Toxicology Study Notes

Chapter 15: Toxicology

Overview of Toxicology

  • Distinction from controlled substances

  • Focus on drugs within human subjects

  • Sample analysis includes blood, urine, organs, etc.

  • Consideration of metabolites

  • Various sub-disciplines of toxicology include:

    • Postmortem toxicology

    • Workplace drug testing

    • Human performance analysis

    • Sports toxicology

Toxicology of Alcohol

  • Alcohol serves as a primary example for understanding drug metabolism in humans.

  • Main objectives:

    • Isolate and detect alcohol

    • Use quantitative data to estimate behavioral effects or cause of death

  • Investigative focus includes:

    • Impact of alcohol on the body

    • Body's processing of alcohol

Definition of Alcohol

  • Specific reference to ethyl alcohol or ethanol.

  • Alcohol-related traffic fatalities:

    • Approximately 30% of all traffic fatalities in the U.S. involve drivers with Blood Alcohol Concentrations (BACs) of $0.08 ext{ g/dL}$ or higher.

    • In 2020, there were 11,654 fatalities attributed to alcohol.

  • Testing for alcohol is common in living subjects, with implications in postmortem cases as well.

Units of Measurement for Alcohol

  • Distinct terminology and units associated with alcohol due to historical context:

    • Proof: Alcohol content in liquid is double its percentage by volume. Example: 100 proof alcohol consists of 50% ethanol.

    • BAC: Legal limit in most states is $0.08 ext{ g/dL (w/v)}$ which translates to $0.08 ext{ g/100 ml}$ or $0.08 ext{%}$.

Alcohol Absorption

  • Mechanism of alcohol affecting behavior through reaching the brain.

  • Route of administration:

    • Primarily oral consumption.

  • Rate of absorption is critical; alcohol needs to be partially absorbed to impair.

  • Factors that influence the rate of absorption include:

    • Type of alcohol consumed.

Alcohol Distribution

  • Distribution through the circulatory system post-absorption.

  • Mechanism allows alcohol to circulate throughout the body, reaching all tissues, including the brain.

Alcohol Metabolism

  • Primarily occurs in the liver through a two-step process:

    • Step 1: Alcohol is converted into acetaldehyde.

    • Step 2: Acetaldehyde is broken down into acetic acid, followed by water and carbon dioxide ($CO_2$).

    • 95-98% of consumed alcohol exits the body as water and $CO_2$.

Alcohol Elimination

  • The remaining 2-5% of alcohol:

    • Exits the body unchanged through breath, urine, and perspiration.

  • Elimination rate varies by up to 30% among individuals.

    • Example: A blood alcohol level of $0.10 ext{%}$ takes approximately 6.5 hours to return to zero.

Pharmacokinetics of Alcohol

  • Definition: What a person's body does to a drug, encapsulated in the acronym **ADME: **

    • Absorption

    • Distribution

    • Metabolism

    • Elimination

Alcohol Level vs. Impairment

  • Forensic toxicologists aim to correlate blood alcohol levels with specific behavioral impairment.

  • Impairment denotes the effects of alcohol on brain functionality.

    • Blood or breath tests are primary matrices for assessment; others might include spinal fluid and vitreous humor.

  • Studies correlate blood alcohol concentration (BAC) with brain alcohol concentration to assess impairment.

Blood Alcohol Concentration (BAC) Chart

BAC (g/dL)

Typical Effects

Predictable Effects on Driving

0.02

- Loss of judgment

  • Relaxation, slight warmth

  • Altered mood | - Decline in visual functions

  • Difficulty performing dual task |
    | 0.05 | - Exaggerated behavior

  • Loss of muscle control

  • Impaired judgment | - Reduced coordination

  • Difficulty steering |
    | 0.08 | - Poor muscle coordination

  • Impaired judgment | - Difficulty detecting danger |
    | 0.10 | - Concentration and memory issues | - Impaired reaction time |
    | 0.15 | - Severe muscle control loss | - Major impairment in vehicle control |

Alcohol Testing Methods

Breath Testing

  • Two types of breath tests:

    • Preliminary Tests: Quick and simple.

    • Evidentiary Tests: More accurate; typically confirmed with blood tests.

  • Fundamentals of breath testing include:

    • Breath-to-blood ratio: Traditionally estimated at 1 ml blood correlating with 2100 ml breath; research suggests closer to 2300:1.

Breath Test Instrumentation

  • Preliminary Breath Testing Instruments: Utilize fuel cells that convert alcohol into an electrical current through a chemical reaction between alcohol and platinum electrodes.

  • Evidentiary Breath Testing Instruments: Use infrared instrumentation to determine breath alcohol concentration based upon absorption of infrared light by alcohol molecules.

  • Considerations include:

    • Minimum flow rate for accurate testing

    • Required deep lung air sampling the need to avoid mouth alcohol from consumption prior to testing.

Field Sobriety Tests (FSTs)

  • Popular method for assessing alcohol impairment.

  • Expanded FSTs for evaluation of other drugs in conjunction with driving.

  • Three main types of tests:

    • Horizontal Gaze Nystagmus (HGN): Involves tracking of eye movements for smoothness and coordination.

    • Walk and Turn Test: Requires participants to walk a straight line and return maintaining balance.

    • One Leg Stand Test: Involves balancing on one leg while counting.

Blood Testing

  • Common method using gas chromatography (GC).

    • Ethanol's volatility makes it suitable for this type of analysis.

    • GC integrates a flame ionization detector for accuracy.

