UN I TED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTO N , D.C. 20460



### EPA Re s pon se to Comment s Received from the Submitter of TSCA Pre manufacture Notice (PMN) P-14-260 regarding EPA's Ri s k As s essment and Derivation of th e Occupational Expos ur e Limit for th e Chemical Substance Rep o rt ed in P

- 14-2 6 0. 

### D a t e of document: Ap ri I 20, 20 1 5

TABLE OF CONTENTS 

### BACKGROUND
................ .. .................. . .. . ....... ...... ....... ...... . .. .. .. . .. ......... .. .. .. .................................. 2 AMPAC-I

- l A LOT RON COMMENTS
........ .. ........... .. ....................................................... . ..... 2 1.1 Co mment**n** 

### Interspecies Uncertai nt y Fac tor. . .... . .. .. .. .. . ....... . .. • .. .................................... 2 • 1.1. I Corn rn ent 1
.............. . .......... .... ....... ..... ........ .. .. . ....... . ............ .. ........ ..... ........................ 

### 2 1.1. 2 Response to Cornn1e nt 1
...... . ............................................. . ......... .... ....... .... ....... ..... ... 2 1 .2 

### Co mment 2 on Intra spec ies Unce rt a inty Facto r. .. ...... .. .. .. ........ ... . . ...... .... .... .. . .... ....... .... .... 3 1.2.1 

### Comment 2
.................................................................................................................

### 3 1
. 2
. 2 Respo nse to Co1n n 1ent 2
................... . .. . ......... . .......... . ............. . .................. .. ............. .3 1 .3 Co mment 3 o n Derma l Exposure
..................................................................................... .4 1.3.1 

### Comn1ent 3
. .. .. ............................. .. ............ .. ....................... .. ........ .. . . ........ .. ...... . .. . ...... 

### 4 1 .3.2 R es po nse to Co mm e nt 3
. . ...... ...... .. . .. ...... . .. . .... . ..... . ............. . ........ .. . .. .... ....... .... . .. . ..... .4 1.4 

### Comment 4 on Select ion of NOAEL
..... . ......... ..... ......... . .......... . ........... . ........ .... .............. .4 

### 1.4.1 

### Con1ment 4
..... .. . . ... . . ... . .. .. .. . ... . ... ..... .. . .. . .. .. ..... .. .. . ...... .. . .. ......... .. . .. .... .. . ..... . . . .... . .......... . 4 1.4. 2 

### R espo nse to Con1men t 4
..... . ..................................................................................... . 4 1.5 Comment 5 on Allowable Exposure Limit
.. ..... . ............................................................... 5 1 .5. 1 Co1n n1 e nt 5
. . . .. .................................................................. . ......... ..... ...... .. . .. ................ 5 1.5. 2 Response to Comn1ent 5
...... ... ................................................................................... 5 1.5.2. 1 Expo s ure Com111e nt s .... .. .. .. ..... ..... ........ .. .. . ...... ..... .......... . ....... .... ... ..... ...... . .......... 5 1. 5
. 2
. 2 Question about EPA derivation of POD
............................................ . .......... . ..... 7 1. 5.2.3 Allowable worker expos ur e limit
............... ...... ............ ..... .. .. . .......... .. ......... ... .... ? 

### 2 REFEREN C ES
........ .. . . ..... .. .. .. ..... . .. .. ......... .. .. . ...... . .. .. ........ ...... ..... .. . .. ......... . .......... . .......... .. . . . 1 0 LI ST OF TABLES 

### Table 1-1 Sunrn1ary of Postnatal S ur v ival (%pe r litter)
................................. ... ...... . . ..................... 5 LIST 

### OF FIGURES 

### Figure 1 - 1 P-14- 0260 

### s tructurc ..... ..... .. ....................... . ......... .. ............ .. ............................... ............ 2 Figure 1-2 Calc ulation of hum a n exposure var iab les .... .. . .. ...... . .. .. .... . .... .. .. . ...... .... . .. ...... .. .. . ............ 8

I nternet Address ( U R L ) • htt p://www.cpa.gov Recy c l od/Recy c l ab l o • Pt1ntcd with Ve9ctable 011 Based Inks on 100% Postconsumer
. Process Chlonne Free Recycled Paper

