Determination of Toluene and Xylene Levels in Postmortem Tissues of Rats as a Human Autopsy Process

Determination of Toluene and Xylene Levels in Postmortem Tissues of Rats as a Human Autopsy Process | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Determination of Toluene and Xylene Levels in Postmortem Tissues of Rats as a Human Autopsy Process Eda Oflaz, Celal Butun, Merve Kuloglu, Tugba Tekin, Murat Yayla, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3292516/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Toluene and xylene are frequently used aromatic hydrocarbons in industry. It is also a subject of abuse by inhalation since they have lipid solubility and may affect the blood-brain barrier easily. Toluene or xylene exposure has been reported to cause death. Analyzing the levels of Toluene and xylene in toxicological samples obtained during the autopsy process is important for determining the cause of death. It is also known that the levels of toxic substances show differences during the postmortem period. To make a differential diagnosis of toluene or xylene exposure-related deaths, it is necessary to consider the changes in the levels of these two substances in tissues during the postmortem period. This study aimed to examine the changes in toluene or xylene levels in toxicological samples obtained from rats exposed to lethal doses of Toluene or xylene in the postmortem period. Methods; In our study, intraperitoneal administration of toluene, xylene, and corn oil for the control group was administered to the female Wistar Albino rats. All three groups of rats were also classified according to their postmortem sampling after 0, 2, 4, and 6 hours. Each group (Toluene, Xylene, Control) had 16 samples in the pool chart. Toluene and xylene levels in all tissue specimens were investigated by Head Space-Gas Chromatography-Mass Spectrometry. Statistical analysis of the data were performed by using IBM SPSS Statistics 21 windows based statistical package program. Results Xylene was detected at the maximum level at hour zero in liver, adipose and brain tissues. Toluene was measured at its highest level at hour zero in liver, followed by brain, adipose and blood tissues. Conclusion The changes among tissue levels of these two substances in the postmortem period showed different patterns. This Head Space-Gas Chromatography-Mass Spectrometry method validated for tissue procedures, is highly valuable for determining the amounts of toluene and xylene in tissues Toluene Xylene Postmortem period Cause of death Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Background In recent years, due to developments in petrochemical and related industries, the abuse of organic volatile substances, which has found widespread use, has become an increasing public health issue among young adults worldwide. Adhesives, paint solvents, thinners, aerosols, oil and stain removers, room and hair sprays, deodorants, and organic volatile substances used in cosmetic products have a wide chemical spectrum. ( 1 ) Among these compounds, which are chemically divided into two groups as aromatic and aliphatic hydrocarbons, two of the most well-known aromatic hydrocarbons are toluene and xylene. ( 2 ) Occupational and environmental exposure to toluene and recreational abuse are known. Due to its easy accessibility and low cost, it is widely abused among young people, especially in low-income societies. The effects of toluene use vary according to the duration of use, dose, and whether it is repeated or not. In acute use, general symptoms are euphoria, decreased attention, and excitability due to central nervous system depression. Memory impairment has been reported with repeated use. Again, toluene-related deaths due to respiratory failure, cardiac arrhythmia, and cardiac arrest, which occur at repetitive doses, have been reported in the literature as 'glue sniffing death. ( 3 , 4 ) Xylene-related health problems are especially prominent in environmental and occupational exposure. The use of xylene is mainly concentrated in the paint and plastic industry. It is reported that xylene exposure is mostly in breath, oral, eye, or skin contact. It has been revealed that symptoms such as weakening muscle strength, vomiting, loss of appetite, chest pain, increased heart rate, deterioration in respiratory functions, memory and balance problems, and increased excitability are observed in xylene exposure. ( 5 , 6 ) It is stated that deaths due to acute xylene poisoning are mostly due to oral or respiratory ingestion of mixed chemical substances (toluene, xylene, benzene mixtures) due to accidents or suicide. ( 7 ) Toxicological analyzes performed in autopsies are very helpful in elucidating the cause of death. Due to the inadequacy of toxicological analyzes and the scarcity of studies in some case reports where death is thought to have developed due to toluene and xylene, the need to reveal the relationship between toluene and xylene levels detected in toxicological analyses with the cause of death and the time elapsed after death has arisen. This study aims to investigate the levels of toluene and xylene in the blood, organ, and tissue samples obtained in autopsies performed at certain hours in the postmortem period in rats exposed to lethal doses of toluene and xylene and to contribute to the correlation of toluene and xylene levels determined in postmortem toxicological analyzes with the cause of death and time of death. 2. Material and Method This study was carried out prospectively after being approved by the decision of Cumhuriyet University Animal Experiments Local Ethics Committee dated 05/05/2016 and numbered 59. The rats and their feeds used in the experiment were obtained from the Animal Experiments Laboratory of Cumhuriyet University. In this study, 48 Wistar Albino rats, 16 weeks old and weighing approximately 250 g, were used. 2.1. Animal Experiment Procedure Experimental animals were housed in a 12-hour light and 12-hour dark cycle, at 21 ± 1 0 C, in a 50% humidity environment. The total amount of feed consumed by the animals during their stay is 5-6gr/50gr/day per 48 animals, and the feed consumption is 2400gr/day in total. Standard pellet feed and water were provided ad libitum. Experimental animals were divided into 3 main groups (toluene, xylene, and control). Every three groups were divided into 4 small groups (0, 2, 4, and 6 hours) according to the time elapsed after death, and a total of 12 experimental groups were formed (toluene 4 groups, xylene 4 groups, control 4 groups) (Table 1 ). Experimental animals (n;16) in the toluene main group were injected intraperitoneally with 1.1 g/kg toluene (0.1 g/ml in corn oil). Experimental animals (n;16) in the xylene main group were injected intraperitoneally with 0.814 mmol/kg xylene (0.1 g/ml in corn oil). Experimental animals (n;16) in the control main group were injected intraperitoneally with 0.1 ml/10 g/day corn oil. Euthanasia was performed by cervical dislocation at 30 minutes following the injection. Each experimental animal was autopsied at the postmortem hour, symbolized by the small group it belongs to, and brain, adipose tissue, liver tissue, and heart blood were collected, and the samples were stored at -20 0 C. Table 1 Animal Experimental Protocol Experiment and Control Groups Number of rats per each group Number of repeat Total Number of rats 1 Toluene (0. Hour) 4 1 4 2 Toluene (3. Hour) 4 1 4 3 Toluene (6. Hour) 4 1 4 4 Toluene (12. Hour) 4 1 4 5 Xylene (0. Hour) 4 1 4 6 Xylene (3. Hour) 4 1 4 7 Xylene (6. Hour) 4 1 4 8 Xylene (12. Hour) 4 1 4 9 Control (0. Hour) 4 1 4 10 Control (3. Hour) 4 1 4 11 Control (6. Hour) 4 1 4 12 Control (12. Hour) 4 1 4 2.2. Chemicals The animal experiment protocol used xylene (0.86 g/ml density at 25 0 C/liter temperature) and toluene (0.865 g/ml density at 25 0 C/liter temperature) chemicals. 