Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
(2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene; (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene; (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene
EC Number:
700-755-2
Molecular formula:
C8H3F13O
IUPAC Name:
(2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene; (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene; (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene
Details on test material:
- Purity: 99.1%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 231-314 g (males); 176-217 g (females)
- Fasting period before study: no
- Housing: Except during exposure, animals were housed individually in solid bottom caging with bedding.
- Diet (e.g. ad libitum): ad libitum, except during exposure
- Water (e.g. ad libitum): ad libitum, except during exposure
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26ºC
- Humidity (%): 30-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass (cylindrical) chamber with a nominal internal volume of 19 L. A 1-inch circular glass baffle at the chamber inlet promoted uniform chamber distribution of the test atmosphere.
- Method of holding animals in test chamber: The rats were placed inside a wire-mesh module (sexes separate) that was placed on a stainless steel stand inside the exposure chamber so that the rats were elevated off of the bottom of the glass chamber.
- Source and rate of air: Houseline generation air, was metered to the round-bottom flask with a mass flow controller and carried the vapour and air mixture into a glass transfer tube that led to the exposure chamber. Supplemental or dilutional chamber air was metered via another mass flow controller and was added to the vapour and air mixture in the glass transfer tube.
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: Chamber atmospheres were generated by flash evaporation of the test substance in air. The test substance was metered into a heated round-bottom, flash evaporation flask with a Harvard Apparatus Syringe Infusion Pump. The round-bottom flask was heated to approximately 175°C to vapourize the test substance. Houseline generation air, was metered to the round-bottom flask with a mass flow controller and carried the vapour and air mixture into a glass transfer tube that led to the exposure chamber. Supplemental or dilutional chamber air was metered via another mass flow controller and was added to the vapour and air mixture in the glass transfer tube. Chamber concentrations of the test substance were controlled by varying the test substance feed rate to the round-bottom flask. Chamber airflow was 8 L/min which provided at least 10 air changes per hour.
- Treatment of exhaust air: The test atmosphere was exhausted through a dry-ice cold trap followed by an MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood.
- Temperature, humidity, pressure in air chamber: 20-24°C, 53-84%, pressure not reported; oxygen concentration ranged from 20 to 21%.

TEST ATMOSPHERE
- Brief description of analytical method used: The vapour concentration of the test substance was determined by gas chromatography 13 or 14 times during each test-substance exposure. Chamber concentration was analysed only once during the 0 ppm exposure.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2000, 5000, 9700, 15000 ppm
No. of animals per sex per dose:
5/sex/concentration
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for mortality and response to alerting stimuli 3 times during each exposure and observed for mortality and clinical signs of toxicity immediately after they were removed from the exposure chamber following exposure. During the recovery period, all rats were observed each day for mortality. Rats were observed for clinical signs of toxicity on the day following exposure and at least twice more during the recovery period.
- Frequency of weighing: Rats were weighed on the day following exposure and at least twice more during the recovery period.
- Necropsy of survivors performed: yes
- Other examinations performed: The respiratory tract, liver and kidney tissues were collected for microscopic histopathological evaluation and were examined for the 0 and 15000 ppm groups only. Since there were no test-substance related changes at the highest concentration, tissues from lower test concentrations were not evaluated.
Statistics:
Not reported

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 15 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: highest practical vapour concentration achievable for this test substance
Sex:
male/female
Dose descriptor:
other: NOAEL (histopathology)
Effect level:
15 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No adverse histopathological effects observed in the respiratory tract, liver, and kidneys.
Sex:
male/female
Dose descriptor:
other: Clinical signs
Effect level:
5 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Decreased to no activity, periodic rapid head-bobbing, rapid ear-twitching, excessive grooming, chewing motions, increased startle response at 9700 ppm; no activity at 15000 ppm. No clinical signs upon removal from chamber and during 14-day recovery.
Mortality:
No test substance-related animal deaths occurred during or following any of the exposures.
Clinical signs:
other: There were no noteworthy clinical signs of toxicity observed during the 0, 2000, or 5000 ppm exposures. During the 9700 ppm exposure, rats displayed decreased activity approximately 10 minutes into the exposure, and after approximately 45 minutes, the rat
Body weight:
Two to 5 female rats at all levels (including the 0 ppm exposure group) displayed body weight losses ranging from 1.2 to 10 grams up to the second day after exposure, followed by normal weight gain throughout the remainder of the 14-day recovery period. Four of 5 male rats in the 9700 ppm exposure group, and all 5 male rats in the 15000 ppm exposure group displayed body weight losses ranging from 0.1 to 9.3 grams on the day after the exposure, followed by normal weight gain throughout the remainder of the recovery period.
Gross pathology:
There were no test substance-related gross observations in this study.
Other findings:
There were no test substance-related microscopic observations. All microscopic changes noted occurred in similar incidences across control and treated groups and were consistent with background lesions commonly observed in rats of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information very low toxicity Criteria used for interpretation of results: EU
Conclusions:
4-hour LC50 (rats) >15000 ppm
NOAEL (histopathological changes in respiratory tract, liver, kidney) >15000 ppm

This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

Five groups of 5 male and 5 female rats were exposed whole-body for 4 hours to mean concentrations of 0, 2000, 5000, 9700 and 15000 ppm test substance vapour. Rats were sacrificed 14 days after the exposure and given gross examination at necropsy. The respiratory tract, liver, and kidney tissues were collected for microscopic histopathological evaluation.

No test substance-related animal deaths occurred during or following any of the exposures. There were no noteworthy clinical signs of toxicity observed during the 0, 2000 and 5000 ppm exposures. During the 9700 ppm exposure, male and female rats displayed decreased activity approximately 10 minutes into the exposure, and after approximately 45 minutes, the rats became motionless, except when the startle response was checked. Rats exposed to 15000 ppm periodically displayed rapid head-bobbing, rapid ear-twitching, excessive grooming, chewing motions and an increased startle-response, during the first 45 minutes of the exposure. The rats became motionless (except for when startle response was checked) throughout the remainder of the exposure. The rats’ startle response was normal after approximately 45 minutes of exposure to either 9700 or 15000 ppm. There were no abnormal clinical signs of toxicity observed in any rats when they were removed from the exposure chamber or throughout the 14-day recovery period. Two to 5 female rats at all levels (including the 0 ppm exposure group) displayed body weight losses ranging from 1.2 to 10 grams up to the second day after exposure, followed by normal weight gain throughout the remainder of the 14-day recovery period. Four of 5 male rats in the 9700 ppm exposure group, and all 5 male rats in the 15000 ppm exposure group displayed body weight losses ranging from 0.1 to 9.3 grams on the day after the exposure, followed by normal weight gain throughout the remainder of the recovery period. Gross examinations were performed on all rats at the time of necropsy, and respiratory tract tissues (lung, larynx/pharynx, trachea, and nose), liver and kidneys from the 0 and 15000 ppm exposure groups were evaluated microscopically. There were no test substance-related gross pathology findings in any rats in this study, and there were no test substance-related microscopic findings in the respiratory tissues, liver and kidneys of rats from the 0 or 15000 ppm exposure groups. Since no test substance related changes were observed in rats from the 15000 ppm exposure group, tissues from the lower concentration exposure groups were not evaluated. Under the conditions of this study, the 4-hour LC50  is considered to be greater than 15000 ppm test substance, the highest practical vapour concentration achievable for this test substance. The no-observed-adverse-effect-level (NOAEL) for histopathological changes of the respiratory tract, liver and kidneys is also 15000 ppm.