Toxicological Overview of TCDD What is TCDD? How Toxic is TCDD? How Much TCDD Will Cause Adverse Health Effects? How Does TCDD Affect Our Bodies? Can TCDD Cause Cancer? How Does TCDD Get Into Our Bodies? How Does TCDD Cause Damage to Our Bodies? How Do Health Professionals Calculate Dioxin Toxicity? How Are TEFs Expressed and What Do They Mean? What's the Difference Between a TEF and a TEQ? Why Are TEFs and TEQs Important? What is the Average Person's Dioxin TEQ? Is the General Population at Risk from TCDD Contamination? How Can a TCDD-Exposed Community Ensure Good Health? Prepared by TCAS, LLC Toxicology Consultants and Assessment Specialists 6450 Pine Avenue, Sanibel, FL North Road, Auburn, NY © Copyright 2014 TCAS LLC. This document may be reproduced and/or distributed without prior written consent of Toxicology Consultants and Assessment Specialists, provided that it is used solely for non-commercial educational or instructional purposes.

What is TCDD? TCDD is an acronym for 2,3,7,8- T etra C hloro D ibenzo-p- D ioxin. TCDD is a cancer-causing agent (classified by IARC as a Group 1 Carcinogen). TCDD permanently alters cells by "attaching" to proteins (somewhat like a key fitting into a lock). TCDD accumulates and builds up in the body over time (bioaccumulation). TCDD has a simple chemical structure This simple structure allows it to attach easily to proteins.

TCDD is EXTREMELY TOXIC. Just a few parts per TRILLION can cause adverse health effects. How Toxic is TCDD? Toxicologists measure toxicity based on Dose Response. “50% Lethal Dose” (LD50) is dose causing 50% Fatalities. Among non-biological agents, TCDD's toxicity is second only to radioactive waste

Each grain in this pile is equal to One Part Per Trillion (1 PPT). 1 Part Per Trillion The average TCDD blood level in the U.S. is about 2 PPT (1.9ppt per EPA). 1 1 grain of sand weighs about oz. The entire sand pile weighs about 1,500 tons (roughly 150 loads). How Much TCDD Will Cause Adverse Health Effects? There is no “safe” TCDD threshold. The U.S. background TCDD level is about 2 parts per trillion (PPT). This trillion-grain sand pile helps us visualize how small 2 PPT really is – about the equivalent of 2 grains of sand. 1.Extrapolated from Patterson et. al., 2008 using [LOD / √ 2]

How Does TCDD Affect Our Bodies? TCDD affects the body at the GENETIC level. TCDD affects the body at the GENETIC level. Just a small number of parts per trillion in the blood can cause: Cancer & Tumors Thyroid disorders Immune System damage Endometriosis Central Nervous System disorders Diabetes Cancer & Tumors Thyroid disorders Immune System damage Endometriosis Central Nervous System disorders Diabetes

Yes. TCDD can cause cancer. TCDD is a MULTI-SITE CARCINOGEN. It can cause multiple types of cancer in different locations. This fact has been demonstrated in both human and animal studies. The International Agency for Research on Cancer (IARC) has classified TCDD as a Group 1 Carcinogen, the highest rating. The National Toxicology Program (NTP) has added TCDD to its list of “Substances Known to be Human Carcinogens.” TCDD produces cancer through a process called tumor promotion. Can TCDD Cause Cancer?

How Does TCDD Get Into Our Bodies? Primary Emission Source Homes Soil The Environment Food Inhalation Direct Contact Dioxins can enter the body in a variety of ways. Widespread contamination creates multiple exposure pathways: Ingestion

How Does TCDD Cause Damage in Our Bodies? 1.Vezina, Walker et. al., "Subchronic Exposure to TCDD, PeCDF, PCB126, and PCB153: Effect on Hepatic Gene Expression," Environmental Health Perspectives, November, 2004; 112(16): 1636–1644. TCDD causes cancer and genetic damage by activating specific gene subgroups through an AHR (Aryl Hydrocarbon Receptor). These are complex cellular reactions and researchers are still gathering data about TCDD's full range of health effects. “It is unclear how activation of AHR-dependent genes produces the multiplicity of toxic responses characteristic of dioxin exposure.” 1

How Do Health Professionals Calculate Dioxin Toxicity? Dioxins come in many forms called congeners. The World Health Organization (WHO) created a system for expressing dioxin congener toxicity. Toxic Equivalence Factors (TEFs) allow health professionals to assess risks by rating dioxin congeners in terms of TCDD (the most toxic). TCDD has a TEF of 1.0, the highest toxicity. The TEF rating system has been adopted by most countries including the United States, European Union, Canada, Japan and many others.

How Are TEFs Expressed and What Do They Mean? A TEF expresses the toxicity of a single dioxin or “dioxin-like” compound as compared to TCDD, the most toxic dioxin congener, which has a TEF of 1.0. TEFs have been assigned by the World Health Organization to 29 different dioxin or “dioxin-like” compounds, consisting of 17 DIOXINs and 12 PCBs: 1 PolyChlorinated Biphenyl

What's the Difference Between a TEF and a TEQ? A Toxic EQuivalent (or TEQ) expresses the total toxicity of a mixture of dioxins. TEQ is each dioxin congener's TEF multiplied by its blood level (in pg/g). By adding the individual results together, health professionals can express toxicity as a single value. Example:

Why Are TEFs and TEQs Important? TEFs and TEQs allow toxicologists, health professionals and organizations worldwide to calculate dioxin toxicity using a standardized methodology. TEFs are used by: EPA (Environmental Protection Agency) CDC (Center for Disease Control) ATSDR (Agency for Toxic Substances and Disease Registry) NTP (National Toxicology Program) NIH (National Institutes of Health) WHO (World Health Organization) TEFs were last updated by WHO in 2005

What is the Average Person's Dioxin TEQ? TCDD levels in the general population have been steadily decreasing for years. 1 The current average TCDD level is approximately 1.9 parts per trillion (PPT) or LESS. 2 1.Aylward, Hays et. al., "Temporal trends in human TCDD body burden: Decreases over three decades and implications for exposure levels," Extrapolated from Patterson et. al., 2008 using [LOD / √ 2] 2012 PPT <1.9 PPT

Is the General Population at Risk from TCDD Contamination? NO. TCDD contamination in the U.S. is extremely rare. Only a few sites in the U.S. exhibit severe or acute dioxin contamination. 1.ATSDR, "Priority List of Hazardous Substances," 2011, 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ATSDR's "Substance Priorities List" gives priority to the most widespread contamination (arsenic, lead, etc). Substances affecting smaller populations rank lower, so TCDD ranks only 71st on the list. 1 71

How Can a TCDD-Exposed Community Ensure Good Health? There is NO KNOWN CURE for TCDD contamination. The only effective way to ensure good health is to (1) MONITOR exposed residents, (2) ASSESS symptoms, and (3) TREAT when appropriate.