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Exposure in susceptible individuals can lead to asthma or allergic contact dermatitis (Kusnetz and Condon, 2003). Risks to personnel working with HDs are a function of the drugs' inherent toxicity and the extent of exposure. Early speculation noted inhalation was the primary route of exposure. However, with the advent of more sensitive drug assays, surface wipe sampling of a number of "marker" HDs has provided a method of examining work areas for HD residue (Sessink, 1992a & b; Sessink, 1997; Kopp, 2013; Fransman, 2005; Fransman, 2007).

Studies have detected the presence of HDs in the urine of HCWs who have handled these drugs, and in others who did not work directly with the drugs but who were only in the work area (Sessink, 1997; Wick, 2003; Fransman, 2004; Suspiro, 2011; Hon, 2015). Current belief is that dermal absorption of HD residue from contaminated surfaces is the primary route of exposure for at least some agents, such as cyclophosphamide (Kromhout, 2000; Fransman, 2004; Fransman, 2005).

Exposure is also likely to result from ingestion of contaminated food or drink or through mouth contact with contaminated hands or cigarettes. Accidental injection from the use of needles or contact with broken glass fragments is also of concern. Opportunity for exposure to HDs may occur at many points in the process of handling these drugs.

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The US Pharmacopeial Convention (USP) is a scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed and consumed worldwide. USP's drug standards are enforceable in the United States by the Food and Drug Administration. USP chapter 797 ("Pharmaceutical Compounding—Sterile Preparations"), notes that when compounding sterile preparations of HDs, they should be handled with caution at all times during receiving distribution, stocking, inventorying, preparation, and disposal (USP 797, 2012).

NIOSH, ASHP, and others have reported on studies that found drug residue on the outside of HD vials when they arrive at the workplace from the manufacturer or distributor (NIOSH, 2004; ASHP, 2006; Power, 2014). Packing cartons have also been identified as sources of measurable HD contamination (Kiffmeyer, 2000). HDs may be dispensed as sterile intravenous (IV), intramuscular (IM), intrathecal (IT), subcutaneous (SQ), or other doses, which must be compounded prior to administration, oral doses of solids or liquids which must be prepared or packaged, or occasionally as a topical preparation that may require special mixing.

Initial decontamination (cleaning) should consist of surface cleaning with water and detergent followed by thorough rinsing. Detergents, as surfactants, may assist in removing HD residue from the C-PEC (Lamerie, 2013). No single accepted method of chemical deactivation for all HDs has been identified (Castegnaro, 1985; Benvenuto, 1993; Castegnaro, 1997). Several studies have shown standard cleaning methods may leave HD residue or result in moving the residue to other areas (Sessink, 1992b; Turci, 2011).

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Newer agents, such as high level disinfectants containing hydrogen peroxide and peracetic acid, may provide alternatives to bleach when used in HD equipment cleaning programs. C-PECs used for sterile compounding should be disinfected routinely, per USP (USP 797, 2012). Class II BSCs and CACIs that have laminar flow in the work area may have a removable work tray as the work surface.

USP describes a cleaning process and recommends at least a monthly clean of this area (USP 800, 2016). The interior of the Class II BSC and the CACI should be thoroughly cleaned and rinsed prior to accessing the area under the tray. During cleaning, the worker should wear PPE similar to that used for spills.

The exhaust fan/blower should be left on. Cleaning should proceed from the least to the most contaminated areas. Any trough area should be cleaned at least twice since it can be heavily contaminated. All materials from the decontamination process should be handled as HDs and disposed of in accordance with federal, state and local laws (ASHP, 1990; ASHP, 2006).

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The outer surface of HD vials has been shown to be contaminated with HD residue in numerous studies (Sessink, 1992b; Kiffmeyer, 2000; Connor, 2005; Touzin, 2008; Power, 2014) (click to book plumber in ). This residue may transfer to workers when receiving HDs, storing HDs, performing inventory control, selecting HDs for compounding, and all other times when workers interact with potentially contaminated vials.

Cyclophosphamide (CP) was removed, to varying extents, from vial surfaces by using several methods of wiping with a tissue wetted with soapy water, followed by a dry wipe and a wipe down with a pre-wetted commercial wiper (Touzin, 2008). A larger study used wipers wetted with selected cleaning solutions to wash off vials of 10 different HDs (Lamerie, 2013).

5 percent solution in water, dish washing liquid in water, and anionic surfactants in 20 percent isopropyl alcohol all achieved greater than 90 percent removal of most of the 10 drugs (Lamerie, 2013). Wiping solutions for both studies were selected due to their ease of use and lack of toxicity.

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Storage areas should be cleaned and decontaminated routinely to avoid transfer of HD residue to gloves and other surfaces. Sodium hypochlorite solution, detergent, neutralizer and rinsing have been shown to be effective on hard surfaces (Touzin, 2010). USP notes that a C-PEC used for sterile compounding be certified by a qualified technician every six months using an approved procedure, such as the Controlled Environment Testing Association (CETA)-approved procedure.

ASHP recommends that BSCs be serviced and certified by a qualified technician every six months, or any time the cabinet is moved or repaired (ASHP, 1990; ASHP, 2006). Technicians servicing these cabinets or changing the HEPA filters should be aware of HD risks through hazard communication training from their employers and should use the same PPE as recommended for large spills.