Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976-06-03 to 1976-07-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Sufficiently reported study with some details misssing as: batch number, purity of substance (but available in a pretest information) clinical signs of all animals and description of analytics to determine the concentrations of test item in air. The animal room temperature exceeds the required 22+/- 3°C. The study was performed prior to implementation of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Remarks:
Study was performed prior to implementation of GLP
Test type:
other: acute inhalation
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: salmon pink liquid
Details on test material:
- Name of test material (as cited in study report): perfluorhexylaethyljodid
- Molecular formula (if other than submission substance): C6 F13 C2 H4 J
- Physical state: salmon pink liquid
- Analytical purity: 97 % (GC method) chemical pure; not mentioned in this report but according to other archived company data files performed with Perfluohexylaethyljodid in 1976.
- Purity test date: not applicable
- Lot/batch No.: not applicable
- Expiration date of the lot/batch: not applicable

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
RATS:
- Source: SPF Wistar rats, females only
Weight at study start: 93-168 g (mean 118g)
- Age at study initiation: n.a.
- Fasting period before study: no
- Diet (e.g. ad libitum): ALTROMIN 1324 (Company: Altromin GmbH, in Lage/Lippe Germany)
- Water (e.g. ad libitum): yes
- Acclimation period: n.a.
-Makrolon cages with wood shavings
ENVIRONMENTAL CONDITIONS
- Humidity (%): n.a.
- Temperature in room (°C): 26°C to 27°C
- Atmospheric pressure: 750.6 - 760.5 Torr
- Air changes (per hr): not mentioned for animal room
- Photoperiod (hrs dark / hrs light): n.a.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test was performed in an apparatus for dynamic spraying of aerosols (manufacturer Joh. Friedrich Bundschuh, Griesheim, Germany). The apparatus consits of a cylinder with several tubes. Through a special nozzle welded with a specific substance-tube the air was pushed via a special filter with a compressor into the cylinder.
- Method of holding animals in test chamber: Tubes connected with the cylinder were configured like restrainer tubes, in the way that only the noses of animals extend into the cylinder.
- Source and rate of air: The air supply was kept constant at 600L/hour with an air-calibrated Rotameter.
- Treatment of exhaust air: At the bottom of the apparatus an exhaust device was installed over which the aerosol was sucked off via cotton and a 10% sodium hydroxide solution for detoxification.
- consumed oxigene replacement: n.a.
- Temperature in closed apparature during exposure (°C): 27°C to 30°C
- humidity, pressure in air chamber: n.a.

TEST ATMOSPHERE
- Method of conditioning air: The Perfluorhexylaethyljodide was injected undiluted using a saline drip with a constant flow.
- Brief description of analytical method used:
Analytical determination of the aerosol concentration was performed with an electron capture detektor (Labor für Rückstandanalysen, Pflanzenschutz, Dr. Gorbach, Germany). Results are presented as concentrations of Perfluorhexylaethyljodide in mg/m3 air.
- Distribution of particle sizes were performed with an particle counter system (Modell 225, Manufacturer KRATEL KG, Germany)
- Samples taken from breathing zone: n.a.

VEHICLE
- Composition of vehicle (if applicable): air
- Justification of choice of vehicle: n.a.

TEST ATMOSPHERE (if not tabulated): concentration of Perfluorhexylaethyljodide aerosol as mentioned mixed with normal air.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Analytical determination of the aerosol concentration was perforemd with an electron capture detektor (Labor für Rückstandanalysen, Pflanzenschutz, Dr. Gorbach, Germany). Results are presented as concentrations of Perfluorhexylaethyljodide in mg/m3 air.
Duration of exposure:
4 h
Concentrations:
Aerosol concentration in air:
Group 1: 3'380 mg/m3 (3.4 mg/L)
Group 2: 10'328 mg/m3 (10.33 mg/L)
Group 3: 11'080 mg/m3 (11.08 mg/L)
Group 4: 11'150 mg/m3 (10.15 mg/L)
Group 5: 27'728 mg/m3 (27.73 mg/L)
Group 6: 58'638 mg/m3 (58.64 mg/L)
No. of animals per sex per dose:
10 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Any clinical sign of the animals was observed and registered during the inhalation phase. Rats were weighted daily with the exception of weekends. Tap water and food (Altromin 1324, manufacturer Altromin GmbH, Lage /Lippe Germany) was available ad libitum with the exception of the 4h treatment phase.
- Necropsy of survivors performed: yes. Deceased animals were dissected and examined macroscopically. Hearts, lungs and trachea of these animals were retained in formalin for histopathology.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 10 600 mg/m³ air
Based on:
test mat.
Remarks:
analytical
Exp. duration:
4 h
Mortality:
Group 1 (3'380 mg/m3): 0/10 animals;
Group 2 (10'328 mg/m3): 3/10 animals; death occured in 3 animals within 156 and 215 minutes after start of treatment
Group 3 (11'080 mg/m3): 9/10 animals; death occured in 8 animals within 105 and 226 minutes after start of treatment and in one rat within day 1 to 2.
Group 4 (11'150 mg/m3): 10/10 animals; death occured in 10 animals within 100 and 173 minutes after start of treatment
Group 5 (27'728 mg/m3): 10/10 animals; death occured in 10 animals within 86 and 211 minutes after start of treatment
Group 6 (58'638 mg/m3): 10/10 animals; death occured in 10 animals within 73 and 158 minutes after start of treatment
Clinical signs:
no detailed information
Body weight:
During the 14 day post treatment observation period bodyweight develpment of the survivors was regular.
Gross pathology:
Few specific gross pathological changes were recorded for the deceased rats. Lungs were colored dark red to deep black partly with small white areas.
Microscopically an excessive hyperemia of the heart muscle was recorded with no damage of the muscle fiber. At the trachea and the great bronchus-branches there was no indication for damage of the ciliated epithelium. For the examined sections of the lung of all deceased animals hyperemia, distinct lung-edema as well as focal bleeding into the alveolar region was recorded. From the lung results it could not be concluded whether it was a direct effect from the inhaled aerosol or whether it was a sign of terminal heart failure. In conclusion of the pathology report it is mentioned that inhalation of the test item 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodooctane caused death within 226 minutes in all rats that died. Morphological a distinct lung edema was in the foreground. There is no information of effects in survivors mentioned in the report.

Any other information on results incl. tables

Particle size distribution: 95.5 to 99% of particles were determined to be smaller than 5 µm.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of a 4h nose-only study in female rats the LC50 was determined to be 10'600 mg/m3 (10'100 – 10'800 mg/m3).
Executive summary:

A sufficiently reported acute inhalation toxicity study with reliability of 2 is available with the test substance. The study was performed prior to implementation of GLP. In order to determine the acute inhalation potential of the test item 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-iodooctane (purity 97%) 10 female rats per dose group were exposed to the test substance by nose-only inhalation for 4 hours. The aerosol concentration in air was measured to be 3'380, 10'328, 11'080, 10'150, 27'728 and 58'638 mg/m3, respectively. The particle size distribution was determined to be 95.5% to 99% smaller than 5 µm. Based on the results of this study the LC50 was determined to be 10'600 mg/m3 (10'100 – 10'800 mg/m3).