FORENSIC Barry Levine Office of the Chief Medical Examiner State of Maryland 111 Penn St. Baltimore, MD 21201 and Forensic Toxicology Laboratory Armed Forces Institute of Pathology Washington, DC 20806-6000
Forensic toxicology is defined by the American Board of Forensic Toxicology as the application of toxicology for legal purposes. The classic domain of the forensic toxicologist is the medical examiner's or coroner's office where analyses are performed on specimens from deceased individuals. The postmortem toxicology laboratory identifies and q u a n t i t a t e s drugs or other foreign substances in biological specimens. Postmortem forensic toxicological analyses are well suited for s u s pected drug overdose cases because generally no identifiable lesions are found at autopsy; a recent injection site or a large number of unabsorbed tablet fragments in the stomach may be the only remarkable findings. Toxicological inquiries are also imp o r t a n t in other d e a t h investigations. For instance, patient noncompliance with drug therapy becomes an issue in deaths resulting from seizure disorders and asthma; it may also be a factor in deaths of individuals being treated for depression or mental illness. Toxicological results are used by the pathologist along with findings from the autopsy and police investigation to assign a cause and manner of death. Over the past 25 years the field of forensic toxicology has expanded into other areas. For example, all states have laws prohibiting the operation of motor vehicles by people whose judgment has been impaired by their consumption of alcoholic beverages. State and local government laborato-
ries administer or regulate the testing of blood, urine, or breath for ethanol from drivers suspected of being intoxicated. Many states have analogous statutes forbidding the use of other psychoactive drugs when driving, and these same labs have been required to establish testing procedures for the presence of such drugs in blood and urine specimens. The field of forensic t e s t i n g for drugs of abuse in urine samples has exploded during the past 10 years. Urine specimens may be collected for pre-employment screening, accident investigations, or identification of illicit drug use. The National Institute on Drug Abuse (NIDA) has formulated guidelines for laboratories performing drug testing of urine samples for federal a g e n c i e s . T h e s e g u i d e l i n e s m a n d a t e m e t h o d s for identifying and reporting five drug classes: a m p h e t a m i n e s / m e t h a m phetamines, cannabinoids, cocaine, morphine/codeine, and phencyclidine. Specimens The proper selection of specimens for analysis is an underrated but important aspect of the toxicological analysis. For instance, it is difficult if not impossible to acquire quality specimens after an autopsy has been completed; therefore, t h e pathologist must ensure t h a t all necessary specimens are obtained at autopsy. Obviously, a varied choice of specimens is available in d e a t h cases. Blood should always be obtained. Ideally, two blood specimens should be collected, one from the heart and the other from a peripheral site such as the femoral or jugular vein. In c e r t a i n s i t u a t i o n s such as motor vehicle accidents in which significant chest t r a u m a h a s occurred, h e a r t blood can be contaminated and the alternate blood specimen can be used for interpretation of results. Blood is also the specimen of choice if impair-
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ment caused by drugs is suspected in d r i v e r s or e q u i p m e n t o p e r a t o r s . Blood collected for toxicological analyses should be preserved with sodium fluoride to limit microorganism formation and to enhance the stability of certain drugs. Urine has several advantages over blood. Many drugs and/or metabolites are present in higher concentrations in the urine t h a n in the blood. Some classes of drugs also remain in the urine for days or longer following their use. Urine can be collected noninvasively, and skilled personnel are not required to perform this task. The major drawback to urine screening is that no statement about impairment can be made. The presence of drugs or metabolites in urine is indicative only of prior exposure to the drug. In postmortem cases, urine (if p r e s e n t ) can be collected directly from the bladder. Blood and urine are the two most versatile specimens in forensic toxicology. However, other specimens can be useful if acquired under certain conditions. Breath is an easily obtained specimen for ethanol analysis. Vitreous humor should be collected in postmortem cases because it is more r e s i s t a n t to putrefactive changes t h a n are other specimens. In overdose drug ingestions, analysis of stomach contents can provide easy identification of t h e substance or substances taken if intact tablets are present. Recent work indicates that hair retains some drugs of abuse. For example, cocaine and heroin can be detected in hair. Because scalp hair grows at a fixed rate of about 1 cm per month, one can perform segmental analysis of the hair to establish a time frame of drug usage. The use of hair analysis in testing for drugs of abuse is still controversial; one major issue is t h e m e c h a n i s m by which drugs enter hair. A related issue is the concern about external contami0003 - 2700/93/0365 -272A/$04.00/0 © 1993 American Chemical Society
