Registration Dossier

Administrative data

Description of key information

LD50 (oral, rabbit): >5000 mg/kg bw

LD50 (inhalation, rabbit): Not determinable

LD50 (dermal): not tested

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 26, 2009 / November 13, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
Limit test:
yes
Specific details on test material used for the study:
Physical description: Pale yellow liquid
pH: 7.0 (as determined)
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Sex: Female, nulliparous and non-pregnant.
Age/Body weight: Young adult (11 weeks)/199- 223 grams at experimental start.
Source: Received from Ace Animals, Inc., Boyertown, PA on October 6, 2009.
Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NRC). Enrichment (e.g. nylabone) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges: 19 - 21 ºC and 35 - 69%, respectively.
Photoperiod: 12-hour light/dark cycle.
Acclimation Period: 22 or 24 days
Food: Purina Rodent Chow #5012
Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Eurofins PSL.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was administered to the stomach using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. Following administration, each animal was returned to its designated cage. Feed was replaced approximately 3 - 4 hours after dosing.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
3 females
Control animals:
no
Details on study design:
Prior to each dosing, experimentally naive rats were fasted overnight by removing the feed from their cages. During the fasting period, the rats were examined for health and weighed (initial). Three healthy naive female rats (not previously tested) were selected for test.
Individual body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing.
The animals were observed for mortality, signs of gross toxicity, and behavioral changes approximately 30 minutes post-dosing, during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.
All rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived
Clinical signs:
No clinical signs were shown by animals during the study
Body weight:
All animals gained body weight
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
Test item induced no effects in 3 female rats after oral gavage at a dose of 5000 mg/kg bw.
LD50 has been determined to be greater than 5000 mg/kg bw.
According to the Globally Harmonized System (GHS) of classification and labeling of chemicals and under the conditions of this study, classification is not required.
Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with rats to determine the potential for test item to produce toxicity from a single dose via the oral route. An initial limit dose of 5000 mg/kg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, two additional females received the same dose level, simultaneously.

Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice. All animals survived, gained body weight, and exhibited no clinical signs during the study. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period. Under the conditions of this study, the acute oral LD50 of the test substance is greater than 5000 mg/kg of body weight in female rats.

According to the Globally Harmonized System (GHS) of classification and labeling of chemicals and under the conditions of this study, classification is not required

