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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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (© 2018 Wiley Periodicals, Inc.)

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.

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., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Two simplified sample preparation procedures for simultaneous extraction and clean-up of tetrabromobisphenol A, α-, β-, 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 × 10 4 ng/g lipid weight were found in occupational workers., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Background: Multiple chemical sensitivity (MCS), although poorly understood, is associated with considerable morbidity., Aim: To investigate potential biological mechanisms underlying MCS in a case-control study., Methods: Two hundred and twenty-three MCS cases and 194 controls (urban females, aged 30-64 years) fulfilled reproducible eligibility criteria with discriminant validity. Routine laboratory results and serum levels of volatile organic compounds (VOCs) were compared. Dose-response relationships, a criterion for causality, were examined linking exposures to likelihood of case status., Results: Routine laboratory investigations revealed clinically unimportant case-control differences in means. Confounder-adjusted odds ratios (OR) showed MCS was negatively associated with lymphocyte count and total plasma homocysteine, positively associated with mean cell haemoglobin concentration, alanine aminotransferase and serum vitamin B6, and not associated with thyroid stimulating hormone, folate or serum vitamin B12. More cases than controls had detectable serum chloroform (P = 0.001) with the OR for detectability 2.78 (95% confidence interval = 1.73-4.48, P < 0.001). Chloroform levels were higher in cases. However, cases had significantly lower means of detectable serum levels of ethylbenzene, m&p-xylene, 3-methylpentane and hexane, and means of all serum levels of 1,3,5- and 1,2,3-trimethylbenzene, 2- and 3-methylpentane, and m&p-xylene., Conclusions: Our findings are inconsistent with proposals that MCS is associated with vitamin deficiency or thyroid dysfunction, but the association of lower lymphocyte counts with an increased likelihood of MCS is consistent with theories of immune dysfunction in MCS. Whether avoidance of exposures or different metabolic pathways in cases explain the observed lower VOC levels or the higher chloroform levels should be investigated.

In recent years, there has been increased interest in the development and use of quantitative structure-activity/property relationship (QSAR/QSPR) models. For the most part, this is due to the fact that experimental data is sparse and obtaining such data is costly, while theoretical structural descriptors can be obtained quickly and inexpensively. In this study, three linear regression methods, viz. principal component regression (PCR), partial least squares (PLS), and ridge regression (RR), were used to develop QSPR models for the estimation of human blood:air partition coefficient (logPblood:air) for a group of 31 diverse low-molecular weight volatile chemicals from their computed molecular descriptors. In general, RR was found to be superior to PCR or PLS. Comparisons were made between models developed using parameters based solely on molecular structure and linear regression (LR) models developed using experimental properties, including saline:air partition coefficient (logPsaline:air) and olive oil:air partition coefficient (logPolive oil:air), as independent variables, indicating that the structure-property correlations are comparable to the property-property correlations. The best models, however, were those that used rat logPblood:air as the independent variable. Haloalkane subgroups were modeled separately for comparative purposes and, although models based on the congeneric compounds were superior, the models developed on the complete set of diverse compounds were of acceptable quality. The structural descriptors were placed into one of three classes based on level of complexity: topostructural (TS), topochemical (TC), or three-dimensional/geometrical (3D). Modeling was performed using the structural descriptor classes both in a hierarchical fashion and separately. The results indicate that highest quality structure-based models, in terms of descriptor classes, were those derived using TC descriptors.

