Tetradecafluorohexane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study will be available 29/07/2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

maximum level of daily mean target humidity on two days = 72%. Not affecting the results.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

maximum level of daily mean target humidity on two days = 72%. Not affecting the results.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

maximum level of daily mean target humidity on two days = 72%. Not affecting the results.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetradecafluorohexane

EC Number:

206-585-0

EC Name:

Tetradecafluorohexane

Cas Number:

355-42-0

Molecular formula:

C6F14

IUPAC Name:

tetradecafluorohexane

Test material form:

liquid

Specific details on test material used for the study:

Identification: Tétradécafluorohexane
Appearance: Clear colourless liquid
Stable under storage conditions until: 21 February 2020 (expiry date)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose of test item was administered to the appropriate animals by oral gavage on Day
1, using a syringe with a plastic gavage cannula attached.
The dose volume for each animal was based on the body weight measurement prior to dosing.
Dose volume (mL/kg body weight) was calculated as follows:
Dose level (g/kg) / spec.gravity or density (g/mL).
For calculation of dose volume a specific gravity of 1.688 was used, this was later amended to
1.669. Actual given dose based on the amended specific gravity was calculated to be 1977
mg/kg. As the difference between intended dose and actual dose is minor and no differences
in outcome are expected, the dose is reported throughout the report as 2000 mg/kg.
The dosing formulations were stirred continuously during dose administration.
Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and
until 3-4 hours after administration of the test item. Water was available.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

yes

Remarks:

3

Details on study design:

4.8. Experimental Design
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The
absence or presence of mortality of animals dosed at one step determined the next step, based
on the test procedure defined in the guidelines. The onset, duration and severity of the signs
of toxicity were taken into account for determination of the time interval between the dose
groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one
additional group was dosed at 2000 mg/kg.
4.8.1. Administration of Test item
A single dose of test item was administered to the appropriate animals by oral gavage on Day
1, using a syringe with a plastic gavage cannula attached.
The dose volume for each animal was based on the body weight measurement prior to dosing.
Dose volume (mL/kg body weight) was calculated as follows:
Dose level (g/kg) / spec.gravity or density (g/mL).
For calculation of dose volume a specific gravity of 1.688 was used, this was later amended to
1.669. Actual given dose based on the amended specific gravity was calculated to be 1977
mg/kg. As the difference between intended dose and actual dose is minor and no differences
in outcome are expected, the dose is reported throughout the report as 2000 mg/kg.
The dosing formulations were stirred continuously during dose administration.
Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and
until 3-4 hours after administration of the test item. Water was available.
4.8.2. Justification of Route and Dose Levels
The oral route was selected as it is a possible route of human exposure during manufacture,
handling or use of the test item.
The dose levels were based on the OECD test guidelines and were selected from the series 5
(lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting
dose level should be the one that is likely to produce mortality in at least some of the animals
and was selected based on available toxicity data of the test item.
4.9. In-life Procedures, Observations, and Measurements
4.9.1. Mortality/Moribundity Checks
Throughout the study, animals were observed for general health/mortality and moribundity
twice daily, in the morning and at the end of the working day. Animals were not removed
from cage during observation, unless necessary for identification or confirmation of possible
findings.
4.9.2. Clinical Observations
4.9.2.1. Postdose Observations
Postdose observations were performed at periodic intervals on the day of dosing (at least three
times) and once daily thereafter. The observation period was 14 days.
All the animals were examined for reaction to dosing. The onset, intensity and duration of
these signs was recorded (if appropriate). Signs were graded for severity and the maximum
grade was predefined at 3 or 4. Grades were coded as slight (grade 1), moderate (grade 2),
severe (grade 3) and very severe (grade 4). For certain signs, only its presence (grade 1) or
absence (grade 0) was scored.
4.9.3. Body Weights
Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was
recorded on the day of dosing.
4.10. Terminal Procedures
All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation
period. All animals assigned to the study were subjected to necropsy and descriptions of all
internal macroscopic abnormalities were recorded.
5. ANALYSIS
All results presented in the tables of the report are calculated using values as per the raw data
rounding procedure and may not be exactly reproduced from the individual data presented.
The oral LD50 value of the test item was ranked within the following ranges: 0-5, 5-50, 50-
300 or 300-2000 mg/kg b.w. or as exceeding 2000 mg/kg b.w. The LD50 cut-off value was
established based on OECD guideline 423. No statistical analysis was performed (The
method used is not intended to allow the calculation of a precise LD50 value).
The results were evaluated according to:
 Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the
United Nations (2017) (including all amendments).
 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16
December 2008 on classification, labelling and packaging of items and mixtures
(including all amendments).
6. COMPUTERIZED SYSTEMS
Critical computerized systems used in the study are listed below. All computerized systems
used in the conduct of this study have been validated; when a particular system has not
satisfied all requirements, appropriate administrative and procedural controls were
implemented to assure the quality and integrity of data.

