Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
24 Jul - 8 Dec 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions (no analytical purity reported)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Kingston, NY, USA
- Age at study initiation: 8 weeks
- Housing: individually in stainless wire mesh cages.
- Diet: certified Purina rodent chow #5002, ad libitum (except during exposures)
- Water: tap water (delivered via automatic system except during exposures)
- Acclimation period: minimum of 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel exposure chamber
- Exposure chamber volume: 400 L
- Method of holding animals in test chamber: Animals were housed in a nearby room and loaded into cages designed for the inhalation chamber for exposure
- Source and rate of air: Pressurized air passed through the hollow stream of nebulizer and exited at high velocity through holes in its side. This high velocity air stream passed over the top of the hollow feed barrels and caused the aspiration of the liquid test material up into the feed barrel. The liquid was aerosolized as it was drawn into the airstream by the relative negative pressure there.
- System of generating particulates/aerosols: Laskin nebulizers
- Method of particle size determination: The mass median aerodynamic diameter of the aerosol was determined once during exposure by use of a cascade impactor
- Temperature, humidity, pressure in air chamber: 24.4 °C (control group) and 23.8 °C (0.48 and 4.06 mg/L groups); 60% (control and 4.06 mg/L group), 64% (0.48 mg/L)

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of aerosol in the exposure chamber was determined gravimetrically by drawing known volumes of air from the chamber through glass fibre filters and measuring the increase in weight of the filters. The weight increase was divided by volume of air sampled to give aerosol concentration.
- Samples taken from breathing zone: no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.9/1.9 (0.48 mg/L) and 1.1/1.7 (4.06 mg/L)

Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
ca. 4 h
Concentrations:
0.48 or 4.06 mg/L (analytical concentration)
0.60 or 4.07 mg/L (nominal concentration)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weight were recorded on days 1 (day of first exposure), 2, 9, and 17. Clinical signs were recorded daily except of weekends.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
Data on body weights were analyzed by ANOVA and Tukey´s multiple range test for comparison of control and exposed groups.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.06 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy examination revealed no substance-related findings.
Other findings:
- Organ weights: No treatment-related changes were observed in the weights of the liver or kidneys. Both wet and dry weight of the right middle lung lobe tended to be higher in the exposed males at 2 weeks post-exposure. Dry weight was significantly greater in group 3 relative to group 1, but only in males at 2 weeks.
- Histopathology: Histopathological examination revealed no substance-related findings. Since no treatment-related morphologic changes were found at macroscopic post mortem examination of the animals, without this morphologic confirmation, the small changes in lung weight were considered not to be biologically relevant.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.