Pa g e 1 of 3



### O PP T C h a r g e t o E x te r n a l P e e r R e v i e w e r s f o r the r e v i e w o f the TS C A

W o r k p l a n C he m i c a l Ri s k A ss e s s m ent o f T C E

June 2013

O PP T f o c us e d its r i sk a ss e ssm e nt on t h re e sp e c i f ic us e s of T C E: a s a spray d e g re a s e r b y w o r k er s

i n sm a ll c omm erc i a l f

a c iliti e s, a s a spray d e g rea s e r b y c o n su m er s ( hob b y i s t s )

, a nd a s a c l e a r

p r o t ec ti ve c o a ti ng s p r a y ( a n ar t/c ra f t s us e ) b y c onsu m er s ( h o b b y i s t s )

. F o r a l l us e s, o n l y t he

i nh a l a ti on r ou t e of e x posu r e wa s e v a l u a te d, a nd r i sk e s tim a t e s f or i nd i v i du a l s p h y s i ca l l y n ea r t h e

us e r of t h e T C E p r odu c t ( but not us i ng it ; ca ll e d e it h e r b y s t a n d er s or non

- u s er s) w er e al so

ca l c u l a t e d.

G e ne r al Qu e s t i on on th e R i sk A ss e s s m e n t D o cu m e nt

Iss u e 1. Th is r i sk ass e s s me n t i s d iv id e d in t o t h r e e c h a p ter s with six a pp e nd i ce s a n d

t h re e s upp l e m e n t al d o c u m e n t s. Th e f i r st tw o c h a p ter s d e s cr ib e t h e s c o pin g e x erc i se

E P A u s e d a n d b a c k g r o un d i n f o r m a t i on on T C E t h at s et s t h e s t age f or t h e in f o r m a t i on

ava il a b le a n d u s e d i n th e r i sk ass e ss me n t

. C h a p te r 3 in c lud e s t h e e x p os u re , h a z a r d

assessment a nd r i sk c h a r a ct e r i z a t i on a n d a s ect i on on un cert a in t i e s f or e a c h of t h e

t h r e e u s e s of T C E w hi ch a r e t h e f o c u s of t hi s r i s k ass e ss m e n t

. Th e r i sk ass e ss me n t i s

in te nd e d t o p r ov id e a c l e ar a nd tr a n s p a re n t s u mm a r y o f t h e A g e n c y ’ s a n a l ys i s.

Q u e s t ion 1

- 1: Pl ea se c o mm e nt on w h e t h e r t he c h arac t er iz a ti on p r ov i d e s a c l ea r a nd l o g i cal

su mm a r y o f E P A’ s a n a l y s i s. Pl ea se p r ov i de sp ec i f i c sugg e s ti ons f

or im p r o v i ng t he

do c u m e n t

.

Q u e s t ion 1

- 2: Pl ea se c o mm e nt on w h e t h e r a p p r o p r i a t e b ac k g r ound i n f o r m a ti on i s p r ov i d e d

a nd a c c u ra t e l y c h a r ac te r iz e d. Pl ea se p r ov i de a n y o t h e r si g ni f i c a nt lit era tu r e

, re po r ts, or d a t a

th a t w ould be us ef

ul to c ompl e te this c h ar a c t er i z a tion.

Qu e s t i o n s on t h e E x p o s u r e A ss e s s m e nt

Iss u e 2. Wo r kpl a c e e x p os u r e e s t i m a t e s w er e de v e l o p e d f or a dul t s using spray d e g re as er s i n

s m all c o mm e rc i al s ett i n gs. Th e se s ce n a r i os re pr e s e n t s m a l l bu s in e ss e s t h at u se d e g re as er

p r o du ct s on e qu i p m e n t r e g u la r l y, bu t n ot a l l d ay du r in g t h e c o u r se of t h e i r j o b

. A n

e x a m p le w o u l d b e a ga r ag e / c ar mec h a n ic bu s in e ss. Re a dil y ava il a bl e d a t a f r o m so ur ce s

s u c h as t h e N a t i o n al E m i ss i o n s I n v e n t o r y (N E I )

, T ox i c s R el e ase I n v e n t o r y ( T R I )

, a n d

N a t i o n al O cc up a t i o n al E x p o s u r e Su r v e y (N OES )

, o t h e r li ter a t ur e so u rce s a n d

ass u m p t i o n s w ere u s e d t o d e v e l op t h e w o r kp la c e e x p os u r e ass e ss me n t

.