i
TOXICOLOGY nation of the hair t h a t may occur when illicit drugs are smoked. Ethanol Ethanol is the most frequently encountered drug in forensic toxicology. Among the major pharmacologic effects of ethanol are central nervous system depression, vasodilatation, hypothermia, and diuresis. Central nervous system depression plays a role in accidents; its severity can usually be correlated to the blood e t h a n o l c o n c e n t r a t i o n . Complex brain functions are influenced even by low ethanol concentrations. If the blood ethanol concentration exceeds 400 mg/dL, death can occur from respiratory depression. Reference tables list the effects of various blood ethanol concentrations (1). As stated earlier, one complicating factor in the interpretation of postmortem blood ethanol concentrations is that after death a variety of microorganisms are capable of producing ethanol as well as acetaldehyde and w-propanol from various sugars or fatty acids. Urine and vitreous humor are two specimens resistant to this process and should be analyzed whenever a postmortem blood specimen is positive for ethanol. Detection of a positive blood ethanol concentration in conjunction with a positive vitreous humor and urine ethanol concentration would suggest a n t e m o r t e m ethanol consumption. Conversely, a negative vitreous humor and u r i n e ethanol concentration would be indicative of postmortem ethanol formation in the blood. Analysis of blood and urine specimens for ethanol can be achieved by using a variety of methods. Enzymatic methods use alcohol dehydrogenase, which converts ethanol to acetaldehyde and nicotine adenine dinucleotide (NAD) to NADH. The increase in absorbance at 340 nm produced by NADH is directly pro-
portional to the amount of ethanol in the specimen. GC is used to analyze specimens directly after dilution with an aqueous internal standard or after being heated to 60 °C in a sealed vial and sampling the vapor. Analysis of the h e a d space p e r m i t s q u a n t i t a t i o n without interference from the biological matrix. Multiple volatile compounds can be separated, identified, a n d quantified by GC. A sample chromatogram of C 2 , C 3 , and C 4 volatiles is shown in Figure 1. Numerous methods are used for the analysis of ethanol in b r e a t h samples. The oldest breath-testing devices use the metal-catalyzed reduction of dichromate in sulfuric acid to chromic ion. Ethanol is oxidized in the process to acetic acid. The green color of the formed chromic ions can be monitored spectrophotometrically to quantitate the ethanol. An a l t e r n a t i v e b r e a t h - t e s t i n g technology uses a fuel cell to measure the current generated by the electrochemical oxidation of ethanol to acetic acid. There are also breath-
I tant to be aware of several factors. The physical and chemical characteristics of the drugs determine the separation and detection methods used. The disposition of drugs in the body is also critical. For example, in heroin abusers it is exceedingly rare to detect heroin in biological specimens; morphine is the predominant compound found. Similarly, two breakdown p r o d u c t s of c o c a i n e , b e n zoylecgonine and ecgonine methyl ester, remain in the body for much longer periods than does cocaine. Abused drugs include the "NIDA 5" drugs listed previously, barbiturates, benzodiazepines, and m e t h a d o n e . Therapeutic drugs also subject to abuse include over-the-counter and prescription medications. These encompass but are not limited to antiarrhythmics, anticonvulsants, antidepressants, antihistamines, narcotic analgesics, non-narcotic analgesics, and neuroleptic drugs. The initial step in the analytical screening for drugs is analyte separation. Except for some drug classes that can be analyzed directly in urine
ANALYTICAL APPROACH t e s t i n g devices t h a t use gas c h r o m a t o g r a p h i c t e c h n i q u e s . Recently, IR spectroscopy has become the most common analytical method u s e d for b r e a t h - t e s t i n g devices. Greater selectivity for ethanol is provided by including multiple wavelengths or a secondary detection system.