White oils or waxes [mineral hydrocarbons (MHCs)] with substantial levels of saturated hydrocarbons in the range of C18 to C32 have produced hepatic microgranulomas and lymph node microgranulomas (also referred to as histiocytosis) after repeated administration to female Fischer-344 (F-344) rats. Female Sprague-Dawley (S-D) rats are less sensitive to these MHC-induced hepatic and lymph node effects. Studies reported herein characterized the pharmacokinetics and disposition of a representative C-26 MHC, [1-(14)C]1-eicosanylcyclohexane ([(14)C]EICO), in these two rat strains. Female F-344 and S-D rats were administered by oral gavage either a high (1.80 g/kg) or a low (0.18 g/kg) dose of MHC in olive oil (1:4, v/v) containing [(14)C]EICO as a tracer. Blood, urine, feces, liver, and mesenteric lymph nodes (MLNs) were analyzed for [(14)C]EICO and (14)C-metabolites. After the high dose, F-344 rats had a higher blood C(max) of [(14)C]EICO, a longer time to C(max), and a greater area under the systemic blood concentration-time curve from zero to time infinity compared with S-D rats. After the low dose, F-344 rats displayed a unique triphasic blood concentration-time profile, meaning two distinct C(max) values were observed. Fecal excretion was the major route of [(14)C]EICO elimination for both rat strains (70-92% of the dose). S-D rats eliminated the majority of [(14)C]EICO metabolites recovered in the urine by 16 h (8-17% of the dose), whereas F-344 rats did not excrete the same amount until 72 to 96 h. Beyond 24 h, a greater level of [(14)C]EICO was recovered in livers of F-344 rats; at 96 h, 3 and 0.1% of the dose was retained in livers of F-344 and S-D rats, respectively. The major urinary metabolites of EICO in both rat strains were identified as 12-cyclohexyldodecanoic acid and 10-cyclohexyldecanoic acid. Based on the pharmacokinetic parameters and disposition profiles, the data indicate inherent strain differences in the total systemic exposure, rate of metabolism, and hepatic and lymph node retention of [(14)C]EICO, which may be associated with the different strain sensitivities to the formation of liver granulomas and MLN histiocytosis.

This review will introduce petrol (gasoline) sniffing as a specific form of substance abuse. Petrol sniffing is associated with dysfunctions that range in severity from subtle cognitive impairment to encephalopathy and death, and these are discussed with respect to their specific neurological and cognitive bases. Morbidity and mortality rates will also be presented that suggest severe central nervous system damage occurs as a result of petrol sniffing. The neuropharmacological actions of tetraethyl lead and volatile hydrocarbons, the components within petrol, and their contributions to the effects of sniffing petrol are investigated. Reports of human occupational or recreational exposure to either lead additives or volatile hydrocarbons (i.e. inhalants) have provided evidence of the neurological and cognitive effects that may also occur with petrol sniffing. Petrol sniffing causes a progressive decline of cognitive function that eventually leads to permanent neurological changes.

A practical and sensitive method to assess volatile organic compounds (VOCs) from JP-8 jet fuel in human whole blood was developed by modifying previously established liquid-liquid extraction procedures, optimizing extraction times, solvent volume, specific sample processing techniques, and a new on-column large-volume injection method for GC-MS analysis. With the optimized methods, the extraction efficiency was improved by 4.3 to 20.1 times and the detection sensitivity increased up to 660 times over the standard method. Typical detection limits in the parts-per-trillion (ppt) level range were achieved for all monitored JP-8 constituents; this is sufficient for assessing human fuels exposures at trace environmental levels as well as occupational exposure levels. The sample extractions are performed in the field and only solvent extracts need to be shipped to the laboratory. The method is implemented with standard biological laboratory equipment and a modest bench-top GC-MS system.

Optimization for headspace solid-phase microextraction (SPME) was studied with a view to performing gas chromatographic-mass spectrometric (GC-MS) screening of volatile hydrocarbons (VHCs) in blood. Twenty hydrocarbons comprising aliphatic hydrocarbons ranging from n-hexane to n-tridecane, and aromatic hydrocarbons ranging from benzene to trimethylbenzenes were used in this study. This method can be used for examining a burned body to ascertain whether the victim had been alive or not when the burning incident took place. n-Hexane, n-heptane and benzene, the main indicators of gasoline components, were found as detectable peaks through the use of cryogenic oven trapping upon SPME injection into a GC-MS instrument. The optimal screening procedure was performed as follows. The analytes in the headspace of 0.2 g of blood mixed with 0.8 ml of water plus 0.2 microg of toluene-d8 at -5 degrees C were adsorbed to a 100-microm polydimethylsiloxane (PDMS) fiber for 30 min, and measured using the full-mass-scanning GC-MS method. The lower detection limits of all the compounds were 0.01 microg per 1 g of blood. Linearities (r2) within the range 0.01 to 4 microg per 1 g of blood were only obtained for the aromatic hydrocarbons at between 0.9638 (pseudocumene) and 0.9994 (toluene), but not for aliphatic hydrocarbons at between 0.9392 (n-tridecane) and 0.9935 (n-hexane). The coefficients of variation at 0.2 microg/g were less than 8.6% (n-undecane). In conclusion, this method is feasible for the screening of volatile hydrocarbons from blood in forensic medicine.

