Exposur e Mo deling PublicM eeting Oct ober 28, 2014 Gr eg Orrick, Cher yl Sut to n, Katrina W hit e, J ames H etrick, R. Da vid J ones, M ohammed R uhman, MahShamim

# Ov er vie w  

### EFED Guidanc e to a ssist i n evaluating unextr act ed re sidues (UR)  i.e. , re sidues t hat

re maina ssociat ed witht he s olid matrix follo wing extr actionins ubmit te d e - fat e s tudies

2 **Unextracted (W** 

**eakly t**  **o Str**  **ongly**

**S orbed)**  **Extracted**
**The a**  **mounts o**  **f extracted**  **and unextracted**  **residues d**  **epend on**  **the c**  **hemical pr**  **operties, soil**  **pr operties,**  **and the**  **s ystem**  **of e**  **xtraction. Liquid Phase**  **Solid Phase**  **(Soil or**  **Sediment)**

# Guidance Principles  

### Fo st er c onsist ency  Especiall

y inEFED’ s e valuationa nd handling of t he issues 

###  

### Clarif y the issues  Including some e xp lanationo f wh at EFED co nsiders t o be ana dequat e e xtr actiona tte mpt 

###  

### Minimize re quests f

or new d ata  Us ing the available lines o f evidenc e a nd, if nec essar y, indicating the minimumd ata needed t o re duc e unc ertainties 3

# Need f or Guidance  

### Some d egr adations tudies w iths oil/sediment ha ve hig h amounts o f unextr act ed re sidues w ithl it tle a nalytical method dev elopment  It has beenu nclear

wh at is a n a dequat e e xtr actiona tte mpt 

###  

### Ther e has beeninc onsist ency i n:  Evaluating the a dequacy o f extr actions  Re questing data

fr omre gistr ants to a ddr ess the issue  Exposur e modeling appr oaches int he a bsenc e o f data  Ov er all appr oaches to t he issue 4

# Guidance Sc ope  

### Clarif y EFED’ s curr ent

p erspecti

ve onUR issues  

### Pr ov ide a n evaluationp ro ce dur e f or s ubmit te d studies  

### Pr ov ide o ptions fo r e xposur e assessment w hen unextr act ed re sidues c annot r eadily be e xc luded fr om the re sidues o f co nc ern

5

# The Bot to m Line

6 **Dissolv ed**  **Extractable w**  **ith Wa**  **ter Extractable**  **w ith Other**  **S olv**  **ents No**  **n -**  **extractable** 

###  

### All re sidues a

vailable fo r d egr adations hould be e xtr act ed  

### Wh ene xtr actions a re not a dequat e, it

is not c lear w hether the u nextr act ed re sidues include o nly s tr ongly s orbed non - extr actables o r s ome p ot entially e xtr actable r esidues that a re available fo r d egr adation Soil and sediment studies ha

ve t wo ge ner al fr actions: non - extr actables a nd extr actables . Available for degr adation Un available for degr adation

# Issue: Use of Studies  

### Degr adations tudies a re u sed for model inputs  Ne ed a half

- life t hat re fl ects d egr adation, not a co mbinationo f degr adationa nd partitioning to s olids  A s orptionc oeff

icient i s u sed to model partitioning  Ne ed to re fl ect

d egr adationint he to tal sy st em  Including dissol

ve d and we akl

y s or bed re sidues t hat

a re available for

d egr adation  All re sidues available for d egr adations hould be e xtr acted  Str ong ly

s or bed ( i.e. , bound) re sidues n ot available for degr adations hould not b e e xtr act ed  This d ouble - co unts t heir d issipationin ex posure models 7