Drug testing Besides ethanol, a large number of other drugs are assayed in forensic toxicology laboratories. When establishing assays for drugs, it is impor-
specimens, the analytes of interest usually require separation from the biological matrix. Protein precipitation is useful for this purpose and is a relatively simple separation technique. Color tests and HPLC may be amenable to this separation method. The most common s e p a r a t i o n method used in forensic toxicology is liquid-liquid extraction. By using ionization and solubility characteristics, separation of basic, neutral, and acidic drugs can be effected. Solidphase extraction with bonded silica columns is commonly used.
ANALYTICAL CHEMISTRY, VOL. 65, NO. 5, MARCH 1, 1993 • 273 A
ANALYTICAL APPROACH Once separation, if necessary, has occurred, the next step is toxicant identification using either spectrophotometry, chromatography, or an i m m u n o a s s a y . Color t e s t s can be done directly on the specimen or on a protein-free filtrate of the specimen. Their ease of use makes these methods a d v a n t a g e o u s , e s p e c i a l l y a s screening tests. Salicylate and acetaminophen are two drugs for which relatively specific color tests exist. UV spectrophotometry was used with greater frequency in the past, but it lacks the sensitivity needed to detect therapeutic concentrations of many drugs encountered currently. S p e c t r o p h o t o m e t r i c m e t h o d s also lack the specificity required to distinguish between parent drugs and their metabolites. This can be critical if the metabolites have varying degrees of pharmacologic activity. GC has been used to identify and
Figure 1 . Chromatogram of C2, C3, and C4 volatiles. The internal standard is 2-butanone, 10 mg/L; the 2-m column is 0.2% Carbowax 1500 on Carbopack C; and the oven temperature is 120 *C (isothermal).
quantitate many drugs. In general, phenylmethylsilicone packing material with temperature programming can be used to separate a large group of substances (Figure 2). Flame ionization or nitrogen-phosphorus detectors are most commonly used. Benzodiazepines, sedative-hypnotic drugs containing halogens, can be determined at very low detection limits with an electron capture detector. For polar a n d t h e r m a l l y labile compounds, HPLC is the preferred chromatographic technique. UV detection is most desirable, but fluorescence, electrochemical, and refractive index detectors are also available. Electrochemical and fluorescence detectors permit greater detection limits; however, they lack the general applicability of UV detectors. Immunoassays are based on the competition between t h e d r u g or drug class in the specimen and a labeled drug for sites on the antibody to that drug or drug class. A separation step m a y be required before m e a s u r e m e n t . These assays have several advantages over other techniques. They can be performed on urine specimens directly or on blood or tissue specimens after pretreatment and have good sensitivity to a particular drug or drug class. Three common immunoassays are enzymemultiplied immunoassay, radioimmunoassay, and fluorescence polarization immunoassay; each h a s advantages such as cost, amenability to h i g h - v o l u m e a u t o m a t i o n , a n d antibody specificity. In order for a substance to be positively reported it is mandatory that at least two different analytical techniques be used. The use of a second or confirmatory technique is a fundamental principle in forensic toxicology. Numerous combinations of techn i q u e s (e.g., i m m u n o a s s a y a n d chromatography or spectrometry and chromatography) fulfill this requirement. Two different immunoassays would not be acceptable because of antibody similarities between commercially available kits. More definitive confirmatory techniques provide s t r u c t u r a l information about t h e substance itself. GC/MS is c u r r e n t l y the benchmark confirmatory technique used in the field. A gas chromatographic retention time plus a full-scan electron impact mass spectrum can be compared with a s t a n d a r d to provide conclusive identification in most but not all c i r c u m s t a n c e s . For drugs present in lower concentrations, selected ion monitoring of three major
