Detection of helium in a fire victim: A case report.

We report here detection of helium in specimens derived from a burn autopsy case. A male was found in a burnt bedroom. Part of a heat-denatured plastic bag, sealing tape, and flexible tubing remained on his head and neck. In addition, five helium tanks were found near him. His history in conjunction with the discovery conditions suggested a suicide attempt by inhalation of helium. The body had extensive first to fourth degree burns caused by heat. A small amount of soot was deposited in the respiratory tract. Except for the thermal burns, no other injuries were found. Toxicologically, the blood carboxyhemoglobin saturation levels were less than 6%, while combustion-derived volatile hydrocarbons such as benzene or toluene were detected in the blood. In addition, tracheal gas, gastric gas, headspace gas of lung tissue, brain, and heart blood were collected during autopsy for detection of helium. Analysis was performed using headspace gas chromatography with a thermal conductivity detector. Helium was detected in all of the samples tested. Etizolam at a low limit of therapeutic concentration or less was detected in the blood. Neither ethanol nor other drugs of abuse were detected in his blood or urine. Autopsy findings and experiments suggest that the victim inhaled helium and was still alive when a fire broke out. The cause of his death was diagnosed as death from fire and flames. The present result suggests that helium may remain in a burned body and that investigation of helium in cases of fire-related deaths is informative for determination of the cause of death or confirmation of the ante mortem involvement of helium.

An efficient method to simultaneously analyze multi-class organic pollutants in human serum.

The degree of population exposure to various organic pollutants (OPs), including polycyclic aromatic hydrocarbons, organochlorinated pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers, can be determined by measuring their concentrations in human serum. However, performing large-scale measurements with such a variety of compounds in serum is challenging in terms of efficiency and cost. We describe herein the development of a high-efficiency extraction and sample cleanup protocol for simultaneous and quantitative analyses of OPs using gas chromatography-mass spectrometry. OPs, together with crude lipid impurities, were extracted from human serum with a mixture of n-hexane and methyl tert-butyl ether. A disperse sorbent composed of primary secondary amine and C18 (PSA/C18) was used to roughly remove co-extracted impurities. A combined column of neutral silica gel and neutral alumina oxide (AlO/SiG) was then used for deep cleanup. For the removal of impurities, the overall performance of our protocol for the analysis of OPs in serum was comparable to that of traditional gel permeation chromatography (GPC) and dramatically better than that of PSA/C18, which is a frequently used QuEChERS (quick, easy, cheap, effective, rugged, safe) based method. While both the proposed protocol and GPC yielded recoveries of 80%-110% for four classes of OPs, our protocol consumed about 10 times less solvent, resulting in lower experimental expenses and a lower risk of contamination from residual OPs in the solvent and other supplies. In contrast to GPC, our protocol also permits efficient batch processing of serum samples, allowing for large sample sizes such as those encountered in epidemiological studies.

Occupational exposure to asphalt fume can cause oxidative DNA damage among road paving workers.

OBJECTIVES: We designed the present study to determine the effect of occupational exposure to asphalt fumes on oxidative status and DNA damage in road paving workers. METHODS: Sixty road paving workers exposed to asphalt fumes and forty non-exposed control subjects were recruited. Occupational exposure to PAHs was assessed by urinary 1-hydroxypyrene (1-OHP) excretion. Serum thiol disulfide homeostasis (TDH), total oxidant status (TOS) and total antioxidant status (TAS) and urinary 8-hydro-deoxyguanosine (8-OH-dG) level were evaluated by automated colourimetric method. RESULTS: The urinary concentrations of 1-OHP and 8-OH-dG were significantly higher in the exposed group than in the control group (P < 0.001). Disulfide/thiol ratio, TOS, and TAS were also significantly higher for the asphalt workers. A positive correlation existed between urinary 1-OHP and 8-OH-dG, TOS and TAS. CONCLUSION: Study results indicate that exposure to PAHs induces oxidative stress and causes genotoxic effects in asphalt workers.

Tissue-specific insulin signaling mediates female sexual attractiveness.

