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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Toxicokinetics of inhaled bromotrifluoromethane (Halon 1301) in human subjects
Author:
Chu_Wing Lam, Françis W. Weir, Kathryn Williams-Cavender, Miguel N. Tan, Theodore J. Galen and Duane L. Pierson
Year:
1993
Bibliographic source:
Fundamental and applied toxicology 20, 231-239

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
Human inhalation study

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: gas
Details on test material:
- Name of test material (as cited in study report): Halon 1301
- Molecular formula (if other than submission substance): CF3Br
- Molecular weight (if other than submission substance): 148.9 g
- Physical state: gas contained in gas cylinders
- Analytical purity: 99, 9845%
- Impurities (identity and concentrations):
trifluoromethane (0.0009%)
chlorodifluoromethane (0.0040%)
chlorotrifluoromethane (0.0106%)

Test animals

Species:
human
Sex:
male
Details on test animals and environmental conditions:
Eight Heathly adult male subjects between the ages of 20 and 40 years and body weight of 70 to 92 kg were selected.
Human inhalation exposures were conducted in a chamber in the Pulmonary Department of the methodist Hospital maintained under slightly negative pressure (4-6 in; of the water) with respect to the ambient atmosphere of the hospital. Air or the Halon 1301-air mixture was drawn by a pump was drawn by a pump into the chamber inlet plenum and exited at the outlet plenum before being exhausted outside of the hospital via a duct system. During exposures, the pressure of the chamber was maintained slightly negative (0.2 in of the water) with respect to the room.

Administration / exposure

Route of administration:
inhalation
Vehicle:
other: air
Details on exposure:
Flow of Halon 1301 from a gas cylinder was controlled by a two-stage regulator and metered thorough a rotometer into the chamber inlet plenum and mixed with air at the damper before entering the chamber via a diffuser. The chamber flow rate was maintained at greater than 700 liters/min (approximately 10 chamber-volume air changes per hour) by exhaust pump to provide adequate removal of CO2 and moisture. Because a preliminary study revealed Halon 1301 concentrations in the chamber to be higher on the floor, two small oscillating fans were installed at the front end of the chamber by inlet to produce better mixing. Thereafter , the variation of the Halon 1301 concentrations among the nine sample ports was less than 10%.
Duration and frequency of treatment / exposure:
24hr
Doses / concentrations
Remarks:
Doses / Concentrations:
1% (60,875 mg/m3)
Details on study design:
Four pairs of subjects (A, B, D and E) were each exposed for 24 h to a target concentration of 1% Halon 1301 and to air during two separate exposures approximately 1 week apart. Test subjects and investigators (except technicians chambers and others) were blind to the order of exposure. The subjects went into chamber at 1400 hr. They were allotted an 8-hr sleep period (2200-0600 hr) and received three meals. Cognitive performance tests were administered eight times included to stimulate the release of endogenous adrenalin for the cardiac physiology study.
Details on dosing and sampling:
Chamber Halon 1301 concentrations were monitored by a Miran 980 infrared spectrophotometer set with an analytical wavelength of 11.6 µm and a gas-cell path length of 2.5 m. A gas chromatograph (GC) served as a backup instrument. Chamber concentrations were recorded every minute and the data were printed every 1 to 10 min. Oxygen and carbon dioxide concentrations were monitored. Oxygen was maintained at 21 +/- 1% and carbon dioxide was monitored to ensure that the concentration did not exceed 0.5%. The temperature and relative humidity were maintained at 75 +/- 5°F and 50 +/- 5% , respectively.

Two blood samples of about 1.5 mL each were scheduled to be collected from each test subject at 15 and 30 min and 1, 2, 4, 8, 16 and 24 hr during the exposure and 5, 15 and 30 min and 1, 2, 4 and 6 hr after exposure. Samples were drawn using 3-mL syringes from an indwelling catheter while the subjects extended their arms through the chamber arm hole. After collection, the samples were transferred into preweighed 6- or 12-mL venoject vacuum tubes containing 0.1 ml of EDTA. Because of occasional technical difficulties, some blood samples were not collected at scheduled times.

End-tidal breath samples were collected from the subjects at 2,4,8,16 and 24hr during exposure and at 1, 5, 15 and 30 min and 1, 2, 3, 4, 5 and 6 hr after exposure. On occasion, the actual sampling times deviated from the intended schedule.

Analysis of Halon 1301 in blood and breath samples were performed as well as the estimation of the body burden post exposure, the fast and slow elimination compartments (methods not detailed here).

Results and discussion

Any other information on results incl. tables

Halon 1301 exposure concentrations

In general, chamber concentrations were maintained at the targeted levels (1% +/- 0.1 %) except on exposure 7 -D during which the IR spectrophotometer malfunctioned.

Halon 1301 concentration in the blood of exposed subjects

From the blood profiles of all the subjects exposed approximately 1% (60,875 mg/m3), it appears that the steady-state Halon 1301 concentration was approximately 3-4.5µg/mL. The mean Halon 1301 concentration of the eight test subjects 6hr after exposure was 10.8% (SD= 3.6%) of the values obtained immediately before the exposure was terminated.

Applicant's summary and conclusion

Executive summary:

To examine the effects of bromotrifluoromethane on mental performance and physiologic function, four pairs of adult male subjects were each exposed in a double-blind fashion for 24 hr to 1% (10,000 ppm or 60, 875 mg/m3) Halon 1301 and to air in two separate exposures approximately one week apart. The kinetic data obtained showed that Halon 1301 in the body reaches a steady state during a 24-hr continuous exposure. Exposure beyond 24hr, therefore would not increase the body burden of this substance and levels in heart and brain will be similar to that of blood.