Occupational'asthma'(HP)% Maleic%Anhydride%

ACMT%Board%Review%

Miscellaneous%Toxicants%

Brandon'Wills,'DO,'FACEP,'FACMT' Fellowship%Director,%Medical%Toxicology% Department%of%Emergency%Medicine% VCU%Medical%Center% Virginia%Poison%Center% VCU TOX 2.2.10 Miscellaneous Toxicants 2.2.10.1 Acrolein 2.2.10.2 Acrylamides 2.2.10.3 Acrylates 2.2.10.4 Amines 2.2.10.5 Aniline Compounds 2.2.10.6 Azides 2.2.10.7 Bromide Compounds 2.2.10.8 Butadienes 2.2.10.9 Carbon Disulfide 2.2.10.10 Chlorates 2.2.10.11 Coal Tar Products 2.2.10.12 Diamines 2.2.10.13 Dibromochloropropane (DBCP) 2.2.10.14 Dimethylacetamide (DMAC) 2.2.10.15 Dimethylformamide (DMF) 2.2.10.16 Dinitrobenzene 2.2.10.17 Dinitrotoluene (DNT) 2.2.10.18 Epichlorohydrin 2.2.10.19 Ethylene Dibromide (EDB) 2.2.10.20 Ethylenediamine (EDA) 2.2.10.21 Fluoride Compounds 2.2.10.22 Fuels 2.2.10.23 Hexachloro-1,3-Butadiene (HCBD) 2.2.10.24 Isocyanates (eg, toluene diisocyante) 2.2.10.25 Maleic Anhydride 2.2.10.26 Mercaptans 2.2.10.27 Methylene Diamine (MDA) 2.2.10.28 Nitriles 2.2.10.29 O-Phenylenediamine (OPD) 2.2.10.30 Phosphorus/phosphides 2.2.10.31 Phthalates 2.2.10.32 Polymers 2.2.10.33 Resins 2.2.10.34 Styrene 2.2.10.35 Trimellitic Anhydride 2.2.10.36 Triorthocresylphosphate (TOCP) 2.2.10.37 Xylidine Our%Gameplan%

 Organize%your%memory%

 Using%study%aids%(quick%look%at%ﬂashcards)%  60%min:%brief%reviewP%focus%on%test%rather%than%content%%

 20%min:%Miscellaneous+Toxicants+Jeopardy%overview% Sources%

 Dr.%Sean%Bryant%

 Dr.%Mike%Greenburg%

 Sullivan,%2nd%Ed%  Greenburg,%2nd%Ed%

 My%board%review%notes%

 http://pubchem.ncbi.nlm.nih.gov/%(structures)% Legend%for%this%talk%

U=%Uses%

I=%Industry% T=%Toxicity%

M=%Miscellaneous%factoids% Acrylaldehyde, propenal, allyl aldehyde Acrolein% Ethylene aldehyde, aqualin, (CH2=CHCHO)

Acrolein%=%Acrid%=%IRRITATING%

I:%Contact%herbicide% I:%%WWI%Lacrimator%

TP%Water%soluble%irritant%

TP%Cellular%toxin%via%oxygen%free'radicals'

MP%Metabolite%of%cyclophosphamide' Propenamide, acrylic amide, Acrylamides% akrylamid Heating%Starches% UP%Polymer%production%(SDSPPAGE),%ﬂocculator%%

TP%Axonopathy% TP%Dermatitis%(peeling,%red/blue,%hyperhidrosis)%

TP%IARC%2A%(poss%gyn%CA)% MP%Polymer%=%nonPtoxic,%Monomer=%toxic% Acrylates, methylacryates, Cyanoacrylates Acrylates% Ethyl, methyl, 2-ethyl hexyl, butyl…

UP%CrossPlinking%properties%(plexiglass)%

TP%Irritant%(skin,%MM,%and%pulmonary)% TP%Contact%dermatitis%

MP%Penetrates%latex/%rubber%easily%% Dimethylamine Trichlorotriethylamine Benzidine Benzidine Amines% β-naphthylamine

Dimethylamine

AZO Dyes

-Vulcanization Aniline 4-chloroaniline Aniline%Compounds% 4-aminophenol Nitrobenzene 4,4’-Methylene dianiline Aniline

