Trichloroethylene (TCE) Toxicity Values Update Waste Site Cleanup Advisory Committee Meeting March 27, 2014 C. Mark Smith Ph.D., M.S. Deputy Director Office of Research and Standards MassDEP

Trichloroethylene (TCE) Timeline 1989 EPA withdrew TCE toxicity values from IRIS 2001 EPA released draft TCE Health Assessment 2002 EPA SAB reviewed the draft Health Assessment 2006 NAS released report and recommendations 2009 EPA issued draft Health Assessment for TCE 2011: EPA released its Final Assessment for TCE on IRIS. cardiac developmental toxicity a key endpoint : EPA regions address short-term TCE exposures using differing approaches. No national guidance issued : MassDEP develops approach for addressing short- term exposure risk for MCP program

New EPA TCE Toxicity Values RfC (noncaner; inhalation) 2 µg/m 3 Fetal heart malformations Immune system effects RfD (noncancer; ingestion) 0.5 µg/kg/day Fetal heart malformations Immune system effects Developmental immune system effects Oral Slope Factor (cancer; ingestion) 5.0 x per mg/kg-day Carcinogenic to humans via ingestion Kidney cancer Liver cancer non-Hodgkin Lymphoma Unit Risk (cancer; inhalation) 4.0 x per µg/m 3 Carcinogenic to humans via inhalation Kidney cancer Liver cancer non-Hodgkin Lymphoma

Implications of TCE Development Toxicity Cardiac developmental effects are of high concern – Serious, potentially fatal Fetal cardiac development occurs early during pregnancy (1 st 8 weeks) with key stages occurring over periods of days – Exposures to women of childbearing age a concern – Short-term exposures a concern Triggers MCP Imminent Hazard requirements at a low concentration

MCP Imminent Hazard The conditions at the disposal site pose an Imminent Hazard when: 1. ”a Hazard Index equal to 1.0 for OHM that have the potential to cause serious effects (including but not limited to lethal, developmental, or neurological effects) following short-term exposures; and 2. a Hazard Index equal to 10 for all other oil or hazardous materials.”

ORS TCE Review Requested No national guidance from EPA Inconsistent approaches used by EPA regions and ATSDR MassDEP very concerned about developmental risks

ORS TCE Review Focused on developmental effects: – Reviewed weight of the evidence – Considered approaches for addressing short term exposures Reviewed EPA, NAS and SAB documents Considered approaches used by EPA regions Consulted with MassDEP Health Effects Advisory Committee (HEAC) over multiple meetings Developed recommended triggers for addressing short-term exposures to TCE in indoor air attributable to vapor intrusion

Conclusions ORS TCE Review Concurred with EPA that the weight of the evidence is sufficient to consider TCE a developmental toxin – Animal bioassays; epidemiology; mechanistic data Cardiac development toxicity is the most sensitive effect Cardiac development occurs during the first 8 weeks of pregnancy – Exposures to women of childbearing age a concern

Conclusions ORS TCE Review EPA quantitative RfC derivation appropriate and protective of all non-cancer endpoints – Choice of critical studies supported – State-of-the-art physiologically based pharmacokinetic (PBPK) modeling used for cross species and exposure route conversions – Current benchmark dose (BMD) and dose response modeling to extrapolate to low dose risk – Pharmacodynamic (PD) uncertainty factor of 10 applied to conservatively derive the RfC

Imminent Hazard Recommendation ORS toxicologists, with input from the HEAC, concluded that cardiac developmental risk at levels somewhat above the RfC is very low An Imminent Hazard of 6 µg/m 3 recommended for residential and of 24 µg/m 3 for typical workplace exposure scenarios – EPA RfC adjusted by reducing the PD UF by a factor of 3 – Deemed appropriate because the RfC is based on the most sensitive life-stage and cardiac development is well conserved across species. – Better allows for differentiation of IH vs. protective indoor air levels

More Urgent Concern Level Recommendation Additional guidance for indoor air concentration well above the IH – Pose a more significant risk to the fetus – Additional urgency to reduce exposures Residential = 20 µg/m 3 – Concentration estimated by EPA modeling that would result in 1% of people (high metabolizers) attaining an internal metabolized TCE dose associated with a 1% excess risk of cardiac defects in the animal model – Close to median air concentration associated with increased risk of cardiac defects in Endicott, NY epidemiology study. Workplace = 60 µg/m 3, adjusted for 8 hour a day exposure

Summary of TCE Developmental Risk Values Interim Values (EPA RfC) Final Values (Adjusted RfC) Imminent Hazard Residential Workplace More Urgent Concern Level Residential Workplace 2 µg/m 3 8 µg/m 3 None 6 µg/m 3 24 µg/m 3 20 µg/m 3 60 µg/m 3

Effects of Toxicity Value Changes on Method 1 and 3 (Residential; Risk Drivers – cancer or noncancer) No Significant RiskOld MassDEP Value New MassDEP Value Method 1GW-2 = 30 μg/L Basis: Air background of 4.5 μg/m 3 (Cancer risk of 1 x from 30 year exposure to indoor air conc. = 1.4 μg/m 3 ; < background) GW-2 = 5 μg/L Basis: Air background (updated) of 0.8 μg/m 3 (Non-cancer risk (HQ= 0.2), chronic exposure to indoor air conc. = 0.4 μg/m 3 ; < background) Method 314 µg/m 3 Basis: Cancer risk of 1 x from 30 year exposure 2 µg/m 3 Basis: Non-cancer risk (HQ=1) Fetal heart developmental effects and immune effects for all receptors