p. 1 

# Tas k Forc e CBI C Contro l Numbe r 

# 35533 3 P.O . Bo x 331 , Millwood , V A 2264 6 (540 ) 837-160 2



### Jul y 24 , 201 3 o 

### B Y HAN D r o -x? S c n HfT i 

### Mari aJ . Doa , Ph.D . o c E m Director ° Chemica l Contro l Divisio n £ J Environmenta

l Protection Agenc

y 120 0 Pennsylvani aAve. , N.W . Washington , D C 2046

0 oe 

### d&P« ceSSC 

### ll H Re : Testin

g Consen t Orde r fo r Ethylen e Dichloride : Reques t fo r Modificatio n o f

Enforceabl

e Consen t Agreemen t an dAmendmen

t t o Stud y Pla n (Docke t No . OPPT

2003-0010 1 Dea r Dr . Doa : Than k yo u fo r you r respons e o f Jul y 22 , 201 3 to ou

r reques t fo r amodificatio n o f

th e Enforceable Consen

t Agreemen

t fo r Ethylen e Dichloride ("EDC") , 68 Fed . Reg . 3312 5 (Jun e 3 , 2003) , a

s amended

, 74 Fed . Reg . 3619 6 (Jul

y 22 , 2009) , furthe

r amende d b y Addendu

m Modificatio n providedby lette r date d Novembe

r 23 , 201 1 fro mMari aJ . Doa(th e "ECA") . Th e Tas k Forc e understand

s an dshare s you r concern s abou t th e unavoidabl

e delays encountere

d b y WI L Laboratorie s i n preparin g to conduc

t th e Extende dOne-Generatio

n Drinkin g Wate

r Reproductiv

e Toxicit y Stud y o f Ethylen e Dichloride i n Rats , base d o n OEC D Guideline 443 . Th

e stud y pla n submitte

do n Ma y 24 , 201 3 includedastar

t dat e o f Jul y 8 , 201 3 an

dacompletion dat

e o f Jul y 24 , 2014 . Thes

e date s wer e base d o n EPA' s approva l i n advanc

e o f th e star t date . Whe

n thi s wa s no t received , I notifie dth

e laborator

y t o postpon e ordering th

e animals , an

dsen t Joh n Schaeffe

r th e enclose d fa x date d Jul y 1 0 t o thi s effect . Th e addendu mmodificatio n yo

u provide dcontains acompletion dat e o f Jul y 28 , 2014 , base

d o n th e now-inoperative star

t dat e o f Jul y 8 , 2014 . Mr . Schaeffe

r aske d fo r ane w schedul e base d o n a n expecte d acceptanc

e dat e n o late r tha n August 5 . I a minforme db

y WI L that , du

e t o limite dvivariumspace

, th e earliest dat e i t ca n no w initiat e thi s stud y i s Septembe r 1 , makin g th e completion targe

t dat e Septembe

r 15 , 2014 . I n orde

r t o mee t thes e dates , I nee

d t o informWI L b

y August 7 , 2013 . Th

e enclose d schedul e reflect s WIL' sp . 2 Mari aJ . Doa , Ph.D . Jul y 24,201 3 Pag e 2



### curren t estimat e o f th e tim e require d fo r i t t o conduc t th e study , analyz

e an d interpre t th e results , dra

w conclusions , an

d writ e apeer-reviewe

d report . Any shortenin

g o f thi s perio d couldresul

t i n a n incomplet

e stud y tha t woul dnot

b e scientificall y credible , woul db e useless t o th e Agenc y fo r assessin g potentia l huma n risk , an d woul dno

t confor mt o EPA' s own testin g guideline s an

d standards . Ihav e signe d th e enclose d addendu mmodificatio n an

d initiale dne

w handwritte

n deadlin e date s o f Septembe

r 15,201 4 fo r

th e main stud

y (unles s asecon

d generatio

n stud y i s triggered ) an d Decembe

r 15,201 4 fo r

th e route-to-rout

e extrapolation . I loo k

forwardt o receiving th

e countersigne

d addendu mmodificatio n fro myo

u b y August 5 , 201 3 s o tha t w e ca n initiat e an d complet e th e stud y i n accordanc

e with th e ECA .

