted at 18 500 mg/m3 n-butanol. Reduction in fetal weights at 18 500 mg/m3 and 24 700 mg/m3 and a slight increase in skeletal malformations at 24 700 mg/m3 were observed in offspring. The high dose (24 700 mg/m3) was also toxic to the dams (reduced weight gain; two deaths). Feed consumption was decreased in the 18 500 mg/m3 and 24 700 mg/m3 n-butanol exposed dams. No such effect was observed following similar exposures at 10 800 mg/m3 n-butanol. The NOAEL for maternal animals was 10 800 mg/m3 and the NOAEL for offspring was 10 800 mg/m3 (based on slight decrease in fetal weight at 18 500 mg/m3).
This value is used as weight of evidence in hazard assessment.
Read-across justifications and data matrices are presented in IUCLID section 13.
Data source
Reference
- Reference Type:
- publication
- Title:
- Lack of selective developmental toxicity of three butanol isomer administered by inhalation to rats
- Author:
- Nelson B.K., Brightwell W.S., Khan A., Burg J. R., Goad P.T.
- Year:
- 1 989
- Bibliographic source:
- Fundamental and applied toxicology vol 12, Page no. 469-479
Materials and methods
- Principles of method if other than guideline:
- Groups of approximately 15 Sprague-Dawley rats were exposed at 8000, 6000, 3500, or 0 ppm n-butanol, for 7 hr/day on Gestation Days 1- 19 (sperm = 0). The highest concentration was selected to produce maternal toxicity. Dams were sacrificed on Gestation Day 20, and fetuses were individually weighed, tagged, and examined for external malformations. One-half of the fetuses were stained and examined for skeletal abnormalities, and the other half were examined for visceral defects using the Wilson technique
- GLP compliance:
- no
Test material
- Reference substance name:
- Butan-1-ol
- EC Number:
- 200-751-6
- EC Name:
- Butan-1-ol
- Cas Number:
- 71-36-3
- Molecular formula:
- C4H10O
- IUPAC Name:
- 1-Butanol
- Details on test material:
- - Name of test material (as cited in study report): 1-butanol
- Analytical purity: 99%
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source:Charles River breeding laboratories, Wilmington, MA
- Weight at study initiation: Female (176-200) and male (300 g)
- Housing: 32×41×18 cm stainless steel wire mesh cages for all animals except female with sperm placed in 30×34×17 cm poly carbonate cages having autoclavable polyester filter covers.
- Water (e.g. ad libitum): Purina or NIH-07 Lab chow
- Acclimation period: 1-2 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2
- Humidity (%): 50 ± 10
- Photoperiod (hrs dark / hrs light): 12 hr
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Hinners type exposure chamber
- Method of holding animals in test chamber:
- Source and rate of air: heated compressed air was introduced through the second inlet of the three way valve.
- Air change rate: one change per min.
- System of generating particulates/aerosols: vapor generation equipement were housed above the exposure chamber in glove boxes which were maintain under negetive pressure
TEST ATMOSPHERE
- Brief description of analytical method used: Concentration with in the chamber was monitored by Infra red analyzer which was calibrated with in the range.
-Sample of bulk chemical were analyzed by Gas chromatography for purity.
-For independent verification of chamber concentration sample were collected by charcoal tube from chamber atmoshphere
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration within the chamber was monitored continuously with a Miran 1 A general-purpose infrared analyzer
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage:1
- Proof of pregnancy:vaginal plug and/or sperm in vaginal smear referred to as [day 0] of pregnancy
: - Duration of treatment / exposure:
- 7 hrs/day exposure were given to pregnant females from gestation days 1 to 19
- Frequency of treatment:
- 7 h/d
- Duration of test:
- until day 20 of gestation
- No. of animals per sex per dose:
- 15-18 females per group
- Control animals:
- yes
- Details on study design:
- Dose selection rationale: The doses were selected based on the results of an initial pilot study. For the teratology phase, the high concentration was selected to be maternally toxic, but not lethal, and two lower concentrations were included.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: not specified
- Cage side observations: not specified
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: not specified
BODY WEIGHT: Yes
- Time schedule for examinations: Maternal weights were measured on Gestation Days 0, 7, 14, and 20. Females were also weighed each morning for the first week of exposure.
FOOD CONSUMPTION: Yes
Weekly food intake was measured on Gestation Days 0, 7, 14, and 20.
WATER CONSUMPTION: Yes
- Time schedule for examinations: Water intake was measured on Gestation Days 0, 7, 14, and 20.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: uterus with ovaries attached, no futher organs specified - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [half per litter]
- Skeletal examinations: Yes: [half per litter]
- Head examinations: No data - Statistics:
- For maternal data multivariate analysis was used for weight comparisions across groups. A kruskal wallis test for group comaparision of corpora lutea per animal. for fetal data, analysis of variance (ANOVA) was used to compare fetal weight and fisher's exact test used for variables including skeletal variations and visceral malformation
- Indices:
- no data
- Historical control data:
- no data
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
The highest concentration of 1 butanol (8000 ppm) produced mortality in 2 of 18 rats. Food consuption was reduced in both at 6000 and 8000 ppm. The number of corpora leutea was not affected (shown in picture attched below).
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- 10 800 mg/m³ air
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Reduction in fetal weights at 6000 and 8000 ppm and a slight increase in skeletal malformations at 8,000 ppm were observed in offspring.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 10 800 mg/m³ air
- Based on:
- test mat.
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Read-across justifications and data matrices are presented in IUCLID section 13.
Applicant's summary and conclusion
- Conclusions:
- Groups of approximately 15 pregnant Sprague-Dawley rats were exposed via inhalation to 0, 3500, 6000 or 8000 ppm (0, 10 800, 18 500, 24 700 mg/m3) of n-butanol for 7 hours/ day from gestation Day 1 - 19. The NOAEL for maternal animals was 10 800 mg/m3 and the NOAEL for offspring was 10 800 mg/m3.
- Executive summary:
n-Butanol concentration of 24 700 mg/m3 produced narcosis in approximately one-half of the dams. No behavioral effects were noted at 18 500 mg/m3 n-butanol. Reduction in fetal weights at 18 500 mg/m3 and 24 700 mg/m3 and a slight increase in skeletal malformations at 24 700 mg/m3 were observed in offspring. The high dose (24 700 mg/m3) was also toxic to the dams (reduced weight gain; two deaths). Feed consumption was decreased in the 18 500 mg/m3 and 24 700 mg/m3 n-butanol exposed dams. No such effect was observed following similar exposures at 10 800 mg/m3 n-butanol. The NOAEL for maternal animals was 10 800 mg/m3 and the NOAEL for offspring was 10 800 mg/m3 (based on slight decrease in fetal weight at 18 500 mg/m3).
This value is used as weight of evidence in hazard assessment.
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.
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