Prioritizing Risks and Uncertainties from Intentional Release of Selected Category A Pathogens Tao Hong*1, Patrick L. Gurian2, Yin Huang3, and Charles N. Haas2 1. National Exposure Research Laboratory, EPA, Athens, GA, USA, 2. Department of Civil, Architectural, and Environmental Engineering, Drexel University, Philadelphia, PA, USA, 3. Office of Biostatistics and Epidemiology, FDA, Rockville, MD, USA *[email protected] SUPPORTING INFORMATION Supporting Information S1 The simplification of risk assessment model 1 Supporting Information S1 This supporting information describes how the system of equations given by Equation 1 in the main body of the paper can be simplified to allow reduced form solutions to be developed. Retrospective scenario In the retrospective scenario, resuspension makes a negligible contribution to dose, due to the relatively short exposure period compared the rates of resuspension (in this case the exposure period is assumed to be is 8 hours, the duration of a working day). Neglecting re-suspension separates the air compartment from the effects of other compartments so that air concentration follows a simple first order decay model. The inhaled dose can be calculated as: a doseinh_retro Inh M airo e retrot1 dt1 Vol 0 Inh 1 retrot M airo e Vol retro t1 0 Inh 1 M airo 1 e retro 480 Vol retro (Eq. A) where retro ts tf utf w Inhen Q air [1 (1 e) p] Vol Vol (Eq. 31) The ingested pathogens (doseing_retro) are the organisms which deposit on the touched surface (Mts) from the initial release in the air (Mair0) (Equation B): a M ts ts M airo e retrot1 dt1 (Eq. B) 0 2 remain alive until being transferred to the hand (Mhand) (Equation C): a M hand rsh f sh M ts e pros t2 dt2 (Eq. C) 0 and are ingested (doseing_retro) during surface-hand-mouth contact in the exposure period (Equation D): a doseing_retro rhm f hm M hand e hand t3 dt3 0 a t rhm f hm rsh f sh M ts e pros 2 dt2 e hand t3 dt3 0 0 a a a a t = rhm f hm rsh f sh ts M airo e retrot1 dt1 e pros 2 dt2 e hand t3 dt3 0 0 0 (Eq. D) 1 1 a 1 rhm f hm rsh f sh M airo ts (1 eretro a ) (1 e pros ) (1 e hand a ) retro hand pros where pros 2 fomite rsh f sh (Eq. 32) hand rhm f hm + fomite + rhs f hs (Eq. 33) To simplify the calculation, three assumptions are made during the derivation of Equation D: 1) pathogen resuspension and back transfer from hands to the surface are omitted due to their relatively low rates resulting in small fractions being back transferred, which is also health conservative; 2) all integration steps are from t=0 to t=a which provides an upper bound on the amount of pathogen transferred to the next step; 3) the pathogens will not be transferred to hands until depositing on the touched surface, and the pathogens will not be ingested until they are transferred to hands. Prospective scenario 3 In the prospective scenario, the majority of the inhaled dose (doseinh_pros) comes from two sources (Figure S1). The first source consists of organisms that are inhaled right after being resuspended (doseinh1_pros) (Equation E). a Inh pros t1 dt1 eretrot2 dt2 2 M tsoe Vol 0 0 a doseinh1_pros (Eq. E) The second are those organisms which experienced a certain number of "surfacehand-surface" travels before being resuspended and inhaled doseinh2_pros (Equation F). a Inh pros t1 dt1 eretrot2 dt2 2M tsoe Vol 0 0 a doseinh 2_pros (Eq. F) where Θ is the total fraction of resuspended pathogens surviving a number of n "surfacehand-surface" cycles: a a t rhs f hs rsh f sh M tso e pros a1 dta1 e hand tb1 dtb1 n 1 0 0 n (G) Θ is composed as a summation of a geometric series with element of Θn, where n indexes the number of "surface-hand-surface" cycle. In the nth cycle, pathogens survived from the n-1th cycle (Θn-1Mtso) are first transferred to hands (Equation H), and then back transferred to the surface (Equation I). a n _ sh rsh f sh n 1M tso e pros tan