Edward D. Palmes

DEPOSITION OF AEROSOLS IN THE HUMAN RESPIRATORY TRACT DURING BREATH HOLDING

Abstract The anatomical character of both the conducting airways and of the functional gas exchange region exerts an important influence on rates of deposition of inhaled aerosol. In the present studies an attempt is made to use the rate of deposition of aerosol particles in the respiratory tract during breath-holding as an index of the effective lumen diameters of the respiratory branches. During breath-holding for periods up to about 30 sec, the ratio of exhaled to inhaled aerosol decreases exponentially with time; this was observed for all subjects at particle sizes from about 0×15 to 1×0 micron. Calculations of lumen diameter based on these observations yielded estimates which are consistent with those obtained by microscopic measurements on human lungs.

A model for the metabolism of sulfite in mammals.

Abstract The distribution of sulfite in the rabbit fits a two-compartmental open-system model ( Riegelman et al., 1968 ) characterized by rapid distribution and elimination with the rate constants of the order 0.1 to 1.0 min−1. Sulfite clearance can be calculated from this model using plasma decay data obtained after a single iv injection of sulfite, and the theoretical rate thus calculated is in satisfactory agreement with clearance determined at steady state conditions. Measurement of urinary sulfite following iv sulfite administration and demonstration of mass balance in the conversion of the remaining sulfite to sulfate using a mathematical model show that sulfite clearance occurs predominantly by metabolism to sulfate. It is concluded that sulfite clearance is primarily dependent upon the efficiency of sulfite oxidase, the enzyme catalyzing the oxidation of sulfite to sulfate. The results indicate that the efficiency of this enzyme decreases as sulfite dose increases. Preliminary experiments with one rhesus monkey suggest that the pattern of sulfite distribution and elimination is similar to that in rabbits but that the kinetics of the removal mechanisms are different. It is felt that meaningful inter- and intraspecific comparisons can be made using the technique presented, and that these comparisons would provide a quantitative basis for predictions of risks of systemic sulfite toxicity.

Species variability in plasma S-sulfonate levels during and following sulfite administration☆

It has been shown that S-sulfonate compounds (R-S-SO-3) are produced by the action of sulfite on reactive disulfide bonds [4,5]. Plasma S-sulfonate production was determined as a function of sulfite ingestion and intraperitoneal injection in rats, mice and rhesus monkeys. The tendency of these species and of the rabbit [8] to produce S-sulfonates in plasma was related to the availability of sulfite and of reactive disulfide bonds and to the stability of plasma protein S-sulfonates. The rhesus monkey and the rabbit accumulated plasma S-sulfonates much more readily than did the rat, while the mouse produced little, if any, under the same test conditions. Plasma protein S-sulfonate fractions in the rat and rhesus monkey were characterized by half-lives of approximately 4 and 8 days respectively. The sensitivity and precision of the analytical method for plasma protein S-sulfonate were improved by incorporation of 35S into the outer sulfur atom of the S-sulfonate moiety (R-S-35SO-3).

Comparative sulfite metabolism in the rat, rabbit, and rhesus monkey

Abstract The clearance of injected sulfite, which is due principally to its metabolism to sulfate, was measured in rats, rabbits, and rhesus monkeys for the purpose of estimating the in vivo function of sulfite oxidase. The order of clearance was rat > rabbit > rhesus monkey, and the relative rates were 1.00:0.34:0.20. If it is assumed that man clears sulfite similarly to the rhesus monkey, it would appear that the rat is not a good model for prediction of human toxicity. In vitro measurements of the sulfite oxidase activity of the major metabolizing tissues of these three species produced a change in the above rank order to rat > rhesus monkey > rabbit, with relative magnitudes of 1.00:0.12:0.05, respectively. The transposing of the relative order of the rabbit and rhesus monkey with respect to in vitro enzyme activity as compared with in vivo function demonstrates that factors other than the absolute amount of sulfite oxidase play a significant role in the functioning of the enzyme.

