Safety aspects of chemical threats, final report 2014-2016

The aim of the project "Protection against chemical threats" has been to increase the understanding of systemic uptake of nerve agents after dermal exposure and to identify best possible procedures for medical treatment. The knowledge has been dispersed to the Armed Forces through specific reports and by oral presentations, and to the National Board of Health and Welfare through support to the National Center of Disaster Toxicology (KcC) and the Medical Expert Group (C-meg). International collaboration has been undertaken bilaterally with United Kingdom (Dstl), trilaterally with the Netherlands (TNO) and Canada (DRDC), and multilaterally with the NATO scientific research task group in medical countermeasures. An overview of procedures for symptom-based treatment following poisoning with organic phosphorous compounds (OP-compounds), including nerve agents, has been compiled. Treatment regimens were compared between Sweden, UK and USA, showing that oximes, atropine and supplementary oxygen, combined with anticonvulsants are recommended in all three countries. In addition, potential complementary anticonvulsants were described. Experimental research has been performed in the areas of skin penetration/decontamination and medical countermeasures. Within skin penetration and decontamination, the skin penetration properties of a set of OP compounds, including VX, were examined in vitro and the efficacies of different skin decontamination products were compared. In medical countermeasures, anticholinergic effects of atropine were studied in airways ex vivo following exposure to VX and the possibility to administer anticholinergic drugs through dermal application was investigated. The results showed a large variation in skin penetration rates between different OP compounds, to a large extent due to differences in water and lipid solubility. Addition of water was found to increase penetration of concentrated compounds. The experimental studies also showed that absorption of OP compounds in the skin can be studied by Raman spectroscopy. A comparison of penetration through human, pig and guinea pig skin revealed a much higher penetration through guinea pig skin than through human and pig skin. This finding is of high importance when translating in vivo data from percutaneous exposures of guinea pig to human conditions. The studies of skin decontamination demonstrated a high efficacy of RSDL to neutralize VX on the skin, provided that decontamination initiates early after exposure (<30 minutes). The effect of RSDL is a combination of degradation at basic pH and washing off the nerve agent. The lipophilic properties of VX facilitate the RSDL decontamination. The solid decontamination powders PS104 and Fuller's Earth, and the hypochlorite solution alldecontMED showed lower efficacy than RSDL to remove VX. This can be due to a general poor decontamination efficacy of solid powders for lipophilic compounds and an insufficient degradation capability of hypochlorite, respectively. Exposure of VX directly on sections of lung tissue ex vivo resulted in lung contraction and sometimes complete collapse of the airways. This contraction could be counteracted by atropine, but not if airways were completely collapsed. Dermal uptake of anticholinergic drugs can be significantly improved by addition of chemical penetration enhancers, indicating that transdermal administration could be useful for prophylactic treatment and therapeutic treatment in a subacute phase of nerve agent poisoning.