Fundamental Principles of Toxicology Expert Article

In this article, the toxicology experts at Robson Forensic provide an introduction to some of the foundational principles relevant to their analyses, science, and casework. The principles and key terms explained throughout this article may be helpful for non-scientists to better understand the scientific approach, as well as the findings in our expert witness reports.

Fundamental Principles of Toxicology & Expert Witness Investigations

There are typical questions raised in the course of most toxicology investigations. When determined through reliable scientific analyses, the findings of our experts provide an understanding of the manner and degree to which chemicals or drugs contributed to an incident or adverse health outcome.

Our experts specializing in toxicology are frequently tasked with investigating a range of questions relevant to an exposure:

1. What was the dose of exposure?
2. What was the timing of exposure?
3. What effects were caused by the timing and dose of exposure?
4. To what degree were the testing/analysis reliable?
5. What other contributing factors may have affected human physiology or test/analytical accuracy?

Toxicology Investigations

The toxicology and pharmacology experts at Robson Forensic utilize their knowledge and skill sets to evaluate causation as it relates to litigation and other contentious disputes. The scope of this evaluation requires a detailed analysis to determine if a chemical, drug, and/or toxicant exposure caused or contributed to an adverse event, injury, and/or death.

Toxicological investigations can be pertinent to a broad range of incidents, including motor vehicle crashes, industrial mishaps, chemical and gas exposures, alcohol and recreational drug exposures, drug-drug interactions, drug overdoses, etc. The principles of toxicology causation analysis that our experts employ are the same regardless of the nature of the incident.

Scientific determination involves a detailed review of discovery materials, review and analysis of relevant scientific literature, and communication of findings via report and/or expert testimony.

General & Specific Causation

Toxicology causation analysis is a multistep process that evaluates whether a chemical or drug exposure could have caused a deleterious effect; and subsequently, whether or not that exposure caused or substantially contributed to an adverse event or health outcome relevant to the matter at hand.

These separate, but related, scientific components are referred to as General and Specific Causation.

• General Causation: Could the chemical, drug or toxicant cause the intended effect?
• Specific Causation: Did the dose of the chemical, drug, and/or toxicant in a relevant or proximate time period produce an adverse effect or outcome?

The toxicology experts at Robson Forensic have applied the principles of causation analysis to hundreds of cases. In fact, causation analysis is central to every toxicology analysis we perform.

Pharmaco(toxico)kinetics & Pharmaco(toxico)dynamics

Pharmacokinetics and pharmacodynamics are concepts in pharmacology that focus on the manner in which drugs move through the body and the ways in which the body is affected by exposure to drugs, respectively.

Toxicokinetics and toxicodynamics are similar concepts, but are more specifically attributed to chemical exposures. These principles, relevant to each exposure, form the foundation of pharmacological/toxicological analyses.

Pharmacokinetics

What the Body Does to the Chemical/Drug/Toxicant.

A determination of chemical, drug and/or toxicant dose and duration of exposure involves the application of the principles of pharmacokinetics. Pharmacokinetic evaluation involves understanding chemical, drug and/or toxicant absorption, bioavailability, distribution, metabolism, and excretion.

Pharmacodynamics

What the Chemical/Drug/Toxicant Does to the Body.

A determination of the adverse effects of an exposure involves the application of the principles of pharmacodynamics, including understanding the dose–response relationship at the target organ or tissue, mechanism(s) of action, time of exposure, duration of exposure, and ongoing physiological and/or disease processes.

Measurement & Reliability of Chemical, Drug or Toxicant Exposure

Qualitative and quantitative analytical chemical procedures measure the concentration or level of a chemical, drug, and/or toxicant in whole blood, plasma, urine, saliva, breath, etc. The results of these analyses frequently play a prominent role in the determination of liability in civil and criminal proceedings. They can be affected by a variety of internal and external factors.

The toxicology experts at Robson Forensic are well-versed in the critical areas of assessment of possible false positive, false negative, interfering chemicals, and potential postmortem redistribution A list of key terms relevant to measurement & reliability is provided below for your reference.

Accuracy is how closely a calculation or measurement agrees with a standard quantity and is free from error.

