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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 μm 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.