2.3. Analysis Procedure Toluene and xylene levels in all tissue samples, 30 m x 0.25 mm (id) fused silica capillary column (HP-5MS 5% Phenyl Methyl Siloxane, 5% Phenyl Methyl Siloxane, Film thickness 0.25 µm - Agilent Part No. 19091S-433) Head Space-Gas Chromatography-Mass Spectrometer (HS-GC / MS) equipped with For sampling, approximately 0.25 g (wet weight) tissue from each batch was placed in a headspace vial, then 0.5 mL of 5N NaOH, 0.25 g of NaCl, 617 µL of n-BuOH was added, and 5 mL of bottled water was added and filled to. NaCl salt was used to reduce the matrix effect. Static headspace was performed using the following optimized experimental conditions: vial temperature 80°C, gas chromatography cycle time 7 minutes, bottle equilibration time 7 minutes, cycle temperature 90°C, bottle volume 20 mL, sample solution volume 5 mL, injection time 0, 5 minutes, injection volume 0.5 mL. The analysis run time is 6 minutes. The oven temperature is as follows; 25 0C ramp up to 100 0C 75 0C (hold for 4 min) and hold for 1 minute. The split ratio was 55:1. Retention times were 1.77 minutes (N-BuOH). (2.29 minutes Toluene and 3.28 minutes Xylene). All quantitative evaluations were made by the selective ion monitoring (SIM) method based on the ions found for m / z 91, 65 for toluene and m / z 105, 91, 77 for xylene and m / z 41, 56 for n-BuOH. has been achieved. Calibration curves were created with correlation coefficient values ​​of 0.99 between 0.001–0.04 µg/mL for toluene and 0.003–0.12 µg/mL for xylene. N-BuOH was used as an internal standard. In animal studies on long-term exposure to toluene and xylene, it has been noted that there may be a decrease in the movements of the animals and a change in their eating behavior. In our study, it was assumed that the experimental animals could die before euthanasia during the experimental procedures since they were exposed to toluene and xylene at a lethal dose. The animal species used in our study was chosen as the lowest phylogenetic species among the species to be selected to make the experiment results meaningful and reflect the analyses made in humans. The number of experimental animals was determined close to the statistical significance studies. The experimental protocol is based on lethal dose administration of toluene and xylene. The pain that may occur in the experimental animal was terminated with euthanasia at the 30th minute following the injection. 2.4. Statistical analysis The normal distribution of the data was tested with the Shapira-Wilk test. Normally distributed numerical data are presented as mean ± standard deviation, non-normally distributed numerical data are presented as median and categorical data are presented as median. A paired-T (dependent) analysis test compared xylene and toluene levels in different tissues according to postmortem death hours. Significance test of the difference between two means compared to normally distributed numerical variables T-test; Mann-Whitney-U test was used for numerical variables that did not show normal distribution. Statistical data analysis was done with IBM SPSS Statistics version 21 Windows-based statistical package program. A value of less than 0.05 (p < 0.05), the statistical significance expression, was considered statistically significant. 3. Results When the mean level of xylene levels measured in rats is evaluated in postmortem hours regardless of tissue difference, It was determined that it reached the highest level at the 4th hour, and then decreased considerably at the 6th hour and decreased to the measurement level at the 0th hour (Fig. 1 ). In rats measured xylene, the highest xylene level was detected in the liver (0.052) at 0 hours, followed by fat (0.039), brain (0.021), and blood (0.003) tissue. While the xylene level increased in the postmortem adipose and liver tissue until the postmortem 4th hour, it decreased again at the 6th hour and below the values ​​in the 0th hour (p > 0.05). In the blood tissue, on the other hand, although the xylene level reached the maximum level (0.051) at the postmortem 6th hour, no significant difference was found on an hourly basis (p > 0.05). (Fig. 2 ) When the average level of toluene levels measured in rats is evaluated in postmortem hours regardless of tissue difference; It was determined that it increased at the 2nd hour compared to its value at the 0th hour, decreased slightly at the 4th hour, and reached the highest level at the 6th hour (Fig. 3 ) In rats measured toluene, the highest level of toluene was detected in the liver (1,780) tissue at 0 hours, followed by the brain (0.809), fat (0.696), and blood (0.520) tissue. Although it was observed that the toluene level in adipose tissue increased over time, it was slightly lower at the 4th hour than at the 2nd hour. Still, at the 6th hour, it reached approximately 6 times the level at the 0th hour, but this increase was not statistically significant (p > 0.05). Toluene level reached the maximum in the blood tissue at the 2nd hour and decreased afterward (p > 0.05) (Fig. 4 ). In the analyzes made for toluene and xylene, the changes in the levels of both substances in the organs according to the postmortem hours were evaluated between the organs. However, there were hourly differences; these differences were not statistically significant. All dependent analysis comparisons are presented in Table 2 for detailed xylene and Table 3 for toluene. Table 2 Postmortem Xylene levels in brain, blood, liver and adipose tissue Comparison of groups Average diff. SD P Xylene Brain − 0.hour − 2.hour 0,0182 0,0210 0,171 Xylene Brain − 0.hour − 4.hour 0,0002 0,0293 0,990 Xylene Brain − 0.hour − 6.hour 0,0182 0,0213 0,176 Xylene Brain − 2.hour − 4.hour -0,0180 0,0208 0,182 Xylene Brain − 4.hour − 6.hour 0,0180 0,0208 0,182 Xylene Blood − 0.hour − 2.hour -0,0138 0,0275 0,391 Xylene Blood − 0.hour − 4.hour -0,0136 0,0271 0,391 Xylene Blood − 0.hour − 6.hour -0,0482 0,0964 0,391 Xylene Blood − 2.hour − 4.hour 0,0002 0,0446 0,993 Xylene Blood − 2.hour − 6.hour -0,0345 0,0689 0,391 Xylene Blood − 4.hour − 6.hour -0,0347 0,1085 0,568 Xylene Liver − 0.hour − 2.hour -0,0092 0,0998 0,865 Xylene Liver − 0.hour − 4.hour -0,0466 0,1509 0,581 Xylene Liver − 0.hour − 6.hour 0,0308 0,0670 0,425 Xylene Liver − 2.hour − 4.hour -0,0374 0,0660 0,340 Xylene Liver − 2.hour − 6.hour 0,0400 0,0339 0,099 Xylene Liver − 4.hour − 6.hour 0,0774 0,0897 0,183 Xylene Adipose − 0.hour − 2.hour -0,0753 0,1868 0,479 Xylene Adipose − 0.hour − 4.hour -0,0878 0,2245 0,491 Xylene Adipose − 0.hour − 6.hour 0,0174 0,0458 0,502 Xylene Adipose − 2.hour − 4.hour -0,0125 0,0704 0,746 Xylene Adipose − 2.hour − 6.hour 0,0927 0,1632 0,338 Xylene Adipose − 4.hour − 6.hour 0,1053 0,2126 0,395 Table 3 Postmortem Toluene levels in brain, blood, liver and adipose tissue Comparison of groups Average diff. SD p Toluene Brain − 0.hour − 2.hour 0,4335 0,9367 0,423 Toluene Brain − 0.hour − 4.hour 0,4976 0,9901 0,389 Toluene Brain − 0.hour − 6.hour 0,3178 1,2207 0,639 Toluene Brain − 2.hour − 4.hour 0,0641 0,3902 0,764 Toluene Brain − 2.hour − 6.hour -0,1157 0,6854 0,758 Toluene Brain − 4.hour − 6.hour -0,1798 0,3345 0,361 Toluene Blood − 0.hour − 2.hour -3,5306 5,5691 0,294 Toluene Blood − 0.hour − 4.hour -1,8623 2,3049 0,205 Toluene Blood − 0.hour − 6.hour -0,8112 1,3269 0,309 Toluene Blood − 2.hour − 4.hour 1,6682 3,3693 0,395 Toluene Blood − 2.hour − 6.hour 2,7194 6,2468 0,448 Toluene Blood − 4.hour − 6.hour 1,0512 3,1187 0,549 Toluene Liver − 0.hour − 2.hour 1,0132 1,0624 0,153 Toluene Liver − 0.hour − 4.hour 1,0970 1,3441 0,201 Toluene Liver − 0.hour − 6.hour -0,0899 2,3834 0,945 Toluene Liver − 2.hour − 4.hour 0,0838 0,8482 0,856 Toluene Liver − 2.hour − 6.hour -1,1031 1,3389 0,198 Toluene Liver − 4.hour − 6.hour -1,1869 1,7635 0,271 Toluene Adipose − 0.hour − 2.hour -0,6276 1,1206 0,344 Toluene Adipose − 0.hour − 4.hour -0,3906 0,5198 0,230 Toluene Adipose − 0.hour − 6.hour -3,0892 3,8695 0,209 Toluene Adipose − 2.hour − 4.hour 0,2370 0,6431 0,514 Toluene Adipose − 2.hour − 6.hour -2,4616 4,4583 0,350 Toluene Adipose − 4.hour − 6.hour -2,6986 4,1625 0,285 4. Discussion Many studies on postmortem redistribution focus on benzodiazepines, amphetamines, and opiates. ( 8 ) It is known that these substances easily pass through barriers between tissues due to their lipophilic properties and are more likely to undergo postmortem redistribution. ( 9 ). Toluene and xylene used in our study are highly lipophilic substances due to their hydrocarbon structures, and they tend to accumulate in the brain, adipose tissue, and liver like other lipophilic substances. However, factors such as these substances' volatile nature and rapid clearance from the blood in the antemortem period make it difficult to detect these substances in toxicological analyses and interpret the detected levels. Although there are case studies and analytical studies on the detection of hydrocarbons in blood and tissues in the postmortem period in the literature, the number of studies on the changes in the levels of these substances in the postmortem period is limited. ( 10 , 11 ) Toxicological analyzes made in autopsies are very helpful in elucidating the cause of death. Due to the inadequacy of toxicological analyzes and the scarcity of studies in some case reports thought to be death due to toluene and xylene, the need to reveal the relationship between toluene and xylene detected in toxicological analyzes with the cause of death and the time elapsed after death has arisen. Headspace (HS)- Gas Chromatograph (GC)- Mass Spectrometry (MS) instrument offers the greatest specificity, sensitivity, and accuracy for the quantitative analysis of toluene and other volatiles in different matrices ( 12 , 13 ). Karadayı et al., in their toluene analysis with the Headspace-Gas Chromatography technique, stated that this method prevents sample and analyte loss and can be directly collected into vials without extraction. ( 14 ). Recent studies in the literature support that the Headspace-GC-MS device is an important alternative to HPLC ( 15 , 16 , 17 ) Headspace GC-MS