UP%Precursor%for%polyurethane,%indigo=%blue%jean%die% IP%Smells%like%rotten%ﬁsh%

TP%Acute:%MetHb,%irritant%

TP%Chronic:%%Bladder%CA% %%%%%Methylenedianiline:% %%Hepatitis'(Epping'jaundice)'

'''''' ' '''Due to contaminated bread T- Aniline (Spain) Toxic oil syndrome Due to contaminated rapeseed oil (interstitial pulm dz)% Azides%%

UP%Airbag%accelerant;%pesticde,%explosives% IP%Labs%and%manufacturing%plants%

TP%Cellular%asphyxiant,%resp%failure/%pulm%edema% TP%Eye%irritant%% Bromide%Compounds%%

UP%Photographic,%hot%tub%chemicals,%fumigants...%

TP%Crosses%membrane%faster%than%Cl,%replacing%Cl%%

%%%%%%causing%sedation/%neuropsych%(KBrP%19th%century)%

T%(chronic)P%neuropsych,%acne%(30%%facial),%axonopathy% MP%Low%anion%gap%(false%high%Cl)% 1,3-butadiene Hexachloro-1,3- butadiene Butadienes% Many others Butadiene

UP%Monomer%for%plastics%(ABS%plastic*),%tobacco%smoke%

TP%Irritant%(skin%and%mucous%membranes)%

TP%IARC%2A%(lymphohematopoetic,%testicular,%thyroid,%mammary)%

*ABS:%AcrylonitrilePbutadienePstyrene% Carbon%Disulﬁde% UP%Volatile%organic%solvent% IP%%Rayon,%fumigation%

TP%Acute:%Irritant%(defatting),%disulﬁram%rxn% TP%Chronic:%% %%%%%1.%%Distal%axonopathy' %%%%%%%%%%%%%%%%%%%2.%%Optic%nerve%(resembles%optic%neuritis)% %%%%%%%%%%%%%%%%%%%3.%%CV%(HTN,%CAD)% %%%%%%%%%%%%%%%%%%%4.%%Repro%(SAB,%prematurity,%decreased%libido)%% Potassium chlorate Calcium chlorate Chlorates% Sodium perchlorate, etc

UP%Oxidizer,%pesticide,%explosives,%bleaching%paper%

UP%Prior%uses:%%pryotechnics,%mouthwash%

TP%Oxidizer=%MetHb,%hemolysis,%renal%failure%

MP%FYIP%Perchlorates=%%Also%oxidizers%but%more%stable% Coal%Tar%Products%

Sources:% %wood%creosote=%beach%wood%

%%%%%%%%%%%%% % %(phenol,%cresols,%guaiacols,%xylenols)%

%%%%%%%%%%% % %coal%tar%creosote=%byPproduct%of%coal%tar%

%%%%%%%%%%% % %(85%%polycyclic%aromatic%hydrocarbons%(PAH))%

UP%Wood:%%wood%protectant%

%%%%%%Coal%tar:%wood%preservative%(railroad%ties),%Rx%psoriasis%

TP%Dermal%irritant,%pulmonary=%restrictive/%obstructive%

%%%%Cancer%d/t%PAH%(lung,%oral,%stomach,%bladder,%scrotal,%skin)% Diamine (Hydrazine) Hexamethylene diamine Toluene-2,4-diamine (TDI) 2-methyl-1,4- benzenediamene Diamines% TDI Hydrazine

UP%Hydrazine=%Rocket%fuel%(reducer),%insecticides,%plastics%

UP%PPphenylenediamine=%%henna'&'all'hair'dyes...%

TP%Irritant/%sensitizer%(dermal%&%pulmonary),%lupusHlike%

TP%Hydrazine=INH%(seizures,%hepatitis,%MetHb,%skin%sensitizer)% Dibromochloropropane%(DBCP)%