Enclosures cc : Joh

n E . Schaeffe

r Jame s C . Lamb , IV , Ph.D . JimS . Bus,Ph.D . Jacque s Maurissen , Ph.D . W . Caffe y Norman , Esq . Documen t Contro l Offic e (six copies )

4842-J657-7553.1 . 

### Sincerely ,

Pete r E . Voytek , Ph.D . Manage rp . 3

P.O . Bo x 331 , Millwood , V A 2264 6 (540 ) 837-160 2 

# Tas k Forc e DAT E 7/10/1 3 TO : Joh n Schaeffe

r FROM : Pete r Voyte k SUBJECT : ED C Stud y Pla n PAGES : 1 The HAP Task Force submitted

the study plan to EPA dated

May 24, 2013

for the Extended

One-Generation

Drinking Water Reproductive

Toxicity Study of Ethylene

Dichloride

in Rats. An

experimental

start date of July 8, 2013 was provided with a final report to be submitted

to EPA on July 21, 2014. These

dates were based on the assumption

that the study plan would be approved

by EPA in a timely manner in order for the animals to be ordered, acclimated, and clinically examined

prior to the experimental

start date. Since

we have not received any notification

from EPA I told the laboratory

to postpone

ordering

the animals until we have approval

of the work plan. As

your are aware the animals need to be of a certain age at the beginning

of the experimental

stage as required by the protocol. I a m puzzle d b y th e delay . Th e mos t importan t an d essentia l par t o f th e wor k pla n i s th e stud y protoco l tha t has alread y bee n reviewe d an d approve d b y you rpharmacokineticists , neurotoxicolgists , an d reproductiv e an d developmenta l toxicoiogists . I f an y technica l issue s remai n i nee d t o b e informe d s o tha t change s ca n appropriatel y b e mad e t o th e protoco l an d approve d b y th e Agency befor e an y testin g i s possible . Th e tim e t o initiat e an d complet e thi s stud y assume s tha t n o technica l issue s ma y arise . A s wit h al l biologica l testin g th e unexpecte d ma y occu ran d necessar y amendment s wil l b e require d i n orde rt o achiev e th e objectiv e o f th e stud y a s describe d i n th e protoco l an d t o assure technica l quality . However , i n ou rman y previou s toxicit y test s o n bot h 1,1,2-trichloroethan e an d ethylen e dichlorid e conducte d ove rman y years, I d o no t recal l tha t an y technica l issue s aros e t o dela y th e completio n date s onc e th e stud y wa s initiated . Afte rreceivin g approva l o f th e stud y pla n I wil l immediatel y notif y th e Laborator y t o orde rth e animal s an d th e experimenta l star t dat e wil l b e on e mont h afte rth e dat e o f receip t o f th e EP A letter . I f yo u hav e an y question s contac t me .

## Schedul

e fo r Extended One-Generation Drinkin g Wate r Reproductiv e Toxicit y Stud

y o f Ethylene Dichlorid e i n Rat s Date o f EP A Response : 8/5/201 3 Anima l Receip t 8/19/201 3 Firs t Dos e 9/1/201 3 En do f F O breedin g 10/12/201 3 En do f F O Parturitio n 11/3/201 3 Las t Necrops y Cohor t

l a 2/2/201 4 Las t Necrops y Cohor t

l b 3/3/201 4 Las t Necrops y Cohor t

2 a 11/24/201 3 Las t Necrops y Cohor t

2 b 1/20/201 4 Audite dDraf t

Repor t t o HA P Tas k

Forc e 6/9/201 4 Fina l Repor t

t o HA P Tas k

Forc e 9/8/201 4 Fina l Repor t

t o EP A Date 9/15/201 4

4815-9509-5316.1 .p . 5 UNITE D STATE S ENVIRONMENTA L PROTECTIO N AGENC Y

WASHINGTON , D.C , 2046 0

OFFIC E O F CHEMICA L SAFET Y AN D POLLUTIO N PREVENTIO N Dr . Pete r E.Voyte k HAP Tas k Forc e Manage r JU L 2 2 2DJ 3 P.O . Bo x 33 1 Millwood , Virgini a2264 6 Re : Ma