S-Sulfonates in Human Plasma following Inhalation of Sulfur Dioxide

Plasma S-sulfonate was measured in human subjects exposed continuously under controlled conditions to sulfur dioxide for periods up to 120 hours. Subjects were exposed to chamber SO2 concentrations of 0.3, 1.0, 3.0, 4.2, and 6.0 ppm and to a control exposure with ambient air. Plasma levels of S-sulfonate showed positive correlation with atmospheric sulfur dioxide; the regression line fitted to all 80 data points determined in this experiment resulted in a highly significant correlation (correlation coefficient = 0.61, p < 0.001). The slope of the regression line was an estimated increase of 1.1 ± 0.16 (S.E.) nmoles of S-sulfonate per milliliter of plasma for each ppm increment in chamber sulfur dioxide concentration.

REGIONAL AEROSOL DEPOSITION IN THE HUMAN RESPIRATORY TRACT

Abstract Regional deposition of aerosol in the human respiratory tract is estimated from experiments in which aerosol concentration and respiratory flow were measured continuously during individual breaths and from a theoretical analogy with a tubular continuous filter bed model of the respiratory tract. Since the volume of anatomic dead space is uncertain, regional distinction is made by selected boundary volumes which separate the upper tract of the selected volume from the more distal lower tract. The central feature of the estimation procedure is the determination of a combined upper tract penetration, for inspiration, pause, and expiration, derived from expired aerosol concentration corrected for aerosol mixing. The estimations indicate the particle size for maximum alveolar deposition is greater than 2 μ, equivalent diameter of a unit density sphere. This result is consistent with the calculations of Findeisen, Landahl, and Beeckmans and higher than the 1 μ value of Brown et al.

Skin irritation and skin tumor production by beta propiolactone (BPL).

Abstract Skin irritation and skin tumors were produced by application of beta propiolactone to mouse skin. Short term application of undiluted BPL or of its solutions in acetone or corn oil produced reactions varying from erythema to hair loss and scarring with one to six applications of 0.8 to 100 mg BPL. Lifetime painting of acetone and corn oil solutions ranging from 0.25 to 5 per cent BPL produced both papilloma and cancer on mouse skim. Tumor production was concentration related; this relationship was more sharply defined when adjustment for mortality was made by a life-table technique. Tumorigenesis by benzpyrene and BPL applied successively appeared additive.

Explanation of Pressure Effects on a Nitrogen Dioxide (NO2) Sampler

When nitrogen dioxide (NO2) samplers were exposed at several reduced pressures, it was found that the sampling rate was correspondingly decreased; that finding did not agree with accepted diffusional theory. When the experiments were repeated using water vapor as the gas and molecular sieve as the sorbent, the observed sampling rates were in very good agreement with diffusional theory. These findings demonstrated that the pressure effect was not common to all diffusional samplers and suggested that there might be an alternate explanation for the results with NO2-triethanolamine (TEA). The best possibility appeared to be the dehydration of TEA that takes place at reduced pressures. That this is a very significant factor was demonstrated by simultaneous exposure to identical concentrations of NO2 at 1 atm and 50% or 0% relative humidity. In dry air the sampling rate was equivalent to that found previously at about 1/10 atm. The earlier results can be satisfactorily explained as indirect rather than direct effects of reduced pressure.

An Aerosol Inhalation Apparatus for Human Single Breath Deposition Studies

Single breath studies designed to measure deposition of monodisperse aerosols in human subjects required specialized apparatus for the measurement of inhaled and exhaled aerosol. An apparatus was constructed consisting of a three-way valve system and anesthesia bags to contain aerosol before inhalation and after exhalation. The bags were enclosed in boxes which were connected to a spirometer which recorded volumes. The entire system was automated so that the subject inhaled (mouth breathing) a preset volume of aerosol and exhaled a preset, larger volume of air from his lungs. Volumes were controlled by a rider on the spirometer wire which activated a group of solenoid driven valves. Quantities of aerosol in the bags were determined by integrating the photocurrent from an aerosol photometer when a bag was emptied through the photometer.

Relationship of indoor NO/sub 2/ concentrations to use of unvented gas appliances

Measurements were made on NO/sub 2/ concentrations in dwellings in the vicinity of the University of Florida at Gainesville and compared with results from previously reported studies on dwellings in suburban London and suburban and rural New York. Measurements in dwellings with no unvented gas appliances were quite low, averaging 3ppB. When the only unvented gas appliance was the kitchen stove, the kitchen concentrations averaged 55ppB. In two residences a heater was the only unvented gas appliance; NO/sub 2/ concentrations in the room containing the heater was 112ppB, while the kitchen showed the same concentration and the unheated space about half this value. (JGB)