1. November 18, 2003Robert Burr MD1 Toxicology of High Priority Substances Part 3: Cd, Cr, Dioxin and TCE

2. November 18, 2003Robert Burr MD2 Cadmium Forms Forms Inorganic: cadmium salts Inorganic: cadmium salts Elemental: calcium fume and dust Elemental: calcium fume and dust Bound by metallothionein in liver and kidney; saturation leads to appearance of toxicity Bound by metallothionein in liver and kidney; saturation leads to appearance of toxicity Half-life: 8-30 years; poorly excreted Half-life: 8-30 years; poorly excreted Chelation techniques increase the toxic effect Chelation techniques increase the toxic effect Toxic effects progressive Toxic effects progressive Not susceptible to intervention Not susceptible to intervention

3. November 18, 2003Robert Burr MD3 Cadmium: Toxic Responses Cell injury: mechanism not known Cell injury: mechanism not known Physiologic: none Physiologic: none Allergenic: not known Allergenic: not known Mutagenic: poorly Mutagenic: poorly Carcinogenic: lung cancer Carcinogenic: lung cancer Teratogenic: no information Teratogenic: no information

4. November 18, 2003Robert Burr MD4 Cadmium: Target Tissues Lungs: Lungs: Acute chemical pneumonia Acute chemical pneumonia Emphysema, fibrosis Emphysema, fibrosis Lung cancer Lung cancer Kidneys: renal tubular dysfunction Kidneys: renal tubular dysfunction Bone disease, kidney stones Bone disease, kidney stones

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6. November 18, 2003Robert Burr MD6 Measuring and Managing Cadmium Exposure OSHA Standard OSHA Standard Blood and urine cadmium levels Blood and urine cadmium levels Urine β2-microglobulin Urine β2-microglobulin Evidence of renal tubular toxicity Evidence of renal tubular toxicity Medical removal depending on monitoring results Medical removal depending on monitoring results

7. November 18, 2003Robert Burr MD7 Chromium Forms Forms Inorganic Inorganic Chromium III: insoluble, but toxic Chromium III: insoluble, but toxic Chromium VI Chromium VI Soluble, easily absorbed Soluble, easily absorbed Converted to Cr V-IV-III in cells Converted to Cr V-IV-III in cells Elemental and organic forms are not known toxins Elemental and organic forms are not known toxins Half-life: 1-2 months Half-life: 1-2 months

8. November 18, 2003Robert Burr MD8 Chromium: Toxic Responses Cell injury: interferes with cellular respiration Cell injury: interferes with cellular respiration Physiologic: none Physiologic: none Allergenic: allergic dermatitis, asthma Allergenic: allergic dermatitis, asthma Mutagenic: yes Mutagenic: yes Carcinogenic: lung cancer Carcinogenic: lung cancer Teratogenic: probable, little data Teratogenic: probable, little data

9. November 18, 2003Robert Burr MD9 Chromium: Target Tissues Lung: Lung: Acute irritation Acute irritation Asthma Asthma Fibrosis, lung cancer Fibrosis, lung cancer Upper respiratory tract Upper respiratory tract Sinusitis, septal perforation Sinusitis, septal perforation Skin Skin Dermatitis: irritant, allergic Dermatitis: irritant, allergic

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11. November 18, 2003Robert Burr MD11 Measurement and Management of Chromium Exposure Measurement Measurement Blood and urine levels Blood and urine levels Management Management Removal Removal Ascorbic acid to reduce conversion from VI-III Ascorbic acid to reduce conversion from VI-III Topical EDTA for chromium ulcers Topical EDTA for chromium ulcers Chelation has not proven to be helpful Chelation has not proven to be helpful

12. November 18, 2003Robert Burr MD12 Dioxins Family of chlorinated organic compounds Family of chlorinated organic compounds Chlorinated Dibenzo-p-dioxins(CDDs) Chlorinated Dibenzo-p-dioxins(CDDs) 2,3,7,8-tetrachlorodibenzo-p-dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin Persistent: half-life 7-12 years Persistent: half-life 7-12 years Lipophilic: reside in fat Lipophilic: reside in fat Ubiquitous Ubiquitous

13. November 18, 2003Robert Burr MD13 Dioxins: Toxic Responses Cell Injury: upper respiratory irritation, chloracne, immunotoxicity Cell Injury: upper respiratory irritation, chloracne, immunotoxicity Physiologic: none known Physiologic: none known Allergic: none known Allergic: none known Mutagenic: not seen Mutagenic: not seen Carcinogenic: increased overall incidence Carcinogenic: increased overall incidence Teratogenic: changed sex ratio Teratogenic: changed sex ratio

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15. November 18, 2003Robert Burr MD15 Trichloroethylene (TCE) Long use as a solvent and anesthetic Long use as a solvent and anesthetic Short half life: ~hours to a day Short half life: ~hours to a day Metabolites: few days Metabolites: few days

16. November 18, 2003Robert Burr MD16 TCE: Toxic Responses Cell injury: via reactive metabolites, liver, peripheral nerves Cell injury: via reactive metabolites, liver, peripheral nerves Physiologic: brain, heart Physiologic: brain, heart Allergic: none Allergic: none Mutagenic: no Mutagenic: no Carcinogenic: probably Carcinogenic: probably Teratogenic: probably Teratogenic: probably

17. November 18, 2003Robert Burr MD17 TCE: Target tissues Brain: headache, depression, coma Brain: headache, depression, coma Heart: irritability, sudden death Heart: irritability, sudden death Liver: Liver: acute chemical hepatitis acute chemical hepatitis Cirrhosis Cirrhosis Kidney: tubular injury Kidney: tubular injury Skin: dermatitis Skin: dermatitis

18. November 18, 2003Robert Burr MD18 ?

19. November 18, 2003Robert Burr MD19 Thanks for listening