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ions may be sufficient. GC/IR spectroscopy also can provide conclusive identification in most situations. The interpretation of drug-testing results can be straightforward or complex. T h e p r e s e n c e of d r u g s and/or metabolites in urine will indicate exposure, but usually no assessm e n t of i m p a i r m e n t or toxicity is possible. Quantitation of drugs in blood is better correlated with toxicity or fatality. Blood quantitations must be interpreted in light of available history. A postmortem blood sample from an individual who was treated in the hospital for several days, which showed the presence of a drug in therapeutic concentration, may indicate much higher concentration at an earlier time. A series of drugs, each present in therapeutic concentration, may produce synergistic effects when present in combination. A combination of ethanol and other central nervous system depressants, for example, can have potentiating effects and cause death. Analytical approach The analytical approach taken by a forensic toxicology laboratory depends on the missions of that laboratory. If the lab is designed to perform only blood ethanol analyses, then a small setup with a single assay will be sufficient. For a large volume of samples with a limited number of analytes, a forensic urine drug-testing l a b o r a t o r y would perform i m m u noassay screens with confirmation by GC/MS if it were testing according to federal guidelines. In a postmortem forensic toxicology laboratory, where ethanol and therapeutic and abused drugs are assayed, methods should be established for the identification, confirmation, and quantitation of each group. The most common approach is to develop a protocol that comprehensively screens for alcohols and drugs. Once t e n t a t i v e identification h a s been made, more specialized testing can be done for confirmation and q u a n t i t a t i o n . No single analytical method is appropriate for all drugs; a series of methods in combination can provide the necessary breadth of coverage. For example, an alkaline extraction followed by GC with nitrog e n - p h o s p h o r u s detection and temperature programming can identify d r u g s w i t h i n t h e following classes: antiarrhythmics, antidepress a n t s , a n t i h i s t a m i n e s , benzodiazepines, narcotics, neuroleptics, and sympathomimetic amines. Not all drugs within a class can be
detected in appropriate concentra tions, and a toxicologist must know which drugs can be identified and at what detection limits. A weak acid extraction followed by GC or HPLC can identify acid and neutral drugs such as b a r b i t u r a t e s , anticonvul sants, and glutethimide. A variety of commercially available immunoas says can identify a m p h e t a m i n e s , barbiturates, benzodiazepines, cann a b i n o i d s , cocaine, o p i a t e s , a n d phencyclidine. Color tests are still useful for salicylate, acetaminophen, ethchlorvynol, and chloral h y d r a t e (as trichloroethanol). Unusual cases In the vast majority of cases the rou tine analytical approach followed by a forensic toxicology laboratory is sufficient. However, there are times when unusual cases are presented that require special responses. The following examples i l l u s t r a t e t h e need for such special approaches. F e n t a n y l d e a t h (2). A critical component in death investigations is the analysis of the scene. In drug deaths, empty medication containers may provide useful information in
the ensuing toxicological analysis. In this case a 35-year-old anesthesiol ogy resident was found dead in his apartment. At the scene were several syringes, an intravenous line, and a b o t t l e of V e r s e d ( m i d a z o l a m ) , a benzodiazepine often used in the in duction of anesthesia. Subsequent analysis of t h e blood showed the presence of midazolam, but at a sub therapeutic concentration. Fortunately, one of the syringes still contained some m a t e r i a l for analysis. Analysis of the syringe by GC/MS revealed fentanyl, a potent n a r c o t i c also u s e d in o p e r a t i n g rooms. Its presence in the blood at ng/mL concentrations would not be picked up by routine toxicological screening. F u r t h e r analysis of the blood and tissues by GC/MS resulted in the detection of fentanyl; the med ical examiner ruled t h a t the cause of death was fentanyl intoxication. USS Iowa disaster (3). The USS Iowa was engaged in a gunnery exer cise on April 19, 1989, when an explo sion occurred in the number two tur ret, killing 47 seamen. The significant toxicological question was: Which deaths occurred from the explosion
Figure 2. Chromatogram of an alkaline-extractable drug standard. A DB-5 column (15 m χ 0.25 mm i.d., 0.25-μπι film thickness) was used. The oven temperature began at 110 'C for 1 min, increased by 20 'C per min to 200 'C, then increased by 10 'C per min to 280 "C, holding for 15 min. (1) amphetamine, (2) methamphetamine, (3) nicotine, (4) pseudoephedrine, (5) meperidine, (6) lidocaine, (7) phencyclidine, (8) chlorphentramine, (9) methadone, (10) amitriptyline, (11) nortriptyline, (12) codeine, (13) diazepam, (14) nordiazepam, (15) chloroquine, (16) alprazolam, (17) thioridazine.
