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EC number: 261-879-6 | CAS number: 59719-67-4
- 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:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Isobutyraldehyde administered by inhalation (whole body exposure) for up to 13 weeks or two years was a respiratory tract toxicant but was not carcinogenic in F344/N rats and B6C3FI mice.
- Author:
- Abdo, KM, Haseman, JK., Nyska, A.
- Year:
- 1 998
- Bibliographic source:
- Toxicol. Science 42: 136-151
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
- Limit test:
- no
Test material
- Reference substance name:
- Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate
- EC Number:
- 261-879-6
- EC Name:
- Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate
- Cas Number:
- 59719-67-4
- Molecular formula:
- C24H46N4O6
- IUPAC Name:
- bis[2-(2-isopropyl-1,3-oxazolidin-3-yl)ethyl] hexane-1,6-diylbiscarbamate
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: not specified
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 6 weeks
- Weight at study initiation: approx. equal weight
- Fasting period before study: not specified
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not specified
DETAILS OF FOOD AND WATER QUALITY: not specified
ENVIRONMENTAL CONDITIONS: not specified
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- air
- Details on inhalation exposure:
- Vapor was dynamically generated by bubbling nitrogen gas through a column of liquid maintained at a constant temperature in a water bath. Diluting air was added to the nitrogen-isobutyraldehyde vapor immediately above the bubbler to prevent condensation of isobutyraldehyde in the manifold or deliver lines when cooled to room temperature. Inhalation chambers (1.15 cubic meters) of the Rochester design were used. Chamber ventilation provided 12 to 15 clean-air (charcoal and HEPA filtered) changes per hour. A small particle detector was used to ensure that aldehyde vapor and not aerosol was produced. Chamber concentrations were monitored 6 to 14 times per exposure interval with an infrared spectrophotometer, which measured total aldehydes present.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hours per day, 5 days per week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 500 ppm
- Remarks:
- approx. 1.5 mg/L air
- Dose / conc.:
- 1 000 ppm
- Remarks:
- approx. 3 mg/L air
- Dose / conc.:
- 2 000 ppm
- Remarks:
- approx. 6 mg/L air
- Dose / conc.:
- 4 000 ppm
- Remarks:
- approx. 12 mg/L air
- Dose / conc.:
- 8 000 ppm
- Remarks:
- approx. 24 mg/L air
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- In the 13 weeks repeated dose study, B6C3F1 mice were randomized into 5 dose groups (500; 1000; 2000, 4000, 8000 ppm of Isobutyraldehyde) and one control group (air only). The animals were exposed for 6 hours in inhalation chambers for a total of 10 times.
- Positive control:
- no data
Examinations
- Observations and examinations performed and frequency:
- Clinical observations were recorded once per week. Animals were weighed prior to initiation, and then weekly and at the end of the study. Necropsy was performed on all animals. The brain, heart, right kidney, liver, lungs, right testis, and thymus were weighed. Visible lesions and tissues masses were subject to microscopic examination.
- Sacrifice and pathology:
- Complete histopathologic examination was performed on control and 2000 ppm mice.
The following tissues were examined during the gross necropsy. A complete gross necropsy is defined as external examination including body orifices and examination and fixation of these tissues: gross lesions, skin, mandibular lymph node, mammary glands, thigh muscle, sciatic nerve, sternum (including marrow), pancreas, spleen kidneys adrenals, urinary bladder, seminal vesicles, prostate, testes/epididymides/vaginal tunics of the testes and scrotal sac, esophagus, stomach, duodenum, tissue masses or suspect tumors and regional lymph nodes, ileum, colon, cecum, rectum, mesenteric lymph node, liver, costochondral junction (rib), thymus, oral cavity, larynx and pharynx, trachea, lungs and bronchi, heart and aorta, thyroid, parathyroids, ovaries, uterus, nasal cavity and nasal turbinates, jejunum, tongue, brain, pituitary, spinal cord, preputial or clitoral glands, eyes, Zymbal's glands (auditory sebaceous glands), vagina. - Other examinations:
- Hematology, clinical chemistry, sperm morphology and vaginal cytology evaluation
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- One male in the control group, one male in the 1000 ppm group, nine males in the 4000 ppm group, and all males in the 8000 ppm group died before the end of the study as well as all females of the 4000 and 8000 ppm groups.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Final mean body weights and mean body weight gains of male mice were similar to those of the controls. The final mean body weight and mean body weight gain of female mice in the 1000 ppm group were significantly lower than those of the controls.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Kidney weights of males in the 1000 and 2000 ppm groups were increased, liver weights in females in the 1000 ppm and 500 ppm groups were decreased. Thymus weights in females were decreaed in the 2000 and 1000 ppm groups. Because of lack of dose response and the absence of lesions related to exposure to isobutyraldehyde in these organs, these variations in organ weights are not considered to be chemically related.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no gross lesions observed at necropsy that could by associated with isobutyraldehyde exposure.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Increased incidences of non-neoplastic lesions of the nasal cavity were observed in male and female mice exposed to 1000 ppm or greater. These lesions included necrosis, inflammation, hyperplasia, and squamous metaplasia of the epithelium; serous and suppurative exudate within the nasal passages; olfactory epithelial degeneration; and osteodystrophy of the turbinate bone.
- Histopathological findings: neoplastic:
- not examined
Effect levels
open allclose all
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- local
- Effect level:
- 1 500 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- systemic
- Effect level:
- 6 000 mg/m³ air
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- mortality
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 3 000 mg/m³ air
- System:
- respiratory system: upper respiratory tract
- Organ:
- larynx
- nasal cavity
- Treatment related:
- yes
- Dose response relationship:
- yes
Applicant's summary and conclusion
- Conclusions:
- The NOAEC (inhalation) for the read-across substance after repeated exposure to vapour for a period of 13 weeks was determined to be 1500 mg/m3 for local effects and 6000 mg/m3 for systemic effects.
- Executive summary:
The read-across substance was studied for toxicity by exposing male and female B6C3F1 mice. Animals were exposed to vapours 6 h per day, 5 days per week for up to 13 weeks at concentrations of 0, 500, 1000, 2000, 4000, or 8000 ppm corresponding to approx. 1.5, 3, 6, 12, 24 mg/L. One male in the control group, one male in the 1000 ppm group, nine males in the 4000 ppm group, and all males in the 8000 ppm group died before the end of the study as well as all females of the 4000 and 8000 ppm groups. Chemical-related body weight depression and deaths occurred in mice exposed to 4000 and 8000 ppm. Exposure to 8000 ppm or 4000 ppm resulted in necrosis of the epithelium lining of the nasal turbinates. Osteodystrophy of the nasal turbinate bone and squamous metaplasia of the nasal respiratory epithelium were noted in mice exposed 4000 ppm. Degeneration of the olfactory epithelium was noted in males exposed to 2000 ppm and in females exposed to 4000 ppm. The NOAEC was determined to be 1500 mg/m3 (500 ppm) for local effects and 6000 mg/m3 (2000 ppm) for systemic effects.
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