Introduction to Toxicology s1

Introduction to Toxicology EV 460/660 & BI 460/660 Fall 2014

Forensic Toxicology

1. Forensic toxicology – the application of toxicology for the purposes of the law -- may involve civil or criminal law -- dependent upon analytical toxicology -- may also overlap with other areas, such as occupational or regulatory toxicology

2. Dependence on analytical toxicology -- analytical toxicology involves application of the tools of analytical chemistry to qualitative and/or quantitative determination of chemicals which may exert adverse biological effects -- typically the chemical to be measured (the analyte) is a xenobiotic (may have been transformed by metabolism) -- typically the specimen to be analyzed is a fluid or solid tissue sample

3. Majority of forensic toxicological testing involves screening for tissue levels of drugs of abuse -- blood alcohol concentrations (BAC) have been extensively related to impairment in human performance, particularly operation of motor vehicles (DUI or DWI) -- less well established are levels of illicit drugs that impair human performance, particularly operation of motor vehicles (DUID or DWID) --concerns about potential adverse consequences of substance abuse have lead to widespread use or urine analysis for the detection of use of illegal drugs, mandated by military, transportation and nuclear industry, many federal and state agencies, and private industries and businesses -- Forensic Urine Drug Testing (FUDT) laboratories are certified by the Dept. of Health and Human Services (for testing of federal employees) or by the College of American Pathologists -- FUDT consists of an initial test by immunoassays, for those samples that test positive on the initial test a second, confirmatory test is conducted by GC/MS -- test results are reported as positive (at or above cutoff concentrations) or negative (below cutoff concentrations) -- there is a folklore and mini-industry devoted to purported ways to “beat the test” -- false positives may occur, but are rare and usually easily resolved

4. Forensic toxicology investigations in deceased individuals are less common than #3 above -- most often these cases involve BAC determinations in fatal car accidents -- can be informative about circumstances surrounding death, even in cases where poisoning was not the cause of death -- may be useful in alerting medical and legal communities about appearance of new drugs of abuse

5. Toxicological investigation of a poison death -- investigation can be divided into three steps A. Obtaining the Case History and Suitable Specimens -- thorough case history is vital to help narrow the possible chemicals (from thousands of potentially toxic compounds that are readily available) -- specimens collected for chemical analyses, easiest at time of post-mortem examination and if specimen collection is close to the time of death, more difficult if the time of death substantially pre-dates the time of specimen collection B. Toxicological Analyses -- procedures to be followed are guided by case history information, knowledge of possible chemicals, and availability of suitable specimens -- in cases where oral exposure is suspected, GI contents will be analyzed first -- urine, kidney, liver, and bile will often be analyzed since these are major routes of excretion -- if a specific poison is known or suspected, the analysis will be on tissues and fluids known to concentrate the particular chemical or to be critical sites of toxic action C. Interpretation of Analytical Results -- interpretation of the physiological or behavioral effects of the concentrations found -- often the most difficult part of the investigation

6. Courtroom testimony -- forensic toxicologist may be called upon to testify as an “expert witness” -- expert witnesses must be “qualified” as part of the court proceedings -- expert witnesses are allowed to present two types of testimony, objective and opinion