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Toxicological information

Acute Toxicity: inhalation

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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:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1960
Report date:
1960

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexafluoropropene
EC Number:
204-127-4
EC Name:
Hexafluoropropene
Cas Number:
116-15-4
Molecular formula:
C3F6
IUPAC Name:
1,1,2,3,3,3-hexafluoroprop-1-ene
Constituent 2
Reference substance name:
1-Propene, hexafluoro-
IUPAC Name:
1-Propene, hexafluoro-
Details on test material:
Purity: 99.9% (Sample 1); 98.5% (Sample 2)

Test animals

Species:
rat
Strain:
other: Charles River CD
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: Rats were allowed 24 hours to become accustomed to the cages

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: Air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE/CHAMBER DESCRIPTION:
- Exposure apparatus: Chamber was a cubical enclosure constructed of stainless steel and glass.
- Exposure chamber volume: 200- or 10000-liter-capacity chambers were used.
- Method of holding animals in test chamber: Animals were housed without food or water in two raised bottom cages made of galvanized screen. Five rats were placed in each cage, the dimensions of which were 9"X9"X15."
- System of generating particulates/aerosols: HFP was lead in copper tubing from the supply tank through a flow metering system of Fisher-Porter "Tri Flat" precison bore, flowrators and into a mixing manifold. Air was directed into the mixing manifold of the chamber through a high capacity rotometer which was rated at a maximum flow of 165 L/min. For the low flow rates used, a flowrator was employed whose maximum capacity was about 23 L/min. Flows of HFP and air were metered at a pressure slightly above one atmosphere on the intake side of the chamber which was consequently under positive pressure. The HFP-air mixture was exhausted from the chamber through a copper pipe. The exhaust of the chamber was accomplished by adjustment of the dampers in the exhaust ducts. The chamber was cleared of gases by opening the exhaust dampers and using an exhaust fan. When the 10000 L chamber was used, a mixing fan was also used in the chamber.

TEST ATMOSPHERE:
- Brief description of analytical method used: Spectrophotometric technique by adding piperidine and pyridine, and measuring at 420 microns. The concentration was computed from a previously derived calibration curve.
- Samples taken from breathing zone: No data.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Atmosphere was sampled from the center of the chamber, dried w/sulfuricacid scrubbing units and absorbed by absolute methanol; contents of absorbers were placed into 200-mL flasks, liquid was measured spectrophotometrically at a wave length of 420 microns
Duration of exposure:
4 h
Concentrations:
3440 ppm; 3400 ppm; 3020 ppm; 2870 ppm; 2600 ppm; 2520 ppm; 2220 ppm; 1980 ppm; 1520 ppm; 1090 ppm; 690 ppm; 320 ppm; 140 ppm
No. of animals per sex per dose:
10 male albino Charles River CD rats per exposure.
Control animals:
no
Details on study design:
Rats were allowed 24 hours to become accustomed to the cages; the following 24 hours urine was collected for measurements of volume and osmolality, and food and water consumption were determined. Post-exposure measurements where taken daily for 14 days after exposure and again for a 24-hour period at 3 and 4 weeks post-exposure for surviving rats.
Statistics:
LC50 was computed by the method of Litchfield JT and Wilcoxin F (1949) A Simplified Method of Evaluating Dose-Effect Experiments. J. Pharmacol. Experimental Therapeutics, 96:99.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
3 060 ppm
95% CL:
2 780 - 3 370
Exp. duration:
4 h
Remarks on result:
other: Time of death varied from 2 to 12 days
Sex:
male
Dose descriptor:
other: NOAEL
Effect level:
140 ppm
Sex:
male
Dose descriptor:
other: LOAEL (kidney morphology)
Effect level:
320 ppm
Remarks on result:
other: Kidney function adverse effects at >320 ppm. Observed effects from 320 to 2600 ppm were predominantly healing (reversible) nephrosis. However, at concentrations of ≥2870 ppm, kidney effects were identified as nephrosis without evidence of reversibility.
Mortality:
Deaths were observed at concentrations of 2220 ppm and greater.
Clinical signs:
other: Animals showed pallor and discomfort during last hour at 2520 ppm to 3440 ppm exposure. Immediately following the exposures, animals were limp, weak, consumed little food, high urine volume, low urine osmolality and were very thirsty. Some animals had dia
Body weight:
Animals exposed above 320 ppm show retardation of weight gain. Rats which survived usually showed gains in weight by the tenth day after exposure at the latest.
Gross pathology:
At exposures above 140 ppm, animals showed nephrosis; kidney damage was seen in exposures of 320 ppm or greater.
Other findings:
Kidney function adverse effects seen between 320 and 690 ppm; kidney morphology effects were seen at 320 ppm. MIcroscopic examination of the tissues from rats exposed above 140 ppm disclosed that the major anatomical change was nephrosis. The lowest level at which an effect was observed was 320 ppm. At 140 ppm, the rats appeared normal in all respects.

