7.4 - TOXICOLOGY OF SPECIFIC AGENTS

Ethanol

Methanol

Isopropanol

Ethylene Glycol

Alcohol (4)

Alcohol

General CNS Effects: Disorientation, confusion, euphoria → unconsciousness, paralysis, death

CNS depressant

Alcohol

Similar effects across alcohols due to _ _ effects

alcohol dehydrogenase

aldehyde dehydrogenase

Alcohol

Alcohol is converted into aldehyde through the enzyme _ _

Aldehyde is converted into acid through the enzyme _ _

Ethanol

Alcohol

Most common alcohol exposure; major public health issue

80 mg/dL

chain-of-custody

Alcohol

Ethanol

Acute Intoxication:

Legal limit for driving: _

Used in litigation: Requires proper _ _ _

Involved in ~50% of vehicle-related fatalities

liver, cirrhosis

liver enzymes

Alcohol

Ethanol

Chronic Consumption:

Mainly affects _: Fatty liver → alcoholic hepatitis → _

Increases in _ _ and other markers

acetaldehyde

acetate

acetaldehyde adducts

Alcohol

Ethanol

Ethanol → _ → _ → _ _

0.01-0.05

ETHANOL IMPAIRMENT STAGES
Alcohol Level (% or w/v)	Signs and Symptoms
_	No obvious impairment; some changes observable on performance testing

0.03-0.12

ETHANOL IMPAIRMENT STAGES
Alcohol Level (% or w/v)	Signs and Symptoms
_	Mild euphoria, decreased inhibitions, some impairment of motor skills

0.09-0.25

ETHANOL IMPAIRMENT STAGES
Alcohol Level (% or w/v)	Signs and Symptoms
_	Decreased inhibitions, loss of critical judgment, memory impairment, diminished reaction time

0.18-0.30

ETHANOL IMPAIRMENT STAGES
Alcohol Level (% or w/v)	Signs and Symptoms
_	Mental confusion, dizziness, strongly impaired motor skills

0.27-0.40

ETHANOL IMPAIRMENT STAGES
Alcohol Level (% or w/v)	Signs and Symptoms
_	Unable to stand or walk, vomiting, impaired consciousness

0.35-0.50

ETHANOL IMPAIRMENT STAGES
Alcohol Level (% or w/v)	Signs and Symptoms
_	Coma and possible death

Methanol

Alcohol

Found in solvents, cleaners, homemade liquor

formaldehyde

formic acid

Alcohol

Methanol

Metabolized to _ → _ _ (similar to ethanol, via ADH/ALDH)

metabolic acidosis

optic neuropathy

Alcohol

Methanol

Causes _ _, _ _ → blindness, death

Isopropanol (Rubbing Alcohol)

Alcohol

CNS depressant like ethanol; prolonged symptoms due to acetone’s long half-life

acetone

Alcohol

Isopropanol (Rubbing Alcohol)

Metabolized to _

Ethylene Glycol

Alcohol

Found in antifreeze, hydraulic fluid

alcoholics

children

Alcohol

Ethylene Glycol

Ingestion: Common in _ and _ (sweet taste)

glycolic acid

oxalic acid

Alcohol

Ethylene Glycol

Metabolized to _ _, _ _ → metabolic acidosis

calcium oxalate

Alcohol

Ethylene Glycol

Forms _ _ crystals in renal tubules → renal damage

Serum, plasma, whole blood

Alcohol

Alcohol Determination

Specimens: (3)

alcohol-free

Cap

sodium fluoride

Alcohol

Alcohol Determination

Preanalytical Considerations:

Use _-_ disinfectants

_ specimens to prevent evaporation

Preserve with _ _ if needed

Osmometry

Alcohol

Alcohol Determination

Methods

Screening

10

60

Alcohol

Alcohol Determination

Methods

Osmometry (screening): _ mOsm/kg increase per _ mg/dL ethanol

Gas Chromatography (GC)

Alcohol

Alcohol Determination

Methods

Reference method

Gas Chromatography (GC)

