superfund advisory committee january 23, 2014 tetrachloroethylene: cancer risk values office of...
TRANSCRIPT
Superfund Advisory Committee January 23, 2014
Tetrachloroethylene:Cancer Risk Values
Office of Research and Standards
Sandra Baird, Ph.D.
1
Road Map
2
Brief History
2012 US EPA final based on liver tumorsDerived values for leukemia and liver
• 2008 MassDEP based on leukemia and liver• 2008 US EPA draft based on leukemia• 2010 NRC Review lacked consensus on
leukemia• 2011 US EPA Interagency draft based on
leukemia
3
Why did we review PCE?
• Basis of US EPA 2012 value different from – MassDEP’s 2008 and 1990– US EPA 2008 and 2011
• NRC Committee did not reach consensus• US EPA 2012 two IURs >10-fold different• US EPA 2012 liver-based IUR differed
substantially from US EPA 2008 liver and leukemia-based IUR
4
ORS Process
• Review recent data, primary literature, models• MassDEP Health Effects Advisory Committee• Authors of US EPA Harmonized PBPK model• Address concerns from NRC & interested parties– High leukemia background rate– Dose response– NTP data– Relevance to humans– Up to date PBPK model
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Decisions
• US EPA harmonized PBPK model should be used
• JISA 1993 bioassay should be used not NTP 1986
• Leukemia data should be used to derive PCE cancer risk values
• Total metabolized PCE should be used for interspecies extrapolation instead of total PCE
6
Leukemia Endpoint
• Background rate high but…– Treated animal rate higher
• Earlier and more severe in treated animals• Statistically significant dose-response
NTP & JISA• No data to rule out relevance to humans
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Derivation
• JISA 1993 (0, 50, 200, 600 ppm)• Males and Female Rats• Harmonized PBPK model• Total Metabolized Dose
8
Cancer Risk Values
• Inhalation and oral values are based on same extrapolation from inhalation studies
• Inhalation unit risk (IUR)3 x 10-6 per ug/m3
• Oral cancer slope factor (CSF)2 x 10-2 per mg/kg/day
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Method 3 Short-Form
2008-2012 2014
Unit Risk (per ug/m3) 1 x 10-5 3 x 10-6
Residential (ug/m3)
No Significant Risk (NSR) 2 8Imminent Hazard (IH) 10 50Workplace (ug/m3)
No Significant Risk (NSR) 10 40Imminent Hazard (IH) 60 200
10
RiskConc.
Back-ground
Ind
oor
Air
Con
cen
trati
on
(u
g/m
3)
TargetAir
Conc.
RiskConc.
Back-ground
DEP pre-2008 Tox Value DEP 2014 Tox Value
Proposed Target Indoor Air Concentration and GW-2 Standard
TargetAir
Conc.
GW-2 = 50 ug/L GW-2 = 20 ug/L
5
10
0.04
11 11
0.2
4 4
15
11
Thank You!
More information on tetrachloroethylene cancer risk values will be posted on MassDEP Chemical page
http://www.mass.gov/eea/agencies/massdep/toxics/sources/chemical-research-and-standards.html
Questions? Comments?
12
13
RiskConc.
Back-ground
Ind
oor
Air
Con
cen
trati
on
(u
g/m
3)
TargetAir
Conc.
RiskConc.
Back-ground
DEP pre-2008 Tox Value DEP 2014 Tox Value
Proposed Target Indoor Air Concentration and GW-2 Standard
TargetAir
Conc.
GW-2 = 50 ug/L GW-2 = 20 ug/L
5
10
0.04
11 11
0.2
4 4
15
RiskConc.
Back-ground
US EPA 2012 Tox Value
TargetAir
Conc.
GW-2 = 30 ug/L
7.8
4
8
14
Method 3 Short-Form
2008-2012 2014 US EPA
Unit Risk (per u/m3) 1 x 10-5 3 x 10-6 3 x 10-7
Residential (u/m3)No Significant Risk (NSR) 2 8 40Imminent Hazard (IH) 10 50 400
Workplace (u/m3)No Significant Risk (NSR) 10 40 180Imminent Hazard (IH) 60 200 1800
15