Development of a Web-Based Tool for Accessing Chemical Toxicology Information

Pesticide Research Institute

Shauna Stahlman and Susan Kegley Toxicology Data

• Toxicology data: • What dose of a chemical (in mg of chemical per kg body weight) causes acute toxicity, developmental & reproductive toxicity, carcinogenicity, neurotoxicity, or other toxicity? • Observed effects in animal tests • How does info from different organizations differ? • Important for: • Determining the hazards associated with exposure to a chemical and the relationship of dose to adverse effects • Assessing risk based on hazard and exposure potential • Comparing the relative toxicity of different chemicals • Making decisions about whether or not to categorize a chemical as a “low- toxicity” or “reduced-risk” alternative The Need

• Toxicity lists such as Prop 65 are not comprehensive; many chems not on lists for reasons unrelated to toxicity

• Toxicity lists don’t have any details about toxicological effects or doses causing effects

• Comparison of Reference Doses (RfDs) across different pesticides and different data sources (US EPA, CA DPR, EU)

• Finding the most recent detailed toxicology information is like a scavenger hunt! Issues with Existing Toxicology Datasets (1)

• Many different sources of tox data, but little communication between the agencies • US EPA: • Office of Pesticide Programs • Integrated Risk Information System (IRIS) • National Center for Computational Toxicology (NCCT) • CDC’s ATSDR risk assessments • NIEHS NTP risk assessments • Cal EPA risk assessments (DPR, OEHHA) • EU risk assessments (Pesticides, ReACH) Issues with Existing Toxicology Datasets (2)

• Can be difficult to locate the most recent risk assessment, e.g. for US EPA pesticides: • Re-registration Eligibility Decisions (REDs) • Supporting documents for REDs (E-Docket, CD) • Federal Register Notices (FRNs) • Fact sheets for new pesticides • Registration review documents • Sometimes need to go outside EPA documents to find all relevant information Target Audience

• Professionals preparing data for consumption by the layperson • Regulatory staff • Consultants • Researchers PRI Toxicology Database

• Provides oral, inhalation, and dermal toxicology information

• Provides data for acute, short-term, sub-chronic, and chronic exposure durations • Displays data in tables, paragraph summaries, graphs, and symbols • Links to original risk assessments/documents are provided PRI Toxicology Database

• Current universe of chemicals • Pesticides (EPA OPP mostly; some CA DPR, EU )

• Ultimate universe of chemicals • Pesticides (EPA OPP, CA DPR, EPA IRIS, EU, ATSDR, NTP) • Industrial chemicals (EPA IRIS, EU ReACH, ATSDR, NTP) • Chemicals in consumer products

Comparative Acute Toxicity of Currently Registered Organophosphorus Insecticides

Malathion 0.176 Fenitrothion -0.699 Bensulide -0.824 Malathion -0.866 Trichlorfon -1 Tetrachlorvinphos, Z-isomer -1.17 Ethephon -1.22 Phosmet -1.35 Pirimiphos-methyl -1.82 Dimethoate -1.89 Chlorpyrifos -2 S,S,S-tributyl phosphorotrithioate -2 Naled -2 DDVP -2 Chlorpyrifos-methyl -2 Fosthiazate -2.06 Oxydemeton-methyl -2.08 Coumaphos -2.18 Acephate -2.3 Profenofos -2.3 Chlorpyrifos -2.3 Azinphos-methyl -2.48 Methamidophos -2.52 Phorate -2.6 Disulfoton -2.6 Diazinon -2.6 Methidathion -2.7 Phostebupirim -2.78 Dicrotophos -2.78 Methyl parathion -2.96 Chlorethoxyphos -3.22 Propetamphos -3.3 Terbufos -3.52 Ethoprop -3.6 -4 -3 -2 -1 0

Log (Acute RfD Adult (mg/kg-day))

Definitions and Reference

• Equations • Definitions • Study Guidelines

Reference dose (RfD): An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. It can be derived from a NOAEL, LOAEL, or benchmark dose, with uncertainty factors generally applied to reflect limitations of the data used. Generally used in EPA's noncancer health assessments.

No-observed-adverse-effect level (NOAEL): The highest exposure level at which there are no biologically significant increases in the frequency or severity of adverse effect between the exposed population and its appropriate control; some effects may be produced at this level, but they are not considered adverse or precursors of adverse effects.

http://www.epa.gov/riskassessment/glossary.htm

Data Sources Data Sources Comparing data from different agencies Example 1

Example 2 Chemicals included in quintiles are both registered in the US and have acute oral female RfDs available from EPA (214 chemicals). “Low hazard” chemicals were reviewed by EPA but were found to be of low toxicological concern for that endpoint, so data requirements were waived (468 chemicals). Chemicals included in quintiles are both registered in the US and have short-term adult inhalation NOAELs/LOAELs available from EPA (353 chemicals). “Low hazard” chemicals were reviewed by EPA but were found to be of low toxicological concern for that endpoint, so data requirements were waived (~374 chemicals). The Team

• Currently at PRI • Shauna Stahlman (PRI, soon to be UCLA Public Health) • Jacqueline Epps (PRI) • Former PRI staff who contributed • Kathryn Gillick (CA PUC) • Andrew Slocombe (UCB Public Health) • Erin Conlisk (UC Riverside)