7: Medicolegal Interpretive Toxicology

One of the potential areas of collaboration for toxicologists is the medicolegal setting. This includes working with forensic toxicologists, medical examiners, law enforcement, lawyers, and regulators. In this arena, interpretive toxicology, whether based on analytical findings or theoretical concepts, is routinely used or required to explain issues in criminal and civil proceedings and as the basis for policy making. Often, the concepts associated with forensic interpretive toxicology are presumed to be associated with deceased individuals. In practice, the preponderance of cases involving toxicologic interpretation involves living people and includes specialty testing such as human performance toxicology. Regardless, interpreting the role, or potential role, of xenobiotics in an adverse outcome is typically not straightforward. For example, the use of generally applied pharmacokinetic equations is usually inappropriate, especially in the postmortem setting, yet such is in widespread practice by individuals unfamiliar with the nuances of case-related issues.²⁷ Rarely is any given case accurately interpreted solely based on toxicologic assessment. As such, forensic interpretive toxicology generally involves an integrative approach that draws on an understanding of case history in addition to analytical, toxicologic, pathophysiologic, and specimen-related issues. Individuals called on to interpret the role of xenobiotics in any given case must understand the factors that affect such interpretations and associated limitations. Furthermore, although difficult in many situations, they should attempt to have their opinions firmly supported by science. Other chapters in this text (Chaps. 6 and 34, Special Considerations: SC2 and SC6) cover much of the basic science associated with interpretive issues. This section is meant to focus on specific issues as they relate to medicolegal (forensic) interpretive toxicology.

It has been reported that case history plays a role in interpreting toxicologic findings in about 70% of cases.²⁴ A number of specific aspects of a case ­history will lead a seasoned toxicologist in a direction that narrows the ­scientific investigative focus and avoids a shotgun approach to deciphering the role of toxicology in an adverse outcome. Table 7–1 lists some of the more important aspects of the case history that should be considered from the outset to begin the interpretive process. Detailed information about the individual should optimally include anthropomorphic information, vocation, hobbies, medical history, timing of events to the extent possible, and other contextual information.¹⁷ As an example of the importance of this information, consider a case in which an individual suspected of drunk driving worked at a company that manufactured chemicals. One of the chemicals known to be handled by the individual was a substance that coeluted with ethyl alcohol in the gas chromatographic assay used to quantitate the blood alcohol concentration. Without his employment history, the potential for an incorrect interpretation of the data might have occurred.

Unfortunately, toxicology is often not initially considered with respect to field investigation of a case. Therefore, important information is often lost, especially in the case of purposeful poisonings. The longer the time between suspicion of a toxicologic aspect to a case and proper investigation, the greater the chance of lost evidence for explaining the situation. The toxicologist can play a key role in mitigating this hindrance. As a significant point of contact with the poisoned or intoxicated individual, the toxicologist has the opportunity to not only ask the individual questions if he or she is conscious but to also ask police, paramedics, and others questions that could assist in not only treatment of the patient, but also address serious questions that often later arise.

Unlike the confidence in the medical diagnosis of poisoning supported by clinical findings or analytical data, it should be recognized that there is rarely surety in the use of toxicologic analysis for medicolegal purposes. Reasonable degree of certainty, the phrase often used as a measure of acceptability in interpretive toxicology, can only be attained through the weaving of multiple pieces of information into a coherent explanation of events.

Ample evidence exists that the major source of error in analytical toxicology is based not on laboratory error, but on preanalytical issues.^18,39 Preanalytical issues can be defined as those things that can affect an analytical result prior to the specimen(s) arriving at the laboratory. In accordance with ISO (International Organization for Standardization) requirements, mathematical uncertainty should be able to be determined by the analytical testing laboratory.²⁶ It has become an expectation in certain areas of toxicologic testing that such errors be reported for acceptance into legal proceedings.³¹ Although laboratory error can usually be relatively easily quantified, the error associated with issues surrounding samples before arrival at the laboratory is not so easily measured. The myriad of potential preanalytical factors is summarized in Table 7–2.

