Quantitative Exposure of Humans to an Octamethylcyclotetrasiloxane (D4) Vapor

Abstract There is potential for human exposure to cyclic siloxanes by the respiratory route. To determine the pharmacokinetics of octamethylcyclotetrasiloxane (D 4 ), a material commonly found in personal care products, the respiratory intake and uptake of D 4 were measured in 12 healthy volunteers (25–49 years) on two occasions. Subjects inhaled 10 ppm D 4 (122 μg/liter) or air (control) during a 1-h exposure via a mouthpiece in a double-blind, randomized fashion. Inspiratory and expiratory D 4 concentrations were continuously measured. Exhaled air and plasma D 4 levels were measured before, during, and after exposures. Individual D 4 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 D 4 intake was 137 ± 25 mg (SD) and the mean deposition efficiency was equivalent to 0.74/(1 + 0.45 V E ), where V E is the minute ventilation. No changes in lung function were induced by the D 4 vapor. Plasma measurements of D 4 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 D 4 was 5.7 × 10 −5 cm/s from lung air to blood. In an additional eight subjects, we compared D 4 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 D 4 and they should contribute to a meaningful safety assessment of the compound.