# Issue: Solv en ts Used  

### Studies c ommonly

i nvo lve extr actionp ro ce dur es w itha limit ed selectiono f polar s olv ents  Mu ltiple p olar

a nd nonpolar

m ild extr actions olve nts withvaried chemical pr operties s hould be u sed t o  Speed up e xtr action  Extr act a ll re sidues available for d egr adation  Solve nt e xp lor ationis not

int ended t o  Re mo ve b ound re sidues  Chemicall

y a lt er t he te st c ompound or

its p ro ducts  Estimat e b ioa

vailability  Emulat e a ctual en

vir onments  The to xicity

o f solv ents to aquatic o rg anisms i s irrelevant 8

# Solv en t P olarity  Gener all

y, o ne s olve nt

fr ome acho f thr ee g ro ups s hould be used wh enURs a re > 10%  Example polar

a nd nonpolar

s olve nts w itha ra ng e o f dielectric co nstants a re give n  Gr oup 1: polar

s ol ve nts w ithd ielectric co nstants o f 18 - 80  E.g . , water

, formic a cid, methanol, ethanol, isopropanol, ac et one, ac et onitrile, dimethyl sulfo xide  Gr oup 2: polar

s ol ve nts w ithd ielectric co nstants o f 6.0 - 9.1  E.g . , ac etic a cid, ethyl ac etat e, tetr ahydrofur an , dichloromethane  Gr oup 3: nonpolar

s ol ve nts w ithd ielectric co nstants o f 1.9 - 4.8  E.g . , hexane, benzene, toluene, 1,4 - dio xane, chloroform , diethyl ether 9

# Solv en t Selection  

### Ad ditional fact ors a re co nsider ed, including  Te st co mpound chemical pr operties  Solve nt s ys te m p H 

###  

### If t he e xtr actionp ro ce dur e canbe c onsider ed adequat e, the URs a re co nsider ed str ongly s orbed and not o f co nc ernfr oma

re gulat or y p erspecti

ve

10

# Flo wc hart fo r Addr essing URs

**YES** • **Are unextracted residues**  **<10% of the applied; and**  • **No minor transformation**  **product of higher**  **toxicity than**  **the test compound is suspected to be unextracted?**  **YES**

**NO Unextracted**  **residues are considered**  **likely to be irrelevant**  **and not part of the residues**  **of concern. No further**  **work on URs is needed.** 

**Does the extraction method or its development**  **include exploration of multiple solvents with**  **varied chemical**  **properties (**  **e.g. , varied dielectric**  **constants)?**

**NO**
**Evaluating all lines**  **of evidence, which may include**  **the open literature, is**  **there sufficient evidence**  **that the extraction**  **method is adequate?** • **Compare the method efficiency and UR**  **profiles with**  **that of other e**  **- fate data and studies.**  **YES**

**NO**

**Is exposure including URs**  **<LOCs?**

**NO**
**Bound exposure estimates**  **by including**  **and excluding URs for at least the use site of highest**  **exposure. Characterize**  **the bounding**  **estimates. The risk manager has the option to contact**  **the registrant, the latter of which has the option to provide additional**  **data to reduce the uncertainty in the adequacy of the**  **extraction method and/or to decrease and identify**  **the URs. No further**  **work or data on URs is needed for the**  **current assessment.**  **Continue to treat URs as**  **residues of concern.**  **Revisit this**  **issue in**  **future assessments.**  **YES Is exposure including**  **and excluding URs**  **predicted (not modeled) to be similar (due to persistence)?** 

**YES**

**NO**

11 **Unextracted residues can**  **be considered strongly sorbed and not part of**  **the residues of concern.** 

# Flo wc hart Of

f - ra mps  

### Don ’t n eed to c onsider

URs f urther w hen:  <10% of

a pplied, inge ner al  Extr actionmethod uses multiple s olve nts w ithvaried chemical pr operties ( e.g . , dielectric co nstants)  Other d ata indicat e e xtr actionis a dequat e  UR formationd oes not co rr elat e w ithte st

co mpound decline a nd ther e a re no d egr adat es o f co nc ern  Te st co mpound is s uff

iciently p ersist ent

s ucht hat ex posur e e stimat es w itha nd without URs a re s imilar

12

# Lines of E vidence

13 

###  

### Discusses l ines o f evidenc e for e valuating URs  Co nsider

a ll submit te d studies a nd data  Evaluat e formationa nd decline p at te rns  Co nsider

s imilar co mpounds w ithe videnc e o f str ong sorptionto s oil  Fo r example, some c hlorinat ed anilines  Openlit er atur e m ay be u seful 