Individuals choose their mates so as to maximize reproductive success, and one important component of this choice is assessment of traits reflecting mate quality. Little is known about why specific traits are used for mate quality assessment nor about how they reflect it. We have previously shown that global manipulation of insulin signaling, a nutrient-sensing pathway governing investment in survival versus reproduction, affects female sexual attractiveness in the fruit fly, Drosophila melanogaster. Here we demonstrate that these effects on attractiveness derive from insulin signaling in the fat body and ovarian follicle cells, whose signals are integrated by pheromone-producing cells called oenocytes. Functional ovaries were required for global insulin signaling effects on attractiveness, and manipulations of insulin signaling specifically in late follicle cells recapitulated effects of global manipulations. Interestingly, modulation of insulin signaling in the fat body produced opposite effects on attractiveness, suggesting a competitive relationship with the ovary. Furthermore, all investigated tissue-specific insulin signaling manipulations that changed attractiveness also changed fecundity in the corresponding direction, pointing to insulin pathway activity as a reliable link between fecundity and attractiveness cues. The cues themselves, cuticular hydrocarbons, responded distinctly to fat body and follicle cell manipulations, indicating independent readouts of the pathway activity from these two tissues. Thus, here we describe a system in which female attractiveness results from an apparent connection between attractiveness cues and an organismal state of high fecundity, both of which are created by lowered insulin signaling in the fat body and increased insulin signaling in late follicle cells.

Volatile Hydrocarbon Analysis in Blood by Headspace Solid-Phase Microextraction: The Interpretation of VHC Patterns in Fire-Related Incidents.

A headspace solid-phase microextraction (HS-SPME) technique was used to quantitate the concentration of volatile hydrocarbons from the blood of cadavers by cryogenic gas chromatography-mass spectroscopy. A total of 24 compounds including aromatic and aliphatic volatile hydrocarbons were analyzed by this method. The analytes in the headspace of 0.1 g of blood mixed with 1.0 mL of distilled water plus 1 µL of an internal standard solution were adsorbed onto a 100-µm polydimethylsiloxane fiber at 0°C for 15 min, and measured using a GC-MS full scan method. The limit of quantitation for the analytes ranged from 6.8 to 10 ng per 1 g of blood. This method was applied to actual autopsy cases to quantitate the level of volatile hydrocarbons (VHCs) in the blood of cadavers who died in fire-related incidents. The patterns of the VHCs revealed the presence or absence of accelerants. Petroleum-based fuels such as gasoline and kerosene were differentiated. The detection of C8-C13 aliphatic hydrocarbons indicated the presence of kerosene; the detection of C3 alkylbenzenes in the absence of C8-C13 aliphatic hydrocarbons was indicative of gasoline; and elevated levels of styrene or benzene in the absence of C3/C4 alkylbenzenes and aliphatic hydrocarbons indicated a normal construction fire. This sensitive HS-SPME method could help aid the investigation of fire-related deaths by providing a simple pattern to use for the interpretation of VHCs in human blood.

Simple and fast analysis of tetrabromobisphenol A, hexabromocyclododecane isomers, and polybrominated diphenyl ethers in serum using solid-phase extraction or QuEChERS extraction followed by tandem mass spectrometry coupled to HPLC and GC.

Two simplified sample preparation procedures for simultaneous extraction and clean-up of tetrabromobisphenol A, α-, ß-, and γ-hexabromocyclododecane and polybrominated diphenyl ethers in human serum were developed and validated. The first procedure was based on solid-phase extraction. Sample extraction, purification, and lipid removal were carried out directly on an Oasis HLB cartridge. The second procedure was a quick, easy, cheap, effective, rugged, and safe-based approach using octadecyl-modified silica particles as a sorbent. After sample extraction and cleanup, tetrabromobisphenol A/hexabromocyclododecane was separated from polybrominated diphenyl ethers by using a Si-based cartridge. Tetrabromobisphenol A and hexabromocyclododecane were then detected by high-performance liquid chromatography coupled to tandem mass spectrometry, while polybrominated diphenyl ethers were detected by gas chromatography coupled to tandem mass spectrometry. The results of the spike recovery test using fetal bovine serum showed that the average recoveries of the analytes ranged from 87.3 to 115.3% with relative standard deviations equal to or lower than 13.4 %. Limits of detection of the analytes were in the range of 0.4-19 pg/mL except for decabromodiphenyl ether. The developed method was successfully applied to routine analysis of human serum samples from occupational workers and the general population. Extremely high serum polybrominated diphenyl ethers levels up to 3.32 × 104 ng/g lipid weight were found in occupational workers.

