Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-06-27 to 1997-07-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
exposure time: 1 hour
GLP compliance:
yes
Test type:
other: whole body inhalation
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not stated
- Age at study initiation: approx. 5-6 weeks
- Weight at study initiation: approx. 75-100g
- Housing: individually in suspended stainless steel, wire mesh bottom cages,
- Diet (e.g. ad libitum): Purina Certified Rodent Chow
- Water (e.g. ad libitum): via automatic watering system
- Acclimation period: one week prior to initiation of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 65-78°F
- Humidity (%): 40-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: PVC and plexiglas whole body chamber
- Exposure chamber volume: 175 liter
- Source and rate of air: room air, 45 air changes per hour
- Method of conditioning air: filtered (HEPA and activated carbon)
Test article was introduced into the camber through a special designed stainless steel J-tube containing stainless steel beads and wrapped with heating tape and insulation to facilitate vaporization of test article. The test article was metered from a reservoir into J-tube by a Fluid Metering, Inc. pump. Dry air (Michigan Airgas, Zero Grade) flowed through the J-tube at a controlled rate and air/vapour mixture passed into the inlet port at the top of the chamber where it was mixed with chamber supply air prior to introduction into the chamber.
- test atmosphere monitoring:
1. measuring the chloride ion concentration at the end of the delivery stream from the J-tube with an electrolytic conductivity detector (The chloride equivalents calculated for the nominal concentration of the test article were compared with the level of chloride equivalents at the end of the delivery stream from the J-tube).
2. a Hewlett Packard 5890 gas chromatograph (GC) /5972 mass spectrometer (MS) to monitor the test article concentration in the chamber and provide MS analysis of the chamber atmosphere.
- Temperature, humidity, air flow in chamber: 20.3-21.1 °C, 31.5-33%, 129.7-131.0 LPM,
- Nominal concentration:
the amount of test concentration was determined by pre- and post-exposure weight of the test article in the reservoir. The exposure duration, test article used, and volume of air passing through the chamber were used to calculate nominal concentration values.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC/MS
Duration of exposure:
1 h
Concentrations:
nominal concentration: 1123; 1317; 1414 ppm
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
clinical signs: once per day for 14 days following exposure (including respiratory, behavioural, nasal and/or ocular changes.
mortality/morbidity: twice daily on weekday, once on weekends/holidays
body weight: prior to exposure, on day 1, 8, and 15
gross pathology: all animals that died during the study or at the end of 14 day observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
LC50, 95% fiducial limits, and approx. slope of dose response curve were calculated using a SAS/STAT probit program. Body weight means and SD were also calculated.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 352 ppm
Based on:
test mat.
95% CL:
> 1 254 - < 1 455
Exp. duration:
1 h
Mortality:
at 1123 ppm: all animals survived until the end of the 14-day observation period.
at 1317 ppm: 4 animals (2 males, 2 females) died by study day 5.
at 1414 ppm: 7 animals ( 3 males, 4 females) died by study day 4.
Clinical signs:
other: Respiratory, activity, ocular and nasal effects and facial and body soiling were noted in all groups during 14-day observation period. Respiratory effects noted included laboured breathing and rales. The activity effects which were most frequently noted i
Body weight:
Mean body weights for all the groups were depressed at the end of the first week. All surviving animals except for the one female in group 3, gained weight by the end of the 14-day observation period.
Gross pathology:
Test article-related effects observed included corneal opacities, exphthalmos, buphthalmose, and alopecia, lung, nasal, and eye effects. Discoloration of hair were observed in a majority of the animals that died during 14-day observation period. Lung effects noted in these animals included haemorrhage, congestion, and/or consolidation and ectasia.The primary nasal effect was obstructed nostrils. The primary eye effect observed was crusted shut eyelids. Discoloration of the hair was mostly due to porphyrin and greenish staining. Discoloration of the extremities and congestion of the meningeal vessels was noted in a majority of the animals to 1414 ppm that died during the study. Blood in the gastrointestinal tract was noted in few of the animals exposed to 1414 ppm that died during the study. Gaseous distension and a decrease or absence of body fat was noted in a majority of the animals exposed to 1317 that did not survive the observation period.
Other findings:
The nominal exposure concentrations were significantly higher than the measured chamber test article concentrations (394, 440, 510 ppm, respectively) due to the reactivity and hydrolysis of the test article.

Any other information on results incl. tables

                                                    Summary of Mortality data

 

Exposure Group

Nominal Exposure

Concentration (ppm)

Number Dead /Number Exposed

 

     Males                Females 

 Males / Females

       Combined

1

1123

       0/5                      0/5

         0/10

2

1317

       2/5                      2/5

         4/10

3

1414

       3/5                      4/5

         7/10

 

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
A reliable study conducted according to OECD and in accordance with GLP, identified a 1h acute inhalation LC50 value of 1352 ppm in male and female rats.