Any other information on results incl. tables

 

Time of Survival (days)

 

Pathology

Concentration (ppm)

Chamber Size (L)

Mortality

Death

Sacrifice

Decreased Urine Osmolality

Decreased Urine Volume

Decreased Body Weight

Kidney Weight (g)

Kidney

Other

3440

10000

6/10

3-9

15

Not Det'd

Not Det'd

10/10

Not Done

9/10 Nephrosis
1/10 Healing Neph.

None

3400

200

4/10

2-5

12

Not Det'd

Not Det'd

10/10

Not Done

Not Det'd

Not Det'd

3020

10000

4/10

7-12

15

Not Det'd

Not Det'd

10/10

Not Done

6/10 Nephrosis
4/10 Healing Neph.

1/10 Myocarditis

2870

200

8/10

4-9

14

Not Det'd

Not Det'd

10/10

4.34

10/10 Nephrosis

2/10 Myocarditis

2600

10000

0/10

-

15

Not Det'd

Not Det'd

10/10

Not Done

2/10 Nephrosis
8/10 Healing Neph.

1/10 Broncho-pneumonia

2520

200

2/10

5,10

17

Not Det'd

Not Det'd

10/10

4.61

8/10 Healing Neph.
2/10 Acute Neph.

None

2220

200

1/10

4

28

10/10

10/10

10/10

3.17

9/10 Healing Neph.
1/10 Acute Neph.

2/10 Broncho-pneumonia

1980

200

0/10

-

14

Not Det'd

Not Det'd

10/10

3.71

10/10 Healing Neph.

None

1520

200

0/10

-

28

10/10

10/10

10/10

3.61

5/10 Healing Neph.
5/10 Nephrosis

1/10 Pneumonitis

1090

200

0/10

-

28

Not Det'd

10/10

10/10

3.65

10/10 Healing Neph.

1/10 Focal Pneumonia

690

200

0/10

-

28

10/10

10/10

7/10slight

3.22

7/10  Healing Neph.

None

320

200

0/10

-

28

1/10

3/10

5/10

2.82

5/10 Healing Neph.

1/10 Pneumonia

140

200

0/10

-

5,7

0/10

0/10

0/10

2.35

0/10 -0All NP

None

Applicant's summary and conclusion

Conclusions:
The 4-hour inhalation LC50 for male Charles River CD rats exposed to hexafluoropropene was determined to be 3060 ppm. HFP causes damage to the kidneys.

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

Rats were exposed via whole-body inhalation to 140, 320, 690, 1090, 1520, 1980, 2220, 2520, 2600, 2870, 3020, 3440 or 3440 ppm HFP for 4 hours. Animals were observed for clinical signs, body weight, food consumption, water consumption, urine volume, and urine osmolality for approximately two weeks post-exposure. A pathological exam was conducted at the end of the post-exposure period. The 4-hour inhalation LC50 for rats was found to be 3060 ppm. HFP caused damage to the kidneys.