Concentrations in human blood of petroleum hydrocarbons associated with the BP/Deepwater Horizon oil spill, Gulf of Mexico.

During/after the BP/Deepwater Horizon oil spill, cleanup workers, fisherpersons, SCUBA divers, and coastal residents were exposed to crude oil and dispersants. These people experienced acute physiological and behavioral symptoms and consulted a physician. They were diagnosed with petroleum hydrocarbon poisoning and had blood analyses analyzed for volatile organic compounds; samples were drawn 5-19 months after the spill had been capped. We examined the petroleum hydrocarbon concentrations in the blood. The aromatic compounds m,p-xylene, toluene, ethylbenzene, benzene, o-xylene, and styrene, and the alkanes hexane, 3-methylpentane, 2-methylpentane, and iso-octane were detected. Concentrations of the first four aromatics were not significantly different from US National Health and Nutritional Examination Survey/US National Institute of Standards and Technology 95th percentiles, indicating high concentrations of contaminants. The other two aromatics and the alkanes yielded equivocal results or significantly low concentrations. The data suggest that single-ring aromatic compounds are more persistent in the blood than alkanes and may be responsible for the observed symptoms. People should avoid exposure to crude oil through avoidance of the affected region, or utilizing hazardous materials suits if involved in cleanup, or wearing hazardous waste operations and emergency response suits if SCUBA diving. Concentrations of alkanes and PAHs in the blood of coastal residents and workers should be monitored through time well after the spill has been controlled.

Comparative toxicokinetics of low-viscosity mineral oil in Fischer 344 rats, Sprague-Dawley rats, and humans--implications for an Acceptable Daily Intake (ADI).

Oral repeated-dose studies with low-viscosity mineral oils showed distinct species and strain differences, which are hypothesized to be due to differences in bioavailability, with Fischer 344 rats being more susceptible than Sprague-Dawley rats or dogs. Sensitive analytical methodology was developed for accurate measurement of low levels of mineral hydrocarbons and applied in single-dose toxicokinetics studies in rats and humans. Fischer 344 rats showed a 4-fold higher AUC(0-∞) and consistently higher blood and liver concentrations were found than Sprague-Dawley rats. Hepatic mineral hydrocarbon concentration tracked the blood concentration in both strains, indicating that blood concentrations can serve as functional surrogate measure for hepatic concentrations. In human volunteers receiving 1mg/kg body weight of low-viscosity white oil, all blood concentrations of mineral hydrocarbons were below the detection limit. Comparison with threshold blood concentrations associated with NOAELs in both rat strains, indicate that the margin-of-exposure is at least 37-fold. Using an internal dose metric rather than applied dose reduces the uncertainty around the temporary ADI considerably since it intrinsically accounts for intra- and inter-species differences. The current data support replacement of the temporary ADI of 0.01 mg/kg/day by a (permanent) ADI of at least 1.0mg/kg/day for low- and medium-viscosity mineral oils.

Development of a physiologically based pharmacokinetic model for inhalation of jet fuels in the rat.

