Interpretation of Toxicological Results

Toxicology is the study of drugs and poisons and the effects these substances have on the performance or health of the consumer. As such, toxicological analysis represents a tool for assessing the degree of impairment exerted by a drug or combination of drugs. With the ultimate degree of impairment being death, toxicological findings are also used to determine cause and manner of death.

Drug distribution throughout the body is a complicated process. It is based upon many factors, including but not limited to the physical and chemical properties of the drug, the formulation of drug, the means by which the drug was ingested (oral, intravenous, inhalation, etc.) and the digestive (for oral ingestion) and circulatory functions of the subject. Therapeutic doses of drugs are those amounts which are prescribed for intended medicinal or therapeutic purposes and which are to be ingested pursuant to a prescribed manner and frequency. Therapeutic doses will result in drug levels within the body at a range of concentrations intended to exert an expected assortment of medicinal or therapeutic effects on the subject.

Non-therapeutic ingestion may occur when drugs are ingested in excess, which will result in supratherapeutic (above therapeutic) concentrations and have potentially toxic or in the extreme, lethal consequences. Conversely, drugs ingested at insufficient or low doses will result in subtherapeutic (below therapeutic) concentrations and have minimal or no apparent effect. Non-therapeutic ingestion may also include a manner or frequency not prescribed. This may include multiple drug combinations, repeated ingestion and subversion of the formulation. An example of the latter is where a drug formulated for oral, sustained release is crushed, dissolved and injected intravenously.

Interpretation of toxicological results begins with an understanding of which drugs and concentrations are therapeutic and which are not.

The presence of one or more drugs at concentrations significantly higher than those expected from therapeutic doses may be considered, along with other anatomical conditions or defects, in determining whether drug ingestion caused or contributed to death. Conversely, the lack of adequate drug in a subject may indicate non-compliance to therapy and allow for the conclusion that death was due to conditions that might otherwise have been survivable had the decedent been compliant with prescribed medication. An example of the latter is death from a seizure disorder which could have been prevented with anticonvulsant drugs.

The most common application of toxicological findings to assess or explain performance impairment is to determine whether an individual has been driving under-the-influence (DUI) of ethanol (alcohol) and/or drugs (DUID). Another application is to determine whether the actions, behavior or demeanor of a homicide subject or suspect were affected by drugs or alcohol at the time of the incident and, thereby, offer potentially mitigating circumstances when the case is brought before a jury.

In order to establish impairment from toxicological findings, a relevant substance must be identified within a relevant specimen. Drugs exert their pharmacological effects only when they are present in a target organ or organ system that is susceptible to or affected by the substances which are present.

A relevant substance is one that exerts pharmacological activity. Most ingested drugs are called “parent” drugs and are typically pharmacologically active. However, the body’s normal metabolic processes act upon the ingested parent drugs and convert them into metabolites, which may keep or lose the pharmacological activity of the parent drug. Metabolites may co-exist with the parent drug or they may persist after the parent drug has been totally converted and/or eliminated. In the end, impairment may be established only if active substances are identified, be they parent drugs or metabolites.

That is not to say the identification of inactive metabolites is without value. Identification of inactive metabolites may be sufficient to establish ingestion of or exposure to a related substance or to distinguish acute (single or short-term) from chronic (continuous or long-term) drug use.

The most significant target organs of forensic toxicological interest are the brain and nerves that comprise the central and peripheral nervous systems. Blood circulates within the nervous systems and as such, is the most recognized, relevant specimen for toxicological analysis. Urine is commonly collected for toxicological analysis. However, urine does not circulate within the nervous systems and, therefore, cannot qualify as relevant for establishing impairment from a toxicological finding. In fact, substances in urine have been excreted and are no longer in the “system”. Nonetheless, findings in urine may be used to establish ingestion or exposure and may be used to explain certain observed behavior. Toxicological findings in tissues may be considered in postmortem cases where sufficient medical literature exists to relate such findings to death or impairment.

The effects of drugs (and ethanol, which is a drug) are continuous and progressive, which means generally, the greater the dose, the greater the effect. However, the progression of these effects may appear to be different amongst individuals because impairment is the sum of all of the individual’s mental and physical functional responses to drugs, which are not uniform. For example, with depressant drugs, low doses will impair one's inhibitions, which may result in seemingly paradoxical excited behavior. However, with greater doses, this excitation is overcome. With still greater doses, lethargy, sleepiness, coma and, ultimately, death from respiratory depression will ensue. Therefore, depending upon the dose, outward appearance may appear vastly different. The point where one subject is excited and another is lethargic or one is asleep and another is dead depends upon the biological characteristics and tolerance of the individual. Tolerance is (1) the resistance to some effects of drugs and (2) the physiological dependency on continued doses acquired through frequent and repeated exposure to ethanol and/or drugs. Therefore, while it may be said that people respond differently to drugs (and ethanol), the truth is that people respond the same but to different degrees.

Substances progress from innocuous to therapeutic to toxic depending upon the dose. Accordingly, a substance may be both medicinal and harmful, depending upon how much is ingested and by what means. "All things are poison and nothing is without poison, only the dose permits something not to be poisonous." Or, more commonly, "The dose makes the poison." Paracelsus (Phillippus Aureolus Theophrastus Bombastus von Hohenheim, 1493 – 1541

There is a well-documented relationship between blood ethanol and accuracy of task performance. Specifically, as ethanol content increases, the ability to properly operate a motor vehicle decreases and the likelihood of engaging in a traffic mishap increases. This relationship is reflected in the DUI per se laws. There is also a well-documented relationship between blood drug concentration and accuracy of task performance. However, because the degree of effect by drugs amongst individuals is so much more diverse than is with ethanol, definitive per se limitations are more difficult to scientifically establish and to legally apply. Some jurisdictions have zero-tolerance statutes for DUID whereas others employ the expertise of a toxicologist in Court to reconcile performance impairment with the presence a drug or combination of drugs.