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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:
1993-03-29 to 1993-04-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Post-exposure period of 7 days only
Qualifier:
according to guideline
Guideline:
other: SOP of Life Science Laboratory (Japan)
Deviations:
not specified
Principles of method if other than guideline:
Study conducted in accordance with SOP of Life Science Laboratory (Japan)
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Asahi Glass Co., Ltd. (Japan); Batch no. K3135X
- Expiration date of the lot/batch: Not specified
- Purity test date: Not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Not specified
- Stability under test conditions: Stable

FORM AS APPLIED IN THE TEST (if different from that of starting material): Liquid

OTHER SPECIFICS:
Purity: 99.9 wt%
Molecular weight: 320.05
Boiling point: 70.8°C
Solubility: Oil soluble
Species:
mouse
Strain:
other: ddY
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Japan SLC, Inc.
- Age at study initiation: 4 weeks
- Weight at study initiation: Males: 24.85 - 28.84 grams; Females: 22.74 - 26.58 grams
- Fasting period before study: Food deprivation before and after dosing with the test material
- Housing: 10 animals per cage in stainless steel wire mesh cages
- Diet (e.g. ad libitum): Standard laboratory chow (NMF, Oriental Yeast Co., Ltd.) available ad libitum except before and after dosing with the test material
- Water (e.g. ad libitum): Tap water (from Chihaya-akasuka-mura water supply) available ad libitum from polycarbonate bottles
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 25°C
- Humidity (%): 50 - 70%
- Air changes (per hr): 10 or more air changes per hour
- Photoperiod (hrs dark / hrs light): 8-hour light cycle (09:00 - 17:00)

IN-LIFE DATES: Not specified
Route of administration:
oral: gavage
Vehicle:
other: Gum arabic aqueous solution (5% (w/w))
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.1, 1, 10% (w/w)
- Amount of vehicle (if gavage): 0.5 mL/10 grams body weight
- Justification for choice of vehicle: not specified

MAXIMUM DOSE VOLUME APPLIED: 0.5 ml per 10 grams body weight

DOSAGE PREPARATION (if unusual): Test substance was emulsified in 5% (w/w) gum arabic aqueous solution at 0.1, 1, & 10 % (w/w) concentrations when used.
Doses:
50, 500, and 5000 mg/Kg
No. of animals per sex per dose:
10/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Animals were observed frequently on the day of dosing and thereafter once daily for general conditions, behavior and signs of toxicity for 7 days post exposure.
- Necropsy of survivors performed: yes (gross pathological examination)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality or signs of toxicity observed at the highest dose tested.
Mortality:
None observed
Clinical signs:
other: No abnormal findings in general condition of male or female mice
Gross pathology:
No abnormal findings

Table 2. Experimental Results

Sex

Male

Female

Dose (mg/Kg) and Mortality

5000

0/10

0/10

500

0/10

0/10

50

0/10

0/10
Interpretation of results:
other: Not classified
Remarks:
GHS Criteria
Conclusions:
Based on the results observed in the study, the acute oral LD50 of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane was determined to be >5000 mg/Kg in the mouse.
Executive summary:

In a key acute oral toxicity study, the test material (1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane) was administered via oral gavage at single doses of 50, 500, or 5000 mg/Kg to male and female ddY mice (10/sex/dose).

 

Animals were observed frequently on the day of dosing and thereafter once daily for general conditions, behaviour, and signs of toxicity for 7 days post exposure. At the end of the observation period, all surviving animals were sacrificed under ether anaesthesia and necropsied for gross pathological examination.

 

No mortality was observed through the study period. No adverse effects of treatment were observed in animals of either sex exposed to the test material at doses of 50, 500, or 5000 mg/Kg.  

 

Based on the results observed in the study, the acute oral LD50 of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane was determined to be >5000 mg/Kg in the mouse.

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
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-12-10 to 1994-02-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
fixed concentration procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Asahi Glass Co., Ltd. (Japan); Batch no. 31001
- Expiration date of the lot/batch: Not specified
- Purity test date: Not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, dark place
- Stability under test conditions: Not specified

FORM AS APPLIED IN THE TEST (if different from that of starting material): Liquid

OTHER SPECIFICS:

Purity: 99.939%
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crj:CD, SPF strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan, Inc.
- Age at study initiation: 5 weeks old
- Weight at study initiation: Males: 161 - 179 grams; Females: 134 - 146 grams
- Fasting period before study: No, feeding withdrawn during exposure period
- Housing: 2-3 rats of same sex in polycarbonate cages (Tokiwa Kagaku Kikai Co., Ltd.) with hard wood chip bedding (Beta-chip, Charles River Japan Inc.). Cages were placed on a steel rack (four-tiered; Tokiwa Kagaku Kikai Co., Ltd.)
- Diet (e.g. ad libitum): Pellet diet MF: Oriental Yeast Co., Ltd.) was provided ad libitum via stainless steel feeders (Tokiwa Kagaku Kikai Co., Ltd.); feeding withdrawn during exposure period
- Water (e.g. ad libitum): Tap water (filtered and irradiated by UV) was supplied ad libitum via polycarbonate bottles (700 mL; Tokiwa Kagaku Kikai Co., Ltd.)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 25°C
- Humidity (%): 40 - 70%
- Air changes (per hr): 12 air changes per hour (all fresh air supply)
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light (07:00 - 19:00)

IN-LIFE DATES: Not specified
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: pyramidal shaped exposure chamber (800 mm W x 800 mm D x 450 mm H)
- Exposure chamber volume: 510 L
- Method of holding animals in test chamber: Male and female rats placed individually in a wire mesh cage (150 mm W x 120 mm D x 130 mm H) located in the inhalation chamber
- Source and rate of air: bubbling compressed air (7 L/min; pressure = 1.5 Kg/cm2G); blowing compressed air (2 L/min; pressure = 1.0 Kg/cm2G)
- Treatment of exhaust air: Gas was supplied to the inhalation chamber in one-pass way from the top, and was exhausted from the bottom (105 L/min, ventilation rate: 12.4 times/hr)
- Temperature, humidity, pressure in air chamber: Temperature and humidity measures every hour (Toyama's temperature and humidity measuring apparatus, Toyama Keiki Co.)