Clinical Specimens

With respect to living individuals, where and how specimens are collected from patients, in addition to specimen storage, can adversely affect not only the analytical test but its interpretation as well.⁵¹ For example, although perhaps not protocol, occasionally samples for analysis are collected proximate to the site where they are administered, such as close to an indwelling antecubital fossa catheter. Contamination of such specimens cannot be excluded and can lead to misinterpretation of findings. Although the treatment of patients is the primary concern during medical emergencies, consideration of potential medicolegal issues should be part of the treating professional’s assessment, especially in cases involving children, victims of drug-facilitated sexual assault, motor vehicle operation, workplace incidents, suspected poisoning, and other ill-defined situations. Adequate analysis requires that specimen collection be performed appropriately and consideration given to the types of preservatives used in the collection device. Not all collection devices fit the need for all xenobiotics. For example, although fluoride-containing tubes may work well to prevent microorganism-induced ethanol formation, this same preservative may lead to degradation of some organic phosphorus pesticides and make the sample totally useless in cases of suspected fluoride poisoning.^1,47 In general, it is good practice to collect both preserved and unpreserved blood samples. Serum samples are generally a good choice from living individuals, but this is analyte specific and certainly not preferred for xenobiotics sequestered in red blood cells. Perhaps the most important precaution in this respect is the collection of specimens for legal blood alcohol determination. Not only are tubes containing fluoride (1%–5% w/v) and oxalate (anticoagulant) necessary, but skin cleansing swabs containing ethanol should be avoided.² Specimen storage conditions can significantly adversely affect analyte stability and specimen integrity. Except for specimens such as hair and nail clippings, specimens for toxicologic analysis should not be maintained at room temperature. Minimally, refrigeration is required, but if it is anticipated that a delay between sample collection and testing will occur, then freezing the samples at -20° or -60°C (the choice of temperature being analyte specific) should be considered, making sure to take precautions to prevent tube cracking.¹¹ It is recommended that if a specific xenobiotic or class of xenobiotics is suspected that laboratory personnel should be contacted before specimen collection for guidance on proper collection, preservation, and storage of specimens. Hospitals should have in place a mechanism that ensures retention of specimens beyond the routine time frame for suspect cases. Typically, hospitals maintain specimens from a few days to a few weeks after use compared to up to one year or longer in most forensic cases.^44,58 In this regard, all available specimens should be maintained. This is especially important in cases in which death is preceded by a relatively long clinical course. Although it cannot be expected that a hospital maintain specimens under a legal chain of custody, maintaining tubes with original identifier labels often suffices for this purpose.¹⁹

Postmortem Specimens

In postmortem situations, the potential for sample contamination is substantial, especially in the face of significant trauma. For example, the spread of gastric or intestinal contents containing xenobiotics of interest can contaminate sources of blood collection and visceral organs.¹⁷ Additionally, other postmortem phenomena can mitigate the potential value of laboratory-based testing (Table 7–3) for interpretation purposes (see the Postmortem Redistribution section later). Specimen collection should be done by an experienced pathologist who understands the intricacies of site-specific sample collection. Postmortem blood can be obtained from two broadly categorized sources, central (eg, heart) and peripheral sites (eg, femoral and subclavian veins). Not all peripheral sites have the same interpretive value.⁵³ “Blind stick” samples should not be considered appropriate surrogates for proper dissection and visualization of the specimen source.⁴⁰ For example, heart blood should be collected from the right atrium after opening of the pericardial sack, removal of the pericardium, and drying of the heart.^11,62 Although there is no ideal postmortem specimen, femoral vein blood tends to better reflect circulating concentrations of xenobiotics closer to the time of death, but this is not always the case. It is realized today that even femoral blood may be subject to the same issues as other blood sources (eg, postmortem redistribution {PMR}). Whenever possible, both cardiac and femoral blood should be collected. Because of postmortem changes, heart blood tends to contain higher concentrations of xenobiotics than peripheral blood sites, thus making it a valuable screening specimen but limiting its actual interpretive value. To properly collect femoral vein blood, a dissection and visualization of the femoral vein followed by ligation or clamping of the vessel above the point of collection is recommended to avoid contamination by iliac blood, the latter seemingly representing a cross between peripheral and central blood.¹¹ Visceral organ specimens can be of value in the interpretation of the meaning of blood concentrations in certain situations.^5,41 Although a plethora of data exist regarding toxicologic findings in blood, there tends to be less data regarding tissues. Nevertheless, certain organs can be of substantial value when considering specific xenobiotics (Table 7–4). Specimen collection tubes and storage conditions, although similar to those described with clinical specimens, tend to be more important with postmortem specimens because of continuous postmortem changes in blood pH, autolysis, and cell lysis, which can affect analyte stability, recovery, and interpretation.⁶¹

