Hexamidine diisethionate-application, Health Hazard and Toxicity

Hexamidine diisethionate (chemical name: 2-hydroxyethanesulfonic acid-4, 4’-[1, 6-hexanediylbis(oxy)] dibenzenecarboximidamide, CAS No . 659-40-5) is a very mild and safe antimicrobial agent with good tolerability and low risk of skin irritation. Hexamidine Diisethionate functions as a biocide in cosmetics at concentrations of 0.03% to 0.1% in 38 cosmetic products. Hexamidine Diisethionate is approved at 0.1% in leave-on and rinse-off cosmetic products sold in the European Union. 

Hexamidine diisethionate exhibits a broad antimicrobial spectrum of activity against bacteria, yeasts and fungi. The substance is used inter alia as an antiseptic agent in oral and eye care. Hexamidine Diisethionate was not a photosensitizer in albino rabbits. Hexamidine Diisethionate was not mutagenic in a bacterial reverse mutagenicity assay or clastogenic in mammalian cells. Hexamidine Diisethionate at 0.10% did not provoke primary irritation, inflammation, or sensitization in a clinical test of 200 human subjects. 

The oral bioavailability of Hexamidine Diisethionate was 0.10% or 0.17% with an acute oral dose of 50 or 200 mg/kg, respectively, in rats. The acute oral LD50 values of Hexamidine Diisethionate were 710 mg/kg to 2.5 g/kg in mice and 750 mg/kg in rats. Dermal exposure to 4 g/kg Hexamidine Diisethionate in rats or up to 9.4 ml/kg of a 0.1% Hexamidine Diisethionate solution under occlusion in rabbits produced no mortalities or other signs of toxicity. 

Observations in subchronic oral toxicity studies of Hexamidine Diisethionate in rats included excessive salivation, elevated lymphocyte counts, increased alanine aminotransferase and serum calcium in rats given 100 or 200 mg/kg/day and increased aspartate aminotransferase at 200 mg/kg/day. Mortality rates were 30% and 80% in rats given 400 and 800 mg/kg/day Hexamidine Diisethionate, respectively, for 12 weeks. The NOEL for oral subchronic toxicity (4 weeks) of Hexamidine Diisethionate in rats was 50 mg/kg/day. No signs of toxicity were observed when 4 ml/kg of 0.4% Hexamidine Diisethionate was applied to a 240-cm2 area of rabbit skin for 90 days. 

Application of 0.1 ml of 0.11% Hexamidine Diisethionate in aqueous solution to the eyes of rabbits produced slight reactions that disappeared after 72 h. The same volume of 0.05% Hexamidine Diisethionate produced no observable reaction. Slight erythema was observed when 0.50 ml of 0.10% Hexamidine Diisethionate was applied to the abraded skin of an albino rabbit. No other observations were noted in 11 other rabbits given this treatment. When a 40% solution of Hexamidine Diisethionate was applied to 10% of the body surface of rats, slight erythema, slight edema, and scabbing were reported in some animals at varying times after treatment. Hexamidine Diisethionate was not mutagenic in a bacterial reverse mutagenicity assay up to the toxic dose (500 μg/plate). Up to 420 μg/ml Hexamidine Diisethionate was not clastogenic in CHO cells.

References

1.Eric H,  Final Report on the Safety Assessment of Hexamidine and Hexamidine Diisethionate, International Journal of Toxicology, 26(3), 79-90, 2007. 
2.Markus Nahrwold, Naida, Konate, Stable solution of hexamidine salts in alkanedlol-water mixtures, with antimicrobial and skin-moisturising effect.  US10369093B2,2019.

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