Quantitative Exposure of Humans to an Octamethylcyclotetrasiloxane (D4) Vapor

There is potential for human exposure to cyclic siloxanes by the respiratory route. To determine the pharmacokinetics of octamethylcyclotetrasiloxane (D4), a material commonly found in personal care products, the respiratory intake and uptake of D4were 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 D4concentrations were continuously measured. Exhaled air and plasma D4levels were measured before, during, and after exposures. Individual D4uptakes were measured under steady-state conditions during three rest periods (10, 20, and 10 min, respectively) alternating with two 10-min exercise periods. Mean D4intake was 137 ± 25 mg (SD) and the mean deposition efficiency was equivalent to 0.74/(1 + 0.45V̇E), whereV̇Eis the minute ventilation. No changes in lung function were induced by the D4vapor. Plasma measurements of D4gave 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 D4was 5.7 × 10−5cm/s from lung air to blood. In an additional eight subjects, we compared D4deposition 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 D4and they should contribute to a meaningful safety assessment of the compound.