7. RETENTION OF RECORDS
All study-specific raw data, documentation, study plan and final report from this study were
archived at the Test Facility by no later than the date of final report issue. At least five years
after issue of the final report, the Sponsor will be contacted.
Electronic data generated by the Test Facility were archived as noted above.

Statistics:

No statistical analysis will be performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Hunched posture, piloerection and/or chromodacryorrhoea (snout) were noted for the animals on Day 1.

Body weight:

The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
The incidence of slight body weight loss on Day 15 in one animal was considered not indicative of toxicity, based on the absence of any corroborative findings in this animal.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

TABLE 1 MORTALITY DATA

 

 

TEST DAY	1	1	1	2	3	5	6	7	8	9	10	11	12	13	14	15
HOURS AFTER TREATMENT	0	2	4
FEMALES 2000 MG/KG	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
FEMALES 2000 MG/KG	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

   

TABLE 2 CLINICAL SIGNS

TEST DAY		1	1	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15
HOURS AFTER TREATMENT		0	2	4
	MAX GRADE
FEMALES 2000 MG/KG
ANIMAL 1
Posture Hunchedposture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Skin / fur
Piloerection	(1)	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Secretion / excretion
Chromodacryorrhoea(Snout)	(3)	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 2
Posture
Hunchedposture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Skin / fur
Piloerection	(1)	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Secretion / excretion
Chromodacryorrhoea(Snout)	(3)	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 3
Posture
Hunchedposture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Skin / fur
Piloerection	(1)	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Secretion / excretion
Chromodacryorrhoea (Snout)	(3)	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 4
Posture
Hunchedposture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 5
Posture
Hunchedposture	(1)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
ANIMAL 6
Posture
Hunchedposture	(3)	1	1	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-

- = Sign not observed

TABLE 3 Body Weights (Grams)                  

 

SEX/DOSE LEVEL	ANIMAL	DAY 1	DAY 8	DAY 15
FEMALES 2000 MG/KG	1	145	182	188
	2	156	194	199
	3	166	205	213
	MEAN	156	194	200
	ST.DEV.	11	12	13
	N	3	3	3
FEMALES 2000 MG/KG	4	193	216	211
	5	180	212	219
	6	159	189	200
	MEAN	177	206	210
	ST.DEV.	17	15	10
	N	3	3	3

TABLE 4 Macroscopic Findings

                                                      

ANIMAL  ORGAN	FINDING	DAY OFDEATH
FEMALES 2000 MG/KG
1	No findings noted	Scheduled necropsy Day 15 after treatment
2	No findings noted	Scheduled necropsy Day 15 after treatment
3	No findings noted	Scheduled necropsy Day 15 after treatment
FEMALES 2000 MG/KG
4	No findings noted	Scheduled necropsy Day 15 after treatment
5	No findings noted	Scheduled necropsy Day 15 after treatment
6	No findings noted	Scheduled necropsy Day 15 after treatment

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

The oral LD50 value of Tétradécafluorohexane in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, Tétradécafluorohexane does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Conclusions:

The oral LD50 value of Tétradécafluorohexane in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, Tétradécafluorohexane does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The objective of this study was to determine the potential toxicity of Tétradécafluorohexane, when given by oral gavage at a single dose to rats of a single sex at one or more defined doses to evaluate the potential reversibility of any findings.

The study was carried out in compliance with the guidelines described in:

·       OECD No.423 (2001)"AcuteOral Toxicity, Acute Toxic ClassMethod"

·       EC No 440/2008, partB: "AcuteOral Toxicity, Acute Toxic ClassMethod"

·       EPA, OPPTS 870.1100 (2002),"AcuteOralToxicity"

·       JMAFF Guidelines (2000), including the most recentrevisions.

 

Tétradécafluorohexane was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

 

No mortality occurred.

Hunched posture, piloerection and/or chromodacryorrhoea (snout) were noted for the animals on Day 1.

The mean body weight gain shownbythe animals over the study period was considered tobesimilar to that expected for normal untreated animals of the same ageandstrain. The incidence of slight body weight loss on Day 15 inoneanimal was considerednotindicative of toxicity, basedontheabsence ofanycorroborative findings in thisanimal.

No abnormalities were found at macroscopic post mortem examination of the animals.

 

The oral LD50 value of Tétradécafluorohexane in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, Tétradécafluorohexane does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).