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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Published peer reviewed results from high quality research organization

Data source

Reference
Reference Type:
publication
Title:
Experimental exposure to 1,1,1-trifluoroethane (HFC-143a): Uptake, disposition and acute effects in male volunteers
Author:
Gunnare, S. Ernstgard, l., Sjogren, B, Johanson, g.
Year:
2007
Bibliographic source:
Toxicology Letters, 172, 120-130

Materials and methods

Type of study / information:
Nine male volunteers were experimentally exposed to 500 ppm HFC-143a for 2-hr during light exercise (50W) in an exposure chamber. Blood urine and exhaled air were sampled before, during and after exposure and analyzed for HFC-143a by gas chromatography. These data were described by a PBTK model. The electrocardiograms of the volunteers were monitored during exposure. Volunteers rated symptoms related to irritation and CNS-symptoms on a visual analog scale. Inflamatory markers and uric acid were analyzed in plasma collected before and 21 hr after exposure. The exposures were preformed after informed consent and ethical approval.
Endpoint addressed:
acute toxicity: inhalation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Nine male volunteers were experimentally exposed to 500 ppm HFC-143a for 2-hr during light exercise (50W) in an exposure chamber. Blood urine and exhaled air were sampled before, during and after exposure and analyzed for HFC-143a by gas chromatography. These data were described by a PBTK model. The electrocardiograms of the volunteers were monitored during exposure. Volunteers rated symptoms related to irritation and CNS-symptoms on a visual analog scale. Inflamatory markers and uric acid were analyzed in plasma collected before and 21 hr after exposure. The exposures were preformed after informed consent and ethical approval.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
Volunteers were exposed for 2 hr. Blood samples were collected before during (4 times) and after (7 times) exposure. Blood HFC-143a levels were analyzed by gas chromatography. The method error was 3.5%. Partition coefficients were calculated and a PBTK model was constructed. Urine was collected before exposure and 2, 4 and 6 hr after the beginning of the exposure. Urine was analyzed by head space analysis for HFC-143a. Volunteers completed a questionaire that rated their perceived discomfort by answering 10 questions related to irritation and CNS-symptoms.
Exposure assessment:
measured
Details on exposure:
Nine healthy volunteers participated in the study. All had been occupationally exposed to hydrofluorocarbons. Only persons judged to be healthy by a physician following a complete physical examination were allowed to participate. Volunteers were exposed in a 20 m3 chamber for 2-hr. HFC-143a was introduced into the chamber via a preheated glass tube. Flow was controlled using a calibrated mass flow meter. Exposure levels were 500 ppm and were monitored by gas chromatography. During exposure, volunteers exercised at 50W on a computer-controlled bicycle ergometer.

Results and discussion

Results:
The plasma concentration of HFC-143a increased promptly at the start of exposure and decreased in the same mannor post exposure. A stable level of 4.8 +/- 2.0 microM was reached within 30 minutes of exposure. Urinary excretion of HFC-143a was 0.0007% of the inhaled amount. The half time in urine was 53 minutes. The experimental and simulated time courses in blood and exhaled air were in good agreement. The simulated relative uptake during exposure was 1.6 +/- 0.3%. The fibrogen level in plasma had increased by 11% by the next day. While this may be an indicator of irritation, none of the other more sensitive markers for inflamatory responses were elevated nor were levels of uric acid. No effects of exposure were seen either in the electrocardiogram or as symptom ratings. The metabolism is either zero or near zero.

Any other information on results incl. tables

Nine volunteers were exposed to 500 ppm of HFC-143a for 2 hrs under moderate exercise (50W). The experiment is well described by the PBTK model and the uptake is low. An apparent steady-state is reached within minutes. The kinetic behavior is in agreement with a very low blood:air partition coefficient, and zero metabolism. No effects were seen on the electrcardiogram nor were signs of irritation reported on the symptom questionnaire.

Applicant's summary and conclusion

Conclusions:
Nine male volunteers were experimentally exposed to 500 ppm HFC-143a for 2-hr during light exercise (50W) in an exposure chamber. Blood urine and exhaled air were sampled before, during and after exposure and analyzed for HFC-143a by gas chromatography. These data were described by a PBTK model. The electrocardiograms of the volunteers were monitored during exposure. Volunteers rated symptoms related to irritation and CNS-symptoms on a visual analog scale. Inflammatory markers and uric acid were analyzed in plasma collected before and 21 hr after exposure. The exposures were preformed after informed consent and ethical approval. The experiment is well described by the PBTK model and the uptake is low. An apparent steady-state is reached within minutes. The kinetic behavior is in agreement with a very low blood:air partition coefficient, and zero metabolism. No effects were seen on the electrcardiogram nor were signs of irritation reported on the symptom questionnaire.The experiment is well described by the PBTK model and the uptake is low. An apparent steady-state is reached within minutes. The kinetic behavior is in agreement with a very low blood:air partition coefficient, and zero metabolism. No effects were seen on the electrcardiogram nor were signs of irritation reported on the symptom questionnaires.
Executive summary:

Nine male volunteers were experimentally exposed to 500 ppm HFC-143a for 2-hr during light exercise (50W) in an exposure chamber. Blood urine and exhaled air were sampled before, during and after exposure and analyzed for HFC-143a by gas chromatography. These data were described by a PBTK model. The electrocardiograms of the volunteers were monitored during exposure. Volunteers rated symptoms related to irritation and CNS-symptoms on a visual analog scale. Inflammatory markers and uric acid were analyzed in plasma collected before and 21 hr after exposure. The exposures were preformed after informed consent and ethical approval. The experiment is well described by the PBTK model and the uptake is low. An apparent steady-state is reached within minutes. The kinetic behavior is in agreement with a very low blood:air partition coefficient, and zero metabolism. No effects were seen on the electrcardiogram nor were signs of irritation reported on the symptom questionnaire.The experiment is well described by the PBTK model and the uptake is low. An apparent steady-state is reached within minutes. The kinetic behavior is in agreement with a very low blood:air partition coefficient, and zero metabolism. No effects were seen on the electrcardiogram nor were signs of irritation reported on the symptom questionnaires.