###  

### Discusses e videnc e t hat i s not u seful  Fo r example, co rr elationo f miner alizationa nd UR lev els does not indicat e URs a re s tr ongly s orbed

# Ex ample Cases  

### Pr ometr yn  So xhlet e xtr actiond id lit tle to re duc e levels o f highU Rs  Explor ationo f additional mild solve nts wa s needed t o re duc e unc ertainty

inw hether

t hey e xtr act URs 

###  

### Fe nbutatinox ide  Solve nts e xp lor ed: methanol substantiall y re duc ed URs  Gr eat er ce rtainty

int he e xp osur e a ssessment 

###  

### Et hyl p ar athion  URs incr eased for

90 da ys, thend ecr eased ove r the next 270 d ays, indicating degr adationo f URs  Solve nt e xp lor ationwas needed t o re duc e unc ertainty 14

# Re gis tr an t Con ta ct

15 

###  

### Inman y c ases, UR issues a re not c ommunicat ed to re gistr ants t hr oug h risk manag ers u ntil the e xposur e assessment

i s co mplet ed  Re duc es the bur deno n industr y if r isk co nclusions a re not a ffect ed by

the issue 

###  

### Howe ve r, t he e xposur e assessment g ener ally

benef its wh ent he issues a re re solved bef or e it is c onduct ed  This ma

y pr eclude the need t o co nser vativ el y include the URs ina quatice xp osur e e stimat es  E arly co mmunicationto re solve the issues ma y be needed, especiall

y w henhighl

y to xictr ansformation pr oducts a re in

vo lved

# Exposur e Assessmen t

16 

###  

### URs a re modeled only w heno ff - ra mps d o not

a pply  

### Same modeling appr oachfo r  SW and GW  DW As a nd ERAs 

###  

### If e xposur e with URs < L OCs, no f urther w ork needed  

### Ex posur e without

U Rs ma y o nly be c alculat ed for

t he use p at te rno f maximume xposur e  

### Ex posur e estimat es w ithURs s hould alwa ys b e we ll char act erized as a n u pper bound

# PRIA Actions w/ Ne w Studies

17 

###  

### Studies s hould be s cr eened f or a dequat e extr action methods i f URs a re ≥10% of t he a pplied and additional evidenc e is not

a vailable to re duc e u nc ertainty i n wh ether t he URs a re available fo r d egr adation  

### If t he s tudies f

ail the s cr een, EFED should identif y the def icienc y a nd re quest

a dditional evidenc e to re solve the u nc ertainty

i n t he 90 - da

y T echnical Scr een memor andum  Should not

be a re asonto kick

o ut t he a pplication

# Re gis tr at ion Re vie w

18 

###  

### Old studies a re not

g ra ndfather ed inw ithout r eview  

### Da ta a re not re quest ed for

e ve ry o ld study  

### If t her e’ s anu nc ertainty

, re gistr ant

s hould be notif

ied inPr oblemF ormulationDa ta Gaps Sectiont hat

d ata ar e needed f

or o ne s oil/sediment

w ithhigh URs  Solve nt e xp lor ationis ge ner all

y needed, ra ther

t hana new , GLP - co mpliant

s tud y  Studies w ithUR issues a re not a ut omaticall

y do wngr aded at

t he ProblemF ormulationp hase

# Additional Da ta i n R eg. R ev ie w

19 

###  

### If t he a dditional data

indicat e that

U Rs c anbe co nsider ed str ongly

s orbed, this informationc anbe inferr ed t o a pply

to o ther s tudies, inmost

c ases  

### If t he a dditional data

d o not indicat e that

U Rs c anbe co nsider ed str ongly

s orbed  Mo re d ata

ma y be needed for

a ny s tudies w ithhighURs  Exposur e e stimationma y include URs

# Ques tions?

20