Molecular iodine is not responsible for cytotoxicity in iodophors.

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.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)