dtan (H) 0 a n n _ sh n _ hs rhs f hs n _ sh ehand tbn dtbn (I) 0 Combine Equation H and I: 4 a a n t n rhs f hs rsh f sh n1e pros an dtan ehand tbn dtbn 1 0 0 (J) For both sources, pathogen resuspension happens before inhalation. The maximum inhalation dose is reached when the exposure duration goes to infinity (Equation K): doseinh _ pros doseinh1_ pros doseinh 2 _ pros a Inh pros t1 dt1 eretrot2 dt2 2 (1 ) M tso e Vol 0 0 a n a a a hand tb1 Inh retrot2 pros ta1 pros t1 1 r f r f M e dt e dt M e dt dt2 2 hs hs sh sh tso a1 b1 tso 1e Vol 0 0 0 n 1 0 (Eq. K) a 2 Inh 1 rsh f sh rhs f hs M tso pros Vol retro n0 pros hand a 2 Inh 1 Vol retro M tso pros r f r f (1 sh sh hs hs ) pros hand Similarly, the prospective ingestion dose (doseing_pros) comes from two sources (Figure S2). The first source is direct ingestion of the pathogens released on the touched surface (doseing1_pros) (Equation L): a a t doseing1_pros rhm f hm rsh f sh M ts 0e pros 1 dt1 ehand t2 dt2 0 0 a where rsh f sh M ts 0 e pros t1 (Eq. L) dt1 is the mass transferred to victims hand. 0 The second source is those organisms which experience a certain number of "surfacehand-surface" travels before being ingested (doseing2_pros) (Equation M), which contains the common factor Θ as described above. The maximum ingestion dose is reached when exposure goes to infinity (Equation N). 5 a a t doseing 2_pros rhm f hm rsh f sh M ts 0e pros 1 dt1 e hand t2 dt2 0 0 (Eq. M) doseing_pros doseing1_ pros doseing 2 _ pros a a t rhm f hm rsh f sh (1 ) M ts 0e pros 1 dt1 e hand t2 dt2 0 0 n a a a a t t rhm f hm rsh f sh 1 rhs f hs rsh f sh M tso e pros a1 dta1 e hand tb1 dtb1 M ts 0 e pros 1 dt1 e hand t2 dt2 n 1 0 0 0 0 a M tso rsh f sh rhm f hm pros hand rsh f sh rhs f hs n 0 (Eq. N) hand pros rsh f sh rhm f hm M tso pros hand r f r f (1 sh sh hs hs ) pros hand Table S1 compares the exposure dose approximated by the above-mentioned equations with the exact results from solving Equation 18. The overall risk is acquired by inputting inhalation and ingestion doses into Equation 14 separately for the retrospective (Equation 26) and the prospective scenario (Equation 27). riskretro 1 (1 riskinh_retro )(1 riskinh_retro ) 1 (1 k doseinh_retro )(1 k doseing_retro ) Inh 1 1 1 k M airo 1 eretro 480 Vol retro 1 k M 1 1 480 1 r f rsh f sh ts (1 e retro 480 ) (1 e pros ) (1 ehand 480 ) hand retro pros airo hm hm (Eq. 26) risk pros 1 (1 riskinh_pros )(1 riskinh_pros ) 1 (1 k doseinh_pros )(1 k doseing_pros ) 1 (1 k M tso 2 Inh 1 pros Vol retro (1 rsh f sh rhs f hs pros hand rsh f sh rhm f hm )(1 k M tso ) pros hand (1 rsh f sh rhs f hs pros hand ) (Eq. 27) ) 6 Figure S1. Pathogen flow for estimating the inhalation dose in the prospective scenario. 7 Figure S2. Pathogen flow for estimating the ingestion dose in the prospective scenario. 8 Table S1. Comparison Exposure Dose between Approximated Analytical Equation and Simulated Results (1 µm) Release Inhalation dose Ingestion dose Pathogen scenario Approximated Full numerical Approximated Full numerical analytical equation simulation analytical equation simulation Retrospective* 1.12×104 1.12×104 2.75×101 2.37×101 Prospective* 2.07×103 2.10×103 7.62×105 7.64×105 Retrospective* 3.32×103 3.42×103 1.98 1.96 Prospective* 8.83×10-1 8.83×10-1 9.84×102 9.83×102 Retrospective* 3.13×103 3.23×103 3.22 3.15 Prospective* 1.56 1.56 1.94×103 1.94×103 Retrospective* 1.08×104 1.08×104 2.57×101 2.23×101 Prospective* 1.65×102 1.65×102 6.33×104 6.32×104 Retrospective* 3.48×103 3.58×103 1.14 1.14 Prospective* 5.34×10-1 5.30×10-1 5.28×102 5.27×102 B. anthracis Y. pestis F. tularensis Variola major Lassa *Total release quantity is 1 million spores for both retrospective and prospective scenario. The simulation period in retrospective scenario is 8 hours, while it is one year in prospective scenario. 9
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