device has become a preferred method, especially in analyzing volatile ethanol, methanol, and organic solvents such as toluene and xylene, because it is fast and gives reliable results. ( 18 ) In the method used in our study, n-BuOH was used as the internal standard, and the selective ion scanning (SIM) method was used to detect xylene and toluene ions in the tissues. It was thought that the detection of toluene and xylene was achieved with this method and that this method could be used in future studies. The data obtained in our study show that the hour and tissue-based postmortem distribution rates of xylene and toluene differ. The continued passage of substances from the blood to the adipose tissue is an important distribution route, especially for lipophilic substances and volatile substances ( 19 , 20 , 21 ). Adipose tissue is a recently preferred sample for analyzing oil-soluble hydrocarbons such as toluene, xylene, and other lipophilic molecules ( 22 ). This distribution occurs slowly, as adipose tissue perfusion is low, and equilibrium between blood and adipose tissue concentrations may not be reached at the time of death. In such a situation, the sustained distribution of these drugs from blood to adipose tissue may result in lower postmortem blood concentrations ( 23 ). In our study, the xylene level in postmortem adipose tissue increased until the 4th hour, then decreased, and the values ​​at the 6th hour fell below the levels at the 0th hour, but this decrease was not statistically significant. Although it was observed that a slight decrease was observed compared to the level at the 2nd hour and reached the highest level by rising again at the 6th hour, it was determined that this change was not statistically significant. The anatomical relationships of the human liver to postmortem redistribution are with the stomach, pylorus, proximal duodenum, and gallbladder, but this is not as important as redistribution via hepatic vessels ( 24 ). In our study, in rats that measured toluene, the highest level of toluene was detected in liver tissue at 0 hours, followed by brain, fat, and blood tissue. Brain tissue is a valuable sample for the measurement of drugs because it is the primary site of action for many drugs, and lipophilic substances such as antidepressants, narcotics, and halogenated hydrocarbons45 accumulate in central nervous tissue ( 25 ). In our study, the xylene level in the brain tissue at 0 hours was lower than that of the liver and adipose tissue; this value was 0.021 at 0 hours and decreased to 0.003 at the 6th hour. In the other 3 tissues, it was determined that while the level increased postmortem as time passed, it only reduced in the brain tissue. It is thought that this situation can be interpreted as toluene undergoes postmortem transformation more in brain tissue than in fat, blood, and liver tissue. Blood tissue is a complex mixture of dissolved proteins, fats, solids, and suspended cells ( 26 ). Serum or plasma is traditionally used in clinical settings because blood provides advanced use in laboratory procedures ( 27 ). Analytical results from postmortem blood are significantly compared to previously reported levels in therapeutic and toxic conditions ( 28 , 29 , 30 ). In our study, toluene and xylene levels analyzed in the blood had the lowest values ​​compared to liver, adipose, and brain tissue in the first measurement. Still, the xylene level continuously increased in the following hours (from 0.003 to 0.051). In contrast, toluene at 0. hour (0.52 ) at the 2nd hour shows a trend that rises to 8 times (4.05) at the 2nd hour and reaches its peak; it tends to decrease at the 4th hour and reduces to approximately 1/3 of the level in the 2nd hour at the 6th hour. It was found that it was measured at a high level (1.33). One of the limitations of our study is the difficulties encountered in blood sampling in the selected experimental animal species, especially in the postmortem period. In our study, problems were encountered during blood sampling due to coagulation in the body of experimental animals after euthanasia. This problem could be solved by performing the study with an experimental animal in the higher group regarding phylogenetics or in humans under appropriate conditions. This study determined the amount of toluene and xylene in biological samples taken at 0, 2, 4, and 6 hours postmortem with a fast and accurate analytical method. Our study observed that the levels of toluene and xylene in blood and tissues showed different change patterns in the postmortem period. This is due to the use of wet tissue weights during the analysis of the tissues and the volatile character of toluene and xylene. If dry tissue weights are used during the analysis, it was preferred to use wet tissue weights because of the possibility that the substances could not be detected in the tissue due to their volatile properties. Due to the volatile properties of toluene and xylene, the significance levels of the results obtained in the tissues, especially in the early postmortem period, were included in the evaluation. There may be difficulty in detecting the volatile molecule due to the effects of decay and ambient factors in the advancing postmortem period. Therefore, the study's analyses cover the first six hours after death. According to the results obtained in our study, especially in tissue-based analyzes, the increase was observed in the first 4 hours, and the substance levels decreased below the initial level in the 6th hour, which once again highlights the need for analysis in the early period. 5. Conclusions With this study, it was aimed to contribute to the establishment of the correlation of toluene and xylene levels determined in postmortem toxicological analyses with the cause of death and time of death by investigating the levels of toluene and xylene in the blood, organ, and tissue samples obtained in autopsies performed at certain hours in the postmortem period in rats exposed to lethal doses of toluene and xylene. Similar studies need to be developed by human autopsy protocols. Abbreviations HS-GC/MS); Head Space Gas Chromatography-Mass Spectrometry, HPLC; High Pressure Liquid Cromatography, SPSS; Statistical Package for the Social Sciences, SIM; Selective Ion Scanning Declarations Ethics approval and consent to participate We confirm that any aspect of the work covered in this manuscript that has involved experimental animals has been conducted with the ethical approval of Cumhuriyet University Animal Experiments Local Ethics Committee by the decision dated 05/05/2016 and numbered 59. we confirm that all methods were performed in accordance with the relevant guidelines and regulations. Consent for publication* We give our consent for the publication of identifiable details within the text to be published in BMC Pharmacology and Toxicology. Availability of data and materials The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials. Competing interests The athors declare that they have no competing interest. Funding Our Study was financially supported by Cumhuriyet University Scientific Research Projects Coordination Unit with the project numbered T-681. Authors' contributions The authors confirm contribution to the paper as follows: EO, CB: study conception and design, data collection, draft manuscript preparation MK, TT, MY, SM and ZT: laboratory analysis and interpretation of results. MFU: data collection and draft manuscript preparation. AllF authors reviewed the results and approved the final version of the manuscript. Acknowledgements (optional) The authors thank to Cumhuriyet University Head of Scientific Research Project and Istanbul University Cerrahpasa Institute of Forensic Sciences and Legal Medicine. References Barnes, Gordon E. "Solvent abuse: A review." International Journal of the Addictions 14.1 (1979): 1-26. Devathasan, G., et al. "Complications of chronic glue (toluene) abuse in adolescents." 