UP%Nematicide%(D/C’d%in%1979)P>%replaced%by%dibromoethane%

TP%Dermal%/%ocular%irritant%

TP%Testicular%(aspermia,%oligospermia)%

%%%%De+Balls+Can’t+Produce+(DBCP)%% Dimethylacetamide%(DMAC)%

UP%Paint%remover,%solvent%for%plastics%(dissolves%PVC)%

%%%%%Smells%like%ﬁsh/%ammonia%

TP%Potent%hepatotoxin:%↑%LFT,%jaundice,%hepatomegaly,%liver%necrosis%

TP%Irritant:%esophagitis,%conjunctivitis,%dermal%burn% Dimethylformamide%(DMF)% '“Universal'Solvent”'

UP%Penetrates%most%plastics%(makes%them%swell)% IP%%%Acrylic%ﬁber%production,%paint%strippers% %%%%%Vehicle%for%transdermal%drug%delivery%

TP%Potent%hepatotoxin%(CLN,%steatosis)% TP%Disulﬁram%rxn%% TP%Pulm%irritant% Dinitrobenzene%

UP%EXPLOSIVES,%spandex,%dyes%

TP%Retrobulbar%neuritis%&%optic%neuropathy%

TP%MetHb%(potent)%

TP%Subacute%hepatic%necrosis,%aplastic%anemia% TP%May%have%bitter%almond%odor,%hair/skin/%eye%yellowing%% Dinitrotoluene%(DNT)%

UP%EXPLOSIVES,%diisocyanate%production,%dyes%

TP%Uncouples%oxidative%phosphorylation%

TP%MetHb%

TP%Hemolytic'anemia% TP%Retrobulbar%&%optic%neuropathy%%

MP%Turns%skin%yellow' Epichlorhydrin%

UP%Highly%reactive%plastics%production% IP%Production%of%dye,%lubricants,%adhesives,%drugs%

TP%Strong%Irritant'(sensitizer):%respiratory,%dermal,%ocular% TP%Nephrotoxicity,%CNS%depression,%hypotension%

MP%Penetrates%rubber% MP%Sweet,%chloroform%odor%has%poor%warning%property%% Ethylene%Dibromide%(EDB)% (AKA%Dibromoethane)%

UP%Replaced%dibromochloropropane%as%nematicide%

UP%Fumigant%(grainP%banned%1948),%ﬁre%extinguishers,%%lead%scavenger%in% gasoline%

TP%Hepatotoxicity%(GSSH%depletion)%

TP%Strong%irritant%(dermal,%pulmonary)% Ethylenediamine%(EDA)%

UP%Dyes,%solvent,%emulsiﬁer%(skin%creams/%latex)%

UP%Drug%production:%%

%%%%%(EDTA,%imidazolines,%aminophylline,%antihistamines)%

TP%Sensitizer%(contact%dermatitis,%occ%asthma)%

TP%MetHb%% Fluoride%Compounds%

UP%NaF:%electroplating,%toothpaste/%water%additive% %%%%%%HF:%cleaning%brick/%rust,%glass%etching%

TP%Chelates%divalent%cations%(Ca++,%Mg++),%results%%in%↓%Mg/%Ca,%% %%%%%↑%K%=%ventricular%ﬁbrillation%

TP%Chronic=%ﬂuorosis:%%%bone%density,%calciﬁcation%of%ligaments,%% hyperostosis,%whitePbrown%dental%spots%%% (axial%osteosclerosis/%nerve%compression)% Fuels%

UP%EnergyPproducing%hydrocarbons%

TP%PULMONARY%(pneumonitis)% MP%Jet%fuels%(kerosene,%benzene,%xylene,%toluene)%

%%%%%JPP7%&%JPP8%∼%pure%kerosene%% HexachloroP1,3PButadiene%(HCBD)%

UP%Heat%transfer%liquid%(transformers/%hydraulic%ﬂuid)%

UP%Fumigant%in%vineyards%(don’t%confuse%with%Bordeaux=%copper%sulfate)%

TP%Irritant%(Pulmonary'hemorrhage)%

TP%Hepatic%fatty%degeneration%

TP%Renal%tubular%necrosis,%tubular%adenomas%% Methylisocyanate (MIC) Toluene diisocyanate (TDI) Isocyanates% MIC

UP%Producing%polyurethane%polymers%%

%%%%(don’t%confuse%with%aniline%also%a%polyurethane%precursor)% UP%Methylisocyanate%(MIC)P%production%of%carbamates%

