Note: Dose levels were converted from ppm to mg/m3 by the extractor

FROM METHODS:

"Exposure Chamber Design and Operation

Nose-only rather than whole-body exposures were performed, because of limited supply and high cost of the CF3I test material. This decision reduced considerably the amount of test material required to carry out the 90-day study. The chamber selected for nose-only exposure was a stainless-steel flow past system designed by Cannon et al., 1983. Each chamber has 52 ports for exposure of animals. In this study, 30 ports were selected randomly for rat exposure. Rat restraining tubes made of Lucite® were plugged into the animal ports resulting in the outward extension of the tubes radially from the main body of the chamber.

Generation of Test Material

The CF3I and dilution air were delivered from pressurized systems and were controlled through flow meters. Fine control of chamber concentration was made by minor adjustment of the CF3I flow in response to chemical analysis of the chamber atmosphere. Total chamber air flow resulted in the delivery of more than 300 mL/min of mixed CF3l/air at each animal port. A portion of the diluent air passed through a gas washing bottle (Ace Glass, Vinland, NJ, Model 7166-26) containing water to provide adequate relative humidity to the chamber input air stream. Relative humidity and temperature of the exposure atmosphere were constantly monitored and recorded using HY-CAL dual probes (Models CT830, HY-CAL, Atlanta, GA) and a Data Acquisition system. GC/MS analysis of mixed CF3l/air collected from the nose-only ports did not differ from the CF3I vapor collected from the cylinders demonstrating no breakdown products of the test material during the generation of test atmospheres.

Chamber Analysis

Continuous analysis of the chamber air for CF3I was performed using infrared absorption spectrometers (Miran 1A, Foxboro Analytical, South Norwalk, CT). A short path (10-cm) cell in combination with a low intensity absorption band at 9.6 to 9.7 microns facilitated the analysis of the chamber CF3I vapor concentrations involved in this study. Instrumental calibration was performed using known concentrations of freshly prepared CF3I in air contained in tedlar sample bags (231 series, SKC, Eighty Four, PA). Calibration checks were performed at two-week intervals during the study.

Exposure Concentration Selection

In addition to the acute inhalation toxicity studies with CF3I that were described in the Introduction, a two-week inhalation exposure range-finding study was performed (Kinkead et al., 1995). Four groups, each containing five male Fischer 344 rats, were exposed via nose only at target concentrations of 12, 6, 3, or 0 (air-only control)% (vol/vol) CF3I. Exposures were two hr/day, 5 days/wk, for a total of ten exposures. No deaths were observed, though lethargy and slight incoordination were noted in the high- and mid-concentration groups at the conclusion of each daily 2-h exposure. Mean body weight gains were depressed in the high-level group (p<0.01) at 7 days and 14 days, and in the mid-level group (p<0.05) at 7 days only. Serum thyroglobulin (HTG) and reverse T3 (rT3) values were significantly increased at all exposure levels. At necropsy, no gross lesions or differences in absolute or relative organ weights were noted. Histopathologic examination of the thyroid and parathyroids indicated no morphological abnormalities in CF3l-exposed rats. Failure of the high-concentration rats to gain weight during the two-week period, clinical signs of inactivity, and increases in serum HTG and rT3 indicated that 12% CF3I might be too stressful as a target concentration for the 90-day study. The mid-concentration group (6%) showed some minimal clinical signs of stress, such as transient weight-gain suppression and mild increases in serum HTG and rT3 values. Increases in serum HTG and rT3 were the only clinical findings noted in the low-concentration (3%) group. Given that the increases in serum HTG and rT3 were not supported with microscopic findings in the thyroid and parathyroids, target concentrations chosen for the 90-day study were 8, 4, 2, and 0% CF3I. The 8% concentration level was expected to produce clinical signs and, possibly, microscopic effects in the thyroid gland of CF3l-exposed rats. The mid-concentration level (4%) was expected to produce minimal to no adverse effects in rats and the low-concentration level (2%) was expected to produce no adverse effects (i.e., a NOAEL)."

FROM RESULTS:

"Exposure System Analysis

The specified target concentrations of 8, 4, and 2% CF3I were maintained during the daily 2-hr exposures. The exposure mean concentrations were maintained within ± 2% of the desired concentrations. Mean concentrations for each exposure, along with the lowest and highest daily mean concentrations are provided in Table 1. The daily mean relative humidity ranged between 47 and 52%, while the daily mean temperature ranged from 67 to 73 °F.

Table 1. CF3I Concentrations Inhaled By Male And Female F-344 Rats

Target Concentration (%) 8.0, 4.0, 2.0
Mean Concentration (%) 8.05, 4.03, 2.02
Standard Error 0.01, >0.01, >0.01
Lowest Daily Mean (%) 7.94, 3.95, 1.99
Highest Daily Mean (%) 8.18, 4.10, 2.05
Mean Temperature (°F) 70.2, 70.7, 70.5
Mean Relative Humidity (%) 49.6, 49.4, 49.4"

Calculations:

Target concentrations: 2%, 4% and 8% --> 20,000ppm, 40,000 ppm, & 80,000 ppm

20,000 ppm --> 160,253.58 mg/m3; mean % analytical concentration = 2.02%
40,000 ppm --> 320,507.16 mg/m3; mean % analytical concentration = 4.03%
80,000 ppm --> 641,014.31 mg/m3; mean % analytical concentration = 8.05%

Female Fischer-344 Rats