8/24/14 ACMT Board Review Miscellaneous Toxicants Stephen W. Munday, MD, MPH, MS (Toxicology) Medical Toxicology Department of Occupational Medicine Sharp Rees-Stealy Medical Centers CPCS-San Diego Division Much appreciation to Brandon Wills for his previous work on this content Core Content – 2.2.10 Miscellaneous 2.2.10.1 Acrolein 2.2.10.19 Ethylene Dibromide (EDB) 2.2.10.2 Acrylamides 2.2.10.20 Ethylenediamine (EDA) 2.2.10.3 Acrylates 2.2.10.21 Fluoride Compounds 2.2.10.4 Amines 2.2.10.22 Fuels 2.2.10.23 Hexachloro-1,3-Butadiene (HCBD) 2.2.10.5 Aniline Compounds 2.2.10.24 Isocyanates (eg, toluene diisocyante) 2.2.10.6 Azides 2.2.10.25 Maleic Anhydride 2.2.10.7 Bromide Compounds 2.2.10.26 Mercaptans 2.2.10.8 Butadienes 2.2.10.27 Methylene Diamine (MDA) 2.2.10.9 Carbon Disulfide 2.2.10.28 Nitriles 2.2.10.10 Chlorates 2.2.10.29 O-Phenylenediamine (OPD) 2.2.10.11 Coal Tar Products 2.2.10.30 Phosphorus/phosphides 2.2.10.12 Diamines 2.2.10.31 Phthalates 2.2.10.13 Dibromochloropropane (DBCP) 2.2.10.32 Polymers 2.2.10.14 Dimethylacetamide (DMAC) 2.2.10.33 Resins 2.2.10.15 Dimethylformamide (DMF) 2.2.10.34 Styrene 2.2.10.35 Trimellitic Anhydride 2.2.10.16 Dinitrobenzene 2.2.10.36 Triorthocresylphosphate (TOCP) 2.2.10.17 Dinitrotoluene (DNT) 2.2.10.37 Xylidine 2.2.10.18 Epichlorohydrin Our Gameplan Organize your memory 60 min: brief review- focus on test rather than content 1 8/24/14 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 T- Water soluble irritant T- Cellular toxin via oxygen free radicals M- Metabolite of cyclophosphamide Propenamide, acrylic amide, Acrylamides akrylamid Heating Starches U- Polymer production (sodium dodecyl sulfate-polyacrymide gel electrophoresis “SDS-PAGE”), flocculator (waste-water treatment) T- Dermatitis (peeling, red/Blue dermatitis: occurs first and may Be only finding, hyperhidrosis – especially palms and soles) T- CNS (Delirium) T- Axonopathy M- Polymer = non-toxic, Monomer= toxic 2 8/24/14 Acrylates, methylacryates, Cyanoacrylates AcrylatesEthyl, methyl, 2-ethyl hexyl, butyl… U- Cross-linking properties (plexiglass) T- Irritant (skin, mucous membrane, and pulmonary) T- Contact dermatitis (allergic or irritant) M- 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 U- Precursor for polyurethane, indigo= blue jean die I- Smells like rotten fish T- Acute: MetHb, irritant T- 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) Similar to eosinophilia myalgia syndrome 3 8/24/14 Azides U- Airbag accelerant; pesticde, explosives I- Labs and manufacturing plants T- Cellular asphyxiant (like CN, H2S), resp failure/ pulm edema T- Eye irritant Bromide Compounds U- Photographic, hot tub chemicals, fumigants... T- Crosses membrane faster than Cl, replacing Cl causing sedation/ neuropsych (KBr- 19th century) [still common anti-convulsant in dogs] T (chronic)- neuropsych, acne (30% facial), axonopathy M- Low anion gap (false high Cl) 1,3-butadiene Hexachloro-1,3- butadiene Butadienes Many others Butadiene U- Monomer for plastics (ABS “Acrylonitrile-butadiene-styrene” plastic), tobacco smoke T- Irritant (skin and mucous membranes) 4 8/24/14 Carbon Disulfide U- Volatile organic solvent I- Rayon, fumigation T- Acute: Irritant (defatting), disulfiram rxn T- Chronic: 1. Distal axonopathy 2. Optic nerve/retinal microaneurisms 3. CV (HTN, CAD) in occupational cohorts 4. Repro (SAB, prematurity, decreased libido) Potassium chlorate Calcium chlorate Chlorates Sodium perchlorate, etc U- Oxidizer, pesticide, explosives, bleaching paper U- Prior uses: pryotechnics, mouthwash T- Oxidizer= MetHB, hemolysis, renal failure M- FYI- Perchlorates= Also oxidizers But more staBle Coal Tar Products Sources: wood creosote= beach wood (phenol, cresols, guaiacols, xylenols) coal tar creosote= by-product of coal tar (85% polycyclic aromatic hydrocarbons (PAH)) U- Wood: wood protectant Coal tar: wood preservative (railroad ties), Rx for psoriasis T- Dermal irritant, pulmonary= restrictive/ obstructive 5 8/24/14 Diamine (Hydrazine) Hexamethylene diamine Toluene-2,4-diamine (TDI) 2-methyl-1,4- benzenediamene Diamines TDI Hydrazine U- Hydrazine= Rocket fuel and reducing agent, insecticides, plastics T- Hydrazine=INH-like effects (seizures, hepatitis, also MetHb) T- Irritant/ sensitizer (dermal & pulmonary), lupus-like Diamines (continued…) O-Phenylenediamine (OPD) P-Phenylenediamine (PPD) U- OPD: dyes, fungicides, vet antihelminthic PPD U- PPD: hair dyes and henna tattoos T- OPD=severe urticaria/dermatitis (eyeà blindness) Dimethylacetamide (DMAC) U- Paint remover, solvent