Importance of information in forensic toxicology.

Information in forensic toxicology plays a very important role. The forensic pathologist usually seeks toxicologic analyses on basis of the information available at the time of the medicolegal autopsy. Such information may be obtained from different sources: hospitals, authorities, relatives, friends, or neighbors of the deceased and, obviously, macroscopic findings at the time of the autopsy. In order to evaluate the relative importance of these different sources of information, the authors have studied, retrospectively, results of 580 postmortem examinations performed at the Institute of Legal Medicine of Lisbon, wherein toxicologic analyses had been requested. These cases pertain to the years 1987 and 1988, but do not include alcohol determination in the blood in cases of traffic accidents. In 274 (47.4%) of the 580 cases, there were positive findings while in the remaining 306 (52.6%) findings were negative. In cases with positive findings, circumstances and factors, which may have influenced the pathologist's decision to request toxicologic analysis, are discussed. In more than half the cases, hospital information was the decisive factor, while in approximately 25% of the cases, autopsy findings were the justification. In contrast, it is worth mentioning that in approximately 45% of the cases with analytical negative results, requests were made, in cases of blank autopsies, for toxicologic analyses in order to exclude the possibility of poisoning. It is interesting to note that in the same proportion requests were justified on grounds of hospital information. Some of the factors that may explain this apparent discrepancy are discussed. Finally, the relevance of background information is emphasized at the level of the interpretation of analytical results, whether positive or negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

Computer-assisted interpretation in forensic toxicology: morphine-involved deaths

Case data from 200 morphine-involved deaths (Spiehler, V. and Brown, R., Journal of Forensic Sciences, Vol. 32, No. 4, July 1987, pp. 906-916) were analyzed for patterns and relationships using artificial intelligence (AI) computer software. Case parameters were blood unconjugated morphine, blood, brain, and liver total morphine, sex, age, frequency of use, time of death after injection, cause of death, and presence of other drugs. The programs used were Expert 4 (Biosoft-Cambridge), BEAGLE (Warm Boot, Ltd.), and KnowledgeMaker (Knowledge Garden Inc.). Interpretation was defined as estimating the dose, response, and time after drug dosing. The AI programs were used to advise on time and response outcomes for cases, to calculate the probability of the estimate being true, to develop rules for interpretation of morphine-involved cases, and to diagram a decision tree. On known cases the AI programs were successful 70 to 90% of the time in classifying the cases as to response and time. No data on dose were available in this database. The success rate in individual cases was proportional to the program-estimated probability. All three programs found the case parameters of most value in predicting response to be blood unconjugated morphine, blood total morphine, and liver total morphine. The case data most useful in estimating time of death since drug injection were blood unconjugated morphine, percent unconjugated morphine in blood, and brain total morphine. The rule induction programs found that morphine overdoses were characterized by blood unconjugated morphine greater than 0.24 micrograms/mL, liver morphine greater than 0.50 to 0.75 micrograms/g, brain morphine greater than 0.08 micrograms/g or greater than blood unconjugated morphine, and percent blood unconjugated morphine greater than 37%. Rapid deaths were characterized by percent unconjugated morphine greater than 44 to 50%; blood unconjugated morphine, as a function of other drugs present, greater than 0.09 to 0.21 micrograms/mL; and brain total morphine greater than 0.16 to 0.22 micrograms/g. This work demonstrates that inexpensive AI programs commercially available for personal computers can be useful in interpretation in forensic toxicology.     

Development of forensic standards in China: a review

Forensic science is crucial for the administration of justice and case investigation.in China,political-legal organizations,including the courts,public security,procuratorate,and judicial administration,developed their own forensic practices before 2004.As a result,the frequent and repeated appraisals undermined judicial authority and credibility.Thus,a law was published in 2005 to improve the uniform forensic management system by the Standing Committee of the National People’s Congress,leading to the establishment of the Forensic Administration of the Ministry of Justice in 2006.During this process,the increased accreditation and interflow highlighted the role of consensus in forensic standards for forensic service providers to avoid uncertainty regarding the methods used and interpretation of results.in 2017,a policy document was promulgated again to strengthen the importance of the uniform standards,which also proposed to establish a new national technical committee for the standardization of forensic science by the General Office of the State Council.in 2018,despite the continuing problems concerning uniformity,the Forensic Administration of the Ministry of Justice was merged into the Public Legal Services Administration.Yet,there is still a long way to go for the national technical committee for the standardization of forensic science.This paper analyses the evolution of forensic standards internationally and nationally,discusses the existing problems,and proposes relative solutions.Moreover,it discusses the future of standards development with the deepening of the reformation of both the national standardization and judicial system.     