Hair collection should be considered in practically all cases of toxicologic concern, especially in those involving children because this specimen can circumvent arguments of incidental exposure and other issues.⁴⁵ This specimen, after being collected, requires no special storage conditions and can reflect exposure history for the length of hair growth (∼1 cm/mo). Controversy regarding external contamination of hair leading to positive findings, although of some concern, does not outweigh the value of this specimen.^25,33

Last, iatrogenic toxicologic injury or death, whether unintentional or purposeful, are often not considered or poorly investigated. The involvement of hospital-based risk management often occurs late and valuable evidence that can either incriminate or exculpate individuals gets destroyed before collection and preservation. Protocols in suspicious cases should exist for the area where the individual was located to be considered a “crime scene.” That is, potential useful evidence, including devices and medications, should be gathered and stored.⁵⁵

Testing for xenobiotics of interest is varied and inconsistent among laboratories. Hospital-based laboratories tend to be limited in scope compared with toxicology reference laboratories. Even in this latter group, wide variances exist with respect to capability and scope. No interpretation of toxicologic findings should take place without a complete understanding of the testing performed and its limitations in addition to a review of the analytical data by a competent toxicologist. With the development of robust, widely available analytical tools, insufficient testing with respect to medicolegal interpretive matters should no longer occur.

Ideally, all toxicologic analyses are performed under chain of custody, and all findings are confirmed by a separate and distinct analytical test, with at least one, such as mass spectrometry, that provides specific molecular identification.⁴⁶ This process reduces uncertainty in the utility of a finding for interpretive purposes. For example, the use of gas chromatography to identify ethylene glycol in a hospital-based laboratory led to the wrongful conviction and jailing of a mother for poisoning her infant son. The gas chromatographic peak was actually propionic acid. Remarkably, the reporting of ethylene glycol was duplicated by another laboratory. Postconviction analysis determined the misidentification of the peak. In this case, the propionic acid resulted from the inborn error of metabolism disease, methylmalonic acidemia. It has also been determined that 2,3-butanediol also coelutes with ethylene glycol in some gas chromatographic systems.^15,60

It is uncommon for hospital-based drug testing to be analytically confirmed. However, a positive screen using an immunoassay is rarely sufficient for medicolegal purposes given the general cross-reactivity of these tests. Most hospital laboratory reports include a disclaimer to this effect. Also, most of this testing is performed using urine, so such screening tests are neither quantitative nor interpretable with respect to effects on a given individual.

Today, advanced toxicology laboratories use a combination of tools to help identify xenobiotics of toxicological concern. Many of these tests are performed rapidly and, in some sense, inexpensively compared with the offered breadth of testing. Instruments such as liquid chromatography time of flight (LC-TOF) have revolutionized broad-based toxicology testing. This technique allows for the rapid screening of a patient sample in minutes covering hundreds of chemically dissimilar compounds with identification using exact mass.²³ Liquid chromatography/tandem mass spectrometry (LC-MS/MS), although somewhat less amenable to broad-based screening, has a similar utility with an easier approach, in general, to quantitative analysis.⁴² Both devices are appearing in hospital-based laboratories and should help the toxicologist significantly in evaluating potentially poisoned patients.²² Other instruments, such as inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectroscopy used for the analysis of the majority of metals, are still generally found in specialty laboratories and most likely will not be cost effective in the hospital laboratory (Chap. 6). In all cases, however, the toxicologist should understand the limitations of these devices that can lead to false-positive and false-negative findings.

Ultimately, the toxicologist’s role in forensic interpretive toxicology is to correlate analytical findings or theory to an adverse outcome. Although explanations abound, both in concept and practice, plausible explanations are often few. It is rare that findings can simply be taken at face value. For example, it is common for identical findings in two different cases to have two completely distinct interpretations, which should not be surprising or disconcerting. Toxicology has been described as both science and art, with the interpretive aspect based in science, knowledge, and experience.²⁰ Many of the following factors need to be considered in rendering rational opinions.