TP%MIC:%Major%irritant%(pulm,%derm,%ocular)% TP%TDI:%#1'Occupational'asthma'(HP)% Maleic%Anhydride%

UP%Enamels,%bonding,%synthesis%of%malathion%

TP%Allergic%sensitizer%(occupational'asthma)%

%%%%Hypersensitivity%pneumonitis%(HP)=%extrinsic%allergic%alveolitis=%Immunologic%

TP%Irritant%(dermal,%ocular)%' Mercaptans% Mercaptomethane

Chemicals%with%a%–SH%group%(noxious≈%cabbage)%

UP%Odorant%(natural%gas=%tPbutylmercaptan)% UP%Intermediate%in%synthesis%of%fuels,%pesticides…%

TP%Irritant%(derm,%MM,%respiratory)%

TP%MetHb%&%hemolysis%(worse%in%G6PD)%% acetonitrile propane nitrile Nitriles% butanenitrile Acetonitrile Chemicals%with%a%–CN%

UP%Solvents%(eg.%artiﬁcial%nail%remover),%reagents%

TP%Liberation%of%–CN%%Cellular%asphyxiant% TP%Irritants%(derm,%MM,%ocular)% MP%Prolonged%observation%for%delayed%CN%toxicity% OPPhenylenediamine%(OPD)% PPPhenylenediamine%%(PPD)%

*This'compound'is'also'listed'under'“Diamines”*% PPD

UP%OPD:%dyes,%fungicides,%vet%antihelminthic% UP%PPD:%hair'dyes'and'henna'tattoos%%

TP%OPD=severe%urticaria/dermatitis%(eye%blindness)%

TP%PPD=%bladder%cancer%% Phosphorus% Red Phosphides% Zn Phosphide Phosphorus

UP%Making%phosphates,%detergents,%fertilizer,%match%tips%(red)% UP%Zn%&%Al%phosphide:%Insecticides,%rodenticides%

TP%Yellow:%strong%oxidizer,%causes%burns%(Red%is%benign)% %%%%Ingestion:%% '''''''1.'“smoking”,'glowing''stool,'smells'of'garlic%

%%%%%%%2.%%Asymptomatic%(hrsPweeks)% %%%%%%%3.%%Hepatic/%renal%failure% %%%%Chronic:%%“Phossy'Jaw”H%mandibular%necrosis%

TP%Phospine%gas:%%cellular%asphyxiant%+%pulm%edema%+%#3%above% Phthalates% diethylhexyl phthalate

UP%Plasticizing%for%vinyl,%softens%PVC%

TP%Controversial%whether%phthalates%have%health%% %%%%%eﬀects.%%Some%claim%association%with%asthma,%“sickP% %%%%%building%syndrome”,%or%endocrine%problems%but%little%% %%%%%supporting%data%

TP%Diethylhexyl%Phthalate%(DEHP)=%occ%asthma% Polymers% tetrafluoroethylene

*Diverse%group%of%plastics*%

One%class=%Fluoropolymer%plastics:%%

%%%%%%%%%%%%%%%%%%%Polytetraﬂuoroethylene%(PTFE%=%Teﬂon)%

TP%Polymer%Fume%Fever%(heating%polymers)%

%%%%PPulm%irritant,%ﬂuPlike%syndrome%(similar%to%MFF)%

%%%%PResolves%in%24P48%hrs%% Resins% methylenedianiline

Resins%=%Plastics%

Combustion%can%liberate:%CO,%CN,%phosgene%

Methylenedianiline%– %Toxic%hepatitis%(Epping%Jaundice)%

Anhydrides%–% % %Occupational%pneumonitis%% Styrene%

UP%Styrene%=%Styrofoam%

%%Also%ABS,%SBR%plastics%

TP%“Styrene%Sickness”:%HA/fatigue/weakness,%intoxicated%after%exp%to%vapor%

TP%Peripheral%neuropathy%

TP%CNS%(balance,%memory,%color%vision)% TP%Chronic=%Hearing'loss' Trimellitic%Anhydride%

UP%Plasticizer%for%polymers%(PVC)%

TP%Sensitizer/%irritant;%4%syndromes:% %%%1.%%Asthma/%rhinitis%(IgE)% %%%2.%%Irritant%syndrome%(dust/%fumes)%