A comparison of the borate-celite column screening technique with other extraction methods in forensic toxicology.

The comparison of five different extraction techniques from postmortem tissues was reported. The borate/celite column chromatography technique generally gave the best yields and its use as a screening method in forensic toxicology was discussed.     

On statistical analysis of forensic DNA: theory, methods and computer programs

Statistics plays an important role in evaluating the evidential weight of forensic DNA. In this paper, general statistical principles for forensic DNA analysis are presented. We introduce the theory and methods for the statistical assessment in kinship determination and DNA mixture evaluation. In particular, analytical formulas for testing for biological relationship among three individuals and for assessing the DNA mixture evidence in the case of multiple subdivided ethnic groups are developed. Two user-friendly computer programs are demonstrated to exhibit their wide applicability in tackling with complex kinship/paternity and mixture problems. The EasyDNA program can solve a complicated paternity case in 1 min.     

Sensitive and specific multiresidue methods for the determination of pesticides of various classes in clinical and forensic toxicology

Original and sensitive multiresidue methods are presented for the detection and quantitation, in human biological matrices, of 61 pesticides of toxicological significance in human. These methods involved rapid solid-phase extraction using new polymeric support (HLB and MCX) OASIS cartridges. Gas chromatography-mass spectrometry (GC-MS) was used for volatile (organophosphate, organochlorine, phtalimide, uracil) pesticides and liquid chromatography-ionspray-mass spectrometry (LC-MS) for thermolabile and polar pesticides (carbamates, benzimidazoles). Acquisition was performed in the selected ion monitoring (SIM) mode. Extraction recovery varied owing to the nature of pesticides, but was satisfactory for all. Limits of detection (LODs) and limits of quantitation (LOQs) ranged, respectively, from 2.5 to 20 and from 5 to 50ng/ml. An excellent linearity was observed from LOQs up to 1000ng/ml for all the pesticides studied. The proposed procedures yielded reproducible results with good inter-assay accuracy and precision. A few cases of intoxication are presented to demonstrate the diagnostic interest of these methods: in two cases were determined lethal concentrations of endosulfan and carbofuran; in four other cases, the procedures helped diagnose intoxication with, respectively, parathion-ethyl, the association of bromacil and strychnine, bifenthrin and aldicarb.     

药物遗传学在法医学中的应用前景

人类因为基因的差异而表现出对某种药物、毒物、外界有害的化学物质、过敏原作出不同的反应.这种遗传背景的差异使一些人可以快速地清除这些物质,而另一些人却因此产生严重的不良反应.甚至死亡.药物遗传学和药物基因组学,通过对人类基因组测序和大规模基因组多态性的鉴别研究,诠释了个体遗传差异与对药物毒物不同反应之间的关系,这为该类案件的法医学鉴定提供了新的理论基础和研究手段.     

Cyanide poisoning: forensic toxicology observations in the study of 54 cases of fatal poisoning

The present study describes various observations made during the examination of 54 cases of lethal cyanide intoxication at the Institute of Forensic Medicine of the University of Zürich during a period of more than 40 years. Data pertain to the scene of death, the medicolegal inspection, the autopsy, the histological examinations, the chemical analyses, the various types of poisoning observed and the diagnostic criteria used. The intoxicated victims were mostly adults who had professional access to various cyanogenic compounds and had ingested them with the intention of committing suicide. Cases of accidental and criminal poisoning were rare. In spite of this fact, and although its frequency has not increased in the last few decades, cyanide poisoning has maintained undiminished importance.     

Sex identification of forensic specimens by polymerase chain reaction (PCR): two alternative methods

Sex identification of forensic samples (bloodstains and decomposed tissue) by polymerase chain reaction (PCR) was investigated. Amplification of a segment of the amelogenin gene using a pair of primers revealed both Y- and X-specific bands at the same time. The gene has counterparts in both the X and Y chromosomes and a small deletion in the former made it possible to distinguish them. Analysis of the X-specific band is the most reliable method for sex identification. THe locus includes a single copy gene so a sample of 250 ng/tube of deoxyribonucleic acid (DNA) is required for identification. Amplification of part of the DYZ1 locus was attempted as an alternative method for analysis of infinitesimal amounts of sample. Even DNA from putrefied tissue could be analyzed by PCR because the locus consists of thousands of copies of repeating units pHY10.     