The pharmacokinetic behavior of the majority of jet fuel constituents has not been previously described in the framework of a physiologically based pharmacokinetic (PBPK) model for inhalation exposure. Toxic effects have been reported in multiple organ systems, though exposure methods varied across studies, utilizing either vaporized or aerosolized fuels. The purpose of this work was to assess the pharmacokinetics of aerosolized and vaporized fuels, and develop a PBPK model capable of describing both types of exposures. To support model development, n-tetradecane and n-octane exposures were conducted at 89 mg/m(3) aerosol+vapor and 1000-5000 ppm vapor, respectively. Exposures to JP-8 and S-8 were conducted at ~900-1000 mg/m(3), and ~200 mg/m(3) to a 50:50 blend of both fuels. Sub-models were developed to assess the behavior of representative constituents and grouped unquantified constituents, termed "lumps", accounting for the remaining fuel mass. The sub-models were combined into the first PBPK model for petroleum and synthetic jet fuels. Inhalation of hydrocarbon vapors was described with simple gas-exchange assumptions for uptake and exhalation. For aerosol droplets systemic uptake occurred in the thoracic region. Visceral tissues were described using perfusion and diffusion-limited equations. The model described kinetics at multiple fuel concentrations, utilizing a chemical "lumping" strategy to estimate parameters for fractions of speciated and unspeciated hydrocarbons and gauge metabolic interactions. The model more accurately simulated aromatic and lower molecular weight (MW) n-alkanes than some higher MW chemicals. Metabolic interactions were more pronounced at high (~2700-1000 mg/m(3)) concentrations. This research represents the most detailed assessment of fuel pharmacokinetics to date.

Partition coefficients for nonane and its isomers in the rat.

Jet Fuel 8 (JP-8) is a major fuel source used by US and NATO military. JP-8 is a complex mixture of aliphatic and aromatic isomers of hydrocarbons. Tissue/blood partition coefficient (PC) values are chemical-specific parameters used in modeling the kinetic behavior of chemicals. The partition coefficient values for n-alkanes tend to increase with the increasing carbon number, but less is known about the trend for isomers of n-alkanes. PC values were obtained for the n-alkane nonane (C9) and five of its isomers, namely 3-methyloctane, 4-ethylheptane, 2,3-dimethylheptane, 2,2,4-trimethylhexane, 2,2,4,4-tetramethylpentane. The blood:air and tissue:air PC values correlated with the published log octanol/water (O:W) PC values for n-nonane and its isomers. Experimentally determined blood:air and tissue:air PC values for n-nonane with the largest O:W value were greatest and smallest for the isomer 2,2,4,4-tetramethylpentane with the lowest O:W value. As expected the fat tissue had the highest PC values and muscle the lowest for n-nonane and its isomers. For each tissue, a linear relationship was observed between the tissue/blood PC values for the isomers of n-nonane and n-nonane. This suggests that tissue/blood PC values for all isomers of an alkane could be estimated using data collected from only a sub-set of alkanes of equal carbon number. These reported tissue/blood PC values will support the development of a jet fuel physiologically-based pharmacokinetic (PBPK) model.

[Forensic medical evaluation of a burn injury from combustion of flammable fluids on the human body based on morphological changes in internal organs].

The author describes morphological features of splanchnic organs in the patients that suffered an injury from combustion of flammable fluids at the body surface. The burn injury is a specific form of trauma originating from a combination of several injurious factors including thermoinhalation and intoxication with combustion products in the absence of oxygen in the centre of the hot spot. A rather specific combination of morphological changes in internal organs along with results of laboratory studies provides the most reliable criterion for forensic medical diagnosis of burn injuries from combustion of flammable fluids on the human body.

Mathematical description of the uptake of hydrocarbons in jet fuel into the stratum corneum of human volunteers.

The objective of this research was to develop a mathematical description of uptake of aromatic and aliphatic hydrocarbons into the stratum corneum of human skin in vivo. A simple description based on Fick's laws of diffusion was used to predict the spatiotemporal variation of naphthalene, 1- and 2-methylnaphthalene, undecane, and dodecane in the stratum corneum of human volunteers. The estimated values of the diffusion coefficients for each chemical were comparable to values predicted using in vitro skin systems and biomonitoring studies. These results demonstrate the value of measuring dermal exposure using the tape-strip technique and the importance of quantifying of dermal uptake.

JP-8 jet fuel can promote auditory impairment resulting from subsequent noise exposure in rats.

