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

2. 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)

3. 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

4. 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

5. (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.

6. 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.

7. 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

8. 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)

9. 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

10. 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.)