Hexafluoropropene

Acute Toxicity: inhalation

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

Test material information

Constituent 1

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 levels

Effect levels 1

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

Effect levels 2

Sex:

male

Dose descriptor:

other: NOAEL

Effect level:

140 ppm

Effect levels 3

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.