Alcohol

Alcohol Determination

Methods

Measures multiple alcohols simultaneously

Enzymatic Method

340

Alcohol

Alcohol Determination

Methods

_ _: ADH + NAD⁺ → Acetaldehyde + NADH (detected at _ nm)

Enzymatic Method

Alcohol

Alcohol Determination

Methods

Specific to ethanol

Can detect ethanol metabolites such as ethyl glucuronide, ethyl sulfate, phosphatidylethanol

GC-flame ionization

Alcohol

Alcohol Determination

Methods

_-_ _ for methanol, isopropanol, ethylene glycol

Carbon Monoxide

Sources: Combustion of carbon-containing materials

Carboxyhemoglobin

200-225

Carbon Monoxide

Binds Hb, forming _ (COHb): _-_x affinity than O₂

hypoxia

Carbon Monoxide

Major effects in brain, heart: Reduces oxygen delivery → _

100% oxygen

hyperbaric O₂

Carbon Monoxide

Treatment: _ _; _ _ in severe cases

Caustic Agents

Found in households/industries (acids, alkalis)

Pulmonary edema, shock, rapid death

Caustic Agents

Aspiration: (3)

perforation, hematemesis, metabolic imbalance

Caustic Agents

Ingestion: GI tract lesions → (3)

Dilution

Caustic Agents

Treatment: _

Cyanide

“Odor of Bitter Almonds”

Cyanide

Sources: Insecticides, rodenticides, fire smoke (e.g., burning plastics)

heme iron

ATP depletion

venous pO₂

Cyanide

Mechanism: Binds to _ _ in mitochondrial cytochrome oxidase

Uncouples oxidative phosphorylation → _ _

Increases _ _ due to lack of O₂ utilization

thiocyanate

Cyanide

Clearance: Enzymatic conversion to _ (renal excretion)

Ion-selective electrodes (ISE), photometric methods

Urinary thiocyanate

lactic acid

Cyanide

Detection: (2)

_ _ for chronic exposure

Elevated _ _ is a common finding

Arsenic

“Odor of Garlic Breath”

Arsine gas

Inorganic

Organic

Arsenic

Forms: _ _ (most toxic), _ (trivalent), _

renal

Arsenic

Excretion: Primarily _

Urine

Hair/nails

Arsenic

_: Best for exposure within past week

_/_: Long-term exposure; Mees’ lines

kidneys

parathyroid dysfunction, vitamin D deficiency

Itai-itai disease

Cadmium

Toxicity:

Binds proteins → accumulates in _ (renal tubular dysfunction)

Associated with (2)

Long-term exposure → _-_ _ (osteomalacia, osteoporosis)

10-30

Whole blood or urine

Cadmium

Elimination: Very slow; biological half-life = _-_ years

Detection: (2)

Children

Lead

Absorption: _ absorb more than adults (up to 40% in infants)

anemia

zinc protoporphyrin

urinary ALA

basophilic stippling

Lead

Hematologic toxicity: Inhibits heme synthesis → _, ↑ _ _, ↑ _ _, _ _

Whole blood

ICP-MS

Lead

Detection: _ _ (preferred) using _-_ (gold standard)

Elemental

Inorganic

Organic

Mercury

Forms: _ (Hg⁰), _ (Hg²⁺), _ (methylmercury)

Whole blood

24-hr urine

Mercury

Detection: _ _ or _-_ _

Insecticides

herbicides

fungicides

rodenticides

Pesticides

Categories: _ (most prevalent), _, _, _

Organophosphates

carbamates

halogenated hydrocarbons

Pesticides

Types of insecticides: _ (most common), _, _ _

acetylcholinesterase (AChE)

pseudocholinesterase (SChE)

Pesticides

Organophosphates inhibit _ and _

Erythrocytic acetylcholinesterase

Pesticides

_ _ preferred over serum testing due to higher sensitivity

erythrocyte AChE testing

Pesticides

Also, suspected poisoning with low serum SChE should be followed by _ _ _ (confirmed with low AChE)