title: 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 (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 micrograms/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.
authors.affiliation: University of Rochester School of Medicine, New York 14642, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Utell
authors.forename: R
authors.initials: R
authors.lastname: Gelein
authors.forename: C P
authors.initials: CP
authors.lastname: Yu
authors.forename: C
authors.initials: C
authors.lastname: Kenaga
authors.forename: E
authors.initials: E
authors.lastname: Geigel
authors.forename: A
authors.initials: A
authors.lastname: Torres
authors.forename: D
authors.initials: D
authors.lastname: Chalupa
authors.forename: F R
authors.initials: FR
authors.lastname: Gibb
authors.forename: D M
authors.initials: DM
authors.lastname: Speers
authors.forename: R W
authors.initials: RW
authors.lastname: Mast
authors.forename: P E
authors.initials: PE
authors.lastname: Morrow
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012833:Siloxanes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D014835:Volatilization
chemical_list: D012833:Siloxanes; C024064:octamethylcyclotetrasiloxane