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EC number: 202-485-6 | CAS number: 96-17-3
- 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
Carcinogenicity
Administrative data
- Endpoint:
- carcinogenicity: inhalation
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Study period:
- 1990-08-16 to 1992-08-19
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to other study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 998
- Reference Type:
- other: study report abstract
- Title:
- Unnamed
- Year:
- 1 999
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- yes
- Remarks:
- only comprehensive pathohistology: focused on non-neoplastic and neoplastic lesions
- GLP compliance:
- yes
Test material
- Reference substance name:
- Isobutyraldehyde
- EC Number:
- 201-149-6
- EC Name:
- Isobutyraldehyde
- Cas Number:
- 78-84-2
- IUPAC Name:
- 2-methylpropanal
- Details on test material:
- - Analytical purity: approx. 98 %
- Impurities (identity and concentrations): Isobutyic acid approx. 1.4 %
- Lot/batch No.: E080289
-Supplier: Texas Eastman Chemicals
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Simonsen Laboratories (Gilroy, CA)
- Age at study initiation: 6 weeks
- Weight at study initiation:
- Fasting period before study: none
- Housing: 1 animal per cage
- Diet: ad libitum, except during exposure
- Water: ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 - 21.8
- Humidity (%): 43 - 66
- Air changes (per hr): 12 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: To:
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- other: air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- The vapor for the 13-week studies was generated by bubbling nitrogen gas through a column of the liquid maintained at a constant temperature in a water bath.
- Exposure apparatus:
Inhalation chambers of the Rochester design were used in the 2-year studies. The total volume for each chamber was 2.3 m3. The chamber ventilation system provided 12 to 15 charcoal- and HEPA-filtered air changes per hour, and the internal design of the chamber afforded equal exposure to each animal. This flow rate was sufficient to maintain proper temperature and humidity, provide a uniform and reproducible test atmosphere, and remove ammonia.
TEST ATMOSPHERE
- Brief description of analytical method used:
The chamber concentrations of isobutyraldehyde in the 2-years studies were monitored 4x/h using an 8-port stream-select valve with two on-line gaschromatographs (HP Model 5840).
Calibration of the gas chromatograph monitoring the exposure chamber was achieved by independent quantitative analysis of grab samples collected with bubblers containing dimethylformamide and an internal standard. Additionally, the gas chromatograph was calibrated by a comparison of grab samples and gravimetrically prepared standards with an offline gas chromatograph. The off-line gas chromatograph was calibrated with gravimetrically prepared standards of isobutyraldehyde in dimethylformamide.
Particulate matter:
A particle detector (Type CN, Gardner Associates) was used with and without animals to ensure that isobutyraldehyde vapour was produced and not aerosol. No particle counts above the minimum resolvable level (approximately 200 particles/cm ) were detected.
- Samples taken from breathing zone: no
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The times for the chamber concentrations to build up to 90% of the final exposure concentrations (T90) and to decay to 10% of the exposure concentrations (T10) were measured in the 2-year studies with and without animals present in the chambers. At a chamber airflow rate of 15 air changes per hour, the theoretical value for both T90 and T 10 is approximately 12 to 13 minutes; the T90 value chosen for all studies was 12 minutes. The uniformity of isobutyraldehyde concentrations in the exposure chambers was measured.
Uniformity of exposure concentrations in all chambers was acceptable. The persistence of isobutyraldehyde in the 2,000 ppm exposure chamber after shutting off the system was monitored during the 2-year studies, with and without animals present. The concentration of isobutyraldehyde in the exposure chambers fell to less than 1% of the beginning concentration within less than 30 minutes in all cases. - Duration of treatment / exposure:
- 105 weeks
- Frequency of treatment:
- 5 days/week, 6 h/day
- Post exposure period:
- none
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 500, 1000 or 2000 ppm (1.5, 3, and 6 mg/L)
Basis:
nominal conc.
confirmed by regular analysis
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: based on 90-d study (see NTP 1999a)
- Rationale for animal assignment (if not random):
- Rationale for selecting satellite groups:
- Post-exposure recovery period in satellite groups:
- Section schedule rationale (if not random):
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 2x/d
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: recorded at 4-weeks intervals until week 91 and every two weeks thereafter.
BODY WEIGHT: Yes
- Time schedule for examinations: initially, weekly for 12 weeks, monthly therafter until week 91 and then every two weeks and end of the study.
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (Appendices A - D)
HISTOPATHOLOGY: Yes (Appendices A - D) - Statistics:
- The probability of survival was estimated by the product-limit procedure of Kaplan and Meier (1958). The primary statistical method used for the evaluation of tumor incidence was logistic regression analysis (Dinse and Lagakos, 1983; Dinse and Haseman, 1986; McKnight and Crowley, 1984). Additional methods used included the life table test (Cox, 1972; Tarone, 1975), appropriate for rapidly lethal neoplasms, and the Fisher exact test and the Cochran-Armitage trend test (Armitage, 1971; Gart et aL, 1979). Tests of significance included pairwise comparisons of each exposed group with controls and a test for an overall dose-related trend. (see NTP 1999, p. 25).