A pharmacokinetic study of ethyl glucuronide in blood and urine: applications to forensic toxicology

This pharmacokinetic study investigated the kinetics of ethanol and its metabolite ethyl glucuronide (EtG) in blood and urine during the whole time course of absorption and elimination. There are few previous studies on the kinetics of EtG in blood, and we wanted to evaluate whether such knowledge could yield valuable information regarding the time of ethanol ingestion in forensic cases, such as, for instance, drunk driving. Ten male volunteers consumed ethanol at a fixed dose of 0.5 g/kg body weight in a fasted state. Blood samples were collected for 14 h and urine samples were collected for 45-50 h after the start of drinking. EtG reached its maximum concentration (C(max)) in blood after a median of 4 h (range 3.5-5), a median of 3 h (range 2-4.5) after C(max) for ethanol. The ethanol-to-EtG ratios in blood (ethanol in g/L, EtG in mg/L) were >1 only for the first median 3.5 h (range 2.5-3.5) after drinking. EtG elimination occurred with a median half-life of 2.2 h (range 1.7-3.1 h), and the renal clearance was 8.32 L/h (median, range 5.25-20.86). The concentrations of EtG were always much higher in urine than in blood. The total amount of EtG excreted in the urine was median 30 mg (range 21.5-39.7), representing 0.017% (median, range 0.013-0.022) of the ethanol given, on a molar basis. The information from the present study may be a valuable supplement to determine the time of ethanol ingestion. For this purpose, two subsequent increasing EtG values and a high ethanol-to-EtG ratio in blood would support information of recent drinking.     

Difficulties of sex determination from forensic bone degraded DNA: A comparison of three methods

Sex determination is of paramount importance in forensic anthropology. Numerous anthropological methods have been described, including visual assessments and various measurements of bones. Nevertheless, whatever the method used, the percentage of correct classification of a single bone usually varies between 80% and 95%, due to significant intra- and inter-population variations, and sometimes variations coming from secular trends. DNA is increasingly used in a forensic context. But forensic DNA extraction from bone raises several issues, because the samples are very often badly altered and/or in very small quantity. Nuclear DNA is difficult to get from degraded samples, according to low copy number, at least in comparison with mitochondrial DNA. In a forensic context (as in a paeleoanthropological context) DNA sex determination is usually complicated by the weak amount of DNA, the degraded nature of nucleic acids, the presence of enzymatic inhibitors in DNA extracts, the possible faint amplification of Y band and the risk of contamination during either excavation or manipulation of samples.The aim of this work was to compare three methods of DNA sex determination from bones: procedure #1 using a single PCR amplification, procedure #2 using a double PCR amplification, and procedure #3 adding bleaching for decontamination of the bone, instead of simply rubbing the bone. These processes were applied to samples of bones (49 samples coming from 39 individuals) that were in various states of post mortem alteration.The main results are the following. (i) No DNA could be extracted from three skulls (parietal bones, mastoid process), the compact bone of one rib, and the diaphysis of one femur; (ii) there was a contamination in three skulls; and (iii) the Y band did not appear in two male cases, with one of the three procedures (male tibia, procedure #2) and with procedures #2 and #3 (male femur).This study emphasises the main issue while working with altered bones: the impossibility to extract DNA in some cases, and, worth of all, the contamination of the sample or the faint amplification of Y band which leads to a wrong sex answer. Multiple and significant precautions have to be taken to avoid such difficulties.     

Capillary electrophoresis: a new tool in forensic toxicology. Applications and prospects in hair analysis for illicit drugs

Capillary electrophoresis, the modern approach to instrumental electrophoresis, is probably the most rapidly expanding analytical technique that has appeared in recent years. In the hands of forensic toxicologists, capillary electrophoresis (CE) represents a powerful new analytical tool, which has proved suitable for the investigation of illicit drugs in seized preparations and also in complex biological matrices, among which is hair. CE can be applied according to different separation mechanisms, and among those that are toxicologically relevant are capillary zone electrophoresis and micellar electrokinetic capillary chromatography, which display different selectivities. For the investigation of hair for drugs of abuse, capillary electrophoresis proved effective, providing simultaneous determinations of different drugs without derivatization, with acceptable sensitivity (typically better than 1 ng of drug per mg of hair). The possibility of carrying out determinations of the same analytes, based on different separation mechanisms (capillary zone electrophoresis and micellar electrokinetic chromatography) with the same instrumentation, simply changing the buffer composition, provides an interesting possibility of ‘internal’ confirmation of the results.     