Q u e s t ion 2

- 1: Pl ea se c o mm e nt on t he a pp r o ac h u s e d, a nd p r ov i de a n y sp e c i f i c

sug g e s ti ons or r ec o mm e n d a ti ons f or a lt er n a ti ve a p p r o ac h e s, m o d e l s or i n f o r m a ti on th a t

shou l d be c ons i d ere d b y t he A g e n c y f or im p r ov i n g t he w o r kp l a c e e x posu r e a ss e ssm e n t

, i n c l ud i ng estimations for b y s t a nd e r / n on

- us e r s (e.g., women of childbearing age)

.Pa g e 2 of 3

Iss u e 3. E x p os u r e e s t i m a te s w er e d e v e l o p e d f or t w o di f

f ere n t c o n s u me r u s e s: a d e g re as in g

p r o du c t a n d a c l e ar p r o tect i v e c oa t in g s p r ay pr o du ct

. B o t h p r o du ct s a r e a e r osol s p r ays

a n d a p p e ar t o b e ava il a b le f or sa l e a n d u se b y c o n s u m er s /h o bb y i s t s i n t h e U S

. Th er e w ere

n o re li a bl e d a t a re ga r din g t h e h o bb y i st s ce n a r i os, so O P P T e s t i m a te d h o bb y i st e x p o s u re s

u s in g a s t a n d a r d e x p o s u r e ass e s s m e n t m o d e li n g a pp r oa c h (t h e C o n s u me r E x p os u r e

M o dul e [C E M ] of t h e E x p os u r e a n d F a t e A ss e s s me n t S cr e e nin g T oo l

, o r E

- F A ST ).

Q u e s t ion 3

- 1: Pl ea se c o mm e nt on t he a pp r o ac h u s e d a nd p r ov i de a n y s p e ci f i c

sug g e s ti ons or r ec o mm e n d a ti ons f or a lt er n a ti ve a p p r o ac h e s, m o d e l s, or i n f o r m a ti on ( e .g.

, i n f o r m a ti on on du ra ti on a nd nu m b e r of u s e r e v e n t s) t h a t c ou l d be c ons i d e r e d b y t he

a g e n c y i n d e v e l op i ng t h e e x posu r e a ssu m p ti ons a nd e s tim a t e s f or t he hob b y i st d e g r ea s e r

a nd c l e a r p r o te c ti ve c o a t i ng sp r a y us e s, a nd f or t he b y s t a nd e r

/ non

- us e r s (e.g., children,

women of childbearing age)

.

Qu e s t i o n s on t h e H a z a r d A ss e ss me n t

Iss u e 4. I n f

o r m a t i on on t h e inh ere n t h a z a r d s of T C E h as b ee n w e ll

- c h a r a ct e r i ze d

. Th e r e

a r e s i x m a

j or d o m a in s of a d v er se e ff ect s ( p r i m a r ily in a n i m al m o d e ls) f oll o w i n g e x p o s u r e

t o T C E : n o n

- c a n ce r e ff ect s on t h e li v er , kidn e y, n er vo u s sys t e m , i m m u n e sys t e m ,

re p r o du ct i ve ( pr e d o m in a n t l y m a l e ) t ox i c i t y, a n d d e v e l o p m e n t al t ox i c i t y; as w e l l as c a n cer

e ff ect s on t h e li v er , ki d n e y a n d t h e i m m un e sys t e m ( N o n

- H o d g kin s L y m ph o m a, or N HL )

. T C E m e t a b olism is e x t en sive in m a m m alian sys t e m s a n d d i f f ere n t m et a b oli te s a r e li k e ly t o

b e re s p o n s ibl e f

or d i f f ere n t t ox i c i t y. Th e 2011 U S E P A I n te g r a te d R i s k I n f

o r m a t i on S ys t e m

( I R I S ) ass e s s m e n t f

or T C E re v i e w e d m a n y hu m an a n d a ni m al s t udi e s. Th er e w er e 32

e ndp o in t s / 27s tu d i e s id e n t i f i e d as “ c a n d i d a te s” f

or d e v e l o pin g t h e re f

ere n c e c o nc e n tr a t i on

(c a ll e d t h e R f C )

- t hese included both inhalation and oral studies

. P h ys i o l og i c a ll y

- b as e d

ph a r m a c o k i n et i c ( P B P K ) m o delin g w as u s e d b y t he I R IS p r og r am t o d er i ve di f f ere n t HE C

( i

. e

., hu m an e qu iva l e n t c o n ce n t r a t i o n ) va lu e s. O P P T re p o r t s a l l of t h e se va lu e s, bu t

f o c u s e d o n u s in g o nl y t h e 12 i n h a la t ion s t ud i e s. R a t h e r t h an u se a s in g l e va lu e t o re pr e s e n t

h a z a r d

, O P P T u s e d t h e l o w e st l o w e r b o und H E C 9 9

– t h e 99 t h p erc e n t il e p re di cte d HE C

c o n ce n tr a t i on

- - f

or t h e e f f ec t of c o n cer n f

or e a c h t a r g e t o r ga n

. F u r t h e r m o re , O P P T

di s t in g ui s h e d b e t w ee n e ff ect s t h at m ay o cc u r f

o ll o w in g a c u t e e x p os u r e ( i

. e

., n e u r o t ox i c i t y

a n d d e v e l o p m e n t al t ox i c i t y) v er s u s t h ose t h at m ay o cc u r f o ll o w in g chr o ni c e x p os u re s ( i

. e

., li v er , kidn e y, i m m un o t ox i c i t y, a n d m a l e re p r o du ct i ve t ox i c i t y a n d c a n cer)

.