### 2 

### BACKGROUND On February 2, 20 1 5 American Pacific Corp. (AMPAC) -H a lotro n h e ld a conference call with EPA staff to discuss the risk assessment for P-1 4-0260. On February 13. 20 15 they sub mitted a le tter to E P A reque s ting that EPA re-con s ider 5 key items. This paper is a respon se to the 5 items. P-14-0260 is 2

- Brom o-3,3,3-Trifuoroprope ne (B TP) 

### Br

# F")**~** F-1 F Fi g ure 1- 1 P- 1 4-0260 s tructure 

### AMPAC

- HALOTRON C OMMENTS 1.1 Co mm e nt 1 on Inte r s pecies U n certain ty Factor 1.1.1 Co mm e nt 1 Use of an inter-species uncertainty factor of 3 based on the submitted December 20 14 Skaggs report and contrast between human and rat partition coefficients. 

### 1.1. 2 R es p on se to Comm e nt 1 Agree. The default inte rspecies uncertainty factor (UF) 10 is generally cons id ered to have pharmacokinetic and pharmacodynamic components that contribute to the unc e rt aint y . Each compone nt is accorded a factor of about 3 (actua ll y 3.16). Where i nformation allows a m ore precise est imation of the contr ibution of the component, the component's contri bution ma y be reduced to I
. The submitter argue s that relative rat and human blood:air partition coefficients of BTP can be used to adjust the Point of Departure ( P OD) concentrat ion in hum ans. The Skag g's report (20 14) s tates: 

### "T he blo od: air partition coefficient of BTP in humans (0.21) is a/actor o.f2 low e r than th e blood: air partiti on coefficien t measured in rats (0.52). A higher blood: air partition coeffic i e nt in rats, indica tes that BTP is more soluble in rat blood, so BTP will more easily diffuse into the rat blood s tream with a final eq uilibrium that will likely be twice that in humans. " US EPA (20 11) states: 

### "Jn th e RfC Methods, th e DAF derivation.for ER effects is based more on sc ienc e policy than o n an e mpirical pro ce dure. Further, this policy is hi-level; (I) 

### wh e re if Hbl g 

### values are unknown the default valuefor (Hb; g},i 

### I (l-h 1 r}H 

### = 1; (2) [( (Hbl g)A 

### is grea ter than (Hbl g)H 

### th e n a de.fault value of 1 is also used.. ,

### 3
For BTP , the rat b loo d :a ir partition coeffic ie nt is g reater than the human value by a factor of

2.5. 

### If this were u sed to calculate the human POD , the hum an POD would be 2.5 times g reater than the rat va lu e. EPA policy is to u se a n adjustment factor of 1 in thi s case. Howeve r, si nce this proced ure a ll ows for a more precise es tim at ion of th e hum a n PO D conce ntr at ion, the pharmacokinctic component of th e equation can be reduced from 3 to 

### 1. 

### 1.2 Co mment 2 on Intra s pecies Uncertainty Factor 1.2.1 Comment 2 Use of an intra-species uncertainty factor of 3 based on th e san 1 e Skaggs report and EPA precedence. 

### 1.2.2 Respons e to Co mm ent 2 Reject. The Skaggs 

### 20 14 repo rt cited a numb e r of argumen ts about w h y th e intras p ec ie s UF s h o uld be re du ce d from 

### 1 0 to 3
. • Workplace expos ures involve healthy worker populations that do not in volve se n s it ive individu a ls. o Th e hum a n adult fema le an d fet u s are th e susce ptible population s. Women can work in chemica l plants. Therefore , susceptib le populations are not excluded from the wo rkforce
. • Workers are predo min a nt ly mal e a nd toxicity s tudi es indi cate a hi g her No Observ e d Adve rse Effect Leve l (NOAEL) for males than females. o Women can work in chem ica l plants. Th e refo re, th ey mu s t be con si dered in a ny ri s k assessment. 