We report on the transient and persistent effects of JP-8 jet fuel exposure on auditory function in rats. JP-8 has become the standard jet fuel utilized in the United States and North Atlantic Treaty Organization countries for military use and it is closely related to Jet A fuel, which is used in U.S. domestic aviation. Rats received JP-8 fuel (1000 mg/m(3)) by nose-only inhalation for 4 h and half of them were immediately subjected to an octave band of noise ranging between 97 and 105 dB in different experiments. The noise by itself produces a small, but permanent auditory impairment. The current permissible exposure level for JP-8 is 350 mg/m(3). Additionally, a positive control group received only noise exposure, and a fourth group consisted of untreated control subjects. Exposures occurred either on 1 day or repeatedly on 5 successive days. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. In other rats, tissues were harvested following JP-8 exposure for assessment of hydrocarbon levels or glutathione (GSH) levels. A single JP-8 exposure by itself at 1000 mg/m(3) did not disrupt auditory function. However, exposure to JP-8 and noise produced an additive disruption in outer hair cell function. Repeated 5-day JP-8 exposure at 1000 mg/m(3) for 4 h produced impairment of outer hair cell function that was most evident at the first postexposure assessment time. Partial though not complete recovery was observed over a 4-week postexposure period. The adverse effects of repeated JP-8 exposures on auditory function were inconsistent, but combined treatment with JP-8 + noise yielded greater impairment of auditory function, and hair cell loss than did noise by itself. Qualitative comparison of outer hair cell loss suggests an increase in outer hair cell death among rats treated with JP-8 + noise for 5 days as compared to noise alone. In most instances, hydrocarbon constituents of the fuel were largely eliminated in all tissues by 1-h postexposure with the exception of fat. Finally, JP-8 exposure did result in a significant depletion of total GSH that was observable in liver with a nonsignificant trend toward depletion in the brain and lung raising the possibility that the promotion of noise-induced hearing loss by JP-8 might have resulted from oxidative stress.

[The influence of ambulatory tested hypocaloric diet on biochemical indexes of patients of different ages suffering from obesity].

2-5 months-lingth ambulatory tested hypocaloric diet in patients mith obesity makes for normalization of lipid, hydrocarbon metabolism, as creatinine and uric acid in blood against the background of patients body weight reduction.

Using biologic markers in blood to assess exposure to multiple environmental chemicals for inner-city children 3-6 years of age.

We assessed concurrent exposure to a mixture of > 50 environmental chemicals by measuring the chemicals or their metabolites in the blood of 43 ethnically diverse children (3-6 years of age) from a socioeconomically disadvantaged neighborhood in Minneapolis. Over a 2-year period, additional samples were collected every 6-12 months from as many children as possible. We analyzed blood samples for 11 volatile organic compounds (VOCs), 2 heavy metals (lead and mercury, 11 organochlorine (OC) pesticides or related compounds, and 30 polychlorinated biphenyl (PCB) congeners. The evidence suggests that numerous VOCs originated from common sources, as did many PCBs. Longitudinal measurements indicate that between-child variance was greater than within-child variance for two VOCs (benzene, toluene), for both heavy metals (Pb, Hg), for all detectable OC pesticides, and for 15 of the measured PCB congeners (74, 99, 101, 118, 138-158, 146, 153, 156, 170, 178, 180, 187, 189, 194, 195). Despite the relatively small sample size, highest measured blood levels of 1,4-dichlorobenzene, styrene, m-/p-xylene, Pb, Hg, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethene (p,p -DDE), trans-nonachlor, and PCB congeners 74, 99, 105, 118, 138, 146, 153, 156, 170, and 180 were comparable with or higher than 95th percentile measurements of older children and adults from national surveys. Results demonstrate that cumulative exposures to multiple environmental carcinogens and neurotoxins can be comparatively high for children from a poor inner-city neighborhood.

Dermal absorption and penetration of jet fuel components in humans.

