Norflurane

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

publication

Title:

Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) HFC 227 (1,1,1,2,3,3,3-heptafluorpropane) following whole body exposure.

Author:

Emmen HH et al

Year:

2000

Bibliographic source:

Regul Toxicol Pharmacol 32:33-35

Materials and methods

Study type:

study with volunteers

Endpoint addressed:

basic toxicokinetics

repeated dose toxicity: inhalation

Test material

Test material information

Constituent 1

Reference substance name:

Norflurane

EC Number:

212-377-0

EC Name:

Norflurane

Cas Number:

811-97-2

Molecular formula:

C2H2F4

IUPAC Name:

1,1,1,2-tetrafluoroethane

Method

Subjects:

- Number of subjects exposed: 8
- Sex: 4 makes / 4 females
- Known diseases: none - healthy
- Other:

Route of exposure:

inhalation

Reason of exposure:

intentional

Details on exposure:

1 hour / week whole body exposure to air alone for first week and then during 7 suceeeding weeks to ascending concentrations of 1000, 2000, 4000, 8000 ppm HFC 134a.

Examinations:

clinical observation, pulse, blood pressure, electrocardiogram, lung function

Results and discussion

Clinical signs:

No observed adverse effects

Results of examinations:

No evidence of effects on the central nervous system, no symptoms of respiratory irritation, no adverse effects on pulse, blood pressure or lung function.
HFC 134a blood concentrations increased rapidly and in an exposure-dependent manner. They approached steady state within 30 minutes and tended to be higher in males than in females. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration.
The alpha elimination half-life (t½α) was less than 11 minutes, while the beta elimination half-life (t½β) was 42 minutes. The mean residence time was 44 minutes.

Applicant's summary and conclusion

Conclusions:

It was concluded that, under the text conditions, human exposure to HFC-134a did not result in any adverse effects on pulse, blood pressure, electrocardiogram or lung function .

Executive summary:

A clinical study was conducted in which HFC-134a vapour was administered (1 h/wk, whole-body exposure) for 8 weeks to healthy volunteers (4 male, 4 female) by inhalation first to air alone and then to ascending concentrations of 1,000, 2,000, 4,000 and 8,000 ppm (4,170, 8,340, 16,700, 33,400 mg/m3) interspersed with a second air exposure and two exposures to CFC-12 at 1,000 and 4,000 ppm. Blood pressure, blood levels of HFC-134a, pulse, cardiac function, respiratory function and effects on the CNS were measured and evaluated. There were no notable adverse effects, no evidence of effects on the central nervous system, and no symptoms of upper respiratory tract irritation. HFC-134a blood concentrations increased rapidly and in an exposure-dependent manner. They approached steady state within 30 minutes and tended to be higher in males compared to females. Following the end of the exposure period, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. The alpha elimination half-life (t1/2a) was less than 11 minutes, while t1/2ß was 42 minutes. The mean residence time was 44 minutes. It was concluded that, under these text conditions, human exposure to HFC-134a did not result in any adverse effects on pulse, blood pressure, electrocardiogram or lung function