Registration Dossier

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:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: TSCA Guideline for Toxicity of Chemicals (1989)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): NBDI
- Physical state: liquid

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals 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:
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 lowest dose group had no clinical abnormalities.
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)