Results and discussion
Results of examinations
- Details on results:
- Survival and Body Weight:
No differences in survival rates between exposed and chamber control rats were found. The mean body weights of male and female rats were generally similar to those of the chamber controls throughout the study.
Clinical signs: No clinical findings that could be attributed to isobutyraldehyde exposure were observed.
Pathology Findings:
No increase in neoplasm incidences that could be attributed to exposure to isobutyraldehyde was observed in male or female rats.
However three primary nasal neoplasms were observed in male and female rats exposed to isobutyraldehyde. One polypoid adenoma was present in the anterior nose section of a male rat exposed to 1000 ppm, one adenoma of the vomeronasal organ was noted in a 2000 ppm male, and an undifferentiated malignant neoplasm, classified as a sarcoma (mesenchymal origin), was present in the most posterior section of the nose in a 500 ppm (NTP 1999, Tab. 7).
Non-neoplastic lesions related to isobutyraldehyde exposure were limited to the nose and consisted of squamous metaplasia of the respiratory epithelium, degeneration of the olfactory epithelium, and suppurative inflammation. Incidences of minimal to mild squamous metaplasia in 1000 and 2000 ppm males (10/49 and 44/50, respectively) and females (9/49 and 44/50, respectively) and in 500 ppm females (11/50) were significantly greater than those in the chamber controls (1/50, 1/49). Minimal to mild degeneration of the olfactory epithelium occurred in the 2000 ppm males and females (44/50 and 45/50, respectively, vs. no occurrences in controls). Incidences of suppurative inflammation (rhinitis) in both sexes exposed to 2000 ppm were increased (15/50 and 11/50, respectively) compared to controls (5/50 and 2/49).
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 2 000 ppm
- Sex:
- male/female
- Basis for effect level:
- other: overall effects Histopathology: local (nasopharyngeal) and other tissue and organ tumours
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
- Dose descriptor:
- NOAEC
- Effect level:
- < 500 ppm
- Sex:
- female
- Basis for effect level:
- other: overall effects Histopathology: Incidences of minimal to mild squamous metaplasia in 500 ppm females (11/50) were significantly greater than those in the chamber controls (1/50, 1/49).
- Remarks on result:
- other: Effect type: toxicity (migrated information)
- Dose descriptor:
- LOAEC
- Effect level:
- 500 ppm
- Sex:
- female
- Basis for effect level:
- other: overall effects Histopathology: Incidences of minimal to mild squamous metaplasia in 500 ppm females (11/50) were significantly greater than those in the chamber controls (1/50, 1/49).
- Remarks on result:
- other: Effect type: toxicity (migrated information)
- Dose descriptor:
- NOAEC
- Effect level:
- 2 000 ppm
- Basis for effect level:
- other: overall effects Survival; body weight; organ weights; histology (systemic effects)
- Remarks on result:
- other: Effect type: toxicity (migrated information)
Any other information on results incl. tables
NTP 1999 (excerpt Table 7): see below Attached Background Material
[Doc name: NTP1999_Tab7_rat-carcinogenicity]
_________________________________________________________________________________
Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Isobutyraldehyde
|
Male |
Female |
Concentrations |
Chamber control, 500, 1,000, or 2,000 ppm |
Chamber control, 500, 1,000, or 2,000 ppm |
Body weights |
Exposed groups similar to chamber control groups |
Exposed groups similar to chamber control groups |
Survival rates |
12/50, 15/50, 11/50, 10/50 |
27/50, 24/50, 24/50, 32/50 |
Nonneoplastic |
Nose: respiratory epithelium squamous metaplasia (1/50, 1/49, 10/49, 44/50); suppurative inflammation (5/50, 3/49, 6/49, 15/50); olfactory epithelium degeneration (0/50, 0/49, 3/49, 44/50); |
Nose: respiratory epithelium squamous metaplasia (1/49, 11/50, 9/49, 44/50); suppurative inflammation (2/49, 3/50, 5/49, 11/50); olfactory epithelium degeneration (0/49, 0/50, 2/49, 45/50); |
Neoplastic effects |
None |
None |
Level of evidence of carcinogenic activity |
No evidence |
No evidence |
(from NTP1999 TR-472 Abstract-Summary)
Applicant's summary and conclusion
- Conclusions:
- Isobutanal was not cancerogenic in rats after long-term inhalation. The NTP peer review panel concluded: no evidence of carcinogenity in rats and mice.
- Executive summary:
In a 2-years oncogenicity study, male and female Fischer 344 rats were exposed to 1.5, 3 and 6 mg/L isobutanal (measured) 5 d/wk and 6 h/d. There were no significant increases in the incidences of any tumour type that may have been related to the treatment. In particular, no tumours of the respiratory tract were observed. Local adverse effects were produced: Incidences of minimal to mild squamous metaplasia in 1000 and 2000 ppm males (10/49 and 44/50, respectively) and females (9/49 and 44/50, respectively) and in 500 ppm females (11/50) were significantly greater than those in the chamber controls (1/50, 1/49).
No local NOAEC(105 wk) could be established due to histological changes of the nasal region in females at 500 ppm (1.5 mg/L). The LOAEC is considered 500 ppm (1.5 mg/L). The NOAEC for systemic effects was 2000 ppm (6 mg/L).
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