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Toxicological information

Acute Toxicity: inhalation

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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:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Experimental Toxicology and Ecology, BASF SE
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Test substance No.: 07/0285-1
- Physical state: Solid / orange
- Analytical purity: 99.61% (see analytical report 07L00144)
- Lot/batch No.: GV 33900-66
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: young adult animals (male animals approx. 7 - 8 weeks, female animals approx. 10 – 11 weeks)
- Weight at study initiation: mean 235.3 g (males), 189.9 g (females)
- Housing: single housing, H-Temp (PSU) cages, floor area about 800 cm2 (425x266x185 mm); TECNIPLAST, Germany
- Diet (e.g. ad libitum): Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose/head only
Vehicle:
other: Aerosil
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF SE)
- Exposure chamber volume: volume ca. 55 l
- Method of holding animals in test chamber: animals were restrained in glass tubes and their snouts projected into the inhalation system
- Source and rate of air: compressed air, 1.5 m³/h; the flows were adjusted and continously measured with a flowmeter (rota).
The concentration was adjusted by varying the rotation of dosing wheel.
- System of generating particulates/aerosols: dosing-wheel dust generator (Gericke/BASF) with apertural width of 3 mm
- Treatment of exhaust air: 1.35 m³/h; the flows were adjusted and continously measured with a flowmeter (rota).
- Temperature, humidity, pressure in air chamber: air change of about 27 times/h; 21.9 ± 0.2 °C; 28.2 ± 1.2 %


TEST ATMOSPHERE
- Brief description of analytical method used: the nominal concentration was calculated from the amount of substance dosed and the supply air flow
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): 1% (w/w) of Aerosil

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the calculation of the particle size distribution was carried out in the inhalation laboratory on the basis of mathematical methods for evaluating particle measurements
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.3-1.4 µm / 2.7


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The selection of the concentration for the test group was based on the OECD Guidelines, method 403; EU Directive 92/69/EEC, 93/21/EEC and Environmental Protection Agency (EPA) guidelines because from the available information concerning the test substance no pronounced inhalation toxicity was expected.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
For each sample the dust aerosol concentration in mg/L was calculated from the difference between the weight of the filter prior to and after the sampling, with reference to the sample volume of the inhalation atmospheres.
Duration of exposure:
4 h
Concentrations:
5.7 mg/l
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: individual body weights shortly before exposure (day 0), weekly thereafter and at the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
Binomial test was used for statistical evaluation (Steel R.G.D., Torrie J.H. (1984): Principles and procedures of statistics a biometrical approach. McGraw - Hill)

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.7 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
No lethality occurred at the tested concentration of 5.7 mg/L during the study period of 14 days.
Clinical signs:
other: Clinical signs of toxicity comprised visually increased respiration and squatting posture. Findings were observed from hour 1 of exposure through to study day 1. No clinical signs and findings were observed from study day 2 onward.
Body weight:
Mean body weights (g): d0/d7/d14
- Males: 235.3 ± 8.8, 258.3 ± 11.9, 285.9 ± 13.7
- Female: 189.9 ± 7.0, 192.4 ± 6.2, 205.4 ± 10.9
Gross pathology:
All animals underwent gross necropsy after the post-exposure observation period of 14 days.
Diffuse red discoloration of the lung, moderate retraction of the lung tissue and moderate to severe interstitial edema were noted in all male and female animals.
Histopathological examination of the lungs of the one male and one female animals revealed moderate to severe acute diffuse congestion, moderate to severe diffuse intra-alveolar histiocytosis with numerous pigment-loaded macrophages and multifocal interstitial lymphoplasmahistiocytic infiltrates, which is graded as minimal to slight in the male animal and moderate in the female animal. The lung of the examined female animal was more affected. In this female animal, besides the findings described above, emphysema, perivascular cuffing and interstitial fibrosis were noted additionally.

Any other information on results incl. tables

Body weights:

Body weight (g)
d 0 d 7 d 14
Male 1 233.9 256.3 284.2
2 241.8 271.4 303
3 228.3 247.2 272.7
4 246.6 269.8 296.6
5 225.7 246.6 273.1
Mean 235.3 ± 8.8 258.3 ± 11.9 285.9 ± 13.7
Female 1 182 183.4 189.3
2 184.3 198.6 208.3
3 192.4 195.1 201.5
4 199.6 196 219
5 191.3 188.7 208.7
Mean 189.9 ± 7.0 192.4 ± 6.2 205.4 ± 10.9

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met