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Introduction to Toxicology EV 460/660 & BI 460/660 Fall 2014 The use of Bone Marrow as a Matrix for Toxicological Analysis Presentation by Lauren Ditto 1. Forensic Toxicology a. The Field of forensic toxicology is a branch of analytical toxicology devoted to toxicological problems of forensic significance (Peters 2011). i. Analysis is used in determining 1. Overdoes a. Accidental b. Suicides 2. Homicide a. Intentional poisonings 2. Sample types used for Analysis a. Blood i. Most commonly used b. Urine i. Most commonly used c. Hair d. Vitreous humor 3. Sample Types Not Available? a. Putrefaction i. Known as bloat ii. Caused by bacterial gases forming in the body iii. On set dependent on environment iv. Occurs over 2-3 days b. Extreme Decomposition i. Active and advanced decay ii. Skin blackens iii. Happens in a matter of weeks depending on temperature and environment c. Skeletonization i. No soft tissue or bodily fluids remaining 4. Alternative Matrix a. Skeletal remains i. Living bone marrow 1. Bone marrow is richly vascurlarized and has a high lipid content 2. It is also the fourth largest organ of the body by weight a. Following bone, muscle, and fat It is estimated that, in humans b. Bone marrow accounts for approximately 4–5 % of the total body weight (Moulopoulos 14). 3. Two types of marrow a. Red b. Yellow 5. Bones Used for Analysis a. Dependent on availability i. Rib ii. Femur iii. Clavicle iv. Pelvis v. Iliac Crest vi. Vertebrae vii. Sternum 6. Methods a. Gas Chromatography-Mass Spectrometry i. Most widely used b. Gas Chromatography c. Liquid Chromatography 7. Université de Lyon (Cartiser 10) a. Are drugs levels in Bone marrow samples representative of blood concentrations at time of death? b. Analysis included i. Males and females 1. ages 26-47 ii. Manor of death 1. Intoxication 2. Strangulation 3. Asphyxiation iii. Elemental exposure 1. 7mo-5yr c. Marrow samples from i. Rib ii. Femur iii. Vertebrae d. Compounds detected using GC-MS i. Paracetamol ii. Dextropropoxyphene iii. Methamphetamine iv. Amphetamine v. Bromisovalum 8. Lyon Forensic Institute (France) a. Bone marrow was analyzed a along with vitreous humor and bile i. Compared to blood concentration b. Used gas chromatography c. Samples came from autopsies samples testing positive for meprobamates i. Proscription drug 1. Treats tension, anxiety, and nervousness d. Meprobamate bone marrow concentrations observed were generally inferior to blood concentrations (Bévalot 13). 9. Experimental conclusion a. There is a correlation between bone marrow and blood. However, additional research is required to determine the exact correlation between their concentrations 10. Factors to consider a. Condition of the remains i. Broken 1. Bone marrow exposed b. Postmortem changes of bone marrow concentration i. Stability of the drug ii. Postmortem redistribution 11. Case Application a. (Cartiser 11) references a case in which the body of a 47-year-old woman was discovered, virtually skeletonized on her family ranch. b. Analysis of her bone marrow suggested that amitriptyline was present i. Results were deemed unreliable c. Law enforcement used this information to conduct a search of the pharmacies in the region and found a prescription for amitriptyline for the decedent 12. Areas for Further study a. Future experimentation i. In order to pin point the relationship between 1. Concentration of blood vs bone marrow 2. Time of exposure vs time of death 3. Route of expose vs concentration levels in bone marrow b. There is no standardized sampling and storage procedure for collecting Bone marrow i. If these finding were to be used as evidence in a court of law a standard needs to be set 13. Conclusion a. Bone marrow has great potential as a matrix in forensic toxicology. b. However, it is apparent that this particular matrix is in its infancy stage and further experimentation Study guide Questions 1. Name the two most common types of matrices used for toxicological analysis. 2. In what cases is an alternative matrix required? 3. Briefly describe the current knowledge of the relationship between blood concentration and bone marrow concentration. 4. What are some areas for further study of bone marrow as a matrix for toxicological analysis?