Analytical Surprises

It is not uncommon for individuals to render toxicologic opinions without careful review of the analytical data that help form the basis of the opinions. Simple acceptance of reported results can be a fundamental flaw in medicolegal interpretations. It is helpful to review all available information that led to a reported result before interpretation. Table 7–5 lists some of the important facets of analytical data review that can lead to incorrectly reported results. Although there is no expectation that the toxicologist be an expert in analytical chemistry, familiarity with the key elements that can lead to false-positive, false-negative, or poorly quantified findings should become part of the review process. Errors ranging from the wrong patient number on the analytical data to poor control and calibration of an analytical run to poorly integrated chromatographic peaks are all examples of errors that can invalidate any given finding.

Postmortem Redistribuiton

There are many factors related to postmortem changes that complicate the interpretation of well-performed toxicologic test results.^16,17,38,61 Many of these factors are discussed in Chap. 34. However, the importance of PMR, a long-established principle in forensic toxicology, cannot be ignored or underestimated. Although recognized in the early 1980s, Prouty and Anderson authored the first codified report of this phenomenon in 1990.⁵⁴ Succinctly, PMR is the term given to changes in site-specific xenobiotic concentrations after death.⁵⁰ These xenobiotic movements postmortem generally result in elevated concentrations in common collection sites such as heart blood. The elevation for some substances can be dramatic, giving the appearance of overdose when no such conclusion is supported by other evidence, including analysis of sites of blood collection where PMR may occur to a lesser degree, such as femoral blood. Although instructed to do otherwise, many pathologists still collect heart blood as a sole source of postmortem blood. In attempting to assist in such situations, investigators often publish ratios of heart blood concentrations to femoral blood concentrations over a series of cases from a given laboratory. The common observation is a widespread range of values often encompassing three- to fivefold or greater differences in magnitude.⁸ The use of such ratios to convert a heart blood concentration to a femoral blood concentration, and by further analogy to a premortem circulating blood concentration, should not be performed. The greatest use of such ratios is to give an idea of the likelihood of PMR for any given xenobiotic based on the mean and range of ratios.⁴³ Because it cannot be predicted if PMR occurred in any given case and if so to what degree and over what time period, such calculations have no basis for antemortem blood concentration determination. Another confounder to the use of ratios is the possibility that site-specific differences are not due to PMR but merely a reflection of incomplete distribution before death.¹⁷ It is unclear how many of the reported ratios of heart blood to femoral blood actually reflect this process as opposed to true PMR. The proposed mechanisms and influencing factors resulting in PMR are varied and are listed in Table 7–6. It is most likely a combination of factors that lead to PMR in any given case. Interestingly, as noted earlier, PMR is also reported to take place in femoral blood; thus, it should not be taken at face value that any postmortem blood concentration accurately reflects that circulating at and around the time of death.

At one time it was believed that PMR was associated with basic xenobiotics with a large volume of distribution. Seemingly, however, most xenobiotics, including acidic and neutral xenobiotics, undergoes PMR. Furthermore, PMR occurs for xenobiotics with wide-ranging volumes of distribution. Still other xenobiotics that would be predicted to undergo PMR have experimental evidence to the contrary.⁵⁰ Thus, a priori predictions of PMR for any given xenobiotic without experimental evidence should explicitly state the caveats associated with such a conclusion. It must be stated, however, that PMR does not preclude the interpretation of findings for cause of death determination because the findings represent only one piece of data in a potential myriad of other relevant information.

Another similarly related phenomenon is postmortem diffusion of xenobiotics. In this situation, diffusion of xenobiotics from an area of high concentration to that of a lower concentration occurs. This is most noted when the gastric contents contain a substantial amount of a xenobiotic that migrates across the wall of the stomach into neighboring tissues and blood sources, such as abdominal aorta and iliac vessels. Additionally, perimortem aspiration of gastric contents can lead to significant esophageal, tracheal, and lung concentrations of a xenobiotic, further facilitating diffusion processes.^10,52