### • "The RfC intr ahuman variability uncertainty factor is intended to protect for potential
'' unobse rved " re produ c tive medical conditions (e.g., decreased spe rm m o tilit y, amenorrhea and ovulation dysjimction) th at are known to ex ist a m ong otherw ise h e althy populations. However, because we are primarily concerned about exposures in th e

· workplace, not exposu r es to th e ge n e r a l population, . . . we be lieve ii is approp riate to use a lower uncertainty fac t or of 3 instead of the 

### fit!! RfCs un ce rtainty factor of10 for intrahuman variability. " o The wo rkpl ace ex posure wo uld pote nti a ll y expose p regna nt wome n . T h e refo re this argume nt is not valid. 

### • "
... and because exposures would not be continuous (2./ hours /day) in a workplace selling (8 hours /

day, 5 days /

we e k), we bel i eve ii 

### is appropr iate to us e a low er un ce rtaint y factor of 3 inste ad of th e full R}Cs uncertainty facto r of I0fo r intra-human va ria bil it y." o T he worke r sce n ari os are for 4 days a week exposure and I 0 hours a day. The an im al studi es were conducted fo r 7 d ays a week and 6 h o ur s a day. The di s parity in exposu re reg i men is not that g reat. The ex trap o lat io n i s va lid
. • The E PA Office of Air a nd Radiation u sed an intra species UF of 3 for n-propyl bromide a nd 1 for C7 fluoroketone. o PMN exposure results in decrea sed survival of offs prin g at the L ow Observed Adverse Effec t Level ( LOAEL) and hi g h e r co nc en trat ion s . The effects are sev ere a nd th e m ode o f ac ti on is unknown. Without thi s know l edge there are in s uffi c ient grounds to . decrease the default UF of 

### 1 0.4

o The SNA P P rog ram ag rees the intraspecies UF fo r this P MN s h ould be 10. 

### 1.3 C omm e nt 3 on Dermal Expo s ure 1.3.1 Co mm e nt 3 D e t ermination by E PA that derma l expos ure is no t a factor fo r th is PMN based on u se and physical prop ert ies . 

### 1 .3
. 2 R es pon se to Co mm e nt 3 Ag r ee . This comment main ly a ddresses the E PA u se of dermal exposures to wo rkers. Th e s ubmitte r argu es that th e vapor pressure is so hi g h th at thi s exposure will not occur. E PA agrees, dermal exposu r e ha s been r emoved from the worke r scenarios. 

### 1.4 C omment 4 on Selection of NOAEL 1.4
. 1 Co mm e nt 4 Us e of a NOAEL/ P OD of 100 ppm in th e derivat ion of th e adve rse effec t level (AEL) ba sed on the su bmitted inform a tion (Skaggs pap e r), the W IL R esea rch repo rt conclus ion , and pe e r rev iew b y Dr. York. 

### 1.4. 2 R es p o n se t o Co mm e nt 4 Di sag r ee . Th e r e product ive eff ec t s study report s t ate d 

### "'Test s ubstan ce -r e lated, lowe r (not statistically sign ( ficant) pos tnatal su rvi val was noted in th e J OO and 1 7 5 ppm gro ups co mpar ed lo th e concu rren t control g roup durin g postnatal day (PND) 0-1, 1-4 , andfrom birth to PND 4; th e values in th e 1 7 5 ppm g roup were b e low th e minimum m ea n values in th e WIL R esea rc h historical control data, and 1 fe male in this gro up (no. 9 1654) had a total lifl e r loss o n P ND 2
. There.fore, th e pos tnatal survival at this ex posur e leve l was consid ere d adv erse. Th e pos tnata l surv i va l values in th e JOO ppm g roup w ere within the range of valu es in th e WIL R esea r ch historical control data, and th erefo re were co nside red w ithin normal limits and not ad ve rse. " P ostnata l surv ivals are s hown in T abl e 1-1. The postna tal surv i va l rate s s h ow a do se -respon se of decreas ing s urvival w it h increas ing exposure concentration. Whil e the 84.1 % s ur v iva l fro m birth to PND 4 at I 0 I ppm is with th e low ra n ge of th e histori ca l control va lu e of 83.8 %, it i s ju st bare l y withi n th at ran ge and i s in a con tinu u m of decre a s ing surv iva l w ith i ncreas ing expo s ure concentration. Therefore, l 0 I ppm is cons id e re d adverse. The NOA EL for postn a t a l survival i s 50 ppm . The d ose respo n se co ntinuum is also re n ec ted in increased gestat ion le n g th s and inte r ve ntricu lar septa ! d e fect s i n pups fou nd dead
.