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 8 to July 8, 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: guideline test for read across, well documented
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Two groups of 6 male rats each were exposed to aerosol atmospheres of test article in air. Rats were exposed nose-only for a single, 4-hour period. Following exposure, 3 rats from the 0.10 mg/L exposure were retained for a 1-day recovery period; the remaining 3 rats were retained for a 14-day recovery period. Rats from the 1.8 mg/L exposure were retained for a 14-day recovery period.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Composition of material tested, designation H-25777, Lot-No. 478
1.16% F(CF2CF2)3CH2CH2OCOCH=CH2 [CAS# 17527-29-6]
53.29% F(CF2CF2)4CH2CH2OCOCH=CH2 [CAS# 27905-45-9]
25.09% F(CF2CF2)5CH2CH2OCOCH=CH2 [CAS# 17741-60-5]
9.26% F(CF2CF2)6CH2CH2OCOCH=CH2 [CAS# 34395-24-9]
2.58% F(CF2CF2)7CH2CH2OCOCH=CH2 [CAS# 34362-49-7]
0.72% F(CF2CF2)8CH2CH2OCOCH=CH2 [CAS# 65150-93-8]
0.20% F(CF2CF2)9CH2CH2OCOCH=CH2 [CAS# 65104-64-5]
Aspect: Pale yellow liquid
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male
Details on test animals or test system and environmental conditions:
B. Test Species
Young adult, male Crl:CD®(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh, North Carolina. The rats were approximately 7 or 8 weeks old on the day of arrival.
Rats have historically been used in safety evaluation studies for inhalation toxicity testing. The Crl:CD®(SD)IGS BR rat was selected based on consistently acceptable health status and on extensive experience with the strain at Haskell Laboratory.
C. Animal Husbandry
1. Quarantine
Rats were quarantined after arrival for 6 days prior to testing. During the quarantine period, rats were weighed and observed for clinical signs of disease 3 times.
2. Animal Selection
Prior to each exposure, 6 male rats were selected for use on the study from the rats that were released from quarantine. The selected animals had been gaining weight at a normal rate and demonstrated no overt signs of disease, and were the appropriate age and body weight. No attempt was made to randomly group animals.
3. Identification
Each rat was assigned an animal number which was recorded on a card affixed to the cage. Prior to exposure, the tail of each animal and cage card were marked with water-insoluble pens so that each animal could be identified after exposure and during the recovery period.
4. Housing
Except during exposure, rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
5. Animal Room Environment
Rats were housed in proximity to the inhalation chambers. Animal rooms were maintained at a temperature of 18 - 26 °C (targeted to 22 - 24 ºC) and a relative humidity of 30 - 70% (targeted to 40-60%). Animal rooms were artificially illuminated (fluorescent light) on an approximate 12 hour light/dark cycle. Excursions outside of these ranges were of insufficient magnitude and/or duration to have adversely affected the validity of the study.
6. Feed and Water
Except during exposure, PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002 and tap water were available ad libitum.
7. Animal Health and Environmental Monitoring Program
As specified in the Haskell Laboratory animal health and environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below those that would be expected to impact the scientific integrity of the study:
• Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants.
• Feed samples are analyzed for total bacterial, spore, and fungal counts.
• Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers.
Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presence of these contaminants below the maximum concentration stated by the manufacturer would not be expected to impact the integrity of the study.
The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that affected the validity of the study.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
Inhalation Exposure System
1. Atmosphere Generation
Chamber atmospheres were generated by aerosolization of the solid test substance in air with a glass, round-bottom flask placed in a heating mantle. The flask was heated to approximately 100 ºC to melt the test substance. Filtered, high-pressure air, metered into the flask by a Brooks model 5851E mass flow controller, carried the evolved vapor through heated glass tubing. For the 0.10 mg/L exposure, 2 chambers were used. The vapor passed from the heated tubing into the first chamber where a condensation aerosol was formed. The aerosol then passed into the second chamber for animal exposure. For the 1.8 mg/L exposure, the vapor passed from the heated tubing in the exposure chamber where an aerosol was formed.
Test atmospheres were exhausted through an MSA charcoal/HEPA filter cartridge prior to discharge into the fume hood.
2. Chamber Construction and Design
The exposure chambers were constructed of glass (cylindrical) with a nominal internal volume of 34 L. A baffle inside each chamber promoted uniform distribution of the test atmosphere.
3. Exposure Mode
During exposure, animals were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into a polymethylmethacrylate faceplate which was attached to the exposure chamber so that the nose of each animal extended into the exposure chamber.
Characterization of Chamber Atmosphere
1. Test Substance Sampling and Analysis
The atmospheric concentration of H-25777 was determined by gravimetric analysis at approximately 30-minute intervals during each exposure. Known volumes of chamber atmosphere were drawn from the sampling port through a 25 mm filter cassette that contained a pre-weighed Gelman glass fiber (Type A/E) filter. The filters were weighed on a Cahn model C-33 Microbalance®. The atmospheric concentration of H-25777 was calculated from the difference in the pre- and post-sampling filter weights divided by the volume of chamber atmosphere sampled.