for plastics (dissolves PVC) Smells like fish/ ammonia T- Potent hepatotoxin: é LFT, jaundice, hepatomegaly, liver necrosis T- Irritant: esophagitis, conjunctivitis, dermal burn 6 8/24/14 Dimethylformamide (DMF) “Universal Solvent” U- Penetrates most plastics (makes them swell) I- Acrylic fiber production, paint strippers Vehicle for transdermal drug delivery T- Potent hepatotoxin (Centrolobular necrosis, microvesicular steatosis) T- Disulfiram rxn and Degreasers’ Flush (also trichloroethylene) T- Pulm irritant Dinitrobenzene U- EXPLOSIVES, spandex, dyes T- Retrobulbar neuritis & optic neuropathy T- MetHb (potent) T- Subacute hepatic necrosis, aplastic anemia T- May have bitter almond odor, hair/skin/ eye yellowing Dinitrotoluene (DNT) U- EXPLOSIVES, diisocyanate production, dyes T- Uncouples oxidative phosphorylation T- MetHb T- Hemolytic anemia T- Retrobulbar & optic neuropathy M- Turns skin yellow 7 8/24/14 Epichlorhydrin U- Highly reactiveà plastics production I- Production of dye, lubricants, adhesives, drugs T- Strong Irritant (sensitizer): respiratory, dermal, ocular T- Nephrotoxicity, CNS depression, hypotension M- Penetrates rubber M- Sweet, chloroform odor has poor warning property Ethylene Dibromide (EDB) (AKA Dibromoethane) U- Replaced dibromochloropropane as nematicide U- Fumigant (grain- banned 1948), fire extinguishers, lead scavenger in gasoline T- Hepatotoxicity (GSSH depletion) T- Strong irritant (dermal, pulmonary) Ethylenediamine (EDA) U- Dyes, solvent, emulsifier (skin creams/ latex) U- Drug production: (EDTA, imidazolines, aminophylline, antihistamines) T- Sensitizer (contact dermatitis, occ asthma) T- MetHb 8 8/24/14 Fluoride Compounds U- NaF: electroplating, toothpaste/ water additive HF: cleaning brick/ rust, glass etching T- Chelates divalent cations (Ca++, Mg++), results in ê Mg/ Ca, é K = ventricular fibrillation T- Chronic= fluorosis:  increased bone density, calcification of ligaments, hyperostosis, white-brown dental spots (axial osteosclerosis/ nerve compression) Hexachloro-1,3-Butadiene (HCBD) U- Heat transfer liquid (transformers/ hydraulic fluid) U- Fumigant in vineyards (don’t confuse with Bordeaux= copper sulfate) T- Irritant (Pulmonary hemorrhage) T- Hepatic fatty degeneration T- Renal tubular necrosis, tubular adenomas Methylisocyanate (MIC) Toluene diisocyanate (TDI) Isocyanates MIC U- Producing polyurethane polymers (don’t confuse with anilineà also a polyurethane precursor) U- Methylisocyanate (MIC)- production of carbamates T- MIC: Major irritant (pulm, derm, ocular) T- TDI: Occupational asthma and HP (Hypersensitivity Pneumonitis) 9 8/24/14 Maleic Anhydride U- Enamels, bonding, synthesis of malathion T- Allergic sensitizer (occupational asthma) Hypersensitivity pneumonitis (HP) = extrinsic allergic alveolitis = Immunologic T- Irritant (dermal, ocular) Mercaptans Mercaptomethane Chemicals with a –SH group (noxious≈ cabbage) U- Odorant (natural gas= t-butylmercaptan) U- Intermediate in synthesis of fuels, pesticides… T- Irritant (derm, mucous membrane, respiratory) T- MetHb & hemolysis (worse in G6PD deficiency) acetonitrile propane nitrile Nitriles butanenitrile Acetonitrile Chemicals with a –CN U- Solvents (eg. artificial nail remover), reagents T- Liberation of –CN à Cellular asphyxiant T- Irritants (derm, mucous membrane, ocular) M- Prolonged observation for delayed CN toxicity 10 8/24/14 Phosphorus Red Phosphides Zn Phosphide Phosphorus U- Phosphorus- Making phosphates, detergents, fertilizer, match tips (red) phosphorus U- Zn & Al phosphide: Insecticides, rodenticides T- Yellow: strong oxidizer, causes burns (Red is benign) Ingestion: 1. “smoking”, glowing stool, smells of garlic 2. Asymptomatic (hrs-weeks) 3. Hepatic/ renal failure Chronic: “Phossy Jaw”- mandibular necrosis T- Phospine gas: cellular asphyxiant + pulm edema + Hepatic/Renal failure Phthalates diethylhexyl phthalate U- Plasticizing for vinyl, softens PVC T- Controversial whether phthalates have health effects. Some claim association with asthma, “sick- building syndrome”, or endocrine problems but little supporting data T- Diethylhexyl Phthalate (DEHP)= occ asthma Polymers tetrafluoroethylene *Diverse group of plastics* One class= Fluoropolymer plastics: Polytetrafluoroethylene (PTFE = Teflon) T- Polymer Fume Fever (heating polymers) -Pulm irritant, flu-like syndrome (similar to Metal Fume Fever) -Resolves in 24-48 hrs 11 8/24/14 Resins Resins = Plastics Combustion can liberate: CO, CN, phosgene Styrene U- Styrene = Styrofoam Also ABS (acrylonitrile butadiene