### 5
Tab le 1

- 1 S ummar y o f Po s tnata l S ur viva l (% p e r litt e r} Parameter 0 ppm 50 ppm IOI ppm 174 ppm WIL-HC* Mean (Range} PND 0 (relative to 96.5 98.0 95.2 95.4 98.0 (93.3- numb er born) 100.0) PND 0 to PND I 99.2 98.1 96.1 91.7 98.7 (94.6- 100.0} PND I to PND 4 97. 1 95.9 91.7 76.5 98.4 (87.0- 99.8} Birth to PND 4 9 2 .8 " 92 .1 84.1 67.9 " 95.3 (83.8- 98.7) 

## * = W IL hi s torical con tro l data The EPA SNAP Program agrees with the se lection of 50 ppm as a NOAEL. 

### 1.5 C omment 5 on A ll owab le Expos ure Limit 1.5.J Comment 5 Determ in ation of an a ll owable worker ex posure limit , 8-h r time weight ed average, of 11 ppm or above. 

### 1.5.2 Respons e to Co mment 5 

### Di sag ree This response wi ll be subdivided into three sectio ns to address:

- Expos ure comments -Question about EPA derivat io n of POD -Allowable wo rk e r exposure limit 1.5
. 2
. 1 Exposure Comments EPA revised th e occupational ex posure assessme nt taki ng into accou nt yo ur requests; thi s revised assessment in c ludes rev ise d va lu es for exposu r e co ncentrat ion . duration and frequ e nc y . E P A carefully reviewed th e monitoring stud ies that you provided, commented on them and discussed th e m with yo u on three occasions via t e lephone or email excha nge. H e assessed expo s ure concentration at your s i te and at your customer s ite and the associated durat ion and frequ e ncy of exposure based o n the se s tudie s and his di sc u ss ion s you. The re vised assessme nt result s are di scusse d b e low. EPA assessed exposu r e conce ntratio n at yo ur s ite to be 2. 1 ppm 10 hr time-weighted average (TWA) , w hi c h is th e average a irb orne conce nt rat io n th at is r eported in the mo nit oring study of the PM N chemical dated 12/ 8/14. This level is assoc iated w ith eng ineering controls compri s i ng sampling in a closed bott le and a n itrogen purge prior to disconnec t whic h avoids spi ll ed material. EPA did not adopt th e va lue you recommend in Table I of your lette r of2/l3/ l 5, w hi c h i s 0.62 ppm. because the basis of thi s extra p o lated value is not c learly described in the monitoring stu dy. In accordance with his discus s ion with you, E P /\ assessed ex p osu re dura ti o n to be I 0 h rs p er da y and frequency to be 4 consec uti ve days p er m o nth , 12 m on th s a year or 2 consec uti ve da ys tw ice per month , 12 month s per year (or 48 days per year.) Note t h at exposure leve l for an

### 6 ine xperienced operato r is high e r , but the valu e is not clearl y report e d in the s tud y, and you in fo rm e d E PA that an in ex peri e nced operator would qu i ckly lea rn and expo s ure l eve l would dec li ne. EPA assessed exposure concentration at yo ur c ustom e r s ite to be 6.6 ppm I 0 hr TWA. Thi s value wa s derived from ex posure conc e ntration va lu es reported in yo ur report dat e d 11127/ 14. The deri va tion of this va lue is as follows: 

### 1. Average airborne concentrati on of H CFC 1 23 ( Halot ro n I ) outside of booth is 3.2 ppm accord in g to subm itter re port dated 11127114 , pg . 40. Maximum avg. conc e ntrati o n of same in s id e of booth is 31.5 ppm (p g. 39 of re port). Maximum reported values w e re adopted for a conservative a ssess ment. 2
. Time spent with the do o r of b oo th open and operator working in th e booth was estimated to be 1 2.5% of total tim e as foll ows : • 300 bottl es are filled p e r s hift accord in g to our discu ss ion ; • . time spent w ith door ope.n is ab o ut 30 sec . accordil)g to our discu ss ion ; th e refore, tota l tim e with door open = 300 * 0.25 min = 75 min. Fraction of time s pent with bo o th door o pen = 75 min 

