Dioxins and pcbs
Dioxins and PCBs
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
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
Index of acute toxicity: LD50 LDso is the lethal dose for 50% of a population Toxicant A Toxicant B 0 Log Dose Illustration of a dose-response curve in which the response is the death of the organism; the cumulative percentage of deaths of organisms is plotted on the y-axis Dose is expressed as the weight of a chemical consumed by an experimental animal per kg of body weight of the animal
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
LD50 of selected chemicals for rats or mice Chemical LD50(mg/kg) Chemical LD50(mg/kg) Sugar 29,700 Caffeine 130 ethanol 14,000 DDT 100 Vinegar 3,310 Arsenic 48 Table salt 3,000 Parathion 3.6 Atrazine 1,870 Nicotine Malathion 1,200 Dioxin(TCDD) 0.001 Aspirin 1,000 Botulin toxin 0.00001 Almost every chemical is toxic at some level, and the difference between toxic and nontoxic chemicals is a matter of degree
LD50 of selected chemicals for rats or mice Chemical LD50 (mg/kg) Chemical LD50 (mg/kg) Sugar 29,700 Caffeine 130 ethanol 14,000 DDT 100 Vinegar 3,310 Arsenic 48 Table salt 3,000 Parathion 3.6 Atrazine 1,870 Nicotine 1 Malathion 1,200 Dioxin (TCDD) 0.001 Aspirin 1,000 Botulin toxin 0.00001 Almost every chemical is toxic at some level, and the difference between toxic and nontoxic chemicals is a matter of degree
Dioxins(二嗯英): General structures The term dioxins denotes a family of chemical compounds known as polycholorinated dibenzo para-dioxins(Pcdds) and polycholrinated dibenzofurans(PCDFs) General structure Dibenzodioxin Dibenzofuran PCDD PCDF
Dioxins (二噁英): General structures • The term dioxins denotes a family of chemical compounds, known as polycholorinated dibenzopara-dioxins (PCDDs) and polycholrinated dibenzofurans (PCDFs) O O Dibenzodioxin PCDD O Dibenzofuran PCDF Clx Cly Clx Cly General structure
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 PCd congeners Dibenzodioxin Dibenzofuran PCDD PCDF c0、C!c Cl Cl CI o Cl 2378-TCDD 2378-TCDF
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. O O Dibenzodioxin PCDD O Dibenzofuran PCDF 1 2 3 4 7 8 9 6 9 8 7 6 1 2 3 4 O O 2378-TCDD O 2378-TCDF Cl Cl Cl Cl Cl Cl Cl Cl
Toxicity of Dioxins Extraordinary toxic to lab animals (LDso in male guinea pigs is only 0.6 ug/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 ug/kg Hamster, intraperitoneum LD50 is 3000 ug/kg Risk to humans is less clear
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
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
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
Multiple exposure pathways Emissions Affected Water media Biological Domestic Animals Vegetation
Multiple exposure pathways
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
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