and which deaths occurred from the resulting fire? In the case of fire, CO or b u r n s usually cause death. CO binds tightly to hemoglobin, the oxy gen transport vehicle for the body, limiting the delivery of oxygen to the t i s s u e s . This causes hypoxia and death. If death occurred from the explo sion and before the fire, a normal blood carboxyhemoglobin would be measured. Conversely, an elevated carboxyhemoglobin would suggest survival in the initial explosion but death in the fire. Ten of the 47 fatal ities had carboxyhemoglobin satura tion values less than or equal to 10%, which is considered normal. Eight of those deaths were attributed to blunt force injuries, and the two others were caused by a combination of blunt force and thermal injuries. On the other hand, of the 37 victims with elevated carboxyhemoglobin, 30 were judged to have died as a result of the fire. Attempted murder w i t h p a n c u r o n i u m (4). Pancuronium bromide is a nondepolarizing neuromuscular blocking agent that acts by compet ing with acetylcholine for cholinergic receptors at the motor end plate. It is a quaternary amine, which makes its separation from biological matrices a difficult analytical challenge. In this case, a n u r s e was accused of a t tempting to murder her husband by twice administering to him an u n known neuromuscular blocking agent. On both occasions the h u s band was hospitalized, and his urine was collected within 1-2 h of the al leged injections. These specimens were screened using Rose Bengal dye, which forms a fluorophore with pancuronium but not with other qua ternary amines. For confirmation, an ion-pair ex traction followed by thin-layer chro matography was performed. The spot corresponding to pancuronium was scraped, extracted, and s e p a r a t e d u s i n g GC/MS. Although p a n c u r o nium does not show a peak, a ther mal breakdown product that does is produced if the injection port temper a t u r e is sufficiently elevated. The drug was confirmed using selected ion monitoring. The accused pleaded nolo contendere to the charge of at tempted murder. Phenobarbital i n m a g g o t s (5). In badly decomposed bodies the ac quisition of common biological speci mens is often impossible. The decom p o s i t i o n p r o c e s s often l e a d s to infestation of the remains with mag gots. In this case, the body of a
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ANALYTICAL APPROACH 22-year-old female was found badly decomposed and skeletonized in a wooded area. An empty container, which showed a recently filled pres c r i p t i o n for p h é n o b a r b i t a l , w a s found in a purse next to the body. There was a history of previous suicide attempts, and a suicide note was found at the scene. The only available specimens for analysis were the insect larvae. The larvae were homogenized and the proteins precipitated and extracted w i t h chloroform. The extract was concentrated and injected into a gas chromatograph. Phénobarbital was identified by r e t e n t i o n t i m e and quantitated at 100 mg/kg; confirmation was made by GC/MS. The entomologist involved in the case concluded t h a t the phénobarbital had o r i g i n a t e d from t h e t i s s u e s consumed by the maggots. L i d o c a i n e h o m i c i d e s (6). In 1981 a series of deaths within a twomonth period occurred in a California h o s p i t a l i n t e n s i v e care u n i t . Many of the patients experienced seizures, respiratory arrest, and bluish discolorations in the thoracic region. When a similar death