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© 1998 Oxford University Press

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Quantitative Exposure of Humans to an Octamethylcyclotetrasiloxane (D4) Vapor

M. J. Utell*, R. Gelein*, C. P. Yu{dagger}, C. Kenaga*, E. Geigel*, A. Torres*, D. Chalupa*, F. R. Gibb*, D. M. Speers*, R. W. Mast{ddagger} and P. E. Morrow*

*University of Rochester School of Medicine Rochester, New York 14642 {dagger}State University of New York at Buffalo, Amherst, New York 14260 {ddagger}Everest Consulting Associates Midland, Michigan 48686

Received September 22, 1997; accepted May 1, 1998

There is potential for human exposure to cyclic siloxanes by the respiratory route. To determine the pharmacokinetics of octam-ethylcyclotetrasiloxane (D4), a material commonly found in personal care products, the respiratory intake and uptake of D4 were measured in 12 healthy volunteers (25–49 years) on two occasions. Subjects inhaled 10 ppm D4 (122 µg/liter) or air (control) during a 1-h exposure via a mouthpiece in a double-blind, randomized fashion. Inspiratory and expiratory D4 concentrations were continuously measured. Exhaled air and plasma D4 levels were measured before, during, and after exposures. Individual D4 uptakes were measured under steady-state conditions during three rest periods (10, 20, and 10 min, respectively) alternating with two 10-min exercise periods. Mean D4 intake was 137 ± 25 mg (SD) and the mean deposition efficiency was equivalent to 0.74/(1 + 0.45 VE), where VE is the minute ventilation. No changes in lung function were induced by the D4 vapor. Plasma measurements of D4 gave a mean peak value of 79 ± 5 ng/g (SEM) and indicated a rapid nonlinear blood clearance. Using lung volume and respiratory surface area estimates based on functional residual capacity measurements, we developed a model and determined that the effective mass transfer coefficient for D4 was 5.7 x 10–5 cm/s from lung air to blood. In an additional eight subjects, we compared D4 deposition with mouthpiece and nasal breathing at resting ventilations. For these individuals, mean deposition was similar for the two exposure protocols, averaging 12% after correction for exposure system losses. These are the first data describing the intake and absorption of D4 and they should contribute to a meaningful safety assessment of the compound.


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