Molecular iodine is not responsible for cytotoxicity in iodophors
Craig Freeman, E Duan, Jack Kessler
Abstract
Background Ten percent povidone-iodine (PVP-I) was initially promoted as ‘tamed iodine' as the chemical activity of the active biocide, uncomplexed or free molecular iodine (I 2 ), is reduced 30- to 50-fold compared with Lugol's solution. The idea that I 2 is responsible for topical iodine staining and irritation remains widely held. However, there are no controlled studies that characterize the cytotoxicity and staining of the hydrophobic I 2 species compared with the other hydrophilic iodine species that comprise over 99.9% of the total iodine in topical iodine disinfectants. Aims To compare the staining properties of the I 2 species with other topical iodine disinfectants; to evaluate if the concentrations of I 2 in diluted PVP-I used to reduce severe acute respiratory syndrome coronavirus-2 in the nasal cavity are potentially cytotoxic; and to determine if high concentrations of I 2 can be delivered beyond the stratum corneum into the hypodermis, which could provide a mechanistic rationale for I 2 out-gassing. Methods Five liquid compositions that contained complexed and uncomplexed (free) I 2 in aqueous and non-aqueous carriers were used to evaluate the interaction of I 2 with mammalian cells in culture as well as human and pig skin. Findings Concentrations of I 2 (7800 ppm) that are 1500 times higher than that found in PVP-I can be applied to skin without irritation and staining. I 2 is not cytotoxic at concentrations >100 times higher than that found in PVP-I, and does not contribute materially to staining of skin at concentrations found in Lugol's solution (approximately 170 ppm). I 2 can partition into hypodermis tissue, remain there for hours and out-gas from skin. PVP-I and Lugol's solution are highly effective topical disinfectants, but do not facilitate diffusion of I 2 through the stratum corneum. Conclusion The maximum concentration of I 2 found in diluted PVP, approximately 25 ppm, is not cytotoxic or irritating. The potential clinical utility of I 2 has been limited by incorporating this broad-spectrum biocide into acidic aqueous formulations that contain numerous chemical species that contribute toxicity but not biocidal activity. I 2 can be delivered topically into hypodermis tissue without irritation.