occurred at another hospital, a review of personnel records indicated that one nurse was employed at both hospitals and had access to all of the deceased pat i e n t s . P o s t m o r t e m toxicological analysis of some of the decedents indicated massive amounts of lidocaine in the fluids and tissues. The toxic effects of lidocaine are consistent with the symptoms displayed by the dying p a t i e n t s . The n u r s e was charged with and subsequently convicted of 12 of the killings. Morphine intoxication (7). A 26year-old woman diagnosed with acute leukemia was admitted to the hospital. Her extremely high fever was treated with antibiotics. When her heart activity stopped, she was successfully resuscitated and placed on a respirator. Two days later, the respirator was stopped and 90 mg of meperidine allegedly was administered. Two hours later, the patient died. Subsequent investigation indicated t h a t a 9 0 - m g dose of m o r p h i n e r a t h e r t h a n meperidine h a d been given. Morphine is 7 - 1 0 times more potent t h a n meperidine, as a pain killer and as a respiratory depressant. Four months after the death, the body was exhumed for autopsy and collection of specimens for toxicology. The liver, muscle, gall bladder, and kidney were negative for meperidine; however, high concentrations of morphine were found in the
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brain, liver, and muscle. The physician who administered the morphine was charged with manslaughter but was acquitted after a long trial. Summary This article has briefly highlighted some aspects of forensic toxicology, including specimen collection, the identification and measurement of a n a l y t e s , and t h e a n a l y t i c a l a p proach t h a t should be followed to generate toxicological results. The role of a forensic toxicology laboratory may be varied. It can be asked to assign a cause of death or to explain behavior in deaths of known cause. Its findings may also be used to restrict or deny driving privileges. In addition, positive results from a drug screening may provide a reason to refuse employment or to remove an individual from his or her job. Regardless of the intended use, the results must be generated in an accurate scientific manner. References (1) Sunshine, I. In Methodology for Analytical Toxicology; Sunshine, I., Ed.; CRC Press: Cleveland, OH, 1975; p. 148. (2) Levine, B.; Goodin, J. C ; Caplan, Y. H. Forensic Sci. Int. 1990, 45, 247-51. (3) Mayes, R.; Levine, B.; Smith, M. L.; Wagner, G. N.; Froede, R. /. Forensic Sci. 1992, 37, 1352-57. (4) Briglia, E. J.; Davis, P. L.; Katz, M.; Dal Cortivo, L. A. /. Forensic Sci. 1990, 35, 1468-76. (5) Beyer, J. C; Enos, W. F.; Stajic, M. /. Forensic Sci. 1980, 25, 411-12. (6) Starrs, J. Scientific Sleuthing Review 1992, 16, 1-5. (7) Worm, K; Steentoft, Α.; Christensen, H . / Forensic Sci. Soc. 1982, 23, 209-12. Barry Levine received a B.S. degree in chemistry from Loyola College in Balti more, MD, in 1978 and a Ph.D. in pathol ogy from the Medical College of Virginia in 1982. In 1983 he began work as an as sistant toxicologist at the Office of the Chief Medical Examiner (OCME), State of Maryland. He became chief of the Foren sic Toxicology Laboratory for the Armed Forces Medical Examiner at the Armed Forces Institute of Pathology (AFIP) in Washington, DC, in 1989. Recently he re turned to OCME as a toxicologist while re taining a pan-time position at AFIP. He also is a clinical associate professor of pa thology at the University of Maryland at Baltimore.
