Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline and GLP compliant study with good documentation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Hanlbm: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd.; biotechnology & Animal Breeding Division; 4414 Füllingsdorf; Switzerland
- Age at study initiation: males: 9 weeks, females 10 weeks
- Weight at study initiation: males 241.0 to 252.0 g, females: 187.5 to 198.1 g
- Housing: in groups of five of the same sex
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: from 22 to 27th September 2000, i.e., 5 days prior to treatment ( the animal exposure was performed on 28th September 2000)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21°C
- Humidity (%): 33 - 78%
- Air changes (per hr): 5-12/hour
- Photoperiod (hrs dark / hrs light): 12/12 hours,
- Music was played 12 hours/day mainly during the light period

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Source and rate of air: compressed filtered air
- Method of conditioning air: compressed filtered air
- System of generating particulates/aerosols:
The test item (fluid form) was used as supplied and placed in an automatic syringe pump. The test atmosphere was generated in ambient conditions. The generated aerosol was diluted in order to achieve the target aerosol concentration of 5 mg/L air.
- Method of particle size determination: gravimetrically and by chemical analysis
- Temperature, humidity, pressure in air chamber: yes, Temp. 20.7°C, relative humidity 6% RH; O2 concentration: 20.3% Vol.

TEST ATMOSPHERE
- Brief description of analytical method used:
Gravimetricall method:
Samples from the test atmosphere were collected four times during the exposure on Millipore durapore filters (Type HLVP, 0.45 µm), weight determination : prior to and after sampling
Chemical analysis:
After gravimetrical analysis, the filters were put in a light protected glass and covered with 20 g of tert.buthyl-methyl-ether. The filter samples were then kept at approximately 5°C until analysis. The samples were analysed by GC/FID using a method provided by the sponsor.
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air, compressed and filtered
- Concentration of test material in vehicle (if applicable): nominal 5 mg/L

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.50 µm / 2.42 GSD
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
nominal 5 mg/L, measured gravimetric: 5.261 mg/L, analytical: 5.192 mg/L
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0 (prior to exposure), days 3, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
none

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.192 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: no mortality during the test and teh 14 day observation period
Mortality:
none
Clinical signs:
other: The following clinical signs were noticed during and / or after the beginning of the inhalation exposure in all animals: Slightly to marked laboured respiration, slight to marked breathing sounds (rales), ventral recumbency, slight to marked uncoordinated
Body weight:

There was a slight to moderate, transient loss of body weight in three out of five males (about -1.8%) and in three out of five females (mean -2.1%) from day 0 to day 3. During the remainder of the test period, all animals gained body weight normally. The transient body weight losses were attributed to the treatment with the test item.
Gross pathology:
No macroscopic findings

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Executive summary:

The acute 4-h nose-only inhalation toxicity of ITTFEP (purity 82.3%) to rat was determined in a GLP compliant test according to OECD 403, EU method B.2 and EPA OPPTS870.1300 (Decker et al. 2001). Since the study was performed under GLP and according the guideline and based on the good documentation the study was awarded with Klimisch 1.

 

The acute inhalation toxicity testing in 5 male and 5 female rats showed that the LD50 of the test item was > 5.192 mg/L (limit test, analytically measured). Several slight to moderate clinical signs were observed. The body weight evolution was influenced during the first three days but recovered until day 14. All treated animals were free from poisoning symptoms after 5 days at the latest.

 

The obtained results are considered as relevant for the risk assessment.