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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Deviations: some minor deviations from the study plan were present but considered not to affect the validity of the study results.
GLP compliance:
yes
Test type:
acute toxic class method

Test material

Constituent 1
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Test material:
IR5878
Batch number: FCF/T/168-00 (ex 20525/03/9)
Purity: 98.54 ± 0.51 %

Test animals

Species:
rat
Strain:
other: Male and Female HanIbm: WIST (SPF) rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test animals:
Species and Strain: Male and Female HanIbm: WIST (SPF) rats
Age: 6 weeks (males); 9 weeks (females)
Body weight: 180.4 ÷ 194.7 g (males); 183.3 ÷ 189.0 g (females)
Housing: 5 animals per Makrolon type-4 cage with wire mesh tops and standard softwood bedding.
Feed: pelleted standard Kliba 3433, rat maintenance diet ad libitum (except during the exposure period, when they were restrained in exposure tubes). Community tap water from Füllinsdorf ad libitum (except during the exposure period, when they were restrained in exposure tubes).

Environmental conditions:
Temperature and humidity measured during the study were 22 ± 3°C and 30 ÷ 70%, respectively.
Light: 12 hours fluorescent light and 12 hours dark (music during the light period).

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Mass median aerodynamic diameter (MMAD):
ca. 3.02 µm
Geometric standard deviation (GSD):
ca. 2.94
Details on inhalation exposure:
IR5878 was administered to 5 male and 5 female HanIbm: WIST (SPF) rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days.
IR5878 aerosol was generated using a CR 3020 powder generator feeding a micronising Jet-Mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutraliser with a target Mass Median Aerodynamic Diameter (MMAQD) of 1 to 4 μm. Based on preliminary technical trials which showed that the exposure system blocked after about 1 hour at concentration of about 3 mg/L air, two exposure systems were prepared to generate an aerosol concentration of about 2 mg/L. The second aerosol generator/Jet-Mill replaced the first one after 2 hour and 10 minutes of exposure - remaining the animals in the same tower. The changeover took one minute to complete and this time was added to the end of exposure.
The exposure conditions (range of temperature, humidity and oxygen content) measured during the exposure were acceptable. The mean gravimetric concentration was the highest technically achievable concentration.
The animals were examined for mortality, clinical signs and body weight for 14 days. On day 15 the rats were killed by i.p. overdosage of pentobarbitone and examined macroscopically.
Duration of exposure:
ca. 4 h
Concentrations:
Based on preliminary technical trials which showed that the exposure system blocked after about 1 hour at concentration of about 3 mg/L air, two exposure systems were prepared to generate an aerosol concentration of about 2 mg/L. The second aerosol generator/Jet-Mill replaced the first one after 2 hour and 10 minutes of exposure - remaining the animals in the same tower. The changeover took one minute to complete and this time was added to the end of exposure.
No. of animals per sex per dose:
IR5878 was administered to 5 male and 5 female HanIbm: WIST (SPF) rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.19 mg/L air
Based on:
act. ingr.
Exp. duration:
4 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortalities were observed in this test.
Clinical signs:
other: No clinical signs were observed in both sexes
Body weight:
Body weight was unaffected by treatment.
Gross pathology:
At gross necroscopy no macroscopic changes were observed in any animal.

Any other information on results incl. tables

In Table 5.2-1 and 5.2-2 are summarised the technical conditions measured during the exposure and the atmosphere analysis.

 

Table 5.2-1     Exposure conditions measured during the exposure

Temperature (°C)

Relative humidity (%)

O2Concentration (Vol. %)

22.4 ±(n=9)

6.4 ± 1.96 (n=9)

20.7 ±(n=9)

 

Table 5.2-2     Data on the test atmosphere analysis

Group

Test atmosphere concentration (mg/L)

MMAD (µm) and [GSD]

Nominal

Gravimetric ± SD

1

4.641

2.190 ± 0.047 (n=5)

3.02  [2.94]

MMAD: Mass Median Aerodynamic Diameter

GSD: Geometric Standard Deviation

 

No mortalities were observed in this test.

No clinical signs were observed in both sexes.

Body weight was unaffected by treatment.

At gross necroscopy no macroscopic changes were observed in any animal.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute inhalation LC50 of IR5878 in rats was estimated to be greater than the highest technically achievable aerosol concentration of 2.190 mg/L air (gravimetrically determined mean aerosol concentration).
Executive summary:

IR5878 was administered to 5 male and 5 female HanIbm: WIST (SPF) rats by nose-only, flow-past inhalation exposure for a single continuous 4-hour period, followed by an observation period of 14 days.

The acute inhalation LC50of IR5878 in rats was estimated to be greater than the highest technically achievable aerosol concentration of 2.190 mg/L air (gravimetrically determined mean aerosol concentration).