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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1981-07-31 to 1981-08-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report equivalent or similar to OECD guideline 403. GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): SF-0203-41
- Physical state: clear, colorless liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: 49-67 days
- Weight at study initiation: 223-250 g(Males); 166-198g (females)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum except during exposure



ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled but not specified
- Humidity (%): controlled but not specified
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: room air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass inhalation chamber
- Exposure chamber volume: 54-liter
- Method of holding animals in test chamber: individually caged
- Source and rate of air: 40L/min HVAC system and in house air
- Method of conditioning air: particulate filtered and controlled for temp and humidity
- System of generating particulates/aerosols: FMI pump moved test material to a glass atomizing jar to the Spraying Systems atomizer at the top of the jar equipped with a No. 1650 liquid nozzle and No. 64 air nozzle
- Method of particle size determination: Andersen 8 stage cascade impactor


TEST ATMOSPHERE
- Brief description of analytical method used: standard gravimetric techniques and Scott Total Hydrocarbon Analyzer (vapor phase)


VEHICLE
- Composition of vehicle (if applicable): room air



TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 2.9 +/- 2.07mm

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
0, 760 mg/m3, 930mg/m3, 1100mg/m3, 1400 mg/m3, 5100 mg/m3 (actual particulate concentration)
No. of animals per sex per dose:
6 groups of five male and five female rats (total of 30 rats)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:observed during exposure and daily after exposure; body weights recorded prior to exposure and at days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 1 170 mg/m³ air
95% CL:
940 - 1 460
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
1 400 - 2 000 mg/m³ air
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
900 - 1 400 mg/m³ air
Exp. duration:
4 h
Mortality:
Some mortality was observed all groups exposed. Mortality always occurred within two days after the exposure, with about half of the observed deaths occurring on the day of exposure. There were no abnormal signs or mortality observed in the control group.

In the highest exposure group (5100mg/m3) all animals died within two days after exposure.
In the 1400mg/m3 exposure group, 2/5 males and 5/5 females died all within 3 days
In the 1100mg/m3 exposure group, 2/5 males and 2/5 females died all within 3 days of exposure
In the 930 mg/m3 exposure group 2/5 females died within 2 days of exposure, all males in this exposure group survived.
In the 760 mg/m3 exposure group, 3 females died all within 48h of exposure, all males survived.


Clinical signs:
other: Dyspnea was the principal pharmacotoxic sign observed in all groups both during exposure and after exposure to the test material. There was also the observation of a nasal discharge which occurred with less frequency during and after the exposure to the
Body weight:
The control rats gained weight normally over the course of the study.

The male rats of the 770mg/m3 group appeared to gain weight at a lower than normal rate but the surviving females gained weight at a near-normal rate

The surviving males of the 1400mg/m3 exposure group gained less weight than expected during the first post exposure week but then gained at a normal rate during the second post exposure week. There was not sufficient data to evaluate the body weight effects for the females.


The males in the 1100mg/m3 exposure group gained body weight normally during the entire post exposure period while the females gained weight normally only during the second week of the post exposure period.

Males and females of the 940 mg/m3 exposure group appeared to gain weight at a normal rate during the two week post exposure period

There was not sufficient data to evaluate the body weight effects for the 5100 mg/m3 exposure group
Gross pathology:
There were toxicologically significant compound-related macroscopic pathologic changes present in the treated male and female rats. These changes were observed only in animals which died and were not observed in animals sacrificed at study termination. These changes included red or red-brown nasal discharge, red matter or fluid in the nasal passages, and lungs which were red or dark red in total or in part.

There were toxicologically significant compound-related changes in the lungs of male and female animals in the high dose group. All high dose group male and female animals died on study and displayed pulmonary congestion. In 10/10 treated animals there was mild or moderate pulmonary edema and in 3/10 there were mural protein casts in terminal and respiratory bronchioles. The pulmonary congestion was acute and led to intra-alveolar hemorrhage in some cases. The pulmonary edema was manifested at perivascular and/or intraalveolar sites. The edema fluid contained a moderate number of polymorphonuclear cells. Mural protein cast formation consisted of the deposition of condensed proteinaceous material mixed with nuclear debris, along the walls of terminal airways. This change was present in those animals which survived the longest period.

There was an additional finding of mild alveolitis in one animal. This change was not considered a direct compound effect. The probable etiology is either microbial or a secondary compound effect. There was no other incidence of active respiratory disease in the test animals. The presence of mild peribronchial lymphoid hyperplasia in 100% control and treated rats is evidence of prior respiratory tract exposure to unspecified antigenic material.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information R20 Criteria used for interpretation of results: EU
Conclusions:
The LC50 for acute inhalation exposure to the test material is 1170 mg/m3 with 95% confidence limits of 940-1460 mg/m3. This finding warrants classification as a Category 4 acute inhalation toxicant under EU GHS guidelines and as an R20 acute inhalation hazard under EU requirements for dangerous substances and preparations.
Executive summary:

Five groups of Sprague-Dawley rats (5/sex/group) were exposed to an aerosol of the test material at 770, 940, 1100, 1400 or 5100 mg/m3 for 4 hours.  The average aerosol particle size was 2.9 ± 2.07mm.  A control group was similarly exposed to air only.  The animals were observed for 14 days after exposure.  Clinical signs observed during and after exposure included dyspnea and nasal discharge.  Deaths occurred within the first 2 days after exposure in all female groups and the male groups exposed to 1100 mg/m3 or more of the test substance.  The high dose groups gained less body weight during the first week after exposure, but the body weight gain was normal in the second week post-exposure.  Macroscopic changes were observed in the animals that died following exposure and included red nasal discharge and congested lungs.  Microscopic examination was not conducted in the rats exposed to 770-1400mg/m3.  In the 5100 mg/m3 group, pulmonary congestion was observed in all the animals.  Mural protein casts were observed in the terminal and respiratory bronchioles.  The control animals were normal.  The LC50 for acute inhalation exposure to an aerosol of the test material is calculated to be 1170 mg/m3 with 95% confidence limits of 940-1460 mg/m3.  This finding warrants classification of as a Category 4 acute inhalation toxicant under EU GHS guidelines and as an R20 acute inhalation hazard under the EU requirements for dangerous substances and preparations.