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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
Study period:
not specified
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
1992
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Version / remarks:
1984
Qualifier:
according to
Guideline:
other: Japan MAFF Guideline, 59 NohSan No 4200
Version / remarks:
1985
GLP compliance:
yes
Test type:
traditional method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Remarks:
SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks old
- Weight at study initiation: 279-300 g (males); 184-211 g (females)
- Housing: 5 animals per stainless steel wire cage, sexes separately
- Diet: A certified pelleted diet MF ad libitum except during exposure.
- Water: Well water ad libitum except during exposure.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes: At least 10 changes / hour
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Start: 9 Apr., 1996 End: 2 May 1996

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
>= 5.1 - <= 5.6 µm
Geometric standard deviation (GSD):
>= 1.8 - <= 2.1
Remark on MMAD/GSD:
The mean values of MMAD and standard deviations of the test substance were 5.1 µm and 2.1 in group 1, and 5.6 µm and 1.8 in group 2.
Details on inhalation exposure:
EXPOSURE CONDITIONS: Two inhalation exposures of the test substance were conducted. The air flow rate in the chamber was very stable at 20 L/min during the exposure period. The mean actual atmospheric concentrations of the test substance were 1.02 mg/L (group 1) and 3.72 mg/L (group 2). The ratios of the mean actual atmospheric concentrations of the test article to the nominal concentration were 9.4% (group 1) and 6.6% (group 2).

GENERATION OF THE TEST ATMOSPHERE / CHAMBER DESCRIPTION: The test atmosphere was generated using a turn-table type dust feeder with compressed air from an air compressor. The air flow rate in the chamber was regulated by a flow controller at 20 L/minute. The air change was 37.5 times/hour, ensuring an oxygen content of at least 19%. The air in the chamber was filtered with an exhaust filter system consisting of a bag filter, a HEPA filter and an activated charcoal filter, and was emitted to the atmosphere using a vacuum pump. Animals were exposed nose-only to the atmosphere. They were held individually in animal holders attached to the inhalation chamber and were exposed to the test substance for 4 hours.

TEST ATMOSPHERE CONCENTRATION: The particulate concentration of the test atmosphere, close to the animals’ breathing zone, was measured gravimetrically with a balance (Mettler AE 163, Mettler Instrumente AG, Greifensee, Switzerland). The weight percentage of each stage to the total amount of the trapped test substance was calculated. The dust of the test substance was trapped on a glass fiber filter. Then the test substance on the filter was extracted with acetonitrile, and analysed by high-performance liquid chromatography (HPLC). The atmospheric concentration of the test article was calculated by dividing the weight of the test substanced by the sample air volume. The concentration was calculated as follows: Concentration (mg/L) = Weight of test article supplied (g) x 1000 / time (minutes) x airflow (L/minute).

PARTICLE SIZE DETERMINATION: The aerodynamic particle size distribution of the test atmosphere was measured twice during the exposure period, using an Andersen personal sampler, at one and three hours after the initiation of exposure. The amount of the test substance trapped on each stage of the sampler was determined gravimetrically with a balance. The amount of the test substance, by weight, in each size range, was then used to calculate the aerodynamic particle size distribution. The cumulative weight percentage was plotted on a logarithmic-probability paper to obtain the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the test substance dust.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
- Measured particulate concentration: 3.72 mg/L
- Nominal concentration: 1.02 mg/L
- Analysed concentration: mean 1.02 mg/L (group 1) and 3.72 mg/L (group 2)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Prior to the start of the study animals were examined to ensure that they were physically normal and exhibited normal activity.
- During exposure they were observed frequently and, at 2 hours after initial exposure and immediately, at 2 and 4 hours after the termination of exposure.
- The animals were subjected to detailed clinical observations, daily during a 14-day observation period.
- Body weights of the animals were individually measured just prior to exposure and on post-exposure days 7 and 14.
- All animals were necropsied at the end of the observation period.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.72 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No animals were killed as a result of exposure to the test substance.
Clinical signs:
other: After termination of exposure, soiled fur in the nasorostral region was observed at the slight degree in all animals in both groups. This slight sign disappeared by post-exposure day 1 in both group 1 and day 3 in the group 2.
Body weight:
Although 2 females in the group 2 showed slight decreases in body weight on day 7, they recovered their weights by day 14.
Gross pathology:
There were no macroscopic abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
It is concluded that the acute inhalation LC50 of the test substance exceeds 3.72 mg/L.
Executive summary:

In an acute inhalation toxicity study, groups of young adult SPF Sprague-Dawley (Crj:CD) rats (10 male and 10 female) were exposed by inhalation route to pulverized test substance (purity: 98.60%) in the form of a dust for 4 hours (in a nose only exposure chamber) at concentrations of 1.02 (group 1) and 3.72 mg/L (group 2). Animals then were observed for 14 days. Two groups of five male and five female SPF Sprague-Dawley were exposed nose-only for a four-hour period to the test substance at a target formulation concentration of 5 mg/L. Test atmospheres were analysed for particulate concentration. The particle size distribution of the test atmosphere was analysed twice during the exposure period. Following exposure, the animals were retained without treatment for 14 days. Clinical observations and body weights were recorded throughout the study and at the end of the scheduled period, the animals were killed and subjected to a gross examination post mortem. The achieved test atmosphere had the following characteristics: Target concentration (mg/L) = 5; achieved particulate concentration (mg/L) = 3.72 ± 0.73; MMAD (µm) = 5.1, 5.6; GSD = 2.1, 1.8.There were no deaths in either sexes throughout the observation in both groups. The median lethal concentration of the test substance for male and female rats was more than 3.72 mg/L. No abnormalities were found in the major organs in the cranial, thoracic, and abdominal cavities in any animal of either group at necropsy. From these results, it was concluded that the acute inhalation toxicity of the test substance in Sprague-Dawley rats was virtually nontoxic at the atmospheric concentration of 3.72 mg/L and the LC50 for male and female rats was more than 3.72 mg/L.