Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Remarks:
The study was conducted according to the guideline in effect dated 1981.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 84%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 8 weeks old;
- Weight at study initiation: male rats 254 - 314 grams; female rats 196 - 223 grams
- Fasting period before study: not reported
- Housing: individually in solid bottom caging with bedding
- Diet (e.g. ad libitum): ad libitum, except during exposure
- Water (e.g. ad libitum): ad libitum, except during exposure
- Acclimation period: 6 days prior to testing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26ºC
- Humidity (%): 30-70%
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass (cylindrical) chamber with a baffle inside the chamber to promote uniform chamber distribution of the test atmosphere
- Exposure chamber volume: Nominal internal volume of 34 L
- Method of holding animals in test chamber: Individually restrained in perforated stainless steel cylinders with conical nose pieces, that were inserted into a polymethylmethacrylate faceplate attached to the exposure chamber so that the nose of each animal extended into the exposure chamber.
- Source and rate of air: High-pressure air, metered into the nebulizer by a mass flow controller, carried the resulting atmosphere into the exposure chamber at 13 mg/m³ chamber aerosol concentration. Chamber airflow was at least 10 air changes/hour.
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: Atmospheres were generated by nebulizer; the test substance was metered into the nebulizer with a syringe infusion pump.
- Method of particle size determination: Cyclone preseparator/cascade impactor and constant flow air sampler
- Treatment of exhaust air: A scrubber with water followed by an MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood
- Temperature, humidity, pressure in air chamber: 20-24°C, 30-70%, not reported

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric analysis at least 4 times in the test chambers and once during the air-only exposure.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
13, 100 and 5200 mg/m³
No. of animals per sex per dose:
low and middle doses had 3 per sex and high dose group had 5 per sex
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 2 - 14 days
- Frequency of observations: mortality and response to alerting stimuli 3 times during each exposure and observed for mortality and clinical signs of toxicity immediately after they were removed from the restrainers following exposure. During the recovery period, all rats were observed each day for mortality.
- Frequency of weighing: weighed and observed for clinical signs of toxicity on the day following exposure and at least twice more during the recovery period
- Necropsy of survivors performed: yes
- Other examinations performed: Respiratory tract tissues (lung, larynx/pharynx, trachea, and nose) from the 0, 13, and 100 mg/m³ groups were evaluated microscopically. There were no microscopic examinations of rats in the 5200 mg/m³ exposure group.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 200 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: highest concentration tested. Mass median aerodynamic diameter (MMAD) of particles had a geometric mean of 1.7-2.7 µm.
Mortality:
none
Clinical signs:
other: There were no clinical signs of toxicity observed during any exposure in this study. Immediately following the 100 mg/m³ exposure, all rats displayed red nasal discharge. Red discharge around the eyes, nose and mouth were observed in all rats immediately
Body weight:
Some minor body weight losses were observed in male and female rats in the 0, 13 and 100 mg/m³ exposure groups. Since the body weight losses in the 13 and 100 mg/m³ exposure groups were similar to that of the control rats, these body weight losses are not considered toxicologically significant. Rats in the 5200 mg/m³ exposure group lost from 2.5 to 6.8% of their original body weight for one or 2 days post exposure.
Gross pathology:
There were no gross observations noted during necropsy.
Other findings:
- Histopathology: There were no test substance-related microscopic findings ( lung, larynx/pharynx, trachea, and nose) in rats in the 0, 13 and 100 mg/m³ exposure groups. No microscopic examination was performed at 5200 mg/m³.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LC50 > 5200 mg/m³
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

One group of 5 male and 5 female rats was exposed to an aerosol atmosphere containing 5200 mg/m³ of the test substance in air to determine the inhalation median lethal concentration (LC50). Two groups of 3 male and 3 female rats each were exposed to 13 and 100 mg/m³ the test substance in air to evaluate respiratory tract pathology. As a control for the pathology evaluation, an additional group of one male and one female rat was exposed to air only. All rats were exposed nose-only for a single 4-hour period. Aerosol atmospheres were generated by nebulization, and concentrations of the test substance were measured by gravimetric analysis. The ammonia vapor concentration was monitored with Draeger tubes. The ammonia concentration measured during the 0 and 13 mg/m³ exposures was less than 1 ppm. During the 100 and 5200 mg/m³ exposures the ammonia concentrations were 21 ppm and 960 ppm, respectively. Rats in the 0, 13, and 100 mg/m³ exposure groups were weighed and observed for clinical signs of toxicity during a 2-day recovery period. The rats in the 5200 mg/m³ exposure group were weighed and observed for clinical signs of toxicity during a 14-day recovery period. Gross examinations were performed on all rats, and respiratory tract tissues (lung, larynx/pharynx, trachea, and nose) from the 0, 13, and 100 mg/m³ groups were evaluated microscopically. There were no microscopic examinations of rats in the 5200 mg/m³ exposure group. No deaths occurred in any exposure group. There were no clinical signs of toxicity observed during any exposure in this study. Immediately following the 100 mg/m³ exposure, all rats displayed red nasal discharge. Red discharges around the eyes, nose and mouth were observed in all rats immediately after the 5200 mg/m³ exposure. Rats from the 5200 mg/m³ exposure group also displayed red-stained faces and/or heads for up to 2 days post exposure. Other than the stains and discharges noted immediately after the 100 and 5200 mg/m³ exposures, there were no other toxicologically significant clinical signs, gross pathological or microscopic findings in any rats from any exposure group. Body weight patterns in the 13 and 100 mg/m³ exposure groups were similar to those exhibited by the control rats. Rats in the 5200 mg/m³ exposure group lost from 2.5 to 6.8% of their original body weight for one or 2 days post exposure, followed by normal weight gain throughout the remainder of the recovery period. Under the conditions of this study, the 4-hour inhalation median lethal concentration (LC50) for aerosols of the test substance in male and female rats was greater than 5200 mg/m³. No microscopic changes were observed in the upper or lower respiratory tract at concentrations up to 100 mg/m³, the highest concentration evaluated microscopically.