FORENSIC TOXICOLOGY

POISONINGS/TOXINS Toxin/Disease Clinical Signs & Symptoms Histopathologic/ Toxicologic Findings Arsenic alkaline vomitus, rash, GI sx, stocking & glove parasthesias basophilic stippling Acetaminophen Fulminant Hepatic Failure Liver with centrilobular necrosis & congestion. Necrosis may extend to entire lobule. Asbestos amphiboles (crocidolite) more pathogenic than chrysotiles asbestosis and progressive massive fibrosis (PMF); bronchogenic carcinomas and mesotheliomas, also stomach ca. Boric Acid (Boron) GI sx, erythema ("boiled lobster") cystitis, white matter hemorrhages Byssinosis (cotton, flax) histamine mediated bronchiolar constriction   Cadmium (alkaline batteries) acute: ARDS chronic: interstitial fibrosis, honeycombing, emphysema   Cobalt Goiter Thyroid hyperplasia, cardiomyopathy Carbolic Acid (Phenol)     Carbon Monoxide (CO) competes with O2 for hemoglobin, myoglobin, cyt c oxidase and cyto P-450. O2 curve moves left, decreasing tissue release.Also impairs mitoch respiration at cytochrome oxidase. Visible at 35%, Fatal at 50% Average house fire 57%; 30-40% common Before catalytic coverter idle engine 7% CO, now < 0.1% CO 5% CO in idling car accumulates to fatal levels in approx 5 - 10 min (?) Cyanide (CN)     Ethylene glycol (antifreeze) Metabolized to oxalic acid. CNS depression within 12 hrs and metabolic acidosis. Cardioresp sx w/in 12-24 hrs. Acute renal failure and ATN in 24-72 hrs. Min lethal dose 100 mL. Rx: NaCOH, ethanol, hemodialysis. Brain: perivascular hemorrhages, polarizable oxalate crystals Kidney: oxalate crystals in renal tubules. Ephedrine (Ma Huang)     Farmer's Lung (Moldy Hay)   hypersensitivity pneumonitis Flourine convulsions, GI sx, increased citrate, hypermineralization Hexachlorophene   demyelination Iron (FeSO4) GI mucosa, liver   Kerosene     Lead (paint, battery or crystal manufacturing) blood lead > 10 mg/dl. Childhood: encephalopathy with increased ICP, anemia, lead lines on Xray Encephalopathy: global cerebral edema; petechial hemorrhages in white matter; microvessels reveal dilatation, endothelial swelling or thrombosis; white matter microspongiosis with gliosis; astrocytic and vascular proliferation, white matter necrosis, AFB positive intranuclear inclusions (kidney, liver) Lye (NaOH) Chemical burns to mouth, esophagus, stomach. Esophageal stricture common complication. GI: transmural necrosis of stomach & esophagus; perforation & peritonitis. Magnesium     Methane (natural gas)     Mercury   gray matter necrosis, vessel proliferation, hyalinization of vessels, kidneys Nickle     Paraquat (weed killer) Rx: Fuller's earth and bentonite clay proliferative pulmonary reaction leading to interstitial fibrosis Radiation     Salt     Silo Filler's Disease: CO2   bronchiolar desquamation, bronchiolitis obliterans, fibrosis, interstitial lymphocytic infiltrate. Thallium

COCAINE Use assoc with: hyperthermia, rhabdomyolysis, contraction band necrosis, accelerated atherosclerosis, MI, cerebral hemorrhages, dissecting Ao aneurysms Deaths usually not dose-related. Snorted: HCl cocaine (assoc with nasal perforation). Increases blood levels of norepinephrine; blockage of re-uptake in synapse. Route of administration most important factor in increasing blood levels. Cocaine-iduced delerium: not assoc with massive drug levels, due to dopamine receptor binding, associated with hyperthermia and manifested w/psychosis. Paranoid psychosis: induced by prolonged and heavy use. May die in prolonged struggle. Increased D1 receptors assoc with hyperthermia; when increased D3 & decreased D1, increased craving & less euphoria with a given dose; dec D2 assoc with psychotic reactions. a receptors on coronaries cause contraction; b1 receptors chronotropic. Cocaine and cocaethylene both cross blood brain barrier. Illegal processing: gasoline, acetone, KMg (potassium permanganate), HCl + ETOH = cocaethylene, ethylbenzoylecognine Hydrolysis by water = bezoylecognine Plasma esterase = methylecognine Rx intoxication: IV diazepam