Analyte is a substance whose chemical constituents are being identified and measured.

BAC is blood alcohol concentration as expressed or calculated for whole blood.

Comatose or fatal blood concentration is the scientific value reported in the literature to cause coma and/or death.

Confidence interval is a range of values such that there is a specified probability that the measured value lies within it.

Dose-response describes the change in effect on an organism caused by an exposure.

Duration of exposure is the time a substance is interacting at its site of action.

Site of action refers to the target site where the substance interacts with the receptor, tissue, or organ.

False negative for analyte indicates the absence of a chemical, drug and/or toxicant in blood, urine, saliva or breath when it is present.

False positive for analyte indicates the presence of a chemical, drug and/toxicant in blood, urine, saliva or breath when it is not present.

Half-Life refers to the period of time required for the concentration or amount of drug in the body to be reduced by one-half.

Limit of blank (LoB) is the highest apparent analyte concentration expected to be found when replicates of a blank sample containing no analyte are tested.

Limit of detection (LoD) is the lowest analyte concentration likely to be reliably distinguished from the LoB and at which detection is feasible.

Limit of quantitation (LoQ) is the lowest concentration at which the analyte can not only be reliably detected but at which some predefined goals for bias and imprecision are met.

Margin of error indicates the percentage that a result differs from the mean value: equals half the confidence interval when the confidence interval is symmetrical.

Mechanism of action is the specific biochemical interaction through which a drug substance produces its pharmacological effect.

Postmortem redistribution refers to the changes that occur in drug concentrations blood levels after death.

Precision is a measure of experimental variability. The closer the agreement between individual analyses, the more precise is the measurement.

Range is the lower and upper values of a measured or calculated value.

Reference range or reference interval is the range of values for a physiological measurement in healthy persons.

Reliability is the degree that a calculation or measurement can be depended upon to be accurate.

Resolution is the smallest amount of analyte that can be detected by an instrument.

Selectivity is the extent to which a method can determine an analyte without interference from other compounds.

Sensitivity is the smallest amount of change in analyte concentration that can be detected by an instrument.

Specificity is the ability of a test or instrument to properly identify an analyte.

Therapeutic blood concentration is the range of drug concentration that is expected to be effective without producing side or adverse health effects.

Toxic blood concentration is the level at which a chemical, drug and/or toxicant produces clinically relevant side effects.

Validity is the extent to which a calculation, concept or measurement is well-founded and accurate.

Topics of Investigation

Adverse Drug Reactions
(drug interactions, hyper-sensitivities, etc.)
Alcohol
(determination of BAC, number of drinks, clinical signs, visible/obvious intoxication, etc.)

Allergens
(insulin, mold, peanuts penicillin, etc.)

Carcinogens
(dioxins, tobacco smoke, ionizing radiation, etc.)

Drug Safety
(prescription drugs, OTC medications, supplements)

Metals
(arsenic, cadmium, cobalt, lead, mercury, hexavalent chromium, etc.)

Natural Toxins and Poisons
(botulinum toxin, mushrooms/poisonous plants nutritional supplements, etc.)

Neurotoxicants
(DEET, lead, nicotine, mercury, PCBs, pesticides, etc.)

Particulates
(asbestos, silica, diesel exhaust, etc.)

Pesticides and Herbicides
(2,4-D, carbamates, pyrethroids, glyphosate, etc.)

Recreational Drugs / Drugs of Abuse
(amphetamine, benzodiazepines, cocaine, fentanyl, methamphetamine, opioids, synthetic marijuana, THC, , etc.)

Solvents
(benzene, carbon disulfide, hexane, isocyanates, trichloroethylene, etc.)

Toxic Gases
(carbon monoxide, hydrogen sulfide, etc.)

Comprehensive Investigations Involving Standard of Care & Damages

As a national leader in expert witness consulting, Robson Forensic provides technical expertise across many fields within engineering, architecture, science, and a broad range of specialty disciplines. In addition to our toxicology experts, Robson Forensic provides highly credentialed experts specializing in fields that are frequently relevant to toxic exposures, including: Dram Shop, Crash Reconstruction, Healthcare, Biomechanical Engineering, and Industrial/Environmental Safety.

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