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Forensic science international, 165(1):10-29, 2007 Saitman A, Fitzgerald RL, McIntyre IM. Evaluation and comparison of postmortem hydrocodone concentrations in peripheral blood, central blood, and liver specimens: a minimal potential for redistribution. Forensic science international, 247:36-40, 2015 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3292516","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":229831580,"identity":"faa1a78c-a01a-4261-b374-f75746c04da1","order_by":0,"name":"Eda Oflaz","email":"","orcid":"","institution":"Council of Forensic Medicine Yozgat","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Eda","middleName":"","lastName":"Oflaz","suffix":""},{"id":229831581,"identity":"633816ca-3edf-4e06-a2e3-068bebc4498b","order_by":1,"name":"Celal Butun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABH0lEQVRIie3RvWrDMBAH8DOGTCpZL7huXkFFUDKE9lVsCpncEuhiaAebgL2YzMlb5A1qI7AXPUAhGRIM6dLBpVA6tT1T+jHIZO2g/ySd9EPHCcDE5F/GjmALebuyaoARQ1q1WyvqJHTk0R1GWADgX2IfJD2HCOBvXU/6aRw3Hmz8e7wqb6d3eDxI050MYeyu8n7ZaAiqYoYe7P0MryfrRYnMYYoXCiZildv2QkM4+hERSSQ4W7MeshMMoIio0hJdY3y4m719kxv2TmT4uCXy0U3QSn5esY8SagyBE8k7CSo/GXl8LzL1JJzlHNkgC4jwS7GU7dR1E5PyoQk3bpoGpy/T1/EFVlX9HIXn7ryKa+2Uv9rTVrp+0sTExMTkYD4BM7tjyEhyEMEAAAAASUVORK5CYII=","orcid":"","institution":"Balıkesir University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Celal","middleName":"","lastName":"Butun","suffix":""},{"id":229831583,"identity":"4e9713da-1118-4fb6-932e-d66e091fe5f7","order_by":2,"name":"Merve Kuloglu","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Merve","middleName":"","lastName":"Kuloglu","suffix":""},{"id":229831585,"identity":"55450171-408d-476c-b02e-4570b7d5d3ba","order_by":3,"name":"Tugba Tekin","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tugba","middleName":"","lastName":"Tekin","suffix":""},{"id":229831588,"identity":"04242cc5-acd1-4741-b1fe-029cdc1e51e5","order_by":4,"name":"Murat Yayla","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Murat","middleName":"","lastName":"Yayla","suffix":""},{"id":229831590,"identity":"491d5ae3-a1f8-49d0-bdcc-16f6177bd92f","order_by":5,"name":"Selda Mercan","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Selda","middleName":"","lastName":"Mercan","suffix":""},{"id":229831593,"identity":"04b774e5-49f6-4152-a33d-a0e57e5dbcdf","order_by":6,"name":"Zeynep Turkmen","email":"","orcid":"","institution":"Istanbul University Cerrahpaşa","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zeynep","middleName":"","lastName":"Turkmen","suffix":""},{"id":229831595,"identity":"938c256a-e8f6-4364-ac99-07c86605cc0f","order_by":7,"name":"Mehmet Fatih Unver","email":"","orcid":"","institution":"Council of Forensic Medicine Tokat","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mehmet","middleName":"Fatih","lastName":"Unver","suffix":""}],"badges":[],"createdAt":"2023-08-24 12:14:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3292516/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3292516/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":42500931,"identity":"89ea8799-b551-49cd-8abb-b1357f1d88da","added_by":"auto","created_at":"2023-09-01 14:44:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":14427,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3.1 Average levels of xylenes in postmortem hours\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3292516/v1/c8e99aa2bc28e394feecd50f.png"},{"id":42500932,"identity":"d187201f-47db-4459-8458-8dfed393bc18","added_by":"auto","created_at":"2023-09-01 14:44:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":23487,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 3.2\u003c/strong\u003e. Average level of toluene levels at postmortem hours\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3292516/v1/3b345f934dbc01e0aa1e93ab.png"},{"id":42500933,"identity":"a47becf6-5c17-4fe1-abfd-a2fe5265a9f5","added_by":"auto","created_at":"2023-09-01 14:44:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":18686,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3.3. The mean level of xylene levels in tissues according to postmortem hours\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3292516/v1/9ee61529dab35d2dc9e295ba.png"},{"id":42500934,"identity":"3575e85f-4227-4c27-ad14-ad1c0e210547","added_by":"auto","created_at":"2023-09-01 14:44:14","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":21550,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 3.4\u003c/strong\u003e. Average level of toluene levels in postmortem hours according to tissues.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3292516/v1/bda97ea83ef651966d2c9401.png"},{"id":43882703,"identity":"e88f0dd6-15c0-4985-801b-c7c413abe2b2","added_by":"auto","created_at":"2023-09-29 13:52:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":392488,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3292516/v1/cf6f805c-0b58-45e9-884d-13b7ae2f98f6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Determination of Toluene and Xylene Levels in Postmortem Tissues of Rats as a Human Autopsy Process","fulltext":[{"header":"1. Background","content":"\u003cp\u003eIn recent years, due to developments in petrochemical and related industries, the abuse of organic volatile substances, which has found widespread use, has become an increasing public health issue among young adults worldwide. Adhesives, paint solvents, thinners, aerosols, oil and stain removers, room and hair sprays, deodorants, and organic volatile substances used in cosmetic products have a wide chemical spectrum. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Among these compounds, which are chemically divided into two groups as aromatic and aliphatic hydrocarbons, two of the most well-known aromatic hydrocarbons are toluene and xylene. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOccupational and environmental exposure to toluene and recreational abuse are known. Due to its easy accessibility and low cost, it is widely abused among young people, especially in low-income societies. The effects of toluene use vary according to the duration of use, dose, and whether it is repeated or not. In acute use, general symptoms are euphoria, decreased attention, and excitability due to central nervous system depression. Memory impairment has been reported with repeated use. Again, toluene-related deaths due to respiratory failure, cardiac arrhythmia, and cardiac arrest, which occur at repetitive doses, have been reported in the literature as 'glue sniffing death. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eXylene-related health problems are especially prominent in environmental and occupational exposure. The use of xylene is mainly concentrated in the paint and plastic industry. It is reported that xylene exposure is mostly in breath, oral, eye, or skin contact. It has been revealed that symptoms such as weakening muscle strength, vomiting, loss of appetite, chest pain, increased heart rate, deterioration in respiratory functions, memory and balance problems, and increased excitability are observed in xylene exposure. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) It is stated that deaths due to acute xylene poisoning are mostly due to oral or respiratory ingestion of mixed chemical substances (toluene, xylene, benzene mixtures) due to accidents or suicide. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eToxicological analyzes performed in autopsies are very helpful in elucidating the cause of death. Due to the inadequacy of toxicological analyzes and the scarcity of studies in some case reports where death is thought to have developed due to toluene and xylene, the need to reveal the relationship between toluene and xylene levels detected in toxicological analyses with the cause of death and the time elapsed after death has arisen. This study aims to investigate the levels of toluene and xylene in the blood, organ, and tissue samples obtained in autopsies performed at certain hours in the postmortem period in rats exposed to lethal doses of toluene and xylene and to contribute to the correlation of toluene and xylene levels determined in postmortem toxicological analyzes with the cause of death and time of death.\u003c/p\u003e"},{"header":"2. Material and Method","content":"\u003cp\u003e This study was carried out prospectively after being approved by the decision of Cumhuriyet University Animal Experiments Local Ethics Committee dated 05/05/2016 and numbered 59. The rats and their feeds used in the experiment were obtained from the Animal Experiments Laboratory of Cumhuriyet University. In this study, 48 Wistar Albino rats, 16 weeks old and weighing approximately 250 g, were used.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Animal Experiment Procedure\u003c/h2\u003e \u003cp\u003eExperimental animals were housed in a 12-hour light and 12-hour dark cycle, at 21\u0026thinsp;\u0026plusmn;\u0026thinsp;1 \u003csup\u003e0\u003c/sup\u003eC, in a 50% humidity environment. The total amount of feed consumed by the animals during their stay is 5-6gr/50gr/day per 48 animals, and the feed consumption is 2400gr/day in total. Standard pellet feed and water were provided ad libitum. Experimental animals were divided into 3 main groups (toluene, xylene, and control). Every three groups were divided into 4 small groups (0, 2, 4, and 6 hours) according to the time elapsed after death, and a total of 12 experimental groups were formed (toluene 4 groups, xylene 4 groups, control 4 groups) (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Experimental animals (n;16) in the toluene main group were injected intraperitoneally with 1.1 g/kg toluene (0.1 g/ml in corn oil). Experimental animals (n;16) in the xylene main group were injected intraperitoneally with 0.814 mmol/kg xylene (0.1 g/ml in corn oil). Experimental animals (n;16) in the control main group were injected intraperitoneally with 0.1 ml/10 g/day corn oil. Euthanasia was performed by cervical dislocation at 30 minutes following the injection. Each experimental animal was autopsied at the postmortem hour, symbolized by the small group it belongs to, and brain, adipose tissue, liver tissue, and heart blood were collected, and the samples were stored at -20 \u003csup\u003e0\u003c/sup\u003eC.