### I ( l 0 hr* 60 min /hr ) = 0.1 25 3. Therefore , exposure concentration ass ess ed as follow s : 10 hr TWA concentrati on = 3 1. 5 * 0.125 

### + 3 .2 

## * 0.875 = 6.74 ppm ofHCFC 1 23 ( Hal otron 1). 4. E P A adju ste d thi s va lu e for ph ys ical properti es of th e PMN c he mic a l ba sed on th e following ass umption s : a. The volumes of liquid th at is re leased during di s connection of feed lin e to bottle i s eq ui val en t for Halotron 1 and th e PMN chemical (ba se d on E PA ' s di sc u ss io n with you)
. b. All of th e r e leased Hal otron l liquid evaporates ba sed on th e observations repo rt ed in relation t o the exposure monit o ring conducted at you r s ite. All of th e PMN chemica l liquid that i s re lea se d i s a ss umed to evap orate as we ll bec a use the VP of the PMN chemical is s imilar to th e VP ofl

- I C FC 1 23. The above assumpt ion remains valid eve n if the evapora tion ra t e of th e PMN c he mic a l i s lo we r due to a s li g htl y lo we r vapo r pre ss ur e b eca u se any PMN chemical that does not evaporate immed iately will eve ntually evaporate as was observed during the e xposure m o nitorin g at yo ur site. c . Airborne co nce ntration of the c hemi ca l is at a s tead y s tate. This i s ce rtainly the case out s ide th e booth. d. B ase d on thes e assumptions, a mass b a lance on th e che mi cal is as follows: vo lume r e l

ease d * liquid density = volumetric venti la t ion rate* conc e ntration of c he mical in ppm 

## * d e n s ity of c hemi ca l vapo rs . App ly in g this eq u ation to both HCFC 123 and the PMN chem ical and applying th e ideal gas Jaw to the de n s ity of the chemical vapors, the following is d e ri ve d: Concentration of PMN che mi cal = co nce ntrati o n of HCFC 123 

## * rat io of I iquid d e n s i ty of PMN c he mic a l to HC FC 1 23 * rati o o fm o l wt ofHCFC 1 23 to PMN chemical. ppm o f PMN c he mical = 6.7 ppm* (1653 k g/ m3 /1476 kg/ m3) 

## * (152.93 

### I 174. 95) = 6.6 ppm. EPA did no t account adjust th e Harl eto n 1 monitorin g res ult s usin g the multipli e r of 0.4 5 that yo u recommended due to the fo ll owi ng reason s:



### . .

### 7

a. According to yo ur report, this value is hi g hl y uncertain and the expe riment a l re su lt s do not support any va lue s o th e r than s impl y a va lu e that is les s I , which mean s that a va lue eq ual to 1 is the upp e r Iimit and i s appropr iate for a conservati ve assessment. EPA did not adjust the H alotro n I results and th e refore essen ti a ll y used a va lu e of I. b. Even if th e valu e you had report e d were s uffici e ntly accura t e, this val ue is s ite - specific an d not applicable to yo ur customer's s ite. F o r examp l e, n atu ral convection , or th e flo w of r e l ease d PMN c he mi ca l vapo r downward du e to hea v i e r den s ity, can only occ ur if a ir currents a rq s uffici e ntly low but that oo es no t appear to be the Gase at yo ur customer ' s**it ~.**  Two fa n s are r eporte d to be directe d at the b oot h where m o nit o rin g occurred. Fin a ll y, in ac cordance w ith E PA ' s di sc u ss ion with yo u , exposure duration was assessed to be 10 hr per day and exposure fre qu ency was assessed to be I 00 days tot a l co mpri s ing 2 weeks per month and 4 con sec utive days p e r week. 1.5.2.2 Question about EPA d e riv atio n of POD Th e s ubmitte r qu est ion how th e worker POD o f 2,055 m g/da y i s re l ate d to the 8,1 34 m g/day in th e (ollowing se nt e nc e. T hey c;ilso qu es tioned how these.are u sed in Table 4-2.**Th ~**  2, 055 m g/da y number is th e correct value and was u se d in Table 4-2 to calcu late th e Marg in of Exposu re (MO E ). T he va lu e o f 8 , 1 34 m g/day i s not correct. Th e e ntire d e ri vati o n of va lue s ha s been rewritten to refl ec t new ex posure values and th e approach revised to be m o re tran s parent. 1.5.2.3 Allowable worker exposure l imit The risk assessment for P

