Fw: Abstract: Bioavailability of (D4) After Exposure to Silicones by Inhalation and Implantation

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----- Original Message ----- From: Kathi

Sent: Friday, September 27, 2002 2:55 PM

Subject: Abstract: Bioavailability of (D4) After Exposure to Silicones by Inhalation and Implantation

While the original article was published in the November 2001 issue of Environmental Health Perspectives, the responses and rebuttal to this article were published in the August 2002 issue of the same publication. I believe this is an important article because of this:...............Ruby "The accumulation of D4 in fatty tissues should play an important role in the risk assessment of D4 especially in women exposed daily to multiple personal care products and silicone breast implants." Also of interest is how G. Meeks and Kathleen P. Plotzke from Dow Corning, and Melvin E. Andersen, et. al. from Colorado State University tried to discredit this article. I sent that out yesterday and can be found at the below link. http://ehpnet1.niehs.nih.gov/docs/2002/110-8/correspondence.html#furt Please read the "Rebuttal and Critical Review of Andersen et al.'s D4 PBPK Model" by the original authors at the end, also found at the above lin ____________________________________ Environmental Health Perspectives Volume 109, Number 11, November 2001 http://ehpnet1.niehs.nih.gov/docs/2001/109p1095-1101luu/abstract.html Bioavailability of Octamethylcyclotetrasiloxane (D4) After Exposure to Silicones by Inhalation and Implantation Hoan-My Do Luu and ph C. Hutter Center for Devices and Radiological Health, U.S. Food and Drug Administration, Rockville, land, USA Abstract We developed a physiologically based pharmacokinetic (PBPK) model to predict the target organ doses of octamethylcyclotetrasiloxane (D4) after intravenous (IV), inhalation, or implantation exposures. The model used 14C-D4 IV disposition data in rats to estimate tissue distribution coefficients, metabolism, and excretion parameters. We validated the model by comparing the predicted blood and tissues concentrations of D4 after inhalation to experimental results in both rats and humans. We then used the model to simulate D4 kinetics after single and/or repeated D4 exposures in rats and humans. The model predicted bioaccumulation of D4 in fatty tissues (e.g., breast), especially in women. Because of its high lipid solubility (Log Poct/water = 5.1), D4 persisted in fat with a half life of 11.1 days after inhalation and 18.2 days after breast implant exposure. Metabolism and excretion remained constant with repeated exposures, larger doses, and/or different routes of exposure. The accumulation of D4 in fatty tissues should play an important role in the risk assessment of D4 especially in women exposed daily to multiple personal care products and silicone breast implants. Key words: bioavailability, breast implant, D4, implantation, inhalation, octamethylcyclotetrasiloxane, PBPK, physiologically based pharmacokinetic model, risk assessment, silicone. Environ Health Perspect 109:1095-1101 (2001). [Online 11 October 2001] Address correspondence to H-M. D. Luu, U.S. FDA, Center for Devices and Radiological Health, 12725 Twinbrook Parkway HFZ-150, Rockville, MD 20852 USA. Telephone: (301) 827-4711. Fax: (301) 827-4853. E-mail: hml@... We thank R. Kammula, M. Myers, C.S. Kim, and L. Schroeder for helpful suggestions in this investigation. Without their help, this study would not have been possible. This work was presented in part at the 219th Annual Meeting of the American Chemical Society, April 2000, Anaheim, CA. The opinions or assertions about specific products identified by brand name herein are the private views of the authors and are not to be construed as conveying either an official endorsement or criticism by the U.S. Department of Health and Human Services or the Food and Drug Administration. Received 23 March 2001; accepted 5 April 2001