Q u e s t ion 4

- 1: Pl ea se c o mm e nt on t he s t re n g t hs a nd wea kn e s s e s of e v a l u a t i ng d i f f ere nt

e ndpo i n t s b a s e d on e x posu r e du ra ti ons ( i

. e

., ac u t e v er sus c h r on ic )

.

Q u e s t ion 4

- 2: Pl ea se c o mm e nt on t he s t re n g t hs a nd wea kn e s s e s of usi n g multiple v a lu e s

f or e a c h t y pe of a dv er s e eff

e c t

.

Question 4

- 3: PBPK modeling was employed in the 2011 IRIS assessment for route

- to

route extrapolation to develop a corresponding inhalation value from oral studies, some

of which involved endpoints not studied or reported in inhalation studies. OPPT supports

the approac h used in the IRIS assessment. However, OPPT did not use PBPK

- derived

human

- equivalent concentrations from oral studies in the current draft risk assessment,Pa g e 3 of 3

because OPPT focused on a narrow set of TCE consumer uses (e.g., degreasing and

arts/crafts uses) that are subject to TSCA and therefore, OPPT’s draft risk assessment

relied only on inhalation exposure studies that directly mimicked inhalation exposure use

scenarios for both adults and developmental lifestages. Please comment on whether the

2011 IRIS a ssessment's PBPK

- derived inhalation values from oral studies should be used

in the final OPPT risk assessment.

Qu e s t i o n s on t h e R i sk A ss e s s m e n t

Iss u e 5. A m a r g i n of e x p os u r e (M OE ) a pp r oa c h w as u s e d t o e va lu a t e p o te n t i al n o n

- c a n cer

r i sk a n d t h e I R IS i nh a l a t i on un it r i sk ( I UR ) w as u s e d t o e va lu a t e p o t en t i al c a n ce r r i s k

. Th e s m a l l c o mme r c i al d e g re as e r w o r kpl a c e r i s k e s t i m a t e ass u m e d c hr o ni c ( d a il y) inhalation

e x p os u re s t o T C E

. Th e c o n s u m e r u se of b o t h th e d e g re as e r spray a n d t h e c l e a r p r o te c t i ve

c o a t in g s p r ay u s e d i n t h e a rt s / cr a f t s f i e l d r i sk e s t i m a t e s ass u m e d o nl y in te r m i t te n t ( a c u t e )

inhalation e x p os u re s t o T C E

. A s p a r t of t h e r i sk c h a r a c t er i z a t i o n , t h e r e i s a di s c u ss i on o f

t h e un cert a in t i e s s u rr o und i n g t h e r i sk c a l c u la t i o n s.

Q u e s t ion 5

- 1: Pl ea se c o mm e nt on t he s t re n g t hs a nd wea kn e s s e s of t he M OE a pp r o a c h

us e d to e stim a te t he c h r o n i c

, non

- ca n ce r r i sk f or t he w o r kp l a c e e x posu re s; i n c l ud i ng non

us er s.

Q u e s t ion 5

- 2 : Pl ea se c o mm e nt on t he s t re n g t hs a nd wea kn e s s e s of t he M OE a pp r o a c h

us e d t o e s tim a t e t he ac u t e r i sk t o c onsu m er s; i n c l ud i ng non

- u s er s (e.g., children, women

of childbearing age)

. S p e c i f i ca l l y , p l ea se c o mm e nt on t he d ec ision to limit t he a n a l y s i s

t o ac u t e e x posu re s w it hout re s i du a l c on cer n b e t w e e n e v e n t s ( i

. e

., on ce / w e e k f or u s er s of

t he c l e a r p r o te c ti ve c o a ti ng sp r a y

, a nd t w i ce /m on t h f or d e g r ea s e r u s er s ).

Question 5

- 3 : Please comment on the use of a uniform benchmark MOE of 30 rather

than a benchmark MOE equal to the composite U ncertainty Factors for each study as

identified in the 2011 US EPA IRIS assessment for TCE

.

Question 5

- 4 : Please comment on whether the document has adequately described the

uncertainties and data limitations in the methodology used to assess risks to allow the

EPA to reduce risks to human health from TCE. Please comment on whether this

information is presented in a transparent manner.