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnimal Experimental Protocol\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExperiment and Control Groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber of rats per each group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of repeat\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTotal Number of rats\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eToluene (0. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eToluene (3. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eToluene (6. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eToluene (12. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eXylene (0. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eXylene (3. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eXylene (6. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eXylene (12. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (0. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (3. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (6. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl (12. Hour)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Chemicals\u003c/h2\u003e \u003cp\u003eThe animal experiment protocol used xylene (0.86 g/ml density at 25 \u003csup\u003e0\u003c/sup\u003eC/liter temperature) and toluene (0.865 g/ml density at 25 \u003csup\u003e0\u003c/sup\u003eC/liter temperature) chemicals.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Analysis Procedure\u003c/h2\u003e \u003cp\u003eToluene and xylene levels in all tissue samples, 30 m x 0.25 mm (id) fused silica capillary column (HP-5MS 5% Phenyl Methyl Siloxane, 5% Phenyl Methyl Siloxane, Film thickness 0.25 \u0026micro;m - Agilent Part No. 19091S-433) Head Space-Gas Chromatography-Mass Spectrometer (HS-GC / MS) equipped with For sampling, approximately 0.25 g (wet weight) tissue from each batch was placed in a headspace vial, then 0.5 mL of 5N NaOH, 0.25 g of NaCl, 617 \u0026micro;L of n-BuOH was added, and 5 mL of bottled water was added and filled to. NaCl salt was used to reduce the matrix effect. Static headspace was performed using the following optimized experimental conditions: vial temperature 80\u0026deg;C, gas chromatography cycle time 7 minutes, bottle equilibration time 7 minutes, cycle temperature 90\u0026deg;C, bottle volume 20 mL, sample solution volume 5 mL, injection time 0, 5 minutes, injection volume 0.5 mL. The analysis run time is 6 minutes. The oven temperature is as follows; 25 0C ramp up to 100 0C 75 0C (hold for 4 min) and hold for 1 minute. The split ratio was 55:1. Retention times were 1.77 minutes (N-BuOH). (2.29 minutes Toluene and 3.28 minutes Xylene). All quantitative evaluations were made by the selective ion monitoring (SIM) method based on the ions found for m / z 91, 65 for toluene and m / z 105, 91, 77 for xylene and m / z 41, 56 for n-BuOH. has been achieved. Calibration curves were created with correlation coefficient values ​​of 0.99 between 0.001\u0026ndash;0.04 \u0026micro;g/mL for toluene and 0.003\u0026ndash;0.12 \u0026micro;g/mL for xylene. N-BuOH was used as an internal standard.\u003c/p\u003e \u003cp\u003eIn animal studies on long-term exposure to toluene and xylene, it has been noted that there may be a decrease in the movements of the animals and a change in their eating behavior. In our study, it was assumed that the experimental animals could die before euthanasia during the experimental procedures since they were exposed to toluene and xylene at a lethal dose. The animal species used in our study was chosen as the lowest phylogenetic species among the species to be selected to make the experiment results meaningful and reflect the analyses made in humans. The number of experimental animals was determined close to the statistical significance studies. The experimental protocol is based on lethal dose administration of toluene and xylene. The pain that may occur in the experimental animal was terminated with euthanasia at the 30th minute following the injection.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Statistical analysis\u003c/h2\u003e \u003cp\u003eThe normal distribution of the data was tested with the Shapira-Wilk test. Normally distributed numerical data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, non-normally distributed numerical data are presented as median and categorical data are presented as median. A paired-T (dependent) analysis test compared xylene and toluene levels in different tissues according to postmortem death hours. Significance test of the difference between two means compared to normally distributed numerical variables T-test; Mann-Whitney-U test was used for numerical variables that did not show normal distribution. Statistical data analysis was done with IBM SPSS Statistics version 21 Windows-based statistical package program. A value of less than 0.05 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), the statistical significance expression, was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eWhen the mean level of xylene levels measured in rats is evaluated in postmortem hours regardless of tissue difference, It was determined that it reached the highest level at the 4th hour, and then decreased considerably at the 6th hour and decreased to the measurement level at the 0th hour (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn rats measured xylene, the highest xylene level was detected in the liver (0.052) at 0 hours, followed by fat (0.039), brain (0.021), and blood (0.003) tissue. While the xylene level increased in the postmortem adipose and liver tissue until the postmortem 4th hour, it decreased again at the 6th hour and below the values ​​in the 0th hour (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the blood tissue, on the other hand, although the xylene level reached the maximum level (0.051) at the postmortem 6th hour, no significant difference was found on an hourly basis (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWhen the average level of toluene levels measured in rats is evaluated in postmortem hours regardless of tissue difference; It was determined that it increased at the 2nd hour compared to its value at the 0th hour, decreased slightly at the 4th hour, and reached the highest level at the 6th hour (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn rats measured toluene, the highest level of toluene was detected in the liver (1,780) tissue at 0 hours, followed by the brain (0.809), fat (0.696), and blood (0.520) tissue. Although it was observed that the toluene level in adipose tissue increased over time, it was slightly lower at the 4th hour than at the 2nd hour. Still, at the 6th hour, it reached approximately 6 times the level at the 0th hour, but this increase was not statistically significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Toluene level reached the maximum in the blood tissue at the 2nd hour and decreased afterward (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn the analyzes made for toluene and xylene, the changes in the levels of both substances in the organs according to the postmortem hours were evaluated between the organs. However, there were hourly differences; these differences were not statistically significant. All dependent analysis comparisons are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e for detailed xylene and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e for toluene.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostmortem Xylene levels in brain, blood, liver and adipose tissue\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComparison of groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage diff.