**4. Comparison to existing technologies**

### **4.1 Fumigated formaldehyde devices**

Formaldehyde is a naturally occurring compound consisting of hydrogen, oxygen, and carbon which is used as a disinfectant in both its liquid and gaseous states [55]. Used as a laboratory fumigant since the late 19th century, formaldehyde has remained in use due to its efficacy and low cost [56, 57]. For use as a disinfectant, formalin, the aqueous form of formaldehyde, is heated into a vapor producing formaldehyde gas [58]. When encountering microbes, this gas causes a cross-linking of molecules leading to protein clumping and loss of structure [59]. While an effective sterilant, formaldehyde must be handled with extreme care as exposure can cause asthma-like respiratory problems, cancer, or even be fatal to humans [55]. In gaseous form, formaldehyde is used at 8,000–10,000 ppm concentration and leaves behind a residue which must be removed through manual cleaning [56, 60]. Due to the potential health hazards and the required labor-intensive clean-up of residue, formaldehyde use is declining in favor of less hazardous and faster solutions. Indeed, the European Union lists formaldehyde as a substance of very high concern and has issued regulation calling for the progressive substitution when suitable alternatives have been identified [61]. While generally compatible with laboratory materials, formaldehyde can be absorbed into porous materials such as HEPA filters, off-gassing slowly and extending the time needed for safe re-entry [56, 62]. Formaldehyde production equipment ranges from as small as an electric fry pan requiring timers or externally controlled circuits to larger automated devices roughly the size of a household refrigerator and weighing approximately 396 pounds (180 kg) [63].

#### **4.2 Chlorine dioxide devices**

Chlorine dioxide (ClO2) is a synthetic, green-colored gas that gives off a bleachlike odor. Despite the familiar scent, chlorine dioxide gas is toxic and must be

carefully contained when employed as a fumigant [64]. Consisting of unstable chlorine (Cl2) and oxygen molecules (O2), ClO2 disassociates when heated into chloride (Cl-), chlorite (ClO-) and chlorate ions (ClO3-). Some formulations can leave residues of sodium chlorite or inert salts, such as sodium chloride, on surfaces [65]. The disinfection cycle for ClO2 commonly consists of five steps: preconditioning, conditioning, charge (gas injection), exposure (contact time), and aeration [66]. The cycle is humidity-dependent, requiring a dosage increase of approximately 500 ppm for each 10% change in humidity, leading to an operating concentration range of 600–1550 ppm [66]. Similar to formaldehyde, ClO2 can be absorbed into porous surfaces and thus take longer to aerate than non-porous materials [65]. One consideration for system use is material compatibility with laboratory equipment. Some device manufacturers recommend that the ClO2 generating equipment remain outside the space being disinfected to prevent repeated exposure [34]. Instable in solution, chlorine dioxide must be mixed on-site by laboratory personnel. The effectiveness of ClO2 in penetrating treated spaces may also cause concern for personnel safety, as it can migrate out of seemingly enclosed spaces [38, 40]. As a result, facilities employing ClO2 systems must carefully monitor the disinfection cycle to ensure safety [64]. Roughly the size of an office bookcase and weighing approximately 230 pounds (104 kg), one system can treat up to 70,000 ft3 (2,000 m<sup>3</sup> ) which may maximize the treatment space per device compared to other systems. ClO2 can also be dispensed from smaller devices which fit into a biological safety cabinet to treat that equipment [67, 68].
