Bioavailability of D4 after Inhalation and Implantation Exposure to Silicones

By United Nations

Book Id: WPLBN0000187979
Format Type: PDF eBook:
File Size: 0.6 MB
Reproduction Date: 2005

Title:	Bioavailability of D4 after Inhalation and Implantation Exposure to Silicones
Author:	United Nations
Volume:
Language:	English
Subject:	Government publications, United Nations., United Nations. Office for Disarmament Affairs
Collections:	Government Library Collection, Disarmament Documents
Historic Publication Date:
Publisher:	United Nations- Office for Disarmament Affairs (Unoda)


Citation APA MLA Chicago Nations, B. U. (n.d.). Bioavailability of D4 after Inhalation and Implantation Exposure to Silicones. Retrieved from https://self.gutenberg.org/

Description
Government Reference Publication

Excerpt
Excerpt: In the November 2001 issue of EHP, Luu and Hutter (1) described a physiologically based pharmacokinetic (PBPK) model for the bioavailability of octamethylcyclotetrasiloxane (D4) following exposure to D4 by inhalation and implantation. In this paper the authors developed a PBPK model that used a very limited data set obtained after either single or repeated intravenous (iv) administration of D4 as a microemulsion (2). The intravenous pharmacokinetic data reported by Kirkpatrick (2) were obtained from a study I helped design and conduct; I am familiar with the data and with the limitations of the study design for this type of assessment. Kirkpatrick (2) obtained blood and tissue samples at various time intervals after administration of radiolabeled D4 and determined total radioactivity in these samples, but did not attempt to distinguish between parent D4 and D4 metabolites. Although the data obtained by Kirkpatrick were for iv dosing, Luu and Hutter (1) actually used intra-arterial dosing in their PBPK model. They validated their model by predicting inhalation kinetics in rats and comparing their prediction with a data set published by Plotzke et al. (3); they assumed that the radioactivity measured by Plotzke et al. (3) was parent D4, with no contribution from metabolites. Luu and Hutter (1) plan to use their PBPK model to assess risk after exposure to D4 resulting from migration from silicone gel breast implants. In addition to specific issues about their PBPK model, I also have several concerns about the manner in which this model will ultimately influence any risk assessment performed for D4. These concerns relate to a) the assumptions of the level of D4 in a silicone gel breast implant, b) the actual level of exposure to D4 arising from a silicone gel breast implant, c) the limited understanding of the metabolism of D4 reported by Luu and Hutter (1), and d) the prediction from their PBPK model that D4 will bioaccumulate with repeated exposures.