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%