Difference in tumor incidence and other tissue responses to polyetherurethanes and polydimethylsiloxane in long-term subcutaneous implantation into rats.

The long-term (1- and 2-year) adverse tissue responses including tumor formation by subcutaneous implantation of polyurethanes (PUs) and silicone (Sil) films into rats were compared. The weight-averaged molecular weights (Mw) of the PUs prepared from 4,4'-diphenylmethanediisocyanate, poly(tetramethyleneglycol) of Mn = 1000 and 1,4-butanediol are 220,000 (U-4), 124,000 (U-6), and 55,600 (U-8). The 50:50 mixed film of U-6 and silicone (U-6/sil) was prepared by roll-mixing of the noncured silicone and the U-6 solution followed by evaporation of the solvent and heat-curing at 70 degrees C. The tissue responses around implants were classified into four groups as follows: (A) tumor, (B) atypical cell proliferation accompanied by preneoplastic changes, (C) cell proliferation without preneoplastic changes, (D) no obvious responses. In both implantation periods, the PUs gave higher incidents of the adverse responses including tumor formation in comparison to Sil. No significant molecular weight-dependent trend was found in a 1-year study using U-4, 6, and 8. Significant PU-dose-dependent trends were found in a 2-year study: the total active incidence (A+B+C), U-6(22/29) greater than U-6/sil(11/29) greater than sil(7/28); tumor incidence (A), U-6(11/29) greater than U-6/sil(2/29) = sil(2/28). No detectable amounts of 4,4'-methylenedianiline (MDA) were found in the PUs. The methanol extracts from the PUs were negative in the mutagenicity tests. These indicate no relationship between the tumor formation by the PU films and the mutagenicities of the chemicals (mainly oligomers) leached from the PUs.