Jet propulsion fuel 8 (JP-8) is the largest source of chemical exposures on military bases. Dermal exposure to JP-8 has been investigated in vitro using rat or pig skin, but not in vivo in humans. The purpose of this study was to investigate the absorption and penetration of aromatic and aliphatic components of JP-8 in humans. A surface area of 20 cm2 was delineated on the forearms of human volunteers and 1 ml of JP-8 was applied to the skin. Tape-strip samples were collected 30 min after application. Blood samples were taken before exposure (t=0 h), after exposure (t=0.5 h), and every 0.5 h for up to 4 h past exposure. The tape-strip samples showed evidence of uptake into the skin for all JP-8 components. The blood data was used to estimate an apparent permeability coefficient (Kp). The rank order of the apparent Kp was naphthalene>1-methyl naphthalene=2-methyl naphthalene>decane>dodecane>undecane. This rank order is similar to results from rat and pig-skin studies. However, this study demonstrates that rat and pig models of the skin over predict the internal dose of JP-8 components in humans.

Biological monitoring of experimental human exposure to hydrocarbon solvent mixtures.

The aim of the study was to develop and to validate a suitable analytical method in order to assess the internal exposure of persons to commercial products of hydrocarbon solvent mixtures (HSM). Twenty healthy volunteers were exposed to vapours of five commercial HSM for 8h at 200-1,000 mg/m(3) air. Aromatic-rich, aromatic-poor and aromatic-free HSM were used, as well as isohexane and technical hexane mixtures. A total of 300 exposures were carried out at rest or with an exercise period of 10 min/h at 50 and 75 W. Blood samples for the determination of the HSM were collected before and immediately after exposure. They were analyzed with a headspace analyzer by gas chromatography and mass spectrometry. The analytical method has detection limits of 2-50 microg HSM/L blood. With this method we obtained intra- and interassay variation coefficients of 3.7-15.1%, at concentrations of 53-1,500 microg HSM/L blood. The mean values of the HSM of the 20 volunteers after 8h range between 89 mug/L (technical hexane-mixture) and 1,369 microg/L blood (aromatic-free HSM) at rest. Physical exercises of 50 and 75 W, respectively, lead to a significant increase of the blood-concentrations by mean factors between 1.2 and 1.9 for the five HSM. In conclusion, our results demonstrate that physical activity should be considered in the setting of occupational exposure limits.

[Studying chronic effects caused by alkaline products of from bituminous-salt masses obtained through destruction of sarin, soman and RVX].

The authors summarized study results on chronic effects caused by products of leaching from bituminous-salt masses obtained through destruction of sarin, soman and RVX. State of experimental rats was evaluated with integral informative tests (physiologic, biochemical, hematologic and morphologic) presenting changes in objective health parameters and revealing every disorder in organs and systems functioning.

The influence of moderate red wine consumption on antioxidant status and indices of oxidative stress associated with CHD in healthy volunteers.

The effects of moderate red wine consumption on the antioxidant status and indices of lipid peroxidation and oxidative stress associated with CHD were investigated. A randomised, controlled study was performed with twenty free-living healthy volunteers. Subjects in the red wine group consumed 375 ml red wine daily for 2 weeks. We measured the total concentration of phenolics and analysed the individual phenolics in the wine and plasma by HPLC with tandem MS. The antioxidant capacity of plasma was measured with electron spin resonance spectroscopy while homocysteine and fasting plasma lipids were also determined. The production of conjugated dienes and thiobarbituric acid-reactive substances (TBARS) were measured in Cu-oxidised LDL. Plasma total phenolic concentrations increased significantly after 2 weeks of daily red wine consumption (P< or =0.001) and trace levels of metabolites, mainly glucuronides and methyl glucuronides of (+)-catechin and (-)-epicatechin, were detected in the plasma of the red wine group. These flavan-3-ol metabolites were not detected in plasma from the control group. The maximum concentrations of conjugated dienes and TBARS in Cu-oxidised LDL were reduced (P< or =0.05) and HDL cholesterol concentrations increased (P< or =0.05) following red wine consumption. The findings from the present study provide some evidence for potential protective effects of moderate consumption of red wine in healthy volunteers.