Accidental or intentional releases of toxic gases or vapors are the most common occurrence in hazardous material (HAZMAT) incidents that result in human injuries. The most serious hazard from exposure to gases or vapors is via the respiratory system. Dermal uptake, as a secondary route, is still a concern, most acutely for the unprotected public. There is a limited evidence base describing skin absorption of toxic gases and vapors in HAZMAT exposure scenarios, which are relatively brief compared with traditional test periods for skin absorption studies. We describe research designed to provide experimental data to support decision-making by first responders regarding skin decontamination in HAZMAT-focused exposure scenarios involving toxic gases. We present findings for three common fumigants, methyl bromide, sulfuryl fluoride, and chloropicrin assessed using an Organization for Economic Co-operation and Development in vitro toxicology protocol utilizing human skin and gas/vapor exposures. Results indicate that for atmospheric concentrations that would be lethal via inhalation (LCLo), intact skin provides an excellent barrier to exposures up to 30 min, with little influence of common clothing fabric and high temperature and humidity conditions. The findings may challenge the current HAZMAT dogma requiring mass personal decontamination by strip and shower for short-term exposures to sulfuryl fluoride and chloropicrin gas/vapor.