November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 11

Toxicology of High Priority Toxicology of High Priority SubstancesSubstances

Part 3: Cd, Cr, Dioxin and TCE Part 3: Cd, Cr, Dioxin and TCE

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 22

CadmiumCadmium FormsForms

Inorganic: cadmium saltsInorganic: cadmium salts Elemental: calcium fume and dustElemental: calcium fume and dust

Bound by metallothionein in liver and kidney; Bound by metallothionein in liver and kidney; saturation leads to appearance of toxicitysaturation leads to appearance of toxicity

Half-life: 8-30 years; poorly excretedHalf-life: 8-30 years; poorly excreted Chelation techniques increase the toxic effectChelation techniques increase the toxic effect Toxic effects progressiveToxic effects progressive Not susceptible to interventionNot susceptible to intervention

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 33

Cadmium: Toxic ResponsesCadmium: Toxic Responses

Cell injury: mechanism not knownCell injury: mechanism not known Physiologic: nonePhysiologic: none Allergenic: not knownAllergenic: not known Mutagenic: poorlyMutagenic: poorly

Carcinogenic: lung cancerCarcinogenic: lung cancer

Teratogenic: no informationTeratogenic: no information

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 44

Cadmium: Target TissuesCadmium: Target Tissues

Lungs: Lungs: Acute chemical pneumoniaAcute chemical pneumoniaEmphysema, fibrosisEmphysema, fibrosisLung cancerLung cancer

Kidneys: renal tubular dysfunctionKidneys: renal tubular dysfunctionBone disease, kidney stonesBone disease, kidney stones

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 55

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 66

Measuring and Managing Cadmium Measuring and Managing Cadmium ExposureExposure

OSHA StandardOSHA StandardBlood and urine cadmium levelsBlood and urine cadmium levelsUrine Urine ββ2-microglobulin2-microglobulin

Evidence of renal tubular toxicityEvidence of renal tubular toxicity

Medical removal depending on monitoring Medical removal depending on monitoring resultsresults

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 77

ChromiumChromiumFormsForms

InorganicInorganicChromium III: insoluble, but toxicChromium III: insoluble, but toxicChromium VI Chromium VI

Soluble, easily absorbedSoluble, easily absorbed Converted to Cr V-IV-III in cellsConverted to Cr V-IV-III in cells

Elemental and organic forms are not known Elemental and organic forms are not known toxinstoxins

Half-life: 1-2 monthsHalf-life: 1-2 months

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 88

Chromium: Toxic ResponsesChromium: Toxic Responses

Cell injury: interferes with cellular respirationCell injury: interferes with cellular respiration Physiologic: nonePhysiologic: none Allergenic: allergic dermatitis, asthmaAllergenic: allergic dermatitis, asthma Mutagenic: yesMutagenic: yes

Carcinogenic: lung cancerCarcinogenic: lung cancer

Teratogenic: probable, little dataTeratogenic: probable, little data

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 99

Chromium: Target TissuesChromium: Target TissuesLung:Lung:

Acute irritationAcute irritationAsthmaAsthmaFibrosis, lung cancerFibrosis, lung cancer

Upper respiratory tractUpper respiratory tractSinusitis, septal perforationSinusitis, septal perforation

SkinSkinDermatitis: irritant, allergicDermatitis: irritant, allergic

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1010

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1111

Measurement and Management of Measurement and Management of Chromium ExposureChromium Exposure

MeasurementMeasurementBlood and urine levelsBlood and urine levels

ManagementManagementRemovalRemovalAscorbic acid to reduce conversion from VI-IIIAscorbic acid to reduce conversion from VI-IIITopical EDTA for chromium ulcersTopical EDTA for chromium ulcersChelation has not proven to be helpfulChelation has not proven to be helpful

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1212

DioxinsDioxins

Family of chlorinated organic compoundsFamily of chlorinated organic compoundsChlorinated Dibenzo-Chlorinated Dibenzo-pp-dioxins(CDDs)-dioxins(CDDs)

2,3,7,8-tetrachlorodibenzo-p-dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin

Persistent: half-life 7-12 yearsPersistent: half-life 7-12 yearsLipophilic: reside in fatLipophilic: reside in fatUbiquitous Ubiquitous

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1313

Dioxins: Toxic ResponsesDioxins: Toxic Responses

Cell Injury: upper respiratory irritation, Cell Injury: upper respiratory irritation, chloracne, immunotoxicitychloracne, immunotoxicity

Physiologic: none knownPhysiologic: none knownAllergic: none knownAllergic: none knownMutagenic: not seenMutagenic: not seen

Carcinogenic: increased overall incidenceCarcinogenic: increased overall incidenceTeratogenic: changed sex ratioTeratogenic: changed sex ratio

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1414

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1515

Trichloroethylene (TCE)Trichloroethylene (TCE)

Long use as a solvent and anestheticLong use as a solvent and anestheticShort half life: ~hours to a dayShort half life: ~hours to a day

Metabolites: few daysMetabolites: few days

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1616

TCE: Toxic ResponsesTCE: Toxic Responses

Cell injury: via reactive metabolites, liver, Cell injury: via reactive metabolites, liver, peripheral nervesperipheral nerves

Physiologic: brain, heartPhysiologic: brain, heartAllergic: noneAllergic: noneMutagenic: noMutagenic: no

Carcinogenic: probablyCarcinogenic: probablyTeratogenic: probablyTeratogenic: probably

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1717

TCE: Target tissuesTCE: Target tissues

Brain: headache, depression, comaBrain: headache, depression, comaHeart: irritability, sudden deathHeart: irritability, sudden deathLiver: Liver:

acute chemical hepatitisacute chemical hepatitisCirrhosisCirrhosis

Kidney: tubular injuryKidney: tubular injurySkin: dermatitisSkin: dermatitis

November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1818

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November 18, 2003November 18, 2003 Robert Burr MDRobert Burr MD 1919

Thanks for listeningThanks for listening