TEST ATMOSPHERE
- Brief description of analytical method used: From the inhalation chamber, 1 mL of gas was collected with an airtight syringe (2 mL) 0.5, 2.0, and 3.5 hours after the commencement of exposure and then analyzed using GC.
- Samples taken from breathing zone: not specified

VEHICLE
- Composition of vehicle (if applicable): compressed air bubbled or blown
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
10000.0 ppm (mean exposure concentration was 11100.0 ppm)
No. of animals per sex per dose:
5/sex/concentration
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical Signs: From the commencement of exposure to 2 hours after the end of the exposure, observations of all rats on clinical signs were made every hour, therafter once a day for 14 days.
Body weights: All rats were weighed just before 3, 7, & 14 days post exposure.
- Necropsy of survivors performed: yes; At the end of the 14 day observation period, animals were euthanized by severing the abdominal aorta under thiopental sodium anesthesia and then subjected to necropsy.
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LCLo
Effect level:
> 11 100 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No mortality or adverse signs of clinical toxicity observed
Mortality:
No mortality was observed through the study period
Clinical signs:
other:
Body weight:
To the end of the observation period, normal increase of body weight was observed in all male and female rats.
Gross pathology:
Necropsy did not reveal any abnormal findings.

Table 1. Exposure Concentration in the Chamber

Intended Concentration

(ppm)

Measured Concentration (ppm) by time (hours)

Mean Concentration

(ppm)

0.5

2.0

3.5

10000

11000

11400

11000

11,100

 

Table 2. Environment in the Chamber

 

Time after commencement of exposure (hours)

 

0

1

2

3

4

Temperature (°C)

23

24

24

24

24

Relative Humidity (%)

67

60

60

60

60

O2Concentration (%)

20.4

20.4

20.4

20.4

20.4

 

Table 3. Body Weight Results (grams)

Sex

Animal Number

Day After Exposure

0

3

7

14

 

 

 

Male

1

177

205

245

313

2

179

209

246

319

3

165

195

227

289

4

161

194

216

275

5

162

193

233

297

Mean

169

197.0

233

299

S.D.

8.6

10.0

12.6

17.9

 

 

 

 

Female

1

137

157

178

213

2

137

152

168

204

3

146

164

185

210

4

140

155

171

197

5

131

144

164

201

Mean

138

154

173

205

S.D.

5.4

7.3

8.3

6.5

 

Interpretation of results:
other: Not classified
Remarks:
GHS Criteria
Conclusions:
Based on the results observed in this study, the minimal lethal concentration (LCL0) of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane was determined to be >11,100 ppm.
Executive summary:

In a key acute inhalation toxicity study, the test material (1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane) was administered via whole body inhalation (vapour) to male and female SD (Crj:CD, SPF) rats (5/ex/concentration) at a concentration of 10000 ppm (measured concentration was 11,100 ppm) for a period of 4 hours.

 

From the commencement of exposure to 2 hours after the end of the exposure, all rats were observed for clinical signs every hour, and once a day thereafter for a period of 14 days. All rats were weighed just before 3, 7, & 14 days post exposure. At the end of the 14-day observation period, animals were euthanized by severing the abdominal aorta under thiopental sodium anaesthesia and then subjected to necropsy.

 

No mortality was observed through the study period and no clinical signs of test-material related toxicity were observed in animals of either sex. Normal increase in body weight was observed in all male and female rats to the end of the observation period and necropsy did not reveal any abnormal findings.

 

Based on the results observed in this study, the minimal lethal concentration (LCL0) of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane was determined to be >11,100 ppm.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
145.3 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute Oral Toxicity:

In a key acute oral toxicity study (Chihaya-akasaka Laboratory, 1993a) conducted in accordance with SOP of Life Science Laboratory (Japan), the test material (1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane) was administered via oral gavage at single doses of 50, 500, or 5000 mg/Kg to male and female ddY mice (10/sex/dose).

No mortality was observed through the study period. No adverse effects of treatment were observed in animals of either sex exposed to the test material at doses of 50, 500, or 5000 mg/Kg.  

Based on the results observed in the study, the acute oral LD50 of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane was determined to be >5000 mg/Kg in the mouse.

Acute Inhalation Toxicity:

In a key acute inhalation toxicity study (Kashima Laboratory, 1994a), the test material (1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane) was administered via whole body inhalation (vapour) to male and female SD (Crj:CD, SPF) rats (5/ex/concentration) at a concentration of 10000 ppm (measured concentration was 11,100 ppm) for a period of 4 hours.

No mortality was observed through the study period and no clinical signs of test-material related toxicity were observed in animals of either sex. Normal increase in body weight was observed in all male and female rats to the end of the observation period and necropsy did not reveal any abnormal findings.

Based on the results observed in this study, the minimal lethal concentration (LCL0) of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorohexane was determined to be >11,100 ppm (>145.3 mg/m3).

Acute Dermal Toxicity:

No studies were available for review, however the physciochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin.

Justification for classification or non-classification

Not classified for acute lethality by the oral or inhalation routes of exposure under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. A low vapour pressure indicates that exposure via the inhalation route is unlikely.