ACMT%Board%Review%

Miscellaneous%Toxicants%

Brandon'Wills,'DO,'FACEP,'FACMT'Fellowship%Director,%Medical%Toxicology%Department%of%Emergency%Medicine%

VCU%Medical%Center%Virginia%Poison%Center%

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%

10%min:%%!Organize!

!Using!study!aids!(quick!look!at!flashcards) !!

!Miscellaneous!Toxicants!Jeopardy%overview%

50%min:%%

!brief!reviewB!focus!on!test$rather!than!content!!

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%

Acrolein%

Acrolein%=%Acrid%=%IRRITATING%

I:%Contact%herbicide%

I:%%WWI%Lacrimator%

Acrylaldehyde, propenal, allyl aldehyde Ethylene aldehyde, aqualin, (CH2=CHCHO)

TW%Water%soluble%irritant%

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

MW%Metabolite%of%cyclophosphamide'

Acrylamides%Heating%Starches%

UW%Polymer%production%(SDSWPAGE),%flocculator%%

Propenamide, acrylic amide, akrylamid

TW%Axonopathy%

TW%Dermatitis%(peeling,%red/blue,%hyperhidrosis)%

TW%IARC%2A%(poss%gyn%CA)%

MW%Polymer%=%nonWtoxic,%Monomer=%toxic%

Acrylates%

UW%CrossWlinking%properties%(plexiglass)%

Acrylates, methylacryates, Cyanoacrylates Ethyl, methyl, 2-ethyl hexyl, butyl…

TW%Irritant%(skin,%MM,%and%pulmonary)%

TW%Contact%dermatitis%

MW%Penetrates%latex/%rubber%easily%%

Amines% Benzidine

Dimethylamine

Dimethylamine Trichlorotriethylamine Benzidine β-naphthylamine

-Vulcanization

AZO Dyes

Aniline%Compounds%

UW%Precursor%for%polyurethane,%indigo=%blue%jean%die%

IW%Smells%like%rotten%fish%

Aniline

Aniline 4-chloroaniline 4-aminophenol Nitrobenzene 4,4’-Methylene dianiline

TW%Acute:%MetHb,%irritant%TW%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%%

UW%Airbag%accelerant;%pesticde,%explosives%

IW%Labs%and%manufacturing%plants%

TW%Cellular%asphyxiant,%resp%failure/%pulm%edema%

TW%Eye%irritant%%

Bromide%Compounds%%

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

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

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

T%(chronic)W%neuropsych,%acne%(30%%facial),%axonopathy%

MW%Low%anion%gap%(false%high%Cl)%

Butadienes%

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

*ABS:%AcrylonitrileWbutadieneWstyrene%

Butadiene

1,3-butadiene Hexachloro-1,3- butadiene Many others

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

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

Carbon%Disulfide%UW%Volatile%organic%solvent%

IW%%Rayon,%fumigation%

TW%Acute:%Irritant%(defatting),%disulfiram%rxn%%

TW%Chronic%4%things:%%

%%%%%1.%%Distal%axonopathy'

%%%%%%%%%%%%%%%%%%%2.%%Optic%nerve%(resembles%optic%neuritis)%

%%%%%%%%%%%%%%%%%%%3.%%CV%(HTN,%CAD)%

%%%%%%%%%%%%%%%%%%%4.%%Repro%(SAB,%prematurity,%decreased%libido)%%

Chlorates%

UW%Oxidizer,%pesticide,%explosives,%bleaching%paper%

UW%Prior%uses:%%pryotechnics,%mouthwash%

Potassium chlorate Calcium chlorate Sodium perchlorate, etc

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

MW%FYIW%Perchlorates=%%Also%oxidizers%but%more%stable%

Coal%Tar%Products%

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

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

%%%%%%%%%%% % %coal%tar%creosote=%byWproduct%of%coal%tar%

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

UW%Wood:%%wood%protectant%

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

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

%%%%Cancer%d/t%PAH%(lung,%oral,%stomach,%bladder,%scrotal,%skin)%

Diamines%

UW%Diamines:%Manufacture%of%insecticides,%plastics,%rubber,%dyes…%

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

Hydrazine

Diamine (Hydrazine) Ethylenediamine Toluene-2,4-diamine

TW%Diamines:%Irritant/%sensitizer%(dermal%&%pulmonary),%lupusGlike%

TW%Hydrazine=INH%(seizures,%hepatitis,%MetHb,%skin%sensitizer)%

Dibromochloropropane%(DBCP)%

UW%Nematicide%(D/C’d%in%1979)W>%replaced%by%dibromoethane%

TW%Dermal%/%ocular%irritant%

TW%Testicular%(aspermia,%oligospermia)%

%%%%De!Balls!Can’t!Produce!(DBCP)%%

Dimethylacetamide%(DMAC)%

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

%%%%%Smells%like%fish/%ammonia%

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

TW%Irritant:%esophagitis,%conjunctivitis,%dermal%burn%

Dimethylformamide%(DMF)%

'“Universal'Solvent”'

