Lifetime risk from polyurethane covered breast implants.

The recent article by Luu et al. (1) predicting an excess lifetime risk from polyurethane covered breast implants of 1 in 400,000 is based upon numerous questionable assumptions and cannot go unchallenged. I have listed below several of the more obvious problems with this study and its conclusions. The estimated dose of polyurethane was too high. The authors use a weight of foam in their dosage estimates of 4.87 grams, but they do not reference the source for that figure. Presumably they meant two implants, and not one as stated. From the best available data, the Food and Drug Adminstration (FDA) has previously used the figure of 1.35 g of foam per implant, or 2.7 g for two implants (2). Even with two implants, the polyurethane exposure is almost half of that estimated by the authors. Polyurethane oligomers were incorrectly assumed to be 2,4-toluenediamine (2,4-TDA). In one part of the study, 14C-labeled foam was implanted subcutaneously in rats (no information about where or how was provided) at a dose of 80 mg/kg body weight (bw), and counts were measured in urine and feces for up to 56 days. The authors appeared to assume that any radioactive breakdown products of polyurethane were 2,4-TDA and not oligomers or metabolites. Because there is no evidence that polyurethane oligomers are mutagenic or carcinogenic, this difference is of critical importance. Implanted polyurethane in doses up to 267 mg/kg bw did not form DNA adducts in a model where adducts could be demonstrated from 2,4-TDA (3). It has clearly been shown that 2,4-TDA is artifactually created from oligomers in urine during the extraction process (4,5). Luu et al. (1) were unable to measure any quantity of 2,4-TDA in blood or urine after polyurethane implantation, yet they graphically plotted and described data (see Tables 3 and 4 in their paper) and calculated a risk assessment as if they had. There was no mention of any evidence (or lack thereof) of polyurethane-induced neoplasia in this study, either grossly or histologically. There were apparently no controls in this or any other part of the study. An inappropriate scaling factor was used. The authors used a scaling factor of 45 in their extrapolation of rat doses to humans, based on an article by Ramsay and Anderson (6), which reported styrene exposure by inhalation in a rat model. Inhalation studies must take into account many factors, such as alveolar surface area, …