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Brain \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,171\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Brain \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0293\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,990\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Brain \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,176\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Brain \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Brain \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0208\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,182\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Blood \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0275\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Blood \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Blood \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Blood \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,993\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Blood \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Blood \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0347\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,1085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Liver \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,865\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Liver \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0466\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,1509\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,581\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Liver \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,425\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Liver \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0660\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,340\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Liver \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0400\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,099\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Liver \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0774\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,183\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Adipose \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,1868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,479\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Adipose \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0878\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,2245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,491\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Adipose \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0458\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Adipose \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,0704\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,746\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Adipose \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,1632\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eXylene Adipose \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,1053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,2126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,395\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostmortem Toluene levels in brain, blood, liver and adipose tissue\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComparison of groups\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAverage diff.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Brain \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,4335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,9367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,423\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Brain \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,4976\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,9901\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,389\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Brain \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,3178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,2207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,639\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Brain \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0641\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,3902\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,764\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Brain \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,1157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,6854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,758\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Brain \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,1798\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,3345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,361\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Blood \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-3,5306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5,5691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,294\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Blood \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1,8623\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2,3049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,205\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Blood \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,8112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,3269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,309\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Blood \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,6682\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3,3693\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,395\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Blood \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,7194\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6,2468\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,448\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Blood \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,0512\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3,1187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Liver \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,0132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,0624\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,153\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Liver \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,0970\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,3441\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Liver \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,0899\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2,3834\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,945\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Liver \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,0838\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,8482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,856\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Liver \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1,1031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,3389\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Liver \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1,1869\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,7635\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,271\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Adipose \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;2.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,6276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1,1206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,344\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Adipose \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0,3906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,5198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Adipose \u0026minus;\u0026thinsp;0.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-3,0892\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3,8695\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Adipose \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;4.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,2370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0,6431\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,514\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Adipose \u0026minus;\u0026thinsp;2.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2,4616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4,4583\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,350\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eToluene Adipose \u0026minus;\u0026thinsp;4.hour \u0026minus;\u0026thinsp;6.hour\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2,6986\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4,1625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0,285\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eMany studies on postmortem redistribution focus on benzodiazepines, amphetamines, and opiates. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) It is known that these substances easily pass through barriers between tissues due to their lipophilic properties and are more likely to undergo postmortem redistribution. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eToluene and xylene used in our study are highly lipophilic substances due to their hydrocarbon structures, and they tend to accumulate in the brain, adipose tissue, and liver like other lipophilic substances. However, factors such as these substances' volatile nature and rapid clearance from the blood in the antemortem period make it difficult to detect these substances in toxicological analyses and interpret the detected levels. Although there are case studies and analytical studies on the detection of hydrocarbons in blood and tissues in the postmortem period in the literature, the number of studies on the changes in the levels of these substances in the postmortem period is limited. