Acute Respiratory Exposure of Human Volunteers to Octamethylcyclotetrasiloxane (D₄): Absence of Immunological Effects

Abstract

Humans are exposed to silicones in a number of commercial and consumer products. Some of these silicones, including octamethylcyclotetrasiloxane (D4), are volatile. Therefore, there is a potential for respiratory exposure. A pharmacokinetic analysis of respiratory exposure to D4 is presented in the accompanying paper (M. J. Utell et al., 1998, Toxicol. Sci. 44, 206-213). Possible immune effects of respiratory exposure to D4 are investigated in this paper. Normal volunteers were exposed to 10 ppm D4 or air for 1 h via a mouthpiece using a double-blind, crossover study design. Assays were chosen to screen for immunotoxicity or a systemic inflammatory response. Assessment of immunotoxicity included enumeration of peripheral lymphocyte subsets and functional assays using peripheral blood mononuclear cells. Because in humans there is no direct test for adjuvant effect of respiratory exposure, we analyzed proinflammatory cytokines and acute-phase reactants in peripheral blood, markers for a systemic inflammatory response, as surrogate markers for adjuvancy. These tests were repeated when the volunteers were reexposed to D4 approximately 3 months after this initial exposure. Blood was obtained prior to exposure, immediately postexposure, and 6 and 24 h postexposure. In these short-term, controlled human exposures, no immunotoxic or proinflammatory effects of respiratory exposure to D4 were found.

Mass Loading and Fate of Linear and Cyclic Siloxanes in a Wastewater Treatment Plant in Greece

“…5−7 In short-term, controlled human exposure studies, no immunotoxic or pro-inflammatory effects of D4 were observed. 8,9 The Government of Canada declared that D4 does not pose a risk to human health but did recommend environmental regulatory measures. 10 D5 is considered to be a persistent and bioaccumulative compound 11 and has been shown to be effectively removed from the atmosphere via phototransformation.…”

Bioavailability of Octamethylcyclotetrasiloxane (D 4 ) after Exposure to Silicones by Inhalation and Implantation

“…If D 4 exposures were repeated in either case at a frequency shorter than the fat half-life, the net result would be accumulation in the fat tissues, because the input would exceed the elimination output. These results were not evident from previous human exposure studies, because the target tissue disposition was not accurately determined (17,18). Utell et al (17) (Table 7 and Figure 6).…”

“…The model was first calibrated using previously reported data on tissue distribution in female rats after single and repeated IV administrations of 14 C-D 4 (1). We validated the predicted results in rats and in humans after inhalation exposure using published independent data (12,17,18). We then used the validated model to predict the pharmacokinetics of D 4 as leached from saline-filled breast implants in women.…”

Percutaneous Absorption Studies of Octamethylcyclotetrasiloxane Using the Human Skin/Nude Mouse Model

“…The chemical and physical properties of D 4 are well known [17], and the disposition of D 4 following single and multiple inhalation exposure by rats [9] and subcutaneous injection to mice [18] has been reported. However, there is little published data on the biological fate and toxicological effects of D 4 following human exposure [5,15]. Several studies have investigated the dermal absorption of D 4 and other siloxane materials [4,6,[19][20][21][22][23].…”