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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:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
male animals only used
GLP compliance:
not specified
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
A single 600 lb sample of d-limonene stabilised production grade TFE, 99.3% minimum purity, was provided by EI du Pont de Nemours and Company and was used for all studies. The d-limonene present at approximately 4 ppm, was removed prior to atmosphere generation by in-line silica gel traps.
Impurities detected in the TFE sample by gas chromatographic analysis are summarised in table 1.

Test animals

Species:
hamster
Strain:
other: Lak:LVG (SYR)
Sex:
male
Details on test animals and environmental conditions:
Lak:LVG (SYR) hamsters (Charles River Breeding Laboratories, Wilmington MA) were housed in suspended stainless steel, wire-mesh cages which were separate from the exposure rooms. They were caged singly in compartmentalised modules during exposure. Control animals were housed in separate rooms from the TFE-exposed animals. The animal rooms were maintained on a 12-hour photoperiod with temperature and relative humidity averaging 23 +/- 3 °C and 55 +/- 5% respectively.
Certified Purina Rodent Chow® 5002 and tap water were available ad libitum. All animals were monitored for overt manifestation of disease during a pre-test period of 1 week.
During exposure, chamber temperatures were monitored hourly and ranged 21 - 25 °C.

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
During exposure , hamsters were housed in compartmentalized modules and placed in 150 litre glass and stainless-steel chambers.

The TFE was piped from the cylinder manifold through a single ¼” O.D. stainless steel line to a single stage regulator. TFE was carried from the regulator through ¼” O.D. Teflon® lines and metered through a brooks R2-15A flowmeter to the exposure chamber. The stream entered the chamber through a port located in the top of the chamber. Samples were taken from the ports in the side of the chamber.

D-limonene, a stabilizer in the TFE sample, was removed from the TFE with a silica gel trap located between the regulator and flowmeter.

Gas samples were collected from the inhalation exposure chamber every 15 minutes using a 1 ml gas tight Tekmar syringe and analysed by gas chromatography. The TFE concentrations were calculated by comparison with standards. A mean concentration and standard deviation were calculated for each 4 hour exposure.

Chamber temperature was monitored hourly using a mercury thermometer. Oxygen was monitored hourly with a Biomarine Industries Model 225 Oxygen analyser.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Exposure atmospheres were analysed by a Hewlett Packard Model 5710A Gas Chromatograph (CD) equipped with a Flame Ionisation Detector (FID). Samples and standards were chromatographed on a 6 ft x 1/4 in OD glass coil packed with 10% SE 30 on 60/80 mesh Chr
Duration of exposure:
4 h
Concentrations:
0, 10200, 20700, 25000, 30000, 40100 or 78100 ppm
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
Groups of ten 7-week old male hamsters were exposed, whole body, to TFE atmospheres for single 4-hour periods. Hamsters were observed for toxic signs during the exposure period and survivors were weighed and observed daily during a 14-day post-exposure period. Tissue and clinical pathology examinations were not performed.
Statistics:
The LC50 was determined by the probit method of Finney.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
28 500 ppm
Exp. duration:
4 h
Mortality:
1/10 died at 25000ppm; 7/10 at 30000ppm; 10/10 at 40100 and 78100ppm
Clinical signs:
other: Lethargy at 40100 and 78100ppm
Body weight:
Post exposure weight loss wa s mild at 10 200 ppm but moderate at 20 700 ppm or more.

Any other information on results incl. tables

Male hamsters exposed to TFE vapours for single 4 -hour exposure periods exhibited no signs of toxicity at 30 000ppm or less, salivation and lethargy at 40 000ppm, and a clear nasal discharge and lethargy at 78 000 ppm. Post-exposure weight loss was mild at 10 200 ppm but moderate at 20 700 ppm or more. Clear nasal and ocular discharges and lethargy were noted in hamsters exposed to 30 000 ppm or more during the post-exposure period. All deaths occurred from 1 to 10 days after exposure at the highest and lowest lethal concentrations, respectively. The LC 50 of TFE in the hamster was calculated to be 28 500 ppm (116 500 mg/m3) with confidence limits of 26 400 - 31 500 ppm.

Table 2: Mortality of Hamsters vs 4 hour exposure concentrations of TFE

Concentration (ppm)

S.D.

Fractional Mortality No. Deaths / No. Exposed

Time of Death

No. Hamsters / No. of Days

10 200

852

0/10

-

20 700

1239

0/10

-

25 000

1449

1/10

1@7

30 000

1233

7/10

3@6

2@7

2@8

40 100

1945

10/10

6@4

3@5

1@10

78 700

4914

10/10

1@1

2@2

2@3

5@4

Table 3: Observations in Hamsters vs 4 hour exposure concentrations.

Concentration (ppm)

Observations during exposure

Observations post exposure

10 200

None

Slight weight loss

1 day post exposure, normal

weight gain thereafter

20 700

None

Moderate weight loss 1-3 days post exposure, normal weight gain thereafter

25 000

None

Moderate weight loss 1-6 days post exposure, normal weigh gain thereafter

30 000

None

Moderate weight loss 1-11 days post exposure, normal weight gain thereafter

40 100

Salivation, lethargy

Moderate weigh loss until death, sluggishness, discharge from eyes

78 700

Reduced response to sound, clear discharge from eyes

Moderate weight loss until death, sluggishness, clear discharge from eyes and nose, and eyes closed.

Applicant's summary and conclusion

Interpretation of results:
other: Not classifiable for acute toxicity based on the LC50 of 116 508 mg/m3 (28 500 ppm) ie. LC 50 > 20 mg/l
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC 50 of TFE in the hamster was calculated to be 28 500 ppm (116 500 mg/m3).
Executive summary:

The toxic effects of inhaled tetrafluoroethylene (TFE) were investigated in an acute study with male Lak: LVG (SYR) hamsters.

The LC 50 of TFE in the hamster was calculated to be 28 500 ppm (116 500 mg/m3) with confidence limits of 26 400 - 31 500 ppm.