- 14-0 26 0 ha s been rev ise d to refl ec t the exposure inform ation pro v id ed by the subm itte r and EPA ' s evaluation , revised uncer ta inty factors based upon the sub mitter ' s co mme nt s a nd a more transpare nt approach to the de rivation. The s ubmitter talke d abou t an 8 hour TW A but the revi sed exposure s hows a I 0 hour workday for th e workplace. A rat reproductive effects st ud y NOA EL for decreased postn atal s ur viva l and in creased ges tation length i s 50 ppm for 6 ho ur s/day/7 d ays a week. Thi s w ill b e used as the P oi nt of Departure ( POD) for assess ing r e p eated ex posure risk. The accep tab le MOE is 30 based upon the following rationale: T he rat and hum an blood:air coeffic i e nt s are 0.52 and 0.21 res pectively. Thi s m ea n s th e human POD wo uld like ly be ap pro x im a tel y 2.5 tim es the rat POD. However , EPA policy is to u se a dosimetry adjustment factor of I when th e rat blood:air c o e ffici e nt is g r eater th a n th e human. S ince th ere i s infom1 ation to inform the pharrnacok in e tic co mpon e nt of the inter s pec i es UF and the selectio n of the human POD i s conservative, th e inter s p ec ie s UF is r e duced from 3 to I 0. There are no dat a no human variab ility in res p o nse to ex p os ur e to the PMN. The int raspecics UF is I 0. Th e composite MO E is th e factor of th e two U Fs above or 3 

## * 10 

## = 30. The rat NOAEL is 50 ppm for 6 hour s ex po s ure for 7 day s p e r week e xpo s ure. Th e health effects concentratio n ( H EC) from th e rat s tud y is 1 2
. 5 ppm. No te th at the H EC represents a 24 hour TWA for 7 da y s expos ure in a res tin g human. Worker ex p os ures are for I 0 hours per da y for 4 d ays per wee k.**Tl~ e**  HE C adjusted for 4 da y.s expos ure is 2 l.9 ppm (l-!ECA o J).

### 8

The H EC for the worke r scenario is 1 1 .9 ppm (HECs cENA Rlo)
. This i s lowe r than th e 2 1 .9 ppm HEC ADJ noted above b eca use th e worker is assumed to breath 10 m 3 in 8 hours (equ i va le n t to 30 m 3 for 24 h o urs ) w h ereas th e i .:IE D ADJ i s base d u po n a res t in g b rea th in g ra te of 1 6
. 3 m 3 p e r day (The Exposure F actors H andbook gives breath in g rates p er day for age ranges {mea n a n d 95th perce nt i le} of th e human p opulat ion
. The g reates t mean value of 1 6
. 3 m3 per day i s for ag e 1 6 to <21 ). T he H ECscENAR I O was ca lcu l ated by mu lt iply in g th e HE CAnJ by the ratio of th e ( rest in g breathing rate of 16.3 m 3 per da y )/ (worker breath ing rate of30 m 3 pe r da y ). No te that th e H ECsc E NARIO i s a 2 4 h o ur T W A
. T h e T W A u se d in M OE ca lcu lat io n s w ill be adjusted to th e co n ce nt ration appropriate to t h e duration u nder considerat ion . F or I 0 hour s of exposure for 4 days per week of exposure th e 10 ho u r TWA i s 28.5 pp m . D iv i ded by a total UF of 30 th e accep ta bl e wo rk e r expos ure i s 0.95 p pm . ENTER VARIABLES INTO YELLOW CELLS· Exam le I s minutes but ou can uae hours

'1f (H,. 0 )Al(H 09 ( H > 1 entM 1 lor both (H 09 ( v alues Fi g ur e 1-2 C alcu l a ti o n of h u m a n ex po s u re v a ria bl es 

### E Q UAT IO N S 1. 

### C a lcul ate H E C Note. In t hi s exampl e the (C x t) expression i s d iv ide d by 24 h o u r s . If thi s i s the ca se make s ure that th e t unit s are in hours. The C and t re fe r to the co n ce ntrati o n a n d d u rat i o n in th e a ni ma l ex p e rim e nt. 