UW%Penetrates%most%plastics%(makes%them%swell)%

IW%%%Acrylic%fiber%production,%paint%strippers%

%%%%%Vehicle%for%transdermal%drug%delivery%

TW%Potent%hepatotoxin%(CLN,%steatosis)%

TW%Disulfiram%rxn%%

TW%Pulm%irritant%

Dinitrobenzene%

UW%EXPLOSIVES,%spandex,%dyes%

4%Main%Toxicities:%

TW%Retrobulbar%neuritis%&%optic%neuropathy%

TW%MetHb%(potent)%

TW%May%have%bitter%almond%odor,%hair/skin/%eye%yellowing%

TW%Subacute%hepatic%necrosis,%aplastic%anemia%

Dinitrotoluene%(DNT)%

UW%EXPLOSIVES,%diisocyanate%production,%dyes%

5%Main%Toxicities:%(1st%3%shared%with%previous%slide)%

TW%MetHb%

TW%Hemolytic'anemia'

MW%Turns%skin%yellow'

TW%Uncouples%oxidative%phosphorylation%

TW%Retrobulbar%&%optic%neuropathy%%

Epichlorhydrin%

UW%Highly%reactive%plastics%production%

IW%Production%of%dye,%lubricants,%adhesives,%drugs%

TW%Strong%Irritant'(sensitizer):%respiratory,%dermal,%ocular%

TW%Nephrotoxicity,%CNS%depression,%hypotension%

MW%Penetrates%rubber%

MW%Sweet,%chloroform%odor%has%poor%warning%property%%

Ethylene%Dibromide%(EDB)%(AKA%Dibromoethane)%

UW%Replaced%dibromochloropropane%as%nematicide%

UW%Fumigant%(grainW%banned%1948),%fire%extinguishers,%%lead%scavenger%in%gasoline%

TW%Hepatotoxicity%(GSSH%depletion)%

TW%Strong%irritant%(dermal,%pulmonary)%

Ethylenediamine%(EDA)%

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

UW%Drug%production:%%

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

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

TW%MetHb%%

Fluoride%Compounds%

UW%NaF:%electroplating,%toothpaste/%water%additive%

%%%%%%HF:%cleaning%brick/%rust,%glass%etching%

TW%Chelates%divalent%cations%(Ca++,%Mg++),%results%%in%↓%Mg/%Ca,%%

%%%%%↑%K%=%ventricular%fibrillation%

TW%Chronic=%fluorosis:%�%%bone%density,%calcification%of%ligaments,%%

hyperostosis,%whiteWbrown%dental%spots%%%

(axial%osteosclerosis/%nerve%compression)%

Fuels%

UW%EnergyWproducing%hydrocarbons%

TW%PULMONARY%(pneumonitis)%

MW%Jet%fuels%(kerosene,%benzene,%xylene,%toluene)%

%%%%%JPW7%&%JPW8%∼%pure%kerosene%%

HexachloroW1,3WButadiene%(HCBD)%

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

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

TW%Irritant%(Pulmonary'hemorrhage)%

TW%Hepatic%fatty%degeneration%

TW%Renal%tubular%necrosis,%tubular%adenomas%%

Isocyanates%

UW%Producing%polyurethane%polymers%%

%%%%(don’t%confuse%with%aniline%also%a%polyurethane%precursor)%

UW%Methylisocyanate%(MIC)W%production%of%carbamates%

MIC

TW%MIC:%Major%irritant%(pulm,%derm,%ocular)%

TW%TDI:%#1'Occupational'asthma%

Methylisocyanate (MIC) Toluene diisocyanate (TDI)

Maleic%Anhydride%

UW%Enamels,%bonding,%synthesis%of%malathion%

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

TW%Irritant%(dermal,%ocular)%'

Mercaptans%

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

UW%Odorant%(natural%gas=%tWbutylmercaptan)%

UW%Intermediate%in%synthesis%of%fuels,%pesticides…%

Mercaptomethane

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

TW%MetHb%&%hemolysis%(worse%in%G6PD)%%

Nitriles%Chemicals%with%a%–CN%

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

Acetonitrile

acetonitrile propane nitrile butanenitrile

TW%Liberation%of%–CN%%Cellular%asphyxiant%

TW%Irritants%(derm,%MM,%ocular)%

MW%Prolonged%observation%for%delayed%CN%toxicity%

OWPhenylenediamine%(OPD)%PWPhenylenediamine%%(PPD)%

UW%OPD:%dyes,%fungicides,%vet%antihelminthic%

UW%PPD:%hair'dyes'and'henna'tattoos%%

PPD

TW%OPD=severe%urticaria/dermatitis,%eye%blindness%

TW%PPD=%bladder%cancer?%%

Phosphorus%Phosphides%UW%Making%phosphates,%detergents,%fertilizer,%match%tips%(red)%

