november 18, 2003robert burr md1 toxicology of high priority substances part 3: cd, cr, dioxin and...
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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
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