Alternative Matrices

Although most discussions regarding interpretive toxicology tend to focus on blood concentrations of xenobiotics, clearly in both the living and the dead, alternative matrices have become extremely valuable. It should be recognized that there is no perfect specimen to assess exposure or provide analytical findings in support of impairment. In the living, alternative specimens including hair, oral fluid (OF), and breath are useful. Hair gives a longer window of detection than most other easily obtained specimens.⁶² Analytical precautions, such as rinsing procedures, can be used to minimize some concerns with hair testing.⁵⁶ The utility of hair should not be underestimated, and despite some of its limitations, it can represent the best suited specimen in some cases, such as drug-facilitated sexual assault, especially when more than 24 to 48 hours passed before specimen collection from the time of event, thus often limiting the value of urine or blood testing.³⁵ In such cases, waiting 1 to 3 months before collecting hair will capture the potential exposure period in growing hair. It is especially useful in children to demonstrate acute versus chronic exposure to xenobiotics.⁴⁵ Collection of hair should be from the posterior vertex of the head, which can be easily approximated by drawing an imaginary line over the head connecting the tops of both ears and a line from the bridge of the nose to the nape of the neck.^11,56 Where the two lines meet in the back of the head provides hair that grows most consistently on the head.³⁴ About a pencil thickness worth of hair should be clipped as closely to scalp as possible.¹² The root ends should be identified either by tying with string or wrapping in foil.¹¹ Virtually any other source of hair can be tested as well, such as pubic and axillary hair, although practical reasons and shorter growth rates tend to make such samples less suitable for testing.

Oral fluid (OF) is gaining ground as a viable specimen type to assess exposure and impairment because obtaining it is noninvasive, and it can be collected at the site of an event, thus eliminating time delays.⁴ Such delays can result in clearance of a xenobiotic from other specimen types before collection. OF is composed of secretions from the parotid, submaxillary, sublingual, and other smaller glands. Numerous specimen collection devices exist today that circumvent the need to expectorate, which is not a desirable means of specimen collection.⁴⁸ For the most part, non–protein-bound parent compounds appear in OF, although there are exceptions (eg, benzoylecgonine).¹³ Factors that affect how much of a xenobiotic gets into OF include pH of the blood and OF, the pKa of the xenobiotic, and the degree of protein binding. In general, basic xenobiotics get into OF easier than acidic xenobiotics.⁶⁵ OF has been used for therapeutic drug monitoring purposes (eg, theophylline and digoxin).⁶ Although some correlations between blood concentrations and a number of xenobiotics have been made, it must be remembered that OF is susceptible to contamination from residual drug in the oral cavity, smoked drugs, and passive exposure.^4,13 Despite its promise, there is variability in OF concentrations of xenobiotics not only within the same individual but also among individuals based on influencing factors that facilitate or inhibit secretion of a xenobiotic into OF.⁴ Last, based on the relatively small specimen volumes after OF collection, specialized testing, including tandem mass spectrometry, is often needed to detect the concentrations of xenobiotics present.

Breath testing for alcohol is a mature subject matter, yet when it comes to impairment, there is a current trend for states to move back to blood alcohol determinations. Legal arguments have been the force behind some of this movement.⁴⁹ Breath testing for other xenobiotics is still in its fledgling state. Despite this, the future holds promise for the detection of other xenobiotics in breath with the possibility of roadside breath drug-testing devices.³ The major advantage of this specimen is its lack of invasive collection technique and rapid screening capability.

Alternative matrices from decedents are varied and have included virtually all fluids and tissues (Table 7–4). Practically speaking, however, other than providing qualitative information, for most matrices, there is little data to support utility of a measured concentration to either allow for independent interpretation or correlation to blood concentrations. Although numerous studies exist that suggest such correlations, rarely is there consistency between studies. Even so, situational use of alternative matrices is sometimes warranted (eg, the use of fat or brain to detect volatiles). A specific exception is vitreous humor (vitreous), a specimen that is often extremely valuable postmortem. Vitreous electrolyte measurements provide data that cannot be gleaned from virtually any other specimen type (Table 7–7).⁷ For most xenobiotics, vitreous concentrations lag behind blood concentrations by about 1 or 2 hours. Thereafter, some correlations have been made between vitreous concentrations and those in blood, with the greatest example being ethanol, where there is an approximately 1:1 correlation when equilibrium is reached. Vitreous represents a relatively pristine specimen during decomposition, embalming, exsanguinations, severe peritoneal trauma, and other less ideal situations.²¹

Toxicokinetics and Toxicodynamics

The basics of toxicokinetics (TK) and toxicodynamics (TD) are covered in Chap. 9. The large and unpredictable degree of interindividual variability places practical limits on the use of TK and TD in postmortem interpretation. These same variations affect the pharmacologic response in living patients. Multiple elements related to TK and TD affect the ability to render interpretive opinions of xenobiotics related to an adverse outcome (Table 7–8). Many of these issues are covered elsewhere; however, the use of pharmaco- and toxicokinetic equations warrants special attention.

