7.3 - TOXICOLOGY

Toxicology

It studies the adverse effects of xenobiotics (foreign chemicals/drugs not naturally found in the body)

intentional, accidental, occupational

Toxicology

Exposure stats: ~50% _ (suicide), ~30% _, remainder _/homicidal

Suicide

overdose

Toxicology

_ has highest mortality

Accidental exposure common in children/adolescents/adults via _

Forensic toxicology

Toxicology Specialties

Focuses on legal/medical consequences, validating analytical methods, and cause of death

Clinical toxicology

Toxicology Specialties

Examines xenobiotic-disease relationships; includes diagnostic and therapeutic focus

Environmental toxicology

Toxicology Specialties

Evaluates environmental pollutants’ effects on human health

Xenobiotic

Terminologies

external agent potentially causing harm (e.g., drugs, chemicals)

Poison

Terminologies

exogenous harmful agents from animals/plants/minerals/ gases (e.g., snake venom, CO, arsenic)

Toxin

Terminologies

biologically produced harmful substances (e.g., botulinum, mycotoxins)

Toxicant

Terminologies

non-biologic environmental chemicals

Ingestion, inhalation, transdermal absorption

Routes of Exposure

Common routes: (3)

Passive diffusion

pH-dependent absorption

Routes of Exposure

Absorption mechanisms:

_ _ – hydrophobic substances

_-_ _ – weak acids in stomach; weak bases in intestines

Dissolution rate, motility, resistance to degradation, interactions

Routes of Exposure

Other factors: (4)

Unabsorbed toxins

Routes of Exposure

_ _: Cause local (not systemic) effects (e.g., diarrhea, malabsorption)

The dose makes the poison

Dose-Response Relationship

Central concept: “_ _ _ _ _” — Paracelsus

LD50

TD50

ED50

Dose-Response Relationship

Indices:

_: Lethal dose for 50% of population

_: Toxic dose for 50% of population

_: Effective dose for 50% of population

TD50 or LD50 / ED50

Dose-Response Relationship

Therapeutic index = ?

Individual

Quantal

Dose-Response Relationship

Individual vs. population responses:

_: Depends on personal health and exposure.

_: Describes changes in population health based on dose variation

Screening

Confirmatory

Testing Types

_ – rapid, qualitative, sensitive but non-specific

_ – quantitative, specific, confirms screening results

Blood, urine

Hair, nails, oral fluid, blood (also)

Specimen

Clinical: (2)

Forensic: (4)

toxicokinetics

Specimen

Specimen Considerations

Understand _ (absorption, distribution, metabolism, elimination)

exposure window

Specimen

Specimen Considerations

Match specimen and timing to _ _

analyte stability

excretion

collection

Specimen

Specimen Considerations

Account for _ _, _, _ methods

24-hour urine

creatinine

Specimen

Specimen Considerations

Use _-_ _ and adjust for _ to improve accuracy

Acid

Specimen

Specimen Considerations

Prevent contamination via:

Clean collection tools and environments

Certified tubes (e.g., royal blue or tan-top for trace elements)

_-washed equipment

Minimizing in vitro metabolism or loss (e.g., mercury/arsenic)

Immunoassays

Specimen

Methods of Measurement

Common for drug screens (may detect drug classes or specific drugs like THC)

GC-MS (Gas Chromatography-Mass Spectrometry)

Specimen

Methods of Measurement

Reference method

LC-MS/MS (Liquid Chromatography-Tandem MS)

Specimen

Methods of Measurement

Increasingly used for drug quantification

ICP-MS and AA (Atomic Absorption)

Specimen

Methods of Measurement

Quantify inorganic compounds, metals

Nuclear Magnetic Resonance Spectroscopy

Specimen

Methods of Measurement

Identifies organic/inorganic structures

Potential for biomarker discovery and forensic analysis