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EC number: 411-280-2 | CAS number: 74091-64-8 MR-8A; MR-N2; NBDI
Toxicological information
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- October 8, 1992 - Novemver 16, 1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Conducted equivalent to OECD 403 and GLP principles.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: TSCA Guideline for Toxicity of Chemicals (1989)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- no
Test material
- Reference substance name:
- 2,5-bis-isocyanatomethyl-bicyclo[2.2.1]heptane
- EC Number:
- 411-280-2
- EC Name:
- 2,5-bis-isocyanatomethyl-bicyclo[2.2.1]heptane
- Cas Number:
- 74091-64-8
- Molecular formula:
- C11H14N2O2
- IUPAC Name:
- (1R,2R,4R,5R)-2,5-bis(isocyanatomethyl)bicyclo[2.2.1]heptane; (1R,2S,4R,5S)-2,5-bis(isocyanatomethyl)bicyclo[2.2.1]heptane; (1S,2R,4S,5R)-2,5-bis(isocyanatomethyl)bicyclo[2.2.1]heptane; (1S,2S,4S,5S)-2,5-bis(isocyanatomethyl)bicyclo[2.2.1]heptane; bis((1r,2R,4s,6S)-2,6-bis(isocyanatomethyl)bicyclo[2.2.1]heptane); bis((1s,2R,4r,6S)-2,6-bis(isocyanatomethyl)bicyclo[2.2.1]heptane)
- Details on test material:
- - Name of test material (as cited in study report): NBDI
- Physical state: liquid
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: Charles River's Laboratory
- Age at study initiation: 6 to 8 weeks
- Housing: individually in stainless steel, wire bottom cages
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 degrees Celsius
- Humidity (%): 55 +/- 15%
- Air changes (per hr):10 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12 hrs
IN-LIFE DATES: From: November 2, 1992 To: November 16, 1992
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- other: unchanged (no vehicle)
- Details on inhalation exposure:
- Similar to the design described by Cannon et al, 1983
(W.C. Cannon et al, The flow-past chamber: an improved nose-only exposure system for rodents, Amer. Ind. Hyg. Assoc., 44(12), p. 923-928, 1983) - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- Nominal concentrations:
0.015 mg/L (measured: 0.016 mg/L)
0.05 mg/L (measured: 0.053 mg/L)
0.1 mg/L (measured: 0.12 mg/L)
0.25 mg/L (measured: 0.24 mg/L)
0.5 mg/L (measured: 0.65 mg/L)
5 mg/L (measured: 4.65 mg/L) - No. of animals per sex per dose:
- 5 male and 5 female rats per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: twice daily
Body weights: day 1, 8 and at necropsy
- Necropsy of survivors performed: yes;
Each necropsy included examination of the external surface of the body; all body orifices; the cranial, thoracic, abdominal and pelvic cavities and their contents; special attention was given to the lungs and upper respiratory tract.
- Other examinations performed: no
Results and discussion
Effect levelsopen allclose all
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 54 mg/m³ air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Sex:
- male/female
- Dose descriptor:
- other: NOAEC (local effects)
- Effect level:
- 16 mg/m³ air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Sex:
- male/female
- Dose descriptor:
- other: LOAEC (local effects)
- Effect level:
- 53 mg/m³ air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: Based on labored respiration, rales and nasal discharge
- Sex:
- male/female
- Dose descriptor:
- other: NOAEC (systemic effects)
- Effect level:
- 16 mg/m³ air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: Based on mortality at next dose level
- Mortality:
- Male: 0.50 mg/L; Number of animals: 5; Number of deaths: 5 Male: 0.25 mg/L; Number of animals: 5; Number of deaths: 5 Male: 0.10 mg/L; Number of animals: 5; Number of deaths: 5 Male: 0.05 mg/L; Number of animals: 5; Number of deaths: 2 Male: 0.015 mg/L; Number of animals: 5; Number of deaths: 0 Female: 0.50 mg/L; Number of animals: 5; Number of deaths: 5 Female: 0.25 mg/L; Number of animals: 5; Number of deaths: 5 Female: 0.10 mg/L; Number of animals: 5; Number of deaths: 5 Female: 0.05 mg/L; Number of animals: 5; Number of deaths: 1 Female: 0.015 mg/L; Number of animals: 5; Number of deaths: 0
- Clinical signs:
- other: Signs of toxicity related to dose levels: - The surviving animals in the 0.05 mg/l dose group were thin in appearance and had a rough coat. - In the higher dose groups all animals had a laboured respiration and red nasal discharge - The animals in the l
- Body weight:
- The body weights of rats exposed to the lowest dose increased throughout the entire study. Effects on the body weight gain were observed at the next dose: body weights were decreased by 8% on day 8 compared to day 1 in male and female rats.
- Gross pathology:
- Effects on organs: The animals in the dose groups with 0.5 and 0.25 mg/l had a
pale discoloration of the lungs.
One animal of the highest dose group had white contents in the left lung.
Any other information on results incl. tables
Treatment-related abnormal clinical signs were observed in all exposure groups, except the lowest dose group. All animals exposed to the lowest dose were clinically normal throughout the entire study period. These signs were thin appearance, rough coat, labored respiration, rales and red nasal discharge.
Applicant's summary and conclusion
- Interpretation of results:
- Category 2 based on GHS criteria
- Conclusions:
- The 4h-LC50: 0.054 mg/L
NOAEC (local effects): 16 mg/m3
LOAEC (local effects): 53 mg/m3 based on labored respiration, rales and nasal discharge
NOAEC (systemic effects): 16 mg/m3
LOAEC (systemic effects): 53 mg/m3 based on a 8% bodyweight reduction between day 1 and day 8 of exposure in the group of males as well as in the group of females (based on the means)
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