ALCOHOL Metabolism decreases gluconeogenesis, increases triglycerides in liver. ETOH converted to acetaldehyde by alcohol dehydrogenase (depleting NAD), predominantly in liver, producing a fruity odor at autopsy. Elimination shows first order kinetics under 0.2%, zero order 0.2%-03%, Widmark formula can be used. Peak BAC on empty stomach 1.3 hrs after ingestion; main avsorption is in small intestine. Post-absorptive phase: equilibration of BAC Delayed absorption: fatty meal, fear, pain, exercise, amphetamines, decreased GI motility Increased elimination: fructose, glycine or alanine ingestion, liver adaption to ETOH Post-mortem concentrations higher in plasma than whole blood, and is not constant throughout brain. Analysis: gas chromatography Blood Alcohol (g/100 mL) Signs/Symptoms 0.01 - 0.05 Slight physiological impairment detected on careful testing. 0.05 - 0.07 Euphoria, increased self-confidence. Consistent impairment of reactio responses. 0.07 - 0.10 Increased impairment of reaction responses, attention, visual acuity, sensory-motor coordination, and judegmebt. Individual may still appear sober. 0.10 - 0.20 Increasing impairment of sensory-motor activities, reaction times, attention, visual acuity and jedgment. Progressive increase in drowsiness, disorientation and emotional lability. By 0.20g/100 mL loss of coordination, staggering gait and slurred speech. 0.20 - 0.30 Staggering, grossly impaired and drunk; May be lethargic, sleep y and hostile and aggressive. By 0.30 most pass out or fall asleep. 0.30 - 0.40 Impaired consciousness, stupor, unconsciousness 0.40+ Unconsciousness, coma, death.

Ratio of blood to vitreous alcohol is 0.89. Blood ETOH = 0.89 x vitreous ETOH.

Tricyclic Antidepressants: Most common family of drugs in U.S. suicides. Three generations: I. amitriptyline, nortriptyline, imipramine, desipramine, doxepin (DAN ID) II. amoxepine, trazodone, buproprion, maprotiline III. venlafaxine, nefazodone, mirtazapine Mechanism of deatg: cardiac, intraventricular conduction abnormalities, widened QRS. Can also produce: CNS confusion, hallucinations, seizures and coma, hyperpyrexia * Significant post-mortem redistribution

Laboratory Assays Enzyme multiplied immunoassay technique (EMIT): used for urine screen. Detects benzoylecgonine not cocaine. NaF prserves blood at 2.5mg/ml, inhibits bacteria but not fungi (kills neither) & still requires refrigeration. GC-MS (only specific method): Immunoassay (EMIT): screen for opiates, salicylates, cocaine, amphetamines, metamphetamines, barbiturates and cannabinoids in urine. Confirm by GC-MS GC: acetone, isopropyl, ethyl and methyl alcohol, toluene, benzene, trichloroethane and trichloroethylene. UV spectrophotometry: CO

Barbiturates: vitreous levels lower than blood.

Mushroom poisons: Amanita phalloides (almost all fatalities) from CA, Pacific Northwest and Northeast. Contains cyclopeptide toxins (hepatotoxic) not destroyed by cooking with no taste or smell. One can kill you. No symptoms for several hours. Then, nausea/vominting, cramps, diarrhea. Seem better, then hepatorenal failure. Fulminant hepatic necrosis by day 2. Mortality rate 20-30%

Electrolytes you can trust Vitreous Na > 155 mEq/l or < 130 mEq/l VUN (parallels BUN and is only slightly off even after 100 hours). If vitreous humor has glucose, you can R/O hypoglycemia; glucose> 300 mg/100 ml reliable for hyperglycemia if you have ketones, acetone.

IVDA Oxalates: laminated sheaf or fan (ethylene glycol or methoxyflurane toxicity) Magnesium silicate (talc): birefringent, thin pismatic crystals Starch (amylose): maltese cross, PAS+, used in surgical glove powder Talwin (pentazocine) or calcium complexed fillers: larger globules and aggregates of birefringent crystals