Although initial results were promising for an injectable bone substitute (IBS) associating a hydroxypropyl methylcellulose (HPMC) polymer vector (Benecel, 2 w/w %) with biphasic calcium phosphate (BCP), a sensitization reaction occurred probably related to the degree of polymer purity. In this context, Benecel and another HPMC, E4M were investigated in the present study. The expected composition of the polymers was confirmed by gas-liquid chromatography. Studies in the guinea pig showed that Benecel has strong sensitization capacity and E4M none. Benecel manifests impurities (30 times more than E4M) in individual fibers or rounded clumps that are apparently responsible for extreme sensitization. Purification by ultracentrifugation associated with 0.2 microm filtration can decrease sensitization capacity considerably, though with a slight loss of polymer concentration. Fourier transform infrared (FTIR) analysis showed that the impurities were largely cellulose derivatives. However, extraction by organic solvent, followed by FTIR studies and micro-X analysis, detected an oily substance containing carbon and silicon associated with the cellulose derivatives. E4M, a polymer with no sensitization capacity, could replace Benecel and improve results with IBS.