### E q u a ti o n 1 

### C alc lu a t e H EC fro m an i mal d ata H

EC = ( C x t)-7·2 4 

### 2 . D ete rmin e H EC A o . 1 - 

### A dju s t 1-I EC for D ay s of Ex p o s ur e E qu ati o n 2 A dju s t H E C fo r di ffe r e n ces in d ay s of ex p o s ur e/week i n a nim a l s a nd hu ma n s HEC

_ AD } =HECx( DAYS

_ANIMAL+ DAYS_HUMAN) 

### 3. D e ter min e H EC sc £NA R 1 0

- A dj u s t HEC A oJ fo r Sce n a ri o B r ea thin g Rate Eq u at io n 3 A dju s t H EC for di ff ere n ce s in breathin g rat es b e t wee n th e hum a n at r e s t a nd in t h e s pec ifi c s ce n a r · i o HEC

_ SCENAR I O = HEC

_AD} x(RESP

_ RESTING + RESP

_ SCENAR I O)

### 9 

### 4. A dju st H EC srnNA R I O for Sce n ario Duration Equation 4 Determine co ncentr a tion for the sce nario duration C

_ SCENAR IO = HEC

_ SCE NAR/O x(24 hrs-7-t

_ S CENA RIO ) 

### 5. Adju s t th e H EC for Differences in Blood:Gas P a rtiti o n Coefficie nt s Eq uation 5 Calculation of D AF DAF=(H

_ (bl g) ) A l (H

_ (b lg) )H 

### Eq u ation 6 Correction for blood:ga s partion coefficient differences 

## K

ee l _(SCENAR IO -BG))=(C

_ SCENARIO )xDAF



### VARIABLES AND ABBREV I ATIONS Definition of Variable s • 

### C = Concentration in ppm or m g/m3

. 

### Use same unit s thr ou g hout calculations. C scENARI O = Co ncentration for th e duration under considerati o n in the sp ecific human exposure see nano. C scE NARI O -BG = C sc ENARIO co rr ec ted for differences in th e blood:gas part iti on coefficients. O AF = D osimetric adju s tm e nt factor. D AYSANIMAL = Da ys of week th e anima l w as ex posed. DA YS11 uMA N = D ays of week a human i s exposed in the specific scena ri o. (Hh t g )A = Blood gas partition coeffic ient animal. (H b t g ) H 

## = Blood gas partition coe ffici en t hum a n. HEC = Human Eq uivalent Concentration for th e P OD
. This is a 24 hou r a day va lu e. HE CAoJ = T he HEC fo r th e POD adju s ted fo r d iff e r

e nces in numb er of da ys ex po s ure p e r wee k betwee n an im a l and hum a n expos ure sce nario s. H ECscENAR I O =Th e HECAoJ for th e P OD adjusted for d iffe re nces in th e r est ing breathin g rat e and th e scenari o breathing rat e. k = Constan t in Haber' s rule equat ion of C 

## * t = k
. M OE= Marg in of Ex p os ure POD= P o int of Departure RES PRES T ING = Res pira tory rate in a human at r est. · RES PscENARIO = R esp irato r y rate in a human in the sce nario und er co ns id e ra tion. t = D urati on of exposure in minutes or hours. Use same unit s throughout calcu lati o ns . tscE NAR I O = Dur at io n of th e of the spec ifie h uman exposure sce nario. Use sa me unit s throu g hout ca lcu lations.10 

### 2 REFERENC ES S kaggs, S R
. 20 14. Derivation o f a Prop ose d Oc c up a ti o nal Expos ure Li mit for 2

- Bromo

- 3 , 3,3

- T riflu oropropene. U ni ver sa l T echnica l Serv ices , Inc. US EPA. 20 1 1. S T ATUS REPORT : Advances in Inha lation Dos imetry for Ga ses with L owe r Respiratory Tract and Sys t emic Effe ct s. E P A/600 / R- l l / 067.



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