The Consortium for Environmental Risk Management, LLC Elizabeth Becker, Ph.D. Manager of Technical Services Consortium for Environmental Risk Management (CERM) ebecker@cermonline.com With Peter Ranslow, Ph. D. (CERM) and Bernard Gadagbui, M. Sc., Ph. D., DABT (TERA)

Beyond Science and Decisions: From Problem Formulation to Dose-Response Challenge: Evaluating Chemicals In The Absence Of Data Case Study #6 Sustainable Futures™ Screening (Isodecyl Acrylate)

Sustainable Futures™ Approach An Integrated Approach to Chemical Risk Screening Phys/Chem Properties: EPI Suite Environmental Fate: EPI Suite Hazard AIM (mammalian) Exposure / Risk ChemSTEER Release amounts Worker exposure E-FAST Human Risk: Consumer dermal & inhalation exposure

NONCANCER HAZARD ASSESSMENT EVALUATE MAMMALIAN TOXICITY BASED ON EXPERIMENTAL DATA NON-CANCER HEALTH EFFECTS Acute Toxicity Irritation Skin Sensitizer Reproductive Effects Developmental Effects Immune System Effects Neurotoxicity Genotoxicity Mutagenicity Systemic Effects IF NO EXPERIMENTAL DATA, USE ANALOG IDENTIFICATION METHODOLOGY (AIM) TO SELECT ANALOG

(Analog Identification Methodology) AIM (Analog Identification Methodology) The AIM database contains 31,031 potential analogs with publicly available toxicity data Enter chemical by CAS, SMILES, or Drawing structure Uses a chemical fragment-based approach with 645 individual chemical fragments to identify potential analogs.

AIM Uses a “three-pass” methodology to identify analogs: Pass 1- Analogs are selected when a match of 645 possible chemical fragments occurs. If less than 7 analogs are identified, then: Pass 2 - Analogs are selected when a match of 200 fragments occur and allows alkyl substitutions. If less than 7 analogs are identified again, then: Pass 3 - Allows halogens (chlorine, bromine, or iodine) substitutions. Results from first pass (search) are displayed in numerical order by CAS RN, followed by results from second, then third passes. First analog displayed may not be the closest analog with data.

E-FAST HUMAN EXPOSURE Considers human exposures due to Industrial releases Ingestion and inhalation The use of consumer products Inhalation and dermal The disposal of consumer products Ingestion Estimates potential dose rates For assessing cancer risk Potential Lifetime Average Daily Dose (LADDpot) in mg/kg/day For assessing chronic non-cancer risk Potential Average Daily Dose (ADDpot) in mg/kg/day For assessing acute non-cancer risk Potential Acute Dose Rate (ADRpot) in mg/kg/day

CHEMSTEER Chemical Screening Tool for Exposures and Environmental Releases Estimates workplace exposures and releases to a chemical in the absence of monitoring data estimates are screening-level uses EPA methods and models uses EPA assumptions (worst case scenarios)

Risk Assessment HUMAN HEALTH Risk = Hazard x Exposure If Hazard = 0, (Low Toxicity Concern) or If Exposure = 0, (Minimal Exposure Expected) Then LOW Potential for Risk! Quantitative Measures of Risk: HUMAN HEALTH Calculate a “Margin of Exposure” (MOE) to evaluate risk to human health based on NOAEL or LOAEL In Toxicity Studies and Exposure Data From exposure models

Determining Human Health Risk (Typical Non-Cancer Approach For Calculation based on NOAEL (preferred) MOE ≤ 100 (Potential for Risk) MOE ≥ 100 (Low Concern for Risk) For Calculation based on LOAEL MOE ≤ 1000 (Potential for Risk) MOE ≥ 1000 (Low Concern for Risk) Depending on philosophy and framework, these “Assessment Factors” may also be called: Safety Factor Application Factor Uncertainty Factor The typically values used for these factors can vary dramatically depending on the framework you are operating under (EU vs. Canada vs. US vs. New Chemicals vs. Existing Chemicals, etc.)