2. Particle Size Determination
A sample to determine particle size distribution (mass median aerodynamic diameter and percent particles less than 1, 3, or 10 µm diameter) was taken during each exposure with a Sierra® Series 210 cyclone preseparator/Cascade impactor and Sierra® series 110 constant flow air sampler.
3. Environmental Monitoring
Chamber airflow was set at the beginning of each exposure to achieve at least 10 air changes per hour. The airflow was monitored continually with a calibrated Brooks model 5851E mass flow controller and recorded initially and whenever changes were made during each exposure.
Chamber temperature was targeted at 22 ±2 °C. The temperature was monitored continually with a digital traceable thermometer and recorded 3 times during each exposure. Chamber relative humidity was targeted at 50 ±10%. The relative humidity was measured with an Omega model RH5100C digital psychrometer and recorded 3 times during each exposure. Chamber oxygen concentration was targeted to be at least 19%. The oxygen concentration was measured with a Biosystems model 3100R oxygen analyzer and recorded 3 times during each exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.1 and 1.8 mg/l
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Two groups of 6 male rats each were exposed to aerosol atmospheres of H-25777 in air. Rats were exposed nose-only for a single, 4-hour period. Following exposure, 3 rats from the 0.10 mg/L exposure were retained for a 1-day recovery period; the remaining 3 rats were retained for a 14-day recovery period. Rats from the 1.8 mg/L exposure were retained for a 14-day recovery period.
Rats were approximately 8 weeks old and weighed between 258 and 279 grams at the time of exposure.
Animals were observed for mortality 4 times during each exposure and observed for mortality and clinical signs of toxicity immediately after exposure. During the recovery period, all rats were observed each day for mortality. Rats were weighed and observed for clinical signs of toxicity on the day following exposure and at least twice more during the recovery period. At the end of both recovery periods, all rats from the 0.10 mg/L group were sacrificed for anatomic pathology evaluation. All rats from the 1.8 mg/L exposure were sacrificed by carbon dioxide asphyxiation and discarded.
Anatomic Pathology Evaluation
All animals from the 0.10 mg/L exposure underwent a gross pathology examination at sacrifice. In addition, the lungs, trachea, nose (4 cross sections), larynx, and pharynx were processed for histopathology and microscopically examined. Lung weights were obtained for the 3 animals sacrificed 1 day after exposure to 0.10 mg/L.
Statistics:
no applicable
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.8 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Other than slight body weight losses measured in 3 of 6 rats one day after exposure to 1.8 mg/L of H-25777, there were no significant clinical signs observed in the exposed rats at either test concentration.
Mortality:
No deaths occurred during the study.
Clinical signs:
other: No clinical signs of toxicity were observed during the remainder of the recovery period.
Body weight:
No body weight losses were observed in rats exposed to 0.10 mg/L immediately after exposure or after the 14-day recovery period.
Three of 6 rats exposed to 1.8 mg/L showed slight weight loss (<10 grams) on the day following exposure, followed by a normal weight gain rate (approximately 5- 10 g/day) for the remainder of the recovery period.
Gross pathology:
There were no appreciable differences between the 2 groups. The alveolar hemorrhages were very minimal, and were likely agonal changes occurring at the time of sacrifice.
Lung weights in 3 rats sacrificed 1 day after exposure to H-25777 at 0.10 mg/L did not appear to be different from control rats of similar weights in a recent Haskell Laboratory inhalation study.
Although no concurrent controls were provided, the changes present in the tissues examined were considered to be of the type and severity expected in this strain of rats, and none of them appeared to be the result of treatment.
Other findings:
Exposure Conditions
Animals were exposed to H-25777 at mean concentrations of 0.10 or 1.8 mg/L. The atmospheres generated in this study were considered to be marginally respirable in rats, as the mass median aerodynamic diameters (MMAD) were 5.8 and 6.8 µm. Several attempts were made to produce a smaller, more respirable aerosol size; however, it appeared that this could not be accomplished at these high concentrations due to the condensation aerosol forming large particle agglomerates.
Chamber temperature ranged from 23 to 24 °C, chamber relative humidity ranged from 46 to 68%, chamber airflow ranged from 15 to 25 L/min, and the oxygen concentration was 21%.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, it can be concluded that LC50 of test article is considered to be greater than 1.8 mg/L after nose-only for a single, 4-hour exposure.
However, the mass median aerodynamic diameter (MMAD) of the tested aerosol at this concentration was 6.8 µm. Targeted MMADs in inhalation studies are from 1 - 4 µm to allow maximum lung exposure. Several attempts were made to produce smaller, more respirable aerosol size; however, it appeared that this could not be accomplished at these high concentrations due to the condensation aerosol forming large particle agglomerates. Thus the inhalation hazard cannot be determined since the aerosols formed were not respirable to the rats, particularly the pulmonary region.
Executive summary:

The study was performed to determine a 4-hour inhalation approximate lethal concentration (ALC) of test article in male rats. Two groups of 6 male rats each were exposed to aerosol atmospheres of test article in air. Rats were exposed nose-only for a single, 4-hour period. Following exposure, 3 rats from the 0.10 mg/L exposure were retained for a 1-day recovery period. Rats from the 1.8 mg/L exposure were retained for a 14-day recovery period. At the end of both recovery periods, all rats from the 0.10 mg/L group were sacrificed for anatomic pathology evaluation. All rats from the 1.8 mg/L exposure were sacrificed by carbon dioxide asphyxiation and discarded. Other than slight body weight losses measured in 3 of 6 rats one day after exposure to 1.8 mg/L of H-25777, there were no significant clinical signs observed in the exposed rats at either test concentration. Histological examination of rats exposed to 0.10 mg/L showed no treatment- related effects.

Therefore, the LC50 of test article is considered to be greater than 1.8 mg/L based on the results of this study.

However, the mass median aerodynamic diameter (MMAD) of the tested aerosol at this concentration was 6.8 µm. Targeted MMADs in inhalation studies are from 1 - 4 µm to allow maximum lung exposure. Several attempts were made to produce smaller, more respirable aerosol size; however, it appeared that this could not be accomplished at these high concentrations due to the condensation aerosol forming large particle agglomerates. Thus the inhalation hazard cannot be determined since the aerosols formed were not respirable to the rats, particularly the pulmonary region.

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment.
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
From the toxicokinetic assessment as well as from results of the hydrolysis study it is known that the target chemical 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl acrylate becomes hydrolysed in vivo to the alcohol and the acrylic acid moiety. Whereas acrylic acid is intensively investigated for health endpoints and does not show significant acute inhalation toxicity, data was required for the corresponding alcohol, 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanol (the source chemical), thereby being in a position to conclude upon acute toxicity by inhalation of the target chemical.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Both, source chemical as well as target chemical are of high purity (>90%) and it is expected that study results were not compromised by any impurities being present, considering, that typical impurities do only differ by chain length of the fluorinated part of the alcohol moiety.
3. ANALOGUE APPROACH JUSTIFICATION
Based on the TK assessment as well as from results of the hydrolysis study the target chemical 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl acrylate breaks down in vivo to the alcohol and the acrylic acid moiety. The resulting alcohol, 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanol (the source chemical), thereby is being formed in vivo rapidly in the respiratory tract and becomes decisive as metabolite for systemic toxicity as distributed in the organism. Hence, using acute toxicity data from the metabolite 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanol for read-across to 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl acrylate (target chemical) is justified.
4. DATA MATRIX
Log Pow values are not significantly different (4.54 for source chemical versus 5.07 of target chemical). However, the water solubility of the source chemical is by two orders of magnitude higher (18.8 mg/L) than that of the target chemical (0.185 mg/L) suggesting that absorption and distribution in vivo will be quicker, and thus the source chemical may be seen as a worst case surrogate for the target chemical, which requires absorption and metabolisation prior to efficient distribution in vivo. In consequence, the data for acute inhalation toxicity of the source chemical may be seen as a worst case surrogate for the target chemical 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl acrylate, justifying the read-across approach.
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
Qualifier:
according to guideline
Guideline:
other: EEC Methods for the Determination of Toxicity Method B.2 Directive 92/69/EEC
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
Qualifier:
according to guideline
Guideline:
other: MAFF Japan Agricultural Chemicals Regulation Laws 2-1-3 Notification 12 Nousan 8147 and Notification 13 Seisan 1739
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
GLP compliance:
yes
Test type:
traditional method
Limit test:
no
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.2 - < 9.9 mg/L air
Exp. duration:
4 h
Remarks on result:
other: Subsequent Probit analysis of the results listed in this acute inhalation study yielded a 4-hour LC50 in rats of 7.2 mg/L total (5.2 mg/L aerosol). The 5.2 mg/L value will be used for purposes of classification and labelling.
Mortality:
No rats died after the 5.2 mg/L exposure, and all rats died as a result of the 9.9 mg/L exposure.
Interpretation of results:
GHS criteria not met
Conclusions:
LC50 of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanol (the source chemical): > 5.2 mg/L and < 9.9 mg/L (mainly aerosol, 1.6 and 7.1 mg/L, respectively)
The study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

Groups of 5 male and 5 female Crl:CD(SD) rats were exposed nose-only for a single, 4-hour period to 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanol (the source chemical) vapour or vapour/aerosol mixtures in air. After exposure, surviving rats were weighed and observed for clinical signs of toxicity during a 14-day recovery period. Mean exposure concentrations, determined by gas chromatography and by gravimetric measurement were 0.65, 1.7, 5.2, or 9.9 mg/L (combined aerosol/vapour). At the 5.2 and 9.9 mg/L concentrations, there was 1.6 and 7.1 mg/L of aerosol present in the respective chamber atmospheres. There was no appreciable aerosol (approximately <0.1 mg/m³) present in the 0.65 and 1.7 mg/L chambers. All rats died from one to 6 days after exposure at 9.9 mg/L. No deaths occurred at the other 3 exposure concentrations.