Toxicologic emergencies and overdoses often lead to derangement of normal physiological functions. Distortions, especially in liver and kidney function, can significantly alter normal TK parameters.^59,63 Coupled with pharmacogenetics, drug–drug or drug–xenobiotic interactions, pathophysiology, and other significant factors, the use of routine TK equations can lead to grossly under- or overestimates of a specific measured value. Nevertheless, in a living patient, TK equations can be useful to estimate certain parameters (eg, dose and, in part, form the basis of such useful tools as nomograms). Postmortem, because of PMR and postmortem diffusion alone, the use of TK formulas to predict premortem concentrations or dosing is not generally an acceptable practice. For example, the use of the following formulas will lead to either an absurd dose calculation or an inappropriate estimate of predicted concentration compared with that reported for compounds undergoing significant PMR:^14,27

Nevertheless, such calculations, although ill advised, are routinely performed and can provide grossly misleading information. “Back extrapolating” from a postmortem concentration to some concentration earlier in time using half-life is fraught with the same perils in that the beginning assumption of an unchanged postmortem blood concentration can rarely be made.¹⁶ Additionally, it is never known how much of any measured blood concentration resulted from a single or multiple dosing. Despite these issues, the toxicologist may be pressured into providing dosing information or predicting a blood concentration during life. The safest avenue in this respect is not to accede to such pressures because the scientific underpinnings are shaky at best.

Assessing Impairment

There exist two broad areas of concern with respect to impairment, that from alcohol and that from other xenobiotics. Impairment caused by alcohol has been long studied, and general conclusions are usually reached with some confidence. The same cannot be stated for impairment caused by drugs. Ultimately, conclusions of drug impairment are based on physical examination by a trained clinician, dosing information, length of time taking a medication, co-administered medications, pathophysiology, observed behaviors, measured concentrations in blood or serum or plasma, and any other useful information.³² The use of the term “consistent with” is common in assessing impairment in any given individual and might very well be the best opinion that can be offered. Mitigating factors, including tolerance, single versus multiple dosing, reason for the presence of the substance, timing and route of administration, and pathophysiology, all make firm conclusions difficult, especially when blood findings are the first indication of potential impairment (ie, no visible signs of impairment).^28,57 Great care must be exercised in evaluating or predicting impairment from drugs given the implications of such conclusions. There is currently no scientific support for back extrapolation of drug concentrations based on blood findings. It cannot be stressed enough that urine findings should never be used to assess impairment because the predictive value is limited.⁶⁴ Similar to blood alcohol concentration, many states and countries have developed per se drug laws that presume guilt by the presence of certain drugs or metabolites over some prescribed reportable concentration, even in urine, thus mitigating the need for interpretation in most cases. For example, the presence of carboxy-tetrahydrocannabinol, an inactive metabolite of marijuana, is used to convict drivers of impaired driving; for clarity, this is a legal issue, not a scientific, issue.^30,36 Last, tables and texts that list xenobiotics and determined concentrations in blood and other specimens should only be used as a guide for interpretive purposes because every case is unique.

• Toxicologists have the opportunity based on both contact with patients and as consultants to be involved with medicolegal cases.

• To properly assess such cases, a holistic approach should be taken that involves the following integration of detailed historical information: preanalytical issues and understanding of the analytical work performed (including its limitations), specimen-specific utility, and special aspects that can weaken or strengthen the ability to form medically and scientifically sound conclusions.

• It should be understood that the burden on the toxicologist is not generally “absolute certainty” because this is something that is rarely achievable. Reasonable medical or scientific certainty usually carries the day, and in civil cases, a greater than 50% probability is all that is generally required.

• Regardless, the purpose of the conclusions offered should not be lost, that is, to educate someone or a group of individuals who have to make difficult decisions, some of which infringe on civil liberties and freedoms. In that respect, the burden assumed by toxicologists should be recognized as significant and warrant the same attention to detail with medicolegal opinions as treatment and diagnosis of a poisoned patient.

References