Impact of tropical conditions on thin layer chromatography in analytical toxicology: high temperatures and moderate humidities.

The impact of high temperatures (24 to 39 degrees C) and low to moderately high humidities (20 to 70%) on the applicability of TLC systems for drug identification was studied during a 6 month climatologic cycle in Burkina Faso (West Africa). In general, the Rf values as observed on the plates were found to be substantially affected as compared with values obtained at temperate climates. Some TLC systems were more affected than others and the largest deviations of up to 30 Rf units were at low humidities. Tropical conditions also had a negative effect on the reproducibility of Rf values. However, when an Rf-correction procedure was applied, using reference mixtures of known drugs on each plate, accuracy as well as reproducibility of the resulting Rfc values were drastically improved and data thus corrected were found to be compatible with existing TLC data bases developed under moderate climatological conditions. The impact of high to extremely high humidities (70 to 100%) remains to be investigated.     

Frequencies of morphological characteristics in two contemporary forensic collections: implications for identification

Positive identification relies on comparison of antemortem and postmortem data. Some identifications are based on morphological features such as fracture, pathological condition, and surgical hardware, despite little literature indicating the frequencies of such traits. This study examines whether such features are sufficiently rare as to be deemed individualizing. Data were collected on two modern North American skeletal collections (N=482 individuals). Presence/absence of features was scored by skeletal element and side. Results indicate that frequencies vary by geographic region (higher frequency of fractures and pathological conditions in New Mexico while individuals in Tennessee were more likely to have surgical interventions), many features such as fractures are remarkably common and that even suites of traits may not be individualizing. Caution is warranted when using written data rather than radiographic comparisons as the primary source of identification. The implications of these findings to missing person databases are also discussed.     

USGS42 and USGS43: human-hair stable hydrogen and oxygen isotopic reference materials and analytical methods for forensic science and implications for published measurement results

Because there are no internationally distributed stable hydrogen and oxygen isotopic reference materials of human hair, the U.S. Geological Survey (USGS) has prepared two such materials, USGS42 and USGS43. These reference materials span values commonly encountered in human hair stable isotope analysis and are isotopically homogeneous at sample sizes larger than 0.2 mg. USGS42 and USGS43 human-hair isotopic reference materials are intended for calibration of δ(2)H and δ(18)O measurements of unknown human hair by quantifying (1) drift with time, (2) mass-dependent isotopic fractionation, and (3) isotope-ratio-scale contraction. While they are intended for measurements of the stable isotopes of hydrogen and oxygen, they also are suitable for measurements of the stable isotopes of carbon, nitrogen, and sulfur in human and mammalian hair. Preliminary isotopic compositions of the non-exchangeable fractions of these materials are USGS42(Tibetan hair)δ(2)H(VSMOW-SLAP) = -78.5 ± 2.3‰ (n = 62) and δ(18)O(VSMOW-SLAP) = +8.56 ± 0.10‰ (n = 18) USGS42(Indian hair)δ(2)H(VSMOW-SLAP) = -50.3 ± 2.8‰ (n = 64) and δ(18)O(VSMOW-SLAP) = +14.11 ± 0.10‰ (n = 18). Using recommended analytical protocols presented herein for δ(2)H(VSMOW-SLAP) and δ(18)O(VSMOW-SLAP) measurements, the least squares fit regression of 11 human hair reference materials is δ(2)H(VSMOW-SLAP) = 6.085δ(2)O(VSMOW-SLAP) - 136.0‰ with an R-square value of 0.95. The δ(2)H difference between the calibrated results of human hair in this investigation and a commonly accepted human-hair relationship is a remarkable 34‰. It is critical that readers pay attention to the δ(2)H(VSMOW-SLAP) and δ(18)O(VSMOW-SLAP) of isotopic reference materials in publications, and they need to adjust the δ(2)H(VSMOW-SLAP) and δ(18)O(VSMOW-SLAP) measurement results of human hair in previous publications, as needed, to ensure all results on are on the same scales.     

Pattern detection in forensic case data using graph theory: application to heroin cutting agents

Pattern recognition techniques can be very useful in forensic sciences to point out to relevant sets of events and potentially encourage an intelligence-led style of policing. In this study, these techniques have been applied to categorical data corresponding to cutting agents found in heroin seizures. An application of graph theoretic methods has been performed, in order to highlight the possible relationships between the location of seizures and co-occurrences of particular heroin cutting agents. An analysis of the co-occurrences to establish several main combinations has been done. Results illustrate the practical potential of mathematical models in forensic data analysis.