UW%Zn%&%Al%phosphide:%Insecticides,%rodenticides%

Zn Phosphide Red

Phosphorus

TW%Yellow:%strong%oxidizer,%causes%burns%(Red%is%benign)%

%%%%Ingestion:%%

'''''''1.'“smoking”,'glowing''stool,'smells'of'garlic%

%%%%%%%2.%%Asymptomatic%(hrsWweeks)%

%%%%%%%3.%%Hepatic/%renal%failure%

%%%%Chronic:%%“Phossy'Jaw”G%mandibular%necrosis%

TW%Phospine%gas:%%cellular%asphyxiant%+%pulm%edema%+%#3%above%

Phthalates%

UW%Plasticizing%for%vinyl,%softens%PVC%

diethylhexyl phthalate

TW%Controversial%whether%phthalates%have%health%%

%%%%%effects.%%Some%claim%association%with%asthma,%“sickW%

%%%%%building%syndrome”,%or%endocrine%problems%but%little%%

%%%%%supporting%data%

TW%Diethylhexyl%Phthalate%(DEHP)=%occ%asthma%

Polymers%

*Diverse'group'of'plastics*'

One%class=%Fluoropolymer%plastics:%%

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

tetrafluoroethylene

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

%%%%WPulm%irritant,%fluWlike%syndrome%(similar%to%MFF)%

%%%%WResolves%in%24W48%hrs%%

Resins%

Resins%=%Plastics%

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

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

Anhydrides%–% % %Occupational%pneumonitis%%

methylenedianiline

Styrene%

UW%Styrene%=%Styrofoam%

%%Also%ABS,%SBR%plastics%

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

TW%Peripheral%neuropathy%

TW%CNS%(balance,%memory,%color%vision)%

TW%Chronic=%Hearing'loss'

Trimellitic%Anhydride%UW%Plasticizer%for%polymers%(PVC)%

TW%Sensitizer/%irritant %4%syndromes:%

%%%1.%%Asthma/%rhinitis%(IgE)%

%%%2.%%Irritant%syndrome%(dust/%fumes)%

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

%%%%%%%%%%“Trimellitic'Flu”W%Like%MFF,%4W12%hours%after%shift%

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

%%%%%%%%“Pulmonary%diseaseW%anemia”%(PDA)%

%%%%%%%%%Dyspnea,%cough,%hemoptysis,%anemia%

%%%%%%%%%May%lead%to%restrictive%lung%dz;%pulm%hemosiderosis%

Triorthocresylphosphate%(TOCP)%

UW%Plasticizer%in%lacquer,%hydraulic%fluid%

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

%%%% %Inhibits%neuroGtargetGesterase%(NTE)%

TW%Delayed%sensoryGmotor'neuropathy%

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

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

''''' '“Jake%Walk”=%Jake%leg%paralysis%

MW'Morocco:%OPIDN%after%TOCP%adulterated%cooking%oil%

Xylidine%

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

TW%Acute:%%MetHb,%cyanosis,%intoxication%

TW%Chronic:%%Liver/%renal%damage%(animals)%'

Xylidine O-xylidine 2-6-methylaniline

Now…%

Group%by%some%reoccurring%themes%

Irritants%W%Acrolein%

W%Acrylates%

W%Epichlorohydrin%

W%Ethylene%Dibromide%(EDB)%

W%Ethylenediamine%

W%HexachloroW1,3WButadiene%(pulm%hemorrhage)%

W%Nitriles%(e.g.%acetonitrile,%acrylonitrile)%

W%Methylisocyanate%(MIC)%

W%Mercaptans%

-Many more -Decide if this category works for you...

Cancer%Causing%W%Acrylamides%(2A)%

W%Aromatic%Amines%(Benzidine,%βWnaphthylamine)%(1):%bladder%

W%Aniline%(1):% % % % % %bladder%

W%PWPhenylenediamine%(PPD)%(3):% % % %bladder,%leukemia%

W%Butadienes%(2A):% % % % %lymphohematopoetic%

W%Coal%tar%(PAH)%(1):% % % % %lung,%oral,%stomach,%% % % % % %bladder,%scrotal,%skin%

W%Vinyl%Chloride%(1):% % % % %Angiosarcoma%of%liver%

Peripheral%Neuropathy%

WAcrylamide%(A)%

WBromide%(Methyl)%(A)%

WCarbon%disulfide%(A)%

WStyrene%(?)%

WTOCP%

WTrichloroethylene%(M)%

Hepatotoxins%WDimethylacetamide%(DMAC):%Necrosis,%jaundice%

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

WDinitrobenzine%

WEthylene%Bibromide%(EDB)%

WHexachloroW1,3WButadiene%(HCBD):%fatty%degen%

WPhosphorus%(yellow%or%white)%

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

WMethylenedianiline:%Hepatitis%(epping%jaundice)%

MetHb%Inducers%

WChlorates%

WDinitrobenzene%(potent)%

WDinitrotoluene%(DNT)%

WEthylenediamine%

WMercaptans%

WXylidine%

Sensitizers%Pulmonary=%Occupational%Asthma%

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

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

W%Trimellitic%Anhydride:%%Asthma,%“Trimellitic%Flu”%(HP)%

W%Ethylenediamine%(EDA):%occup%asthma,%contact%dermatitis%

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

W%Diethylhexyl%Phthalate%(DEHP):%%occ%asthma%

Hypersensitivity%Pneumonitis%(HP)%

W  Anhydrides%W  Trimellitic%anhydride%

W  Pyrethrum%