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ANALYTICAL APPROACH 22-year-old female was found badly decomposed a n d skeletonized i n a wooded area. An empty container, which showed a recently filled pre s c r i p t i o n for p h é n o b a r b i t a l , w a s found in a purse next to t h e body. There was a history of previous suicide attempts, and a suicide note was found at the scene. The only available specimens for analysis were the insect larvae. The larvae were homogenized a n d t h e proteins precipitated and extracted with chloroform. The extract was concentrated and injected into a gas chromatograph. Phénobarbital was identified by r e t e n t i o n t i m e a n d quantitated at 100 mg/kg; confirmation was made by GC/MS. The entomologist involved in t h e case concluded t h a t t h e phénobarbital h a d o r i g i n a t e d from t h e t i s s u e s consumed by the maggots. L i d o c a i n e h o m i c i d e s ( 6 ) . In 1981 a series of deaths within a twomonth period occurred in a California h o s p i t a l i n t e n s i v e care u n i t . Many of the patients experienced seizures, respiratory arrest, and bluish discolorations in the thoracic region. When a similar death occurred at another hospital, a review of personnel records indicated that one nurse was employed a t both hospitals and had access to all of the deceased pat i e n t s . P o s t m o r t e m toxicological analysis of some of the decedents indicated massive amounts of lidocaine in the fluids and tissues. The toxic effects of lidocaine a r e consistent with the symptoms displayed by the dying patients. The nurse was charged with and subsequently convicted of 12 of the killings. Morphine intoxication (7). A 26year-old woman diagnosed with acute leukemia was admitted to the hospital. H e r extremely high fever was treated with antibiotics. When h e r heart activity stopped, she was successfully resuscitated and placed on a respirator. Two days later, the respirator was stopped and 90 mg of meperidine allegedly was administered. Two hours later, the patient died. Subsequent investigation indicated t h a t a 9 0 - m g dose of m o r p h i n e r a t h e r t h a n meperidine h a d been given. Morphine is 7 - 1 0 times more potent t h a n meperidine, as a pain killer and as a respiratory depressant. Four months after the death, the body was exhumed for autopsy and collection of specimens for toxicology. The liver, muscle, gall bladder, and kidney were negative for meperidine; however, high concentrations of morphine were found in the
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brain, liver, and muscle. The physician who administered the morphine was charged with manslaughter but was acquitted after a long trial. Summary This article h a s briefly highlighted some aspects of forensic toxicology, including specimen collection, t h e identification a n d measurement of analytes, and the analytical a p proach t h a t should be followed to generate toxicological results. The role of a forensic toxicology laboratory may be varied. It can be asked to assign a cause of death or to explain behavior in deaths of known cause. Its findings may also be used to r e strict or deny driving privileges. In addition, positive results from a drug screening m a y provide a reason to refuse employment or to remove an individual from his or her job. Regardless of the intended use, the r e sults must be generated in a n accurate scientific manner. References (1) Sunshine, I. In Methodology for Analytical Toxicology; Sunshine, I., Ed.; CRC Press: Cleveland, OH, 1975; p. 148. (2) Levine, B.; Goodin, J. C ; Caplan, Y. H. Forensic Sci. Int. 1990, 45, 247-51. (3) Mayes, R.; Levine, B.; Smith, M. L.; Wagner, G. N.; Froede, R. /. Forensic Sci. 1992, 37, 1352-57. (4) Briglia, E. J.; Davis, P. L.; Katz, M.; Dal Cortivo, L. A. / Forensic Sci. 1990, 35, 1468-76. (5) Beyer, J. C; Enos, W. F.; Stajic, M. /. Forensic Sci. 1980, 25, 411-12. (6) Starrs, J. Scientific Sleuthing Review 1992, 16, 1-5. (7) Worm, K.; Steentoft, Α.; Christensen, H . / Forensic Sci. Soc. 1982, 23, 209-12. Barry Levine received a B.S. degree in chemistry from Loyola College in Balti more, MD, in 1978 and a Ph.D. in pathol ogy from the Medical College of Virginia in 1982. In 1983 he began work as an as sistant toxicologist at the Office ofthe Chief Medical Examiner (OCME), State of Maryland. He became chief of the Foren sic Toxicology Laboratory for the Armed Forces Medical Examiner at the Armed Forces Institute of Pathology (AFIP) in Washington, DC, in 1989. Recently he re turned to OCME as a toxicologist while re taining a part-time position at AFIP. He also is a clinical associate professor of pa thology at the University of Maryland at Baltimore.