y 24 , 2013 , Reques

t by th e HA P Tas

k Forc e fo r

Modificatio n o f

Enforceabl e Consen

t Agreemen

t fo r Ethylene Dichlorid e (Docket No . EPA-HO-OPPT-2003-0010 ) Dea r Dr . Voytek : EP A ha s complete d it s revie w o f the requeste

d modificatio n t o the "Extende d One

Generation Drinkin g Wate r Reproductiv e Toxicit y Stud y o f Ethylene Dichlorid e i n Rats " tha t i s base d on th e OEC D Extended One-Generation Reproductiv e Toxicit y Stud y Guidelin e 443 (EOGRTS) , an

d your emai l o f Jul y 11,2013 , concernin g the test schedule . The HA P Tas

k Force/WIL Laboratorie s stud y protoco l als o combine s aneurotoxicit y testin g component , an

d wa s approve d b y EP

A o n Novembe

r 23,2011 , Th e modificatio n include s th e requeste d schedul e changes t o the origina l stud

y plan , includin g a

n extensio n t o the submission dat e fo r th e require d fina l reports . EPA ha

s als o reviewe d th e protoco l amendment s tha t Wer e originall y submitte d wit h the protoco l fro mWI L Laboratorie s (Protoco l Amendmen t 1 ) an d th e additional amendmen

t (Protoco l Attachment

2 ) tha t contain s change s to th

e protoco l tha

t wer e requeste d by EPA . EP A furthe r acknowledge s th

e additio n o f

Dr . Sawhne

y Code r a s a n emergenc

y contact fo r th e study . Yo u hav e state d i n your request lette r tha t amodificatio n to th

e tes t schedul e i s neede

d becaus e WI L Laboratorie s ha

d difficultie s obtainin g th e necessar y equipmen

t t o conduct

th e study . Then , a

s testin g was abou

t t o begin , preliminar

y work determined tha

t ther e wa s a n unforesee n proble mwit h maintainin g th e neede d tes t substance concentrations * Whil e EP A understands tha

t solvin g thi s problemtoo k tim e an d effort , suc

h tha t a n extensio n fo r

submittin g th e fina l reports i s needed , the Agenc y remain s concerned abou t th e delay s tha

t hav e occurred . I n grantin g thi s extension , EPA als o understands tha t the'proble mwit h maintainin g th e necessar

y tes t concentration s i s no w resolved . Enclosed , fo r

you r signature , i s the Addendu mModificatio n to the ED C ECA . Th e Addendu mModificatio n confirm s the approve d change s to the revise d testin g a s wel l a s th e revised dates tha

t th e fina l report s ar

e due . Th e Addendumals o include s th e WI L protoco l amendments .

Interne t Addres s UJRL j • htt p rVwwwep a go v

Rticycled/Recyctabl e • Printe d wit h Vegetabl e Oi l Base d Ink s o n "100 % Poslcansumer . Proces s Chlorin e Fre e Recycle d Pape rp . 6 

