Physiologically based pharmacokinetic modeling of the disposition of octamethylcyclotetrasiloxane (D4) migration from implants in humans.
A physiologically based pharmacokinetic model was developed to describe the silicone constituent octamethylcyclotetrasiloxane (D4) and its migration from intact or ruptured silicone gel-filled breast implants into surrounding tissues. D4 is a representative low-molecular weight constituent of silicone gel that is soluble enough in biological fluids to migrate from the implant and into surrounding tissues. The simulations were based on a representative young adult (premenopausal) woman and a mature (postmenopausal) woman using worst-case exposure conditions (i.e., complete rupture of the largest implant available, maximum levels of D4 in silicone, equal solubility of D4 in breast tissue and gel, and a range of breast tissue fat contents). The results indicate that D4 is cleared primarily by exhalation with highest concentrations achieved briefly in breast tissues of a representative postmenopausal woman. Maximum D4 levels in breast tissues for this scenario were estimated to be approximately 750 ppb with over 90% cleared in about 20 days. Thus, it is unlikely that D4 would be detected in any tissue within a few weeks of receiving an implant, even if immediately ruptured, under the assumptions used in this model.
Thrall
Karla D
KD
Battelle, Pacific Northwest Division, Richland, WA 99354-1793, USA. karla.thrall@pnl.gov
Soelberg
Jolen J
JJ
Powell
Thomas
T
Corley
Richard A
RA
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D018427:Breast Implants / Q000009:adverse effects*; D005260:Female; D005548:Foreign-Body Migration / Q000209:etiology*; D006801:Humans; D008954:Models, Biological; D011474:Prosthesis Design / Q000009:adverse effects*; D011475:Prosthesis Failure; D018570:Risk Assessment; D012833:Siloxanes / Q000493:pharmacokinetics*
D000276:Adjuvants, Immunologic; D012833:Siloxanes; C024064:octamethylcyclotetrasiloxane