%%%3.%%Late%respiratory%systemic%syndrome%(LRSS)%

%%%%%%%%%%“Trimellitic'Flu”P%Like%MFF,%4P12%hours%after%shift%

%%%4.%%Hypersensitivity%pneumonitis%+%hemolytic%anemia%

%%%%%%%%“Pulmonary%diseaseP%anemia”%(PDA)% %%%%%%%%%Dyspnea,%cough,%hemoptysis,%anemia% %%%%%%%%%May%lead%to%restrictive%lung%dz;%pulm%hemosiderosis% Triorthocresylphosphate%(TOCP)% UP%Plasticizer%in%lacquer,%hydraulic%ﬂuid%

TP%Weak%AchE%inhibitor%(like%organophosphate)%

%%%% %Inhibits%neuroHtargetHesterase%(NTE)%

TP%Delayed%sensoryHmotor'neuropathy%

''''' '“OPP%ester%induced%delayed%neurotoxicity%(OPIDN)”%

MP'Jamaican%Ginger%(Jake)%adulterated%by%TOCP%

''''' '“Jake%Walk”=%Jake%leg%paralysis% MP'Morocco:%OPIDN%after%TOCP%adulterated%cooking%oil% Xylidine O-xylidine Xylidine% 2-6-methylaniline

UP%Making%dyes/%pharmaceuticals,%gas%additive…%

TP%Acute:%%MetHb,%cyanosis,%intoxication% TP%Chronic:%%Liver/%renal%damage%(animals)%' Now…%

Group%by%some%reoccurring%themes% Irritants%

P%Acrolein%

P%Acrylates%

P%Epichlorohydrin%

P%Ethylene%Dibromide%(EDB)%

P%Ethylenediamine%

P%Methylisocyanate%(MIC)%

P%Mercaptans%

PMany%more%

PSo%many,%decide%if%this%category%works%for%you...% Cancer%Causing%

PAcrylamides%(2A)%

PAromatic%Amines%(Benzidine,%βPnaphthylamine)%(1):%bladder%

PAniline%(1):%bladder%

%%%%%PPPPhenylenediamine%(PPD):%bladder,%leukemia%

PButadienes%(2A):%lymphohematopoetic%

PCoal%tar:%lung,%oral,%stomach,%bladder,%scrotal,%skin%

PVinyl%Chloride:%Angiosarcoma%of%liver%

PCCl4:%Liver% Peripheral%Neuropathy%

PAcrylamide%(A)%

PBromide%(Methyl)%(A)% PCarbon%disulﬁde%(A)%

PStyrene%(?)%

PTOCP%

PTrichloroethylene%(M)% Hepatotoxins%

PDimethylacetamide%(DMAC):%Necrosis,%jaundice%

PDimethylformamide%(DMF):%CLN,%steatosis%

PHexachloroP1,3PButadiene%(HCBD):%fatty%degen% PPhosphorus%(yellow%or%white)%

PXylidine%(in%animals;%also%renal%damage)%

PMethylenedianiline:%Hepatitis%(epping%jaundice)% MetHb%Inducers%

PChlorates%

PDinitrobenzene%(potent)%

PDinitrotoluene%(DNT)%

PEthylenediamine%

PMercaptans%

PXylidine% Sensitizers% Pulmonary=%Occupational%Asthma%

P%Anhydrides:%occupational%pneumonitis%(HP)%

P%Maleic%Anhydride:%%Allergic%&%hypersensitivity%pulm%dz%

P%Trimellitic%Anhydride:%%Asthma,%“Trimellitic%Flu”%(HP)% P%Ethylenediamine%(EDA):%occup%asthma,%contact%dermatitis%

P%Toluene%diisocyante%(TDI)/%isocyanates:%(#1%occ%asthma)%

P%Diethylhexyl%Phthalate%(DEHP):%%occ%asthma% Hypersensitivity%Pneumonitis%(HP)% Some%overlap%with%previous%slide%

P%%%%Anhydrides/%Maleic%Anhydride%

P Pyrethrum%

P%%%%Trimellitic%Anhydride% P Isocyanates%(TDI,%MDI)%

VCU TOX