Dioxins and PCBs

1. Dioxins and PCBs

2. Acute (急性) and chronic (慢性) toxicity • Acute toxicity refers to a rapid and serious response to a high but short-lived dose. • Acute poisons interfere with essential physiological processes, leading to a variety symptoms of distress, even death. • Chronic toxicity refers to a time-lagged response to a relatively low but prolonged exposure. • Effects are more subtle. • Set in motion a chain of biochemical events that lead to disease states, including cancer.

3. Index of acute toxicity:LD50 LD50 is the lethal dose for 50% of a population. Dose is expressed as the weight of a chemical consumed by an experimental animal per kg of body weight of the animal.

4. LD50 of selected chemicals for rats or mice Almost every chemical is toxic at some level, and the difference between toxic and nontoxic chemicals is a matter of degree.

5. Dioxins (二噁英): General structures • The term dioxins denotes a family of chemical compounds, known as polycholorinated dibenzo-para-dioxins (PCDDs) and polycholrinated dibenzofurans (PCDFs) General structure

6. Dioxins: Congeners Congener: a member of the same class, or group. Each individual PCDD or PCDF is termed a congener. There are 75 PCDD congeners and 135 PCDF congeners.

7. Toxicity of Dioxins • Extraordinary toxic to lab animals (LD50 in male guinea pigs is only 0.6 mg/kg) • Birth defects • Cancer • Skin disorders • Liver damage • Suppression of the immune systems • Variation in toxicity among species is large. • Male guinea pig, oral, LD50 is 0.6 mg/kg. • Hamster, intraperitoneum, LD50 is 3000 mg/kg. • Risk to humans is less clear

8. Human risk of dioxin exposure • USEPA concludes that dioxins likely increase cancer incidence. • WHO classifies 2378-TCDD as a probable human carcinogen. • At high levels, PCDDs cause chloracne (氯痤倉), a painful skin inflammation. • Risk from breathing dioxin-laden air is minimal. • The main exposure route for human is dietary (meat, dairy products, and fish). (Due to bioaccumulation of dioxins) • Absorption of dioxins by infant through mothers’ milk is efficient.

9. Multiple exposure pathways

10. Biochemistry of dioxin toxicity • PCDD/Fs are planar aromatic molecules. • The planar structure allows them to bind to Ah (Aryl hydrocarbon) receptor protein that is present in all animal species. • The Ah receptor interacts with the cell’s DNA. • Dioxin toxicity is roughly proportional to the strength of binding to the Ah receptor. • This explains that 2378-TCDD is the most toxic one.

11. Dioxin toxicity varies among the congeners International Toxicity Equivalency Factors (TEF) for PCDDs and PCDFs The TEFs allow the conversion of various congener concentrations into a single toxicity equivalent quantity (TEQ)

12. Dioxin toxicity: general rules • TCDD is the most toxic of the dioxins • Toxicity decreases when Cl atoms are removed from 2,3,7,8 positions or added to the remaining positions on the rings. • There are similar toxicity pattern for PCDD and PCDF series.

13. How much dioxin do we congest?Estimated Dietary Intakes of PCDD/Fs per day Source: An Assessment of Dioxin Emissions in Hong Kong, HKEPD, 2000.

14. Average content of 2378-TCDD in various foodstuff (U.S)

15. Formation of dioxins • Combustion • In any situation where Cl, C, H, and O come into contact with heat, PCDD/Fs could be formed as trace by-products. • Dioxin emission correlates with the Cl content of the combustion feed. • Paper pulp bleaching with chlorine • Chlorine is used to bleach paper pulp. • PCDDs are formed probably through chlorination of the phenolic groups in lignin. • Manufacture of certain chlorophenol chemicals • Dioxin was produced as a contaminant of the herbicide 2,4,5-T, a component of Agent Orange

16. Formation of dioxins in combustion processes • Incomplete combustion of organic wastes in the combustion chamber leads to the formation of organic fragments which serve as organic precursors to the PCDD/F molecule. • The waste provides a source of chlorine, and of metals. The latter are incorporated into fly ash, which carries over to the cooler (250-400oC) post-combustion zone of the incineration system. • The organic precursors adsorb onto the surface of the fly ash in the post-combustion zone, and following a complex sequence of reactions which are catalyzed by metals (primarily copper) in the fly ash, lead to the formation of PCDD/Fs along with other chlorinated trace organics.

17. High-temperature step PCDF contamination from PCB oxidation

18. Dioxin emission inventory (US)

19. Agent orange • 50:50 mix of two herbicides: 2,4-D and 2,4,5-T. • Used as a defoliant for broad-leaf trees during Vietnam war. • Contains dioxins as contaminants. • In 1966, dioxin residues were found in fish, shell-fish, and mother’s milk in the Vietnam target areas. • In 1978 and 1979, Vietnam veterans in the U.S. began complaining of a variety of symptoms such as numbness, skin rashes, liver problems, and birth defects in their children.

20. Estimated Dioxin emission inventory(1997 in HK) Source: An Assessment of Dioxin Emissions in Hong Kong, HKEPD, 2000.

21. Dioxin: Are there natural sources? • Analysis of archived UK soil samples dating from the pre-1900s confirmed the presence of dioxins. (Large scale manufacture and use of chlorinated chemicals started after 1900s.) • Wood burning emits dioxin • NaCl in wood  HCl in combustion zone • Organochlorines are widely produced by a variety of microorganisms.

22. Man-made sources outweigh natural sources • From 1940 to 1970 • deposition increased eightfold. • Great expansion in the use of Cl • Forest fires diminished by more than a factor of four Dioxin deposition on Lake Siskiwit on an island in Lake Superior • After 1970 • Deposition decreased • 2,4,5-T phaseout

23. a total of 209 congeners Polychlorinated biphenyl (PCB) Excellent insulators, chemically stable, low flammability and vapor pressure. Used as coolant in power transformers and capacitors. • Additional uses: • Heat transfer fluids in machinery • Plasticizers for PVC and other polymers • De-inking agents for recycled newspapers

24. Toxicity of PCBs • Less toxic than PCDD/Fs, but more abundant than PCDD/Fs in the environment. • Probable carcinogen • Cause skin chloracne. • Learning deficits. Effects of in utero PCB exposure Test scores of 4-year-old children vs. PCB concentrations in the umbilical cord serum at birth.

25. EPA orders General Electric to dredge PCBs from Hudson River (Source: Pollution Online newsletter, 12/4/2001) WASHINGTON, Dec 04, 2001 (AP WorldStream via COMTEX) – The Bush administration ordered tons of PCBs removed from New York's upper Hudson River, setting in motion one of the largest dredging operations in the nation's history. General Electric Co. dumped 1.3 million pounds (585,000 kilograms) of PCBs into the river before the federal government banned the pollutants in 1977. The company bitterly opposes dredging, which expected to cost GE dlrs 500 million. …. PCBs, used as insulation and a coolant, have been linked to cancer in laboratory animals. The EPA classifies the oily substance as a probable carcinogen and says PCBs pose risks to wildlife and to people who eat fish from the Hudson. GE released PCBs from its plants in Fort Edward and Hudson Falls, about 40 miles (64 kilometers) north of Albany. The cleanup will include locations in that stretch, reaching almost down to the capital city. …..

26. Study questions • What is acute toxicity? What is the index to express acute toxicity? • What is chronic toxicity? Give an example of chronic health effect. • Draw chemical structures of dioxins and PCBs. What are congeners? • Does dioxins bioaccumulate? Why? • What are the major sources for dioxins?