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eToxicological analyzes made in autopsies are very helpful in elucidating the cause of death. Due to the inadequacy of toxicological analyzes and the scarcity of studies in some case reports thought to be death due to toluene and xylene, the need to reveal the relationship between toluene and xylene detected in toxicological analyzes with the cause of death and the time elapsed after death has arisen. Headspace (HS)- Gas Chromatograph (GC)- Mass Spectrometry (MS) instrument offers the greatest specificity, sensitivity, and accuracy for the quantitative analysis of toluene and other volatiles in different matrices (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eKaradayı et al., in their toluene analysis with the Headspace-Gas Chromatography technique, stated that this method prevents sample and analyte loss and can be directly collected into vials without extraction. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Recent studies in the literature support that the Headspace-GC-MS device is an important alternative to HPLC (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHeadspace GC-MS device has become a preferred method, especially in analyzing volatile ethanol, methanol, and organic solvents such as toluene and xylene, because it is fast and gives reliable results. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) In the method used in our study, n-BuOH was used as the internal standard, and the selective ion scanning (SIM) method was used to detect xylene and toluene ions in the tissues. It was thought that the detection of toluene and xylene was achieved with this method and that this method could be used in future studies. The data obtained in our study show that the hour and tissue-based postmortem distribution rates of xylene and toluene differ.\u003c/p\u003e \u003cp\u003eThe continued passage of substances from the blood to the adipose tissue is an important distribution route, especially for lipophilic substances and volatile substances (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Adipose tissue is a recently preferred sample for analyzing oil-soluble hydrocarbons such as toluene, xylene, and other lipophilic molecules (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). This distribution occurs slowly, as adipose tissue perfusion is low, and equilibrium between blood and adipose tissue concentrations may not be reached at the time of death. In such a situation, the sustained distribution of these drugs from blood to adipose tissue may result in lower postmortem blood concentrations (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). In our study, the xylene level in postmortem adipose tissue increased until the 4th hour, then decreased, and the values ​​at the 6th hour fell below the levels at the 0th hour, but this decrease was not statistically significant. Although it was observed that a slight decrease was observed compared to the level at the 2nd hour and reached the highest level by rising again at the 6th hour, it was determined that this change was not statistically significant.\u003c/p\u003e \u003cp\u003eThe anatomical relationships of the human liver to postmortem redistribution are with the stomach, pylorus, proximal duodenum, and gallbladder, but this is not as important as redistribution via hepatic vessels (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). In our study, in rats that measured toluene, the highest level of toluene was detected in liver tissue at 0 hours, followed by brain, fat, and blood tissue.\u003c/p\u003e \u003cp\u003eBrain tissue is a valuable sample for the measurement of drugs because it is the primary site of action for many drugs, and lipophilic substances such as antidepressants, narcotics, and halogenated hydrocarbons45 accumulate in central nervous tissue (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In our study, the xylene level in the brain tissue at 0 hours was lower than that of the liver and adipose tissue; this value was 0.021 at 0 hours and decreased to 0.003 at the 6th hour. In the other 3 tissues, it was determined that while the level increased postmortem as time passed, it only reduced in the brain tissue. It is thought that this situation can be interpreted as toluene undergoes postmortem transformation more in brain tissue than in fat, blood, and liver tissue.\u003c/p\u003e \u003cp\u003eBlood tissue is a complex mixture of dissolved proteins, fats, solids, and suspended cells (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Serum or plasma is traditionally used in clinical settings because blood provides advanced use in laboratory procedures (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Analytical results from postmortem blood are significantly compared to previously reported levels in therapeutic and toxic conditions (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). In our study, toluene and xylene levels analyzed in the blood had the lowest values ​​compared to liver, adipose, and brain tissue in the first measurement. Still, the xylene level continuously increased in the following hours (from 0.003 to 0.051). In contrast, toluene at 0. hour (0.52 ) at the 2nd hour shows a trend that rises to 8 times (4.05) at the 2nd hour and reaches its peak; it tends to decrease at the 4th hour and reduces to approximately 1/3 of the level in the 2nd hour at the 6th hour. It was found that it was measured at a high level (1.33).\u003c/p\u003e \u003cp\u003eOne of the limitations of our study is the difficulties encountered in blood sampling in the selected experimental animal species, especially in the postmortem period. In our study, problems were encountered during blood sampling due to coagulation in the body of experimental animals after euthanasia. This problem could be solved by performing the study with an experimental animal in the higher group regarding phylogenetics or in humans under appropriate conditions. This study determined the amount of toluene and xylene in biological samples taken at 0, 2, 4, and 6 hours postmortem with a fast and accurate analytical method. Our study observed that the levels of toluene and xylene in blood and tissues showed different change patterns in the postmortem period. This is due to the use of wet tissue weights during the analysis of the tissues and the volatile character of toluene and xylene. If dry tissue weights are used during the analysis, it was preferred to use wet tissue weights because of the possibility that the substances could not be detected in the tissue due to their volatile properties. Due to the volatile properties of toluene and xylene, the significance levels of the results obtained in the tissues, especially in the early postmortem period, were included in the evaluation. There may be difficulty in detecting the volatile molecule due to the effects of decay and ambient factors in the advancing postmortem period. Therefore, the study's analyses cover the first six hours after death. According to the results obtained in our study, especially in tissue-based analyzes, the increase was observed in the first 4 hours, and the substance levels decreased below the initial level in the 6th hour, which once again highlights the need for analysis in the early period.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eWith this study, it was aimed to contribute to the establishment of the correlation of toluene and xylene levels determined in postmortem toxicological analyses with the cause of death and time of death by investigating the levels of toluene and xylene in the blood, organ, and tissue samples obtained in autopsies performed at certain hours in the postmortem period in rats exposed to lethal doses of toluene and xylene. Similar studies need to be developed by human autopsy protocols.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eHS-GC/MS);\u003c/strong\u003e Head Space Gas Chromatography-Mass Spectrometry,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPLC;\u003c/strong\u003e High Pressure Liquid Cromatography,\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSPSS;\u003c/strong\u003e Statistical Package for the Social Sciences,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSIM;\u003c/strong\u003e Selective Ion Scanning\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe confirm that any aspect of the work covered in this manuscript that has involved experimental animals has been conducted with the ethical approval of\u0026nbsp;Cumhuriyet University Animal Experiments Local Ethics Committee by the decision dated 05/05/2016 and numbered 59.