Slight weight losses (<5%) occurred in rats exposed to 0.65, 1.7, and 5.2 mg/L, while severe weight losses (>10%) occurred in rats exposed at 9.9 mg/L. At the non-lethal concentrations (0.65, 1.7, and 5.2 mg/L), ocular or nasal discharges were observed in most male rats after exposure and in 1, 3, and 5 females at each of the concentrations, respectively. There was also alopecia observed in one male and one female rat. These are common findings in rats while under restraint in inhalation studies. Other sporadic findings included wet fur in one female rat in the 5.2 mg/L group. At the lethal concentration (9.9 mg/L), laboured breathing was observed in all rats.

Since no rats died after the 5.2 mg/L exposure, and all rats died as a result of the 9.9 mg/L exposure, consisting mainly of aerosol (7.1 mg/L), the 4-hour inhalation median lethal concentration (LC50) was > 5.2 mg/L and < 9.9 mg/L. Subsequent Probit analysis of the results listed in this acute inhalation study yielded a 4-hour LC50 in rats of 7.2 mg/L total (5.2 mg/L aerosol). The 5.2 mg/L value is used for the purposes of classification and labelling, considered as aerosol value.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The mass median aerodynamic diameter (MMAD) of the tested aerosol at this concentration was 6.8 µm. Targeted MMADs in inhalation studies are from 1 - 4 µm to allow maximum lung exposure. Several attempts were made to produce smaller, more respirable aerosol size; however, it appeared that this could not be accomplished at these high concentrations due to the condensation aerosol forming large particle agglomerates. Thus the inhalation hazard cannot be determined since the aerosols formed were not respirable to the rats, particularly the pulmonary region.
In a second read-across study, using 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanol as the source chemical, at 5.2 mg/L no mortality was observed in an acute inhalation study whereas at 9.9 mg/L all animals died within the observation period. The highest concentration tested (9.9 mg/L) consisted mainly of aerosols (7.1 mg/L), whereas the dose at 5.2 mg/L only contained 1.6 mg/L as aerosol. Therefore, comparing with the cut-off value of 5 mg/L for classification of aerosols in CLP, the alcohol, a direct metabolite of the target chemical, is not subject to classification under CLP.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

In a valid study on oral acute toxicity according to OECD TG 425, LD50 of the substance has been determined to be greater than 5000 mg/kg bw. The results are confirmed by a supporting acute oral toxicity study according to OECD TG 420 (Fixed Dose Method) showing no toxicity when dosed at 2000 mg/kg bw.

Therefore, according to criteria of Regulation (EC) No. 1272/2008, classification for oral acute toxicity is not required.

 

There is no direct information of inhalation route for target substance. Considering the structural similarity, another study conducted with the Acrylate Monomer - C8 analogue was chosen for read across. In this study, 6 male rats were exposed nose-only for a single, 4-hour period to test item in air at mean concentrations of 0.10 or 1.8 mg/L. Other than slight body weight losses measured in 3 of 6 rats one day after exposure to 1.8 mg/L of test article, there were no significant clinical signs observed in the exposed rats at either test concentration. Histological examination of rats exposed to 0.10 mg/L showed no treatment-related effects. Thus, 1.8 mg/L was considered to be the LC50 of test article for acute inhalation. The LC50 of target test is therefore expected to be >1.8 mg/L. However, the mass median aerodynamic diameter (MMAD) of the tested aerosol at this concentration was 6.8 µm. Targeted MMADs in inhalation studies are from 1 - 4 µm to allow maximum lung exposure. Several attempts were made to produce smaller, more respirable aerosol size; however, it appeared that this could not be accomplished at these high concentrations due to the condensation aerosol forming large particle agglomerates. Thus the inhalation hazard cannot be determined since the aerosols formed were not respirable to the rats, particularly the pulmonary region.

The LC50 of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanol (the source chemical) used as supportive study for the corresponding acrylate was found to be > 5.2 mg/L and < 9.9 mg/L (mainly aerosol, 1.6 and 7.1 mg/L, respectively). No mortality was observed at 5.2 mg/L in this acute inhalation study whereas at 9.9 mg/L all animals died within the observation period. The highest concentration tested (9.9 mg/L) consisted mainly of aerosols (7.1 mg/L), whereas the dose at 5.2 mg/L only contained 1.6 mg/L as aerosol. Therefore, comparing with the cut-off value of 5 mg/L for classification of aerosols in CLP, the alcohol, a direct metabolite of the target chemical, is not subject to classification under CLP, which supports non-classification of the target chemical 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl acrylate for acute inhalation toxicity.

 

No studies are available for dermal acute toxicity.