  • Prior to analysis:

    • Internal standards are employed (e.g., n-propanol) to compare with alcohol levels, allowing for accurate readings.

  • Hospital labs use autoanalyzers to measure the conversion of alcohol to acetaldehyde using the enzyme alcohol dehydrogenase and NAD, monitored by spectrophotometry.

    • Serum alcohol levels are often converted to BAC by dividing by a factor of 1.16 (example: 250 mg/dL equates to a BAC of $0.215 ext{%}$.

Case Study Example

  • Scenario: A 31-year-old male rear-ended another vehicle; observed with slurred speech, bloodshot eyes, and unsteady gait.

  • Preliminary breath test yielded BAC of 0.062%; failed all FSTs.

  • During evidentiary testing: "interference detected" error indicating potential issues with the test results related to isopropanol consumption.

    • Notable: Isopropanol is a more potent CNS depressant than ethanol.

Blood Collection Procedures

Pre-mortem Blood Collection

  • Utilizes vacuum blood tubes with anti-coagulants and preservatives; laws vary by state regarding who can draw blood.

  • Considerations:

    • Avoid the use of alcohol wipes before collection to prevent contamination issues.

    • Better accuracy through refrigeration; research indicates alcohol verifiable in storage diminishes over time.

Post-Mortem Blood Collection

  • Alcohol levels may be artificially elevated due to decomposition processes.

  • Collect from multiple sites; if consistent, suggests consumption rather than decomposition effects.

  • Vitreous humor or urine can also be tested for BAC.

Alcohol and the Law

  • All states have rigorously defined per se laws relating to blood alcohol levels:

    • Legal limit for driving is $0.08 ext{%}$ except in Utah ($0.05 ext{%}$).

  • Other provisions include commercial drivers ($0.04 ext{%}$) and stricter regulations for drivers under 21.

  • Fifth Amendment considerations regarding self-incrimination and implied consent laws for testing.

  • Schmerber v. California (1966): Supreme Court ruling allowing blood draws without violation of the Fifth Amendment under exigent circumstances pertaining to DUI cases.

  • Recent ruling: Missouri v. McNeely (2013): addresses warrantless blood draws and the implications of new technology for obtaining warrants.

Non-Alcohol Toxicology

Challenges in Toxicology

  • The vast array of drugs and poisons presents significant challenges:

    • Postmortem cases often face limited options for analysis.

    • Concentration levels can be very low; examples include alprazolam at $20 ext{ ng}$ per blood sample.

    • Complexity in drug extraction from matrices such as blood and organs.

  • Drug metabolism also complicates identification; for example, heroin metabolizes quickly into 6-monoacetylmorphine.

Drug Levels and Interpretation

  • Once drugs are identified, implications for patient/victim physiology must be assessed based on therapeutic and toxic level data collated from studies.

  • Important considerations for toxicologists include:

    • Patient age

    • Physical condition

    • Level of tolerance to substances

    • Types of data available (e.g., urine or blood).

Specimen and Analytical Toxicology

Collection for Testing

  • Pre-mortem sample collection aims for performance-related toxicology using gray vacuum tubes.

  • Post-mortem samples sent depend on medical examiner discretion; include blood, stomach contents, and organ samples.

Analytical Techniques and Isolation

  • First step involves isolation of drugs using their chemical properties, focusing on differences in solubility and pH.

  • The pH scale delineates acidic and basic character, impacting solubility and extraction methods leveraging differing reactions between drugs and their environments.

  • Alteration of pH can facilitate drug separation from solution. For instance, cocaine's solubility increases in alkaline environments, permitting extraction with organic solvents.

Screening and Confirmation Tests

  • Workflow includes screening tests which can occur pre or post-extraction.

    • Such tests might involve GC-MS or LC-MS techniques.

  • Confirmatory tests, typically post-extraction, ensure specific identification of drugs via mass spectrometry linked with GC.

Hair Testing Methodology

  • Hair analysis provides insight into longer-term drug use due to diffusion of drugs into the hair shaft, enabling back-calculation based on hair growth rates.

  • Prior washing necessary to eliminate external contamination; samples cut into segments for individual extraction analysis.

Non-Drug Poisons

Heavy Metals

  • Examples: arsenic, bismuth, antimony, mercury, thallium.

  • Access is limited due to strict environmental regulations.

  • Screening tests involve dissolving tissues in hydrochloric acid; confirmatory tests include atomic absorption spectrophotometry and emission spectroscopy.

Carbon Monoxide Poisoning

  • Carbon monoxide binds to hemoglobin, forming carboxyhemoglobin and impeding oxygen transport.

  • Methods to gauge carbon monoxide levels include:

    • Spectrophotometric techniques to measure carboxyhemoglobin relative to oxyhemoglobin.

    • Gas chromatography assessing liberated carbon monoxide concentration.

  • Carbon monoxide saturation levels often considered toxic at 50-60%.

Final Interpretations of Toxicology Levels

  • Core question concerns whether the presence of drugs altered outcomes for individuals involved.

  • Inferences drawn from drug levels require significant contextual data:

    • Individual age and health

    • Pre-existing tolerances

    • Completeness of toxicological data available (urine vs blood, for example).

Drug Recognition Expert (DRE)

  • DREs utilize expanded field sobriety tests involving observational assessments, tests, and questions to ascertain drug impairment.

  • They examine seven drug classes, providing evidence linking impairment to drug levels.

  • DREs cannot infer specific drug use but can relate observed impairment to classifications of drugs.

  • Optimal evidence for drug intoxication combines DRE insights with forensic toxicologist findings to establish reliable conclusions regarding substance influence.