\u0026nbsp;we confirm that all methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication*\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe give our consent for the publication of identifiable details within the text to be published in BMC Pharmacology and Toxicology.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe athors declare that they have no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur Study was financially supported by Cumhuriyet University Scientific Research Projects Coordination Unit with the project numbered T-681.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm contribution to the paper as follows: EO, CB: study conception and design, data collection, draft manuscript preparation MK, TT, MY, SM and ZT: laboratory analysis and interpretation of results. MFU: data collection and draft manuscript preparation. AllF authors reviewed the results and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements (optional)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank to Cumhuriyet University Head of Scientific Research Project and Istanbul University Cerrahpasa Institute of Forensic Sciences and Legal Medicine.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBarnes, Gordon E. \u0026quot;Solvent abuse: A review.\u0026quot; \u003cem\u003eInternational Journal of the Addictions\u003c/em\u003e 14.1 (1979): 1-26.\u003c/li\u003e\n \u003cli\u003eDevathasan, G., et al. \u0026quot;Complications of chronic glue (toluene) abuse in adolescents.\u0026quot; \u003cem\u003eAustralian and New Zealand Journal of Medicine\u003c/em\u003e 14.1 (1984): 39-43.\u003c/li\u003e\n \u003cli\u003eTulsidas, Haresh. \u0026quot;Glue sniffing: A review.\u0026quot; \u003cem\u003eProceedings of Singapore Healthcare\u003c/em\u003e 19.4 (2010): 312-318\u003c/li\u003e\n \u003cli\u003eAlha, Antti, T. Korte, and M. Tenhu. \u0026quot;Solvent sniffing death.\u0026quot; \u003cem\u003eZeitschriftf\u0026uuml;r Rechtsmedizin\u003c/em\u003e 72.4 (1973): 299-305)\u003c/li\u003e\n \u003cli\u003eUchida, Yoko, et al. \u0026quot;Symptoms and signs in workers exposed predominantly to xylenes.\u0026quot; \u003cem\u003eInternational Archives of Occupational and environmental health\u003c/em\u003e 64.8 (1993): 597-605)\u003c/li\u003e\n \u003cli\u003eRajan, Sharada T., and N. Malathi. \u0026quot;Health hazards of xylene: a literature review.\u0026quot; \u003cem\u003eJournal of Clinical and diagnostic research: JCDR\u003c/em\u003e 8.2\u003c/li\u003e\n \u003cli\u003eShepherd, R. T. \u0026quot;Mechanism of sudden death associated with volatile substance abuse.\u0026quot; \u003cem\u003eHuman toxicology\u003c/em\u003e 8.4 (1989): 287-291)\u003c/li\u003e\n \u003cli\u003eOzseker PE, Daglioglu N, Gulmen KG. Postmortem Redistribution of Drugs Toxicological Sampling, Data Assessment and Interpretation. Adli Tıp B\u0026uuml;lteni, 20(2):123-6, 2015)\u003c/li\u003e\n \u003cli\u003eDağlıoğlu N, Efeoğlu P, G\u0026uuml;lmen M, \u0026Ccedil;ekin N. Distribution of Postmortem Tissue in Acute Endosulfan Poisoning: Case Report. Cukurova Medical Journal, 38(3):515-9, 2014)\u003c/li\u003e\n \u003cli\u003eTominaga, Mariko, et al. \u0026quot;Postmortem analyses of gaseous and volatile substances in pericardial fluid and bone marrow aspirate.\u0026quot; \u003cem\u003eJournal of analytical toxicology\u003c/em\u003e 37.3 (2013): 147-151,\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eWille, Sarah MR, and Willy EE Lambert. \u0026quot;Volatile substance abuse\u0026mdash;post-mortem diagnosis.\u0026quot; \u003cem\u003eForensic Science International\u003c/em\u003e 142.2-3 (2004): 135-156.\u003c/li\u003e\n \u003cli\u003eUnlu S, Alpar B. Evaluation of sediment contamination by monoaromatic hydrocarbons in the coastal lagoons of Gulf of Saros, NE Aegean Sea. Marine pollution bulletin, 2017. 56\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDesmedt B, Canfyn M, Pype M, Baudewyns S, Hanot V, Courselle P, et al. HS-GC-MS method for the analysis of fragrance allergens in complex cosmetic matrices. Talanta, 131:444-51, 2015.\u003c/li\u003e\n \u003cli\u003eKaradayi S, Turkmen Z. Determination of Toluene in Antemortem and Postmortem Biological Specimens of Volatile Abusers and Evaluation of User Profile in İstanbul. Turkiye Klinikleri Journal of ForensicMedicine, 10(1):1-6, 2013)\u003c/li\u003e\n \u003cli\u003eCheikh Rouhou M, Haddad S. Modulation of trichloroethylene in vitro metabolism by different drugs in humans. Toxicology in vitro: an international journal published in association with BIBRA, 28(5):732-41, 2014.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHeit C, Eriksson P, Thompson DC, Charkoftaki G, Fritz KS, Vasiliou V. Quantification of Neural Ethanol and Acetaldehyde Using Headspace GC-MS. 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Enzyme alterations in brain tissue during the early postmortal interval with reference to the histomorphology: Review of the literature. Zeitschrift f\u0026uuml;r Rechtsmedizin, 85(2):81-95, 1980.\u003c/li\u003e\n \u003cli\u003eYarema MC, Becker CE. Key concepts in postmortem drug redistribution. Clinical Toxicology, 43(4):235-41, 2005.\u003c/li\u003e\n \u003cli\u003eWhitehead PH. A Historical Review of the Characterization of Blood and Secretion Stains in the Forensic Science Laboratory Part One: Bloodstains. Forensic science review, 5(1):35-51, 1993.\u003c/li\u003e\n \u003cli\u003eToom V. Bodies of science and law: forensic DNA profiling, biological bodies, and biopower. Journal of Law and Society, 39(1):150-66, 2012.\u003c/li\u003e\n \u003cli\u003eKugelberg FC, Jones AW. Interpreting results of ethanol analysis in postmortem specimens: a review of the literature. Forensic science international, 165(1):10-29, 2007\u003c/li\u003e\n \u003cli\u003eSaitman A, Fitzgerald RL, McIntyre IM. Evaluation and comparison of postmortem hydrocodone concentrations in peripheral blood, central blood, and liver specimens: a minimal potential for redistribution. Forensic science international, 247:36-40, 2015\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Toluene, Xylene, Postmortem period, Cause of death","lastPublishedDoi":"10.21203/rs.3.rs-3292516/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3292516/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eToluene and xylene are frequently used aromatic hydrocarbons in industry. It is also a subject of abuse by inhalation since they have lipid solubility and may affect the blood-brain barrier easily. Toluene or xylene exposure has been reported to cause death. Analyzing the levels of Toluene and xylene in toxicological samples obtained during the autopsy process is important for determining the cause of death. It is also known that the levels of toxic substances show differences during the postmortem period. To make a differential diagnosis of toluene or xylene exposure-related deaths, it is necessary to consider the changes in the levels of these two substances in tissues during the postmortem period. This study aimed to examine the changes in toluene or xylene levels in toxicological samples obtained from rats exposed to lethal doses of Toluene or xylene in the postmortem period.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn our study, intraperitoneal administration of toluene, xylene, and corn oil for the control group was administered to the female Wistar Albino rats. All three groups of rats were also classified according to their postmortem sampling after 0, 2, 4, and 6 hours. Each group (Toluene, Xylene, Control) had 16 samples in the pool chart. Toluene and xylene levels in all tissue specimens were investigated by Head Space-Gas Chromatography-Mass Spectrometry. Statistical analysis of the data were performed by using IBM SPSS Statistics 21 windows based statistical package program.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Xylene was detected at the maximum level at hour zero in liver, adipose and brain tissues. Toluene was measured at its highest level at hour zero in liver, followed by brain, adipose and blood tissues.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe changes among tissue levels of these two substances in the postmortem period showed different patterns. This Head Space-Gas Chromatography-Mass Spectrometry method validated for tissue procedures, is highly valuable for determining the amounts of toluene and xylene in tissues\u003c/p\u003e","manuscriptTitle":"Determination of Toluene and Xylene Levels in Postmortem Tissues of Rats as a Human Autopsy Process","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-09-01 14:44:10","doi":"10.21203/rs.3.rs-3292516/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"84e571dd-40b6-4b37-bae2-b90f03b8605c","owner":[],"postedDate":"September 1st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-09-29T13:44:34+00:00","versionOfRecord":[],"versionCreatedAt":"2023-09-01 14:44:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3292516","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3292516","identity":"rs-3292516","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}