### Th e fina l repor

t fo r th e combine dEOGRTS/neurotoxicit

y stud y i s du e Jul y 28,2014 . Th

e fina l repor t fo r route-to-rout

e extrapolatio

n fo r reproductiv

e effects an

dneurotoxicit

y is du e Octobe r 28,2014 . Not

e that , i n accordanc

e wit h th e origina l enforceabl

e consen t agreemen t (ECA) , th e HA P Tas k Forc e mus t submi t interimreport

s describin g th e status o f al l testin g performe dunde r thi s EC A t o EP A ever y si x months . Failur

e t o adher e t o th e condition s o f

th e ECA , including th

e EC A reportin g requirements , coul

dresul t i n penalties a

s specifie d i n 4 0 C.F.R . § 790.65 . Whil

e EP A appreciate

s th e wor k o f th e HA P Tas k Forc e t o bring thi s testin

g t o asatisfactor

y conclusion , i t

i s als o concerne

d tha t thi s EC A ha s incurre dnumerou

s delays . Pleas e sig n an dretur n th e enclose d addendu mt o th e EC A fo r 1,2-ethylen

e dichloride . Thi s signe ddocumen

t wil l b e submitte d t o th e above-reference

dEP A Docke t fo r thi s ECA . Please contact

John Schaeffer

if you have any questions (phone: 202-564-8173; email: schaeffer.john@epa. gov). Sincerely , Mari aJ . Doa^Pfi-D . Directo r Chemica l Contro l Divisio n Enclosure s a/ sW

e th e undersignedagre

e t o th e chang e t o the Enforceabl e Consen t Agreemen

t fo r 1,2-Ethylen

e Dichloride (CA S No . 107-06-2 ) a s describe di n the tabl e below : Original Language (I mModificatio n Addendu mt o Tabl e I o f

th e ED C EC

A (74 F R36196 ) date dNovembe

r 17,2011 , an

db y approva l letter o f Novembe r 23,2011 ) Tier U Testing and/or

Program Review Extrapolation Reporting Reproductiv

e toxicity/Neurotoxicit

y (oral ) Reproductiv

e toxicity/Neurotoxicit

y route-to-rout

e extrapolatio

n ol*dose-respons

e (ora l dat at o inhalation , includin

g Tie r I I testin g an dextan t studie s reporte db y Aiumoi , c

t aJ. , (1976) , Rao

, el aJ..(l980) , an

d Lane , ctal. , (1982) ) Tes t Standar d Deadlin e fo r Fina l Repor t Combine dReproductiv

e Kffect s /Neurotoxicit

y Protoco l EC A appendi x C. 4 an dC 6 Jun

e 28 , 201 3 (Ne w stud y pla n du e Februar y 28 , 2012

) Septembe r 27 , 201 3

Amended , Languag e (chang e i n Tabl e 1 o f th e ED C EC A a s amende d o n Jul y 22,2013 , an d b y approva l lette r

o f Jul y 22,2013 ) Tie r ( I Testin g and/o r

Progra mRevie w Tes t Standar d Deadlin e fo r Fina l Repor t Extrapolatio n Reportin g Reproductiv

e toxicity/Neurotoxicit

y (oral) Reproductiv

e toxicity/Neurotoxicit

y roule-io-rout

c extrapolatio

n o f dose-respons

e (ora l dat at o inhalation , includin

g Tie r 1 1 testin g an dextan t studie s reporte db y Aiumoi , e

t ai. , (1976) . Rao

, c t al. , (1980) , an

d Lane, e t a L (1982) ) 

## 5«*ft»v4^lb/ Combined

Reproductive Effects vJuly38» 2014 /Neurotoxicity Protocol/with WIL ^£

\j Protoco l Amendmen

t i an dWI L Protoco l Attachmen

t 2 Octobe

r 28 , 201 4 EC A appendi x C.4 an dC. 6

Mari aJ . Doa . Ph.D . Dat e Pete

r Directo r Manage r Chemica l Contro l Divisio n HA P Tas k Force ;erE . Voytek , f^D' . Daif eP . 8

Jul y 22,201 3 Addendu mModificatio n T o Enforceabl e Consent

Agreemen t Fo r 1,2-EthyIene Dichlorid e (CA S No . 107-06-2 ) Tier JiffAPs Testing



### Docke tNo . OPPT-2003-001 0p . 9

2550 M Street , N

W Washington , D

C 20037-135 0 

# Rout e EP A Mai l O : Documen t Contro l Mailsto p 2 Department : 7407 M SC L

SCL108573061434- 3