The objective of this study was to investigate the quantitative relationship between steady-state blood concentrations and structural features of aliphatic hydrocarbons. The literature data on steady-state blood concentrations (Cb(ss)) of 11 C6 to C10-aliphatic hydrocarbons (five n-alkanes, three alkenes, and three iso-alkanes) obtained in rats after exposure to 100 ppm of these chemicals were analyzed using a commercially available software (QSAR-PC). Based on a multiple linear regression analysis, the contribution values of (i) the basic structure [=C1H2-CH2-CH2-CH2C5H2-, + 6.8009], (ii) the substituents at carbon position 1 [(-H)2,=CH2, and (-CH3)2, associated with values of - 3.25, + 7.44 and - 2.02, respectively) and (iii) the substituents at carbon position 5 (CH3, C2H5, C3H7, C4H9 and C5H11 associated with values of - 1.20, - 1.69, +0.71, + 1.26 and + 2.82, respectively) were quantified. This analysis explained 98.8% of the variability in rat Cb(ss) among the hydrocarbons investigated. The present work represents the first attempt to characterize the quantitative contributions of specific molecular fragments to the toxicokinetic behavior of aliphatic hydrocarbons.

Physiological changes related to lipid metabolism, behavior, and chemicals released in body exudates were studied during musth in the Asian elephant, Elephas maximus, as a case study. During musth, changes in serum testosterone and triglyceride concentrations followed similar patterns, with the former increasing sooner than the latter. Deviant behavior increased during changing androgen levels. The observed high concentrations of testosterone were positively and significantly correlated with increased triglycerides. Lipase activity elevated significantly immediately before and after musth. Blood pH increased significantly in alkalinity. Urine and temporal gland secretions released variable amounts of compounds, some of which may be chemical signals. During musth, temporal gland and urinary exudates demonstrated increased acetone and other ketones indicative of lipid metabolic alterations. Large quantities of nonmethane hydrocarbons, especially 2-butanone, were released from the seemingly dry orifice of the temporal gland before the start of overt musth and before maximum blood elevations were observed; isoprene release was similar. However, maximal acetone levels occurred simultaneously in blood, temporal gland secretions, and urine. Metabolically, musth is a series of interwoven, changing stages of increasing and decreasing hormones and lipid-related constituents. Released chemicals can be quantitatively related to these internal physiological events; some observed behaviors appear to result from altered chemical signals.

Petroleum products with low content of aromatics have been increasingly used during the past years. This study investigates tissue disposition of dearomatised white spirit. In addition, brain neurotransmitter concentrations were measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg/1), or 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/week up to 3 weeks. Five rats from each group were sacrificed immediately after the exposure for 1, 2, or 3 weeks and 2, 4, 6, or 24 hr after the end of 3 weeks' exposure. After 3 weeks of exposure the concentration of total white spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure. Two hours after the end of exposure the n-decane concentration decreased to about 25% in blood and 50% in brain. A similar pattern of elimination was also observed for n-nonane, n-undecane and total white spirit in blood and brain. In fat tissue the concentrations of n-nonane, n-decane, n-undecane, and total white spirit increased during the 3 weeks of exposure. The time to reach steady-state concentrations is longer than 3 weeks. After the 3 weeks' exposure the fat tissue concentration of n-nonane, n-decane, n-undecane, and total white spirit decreased very slowly compared with the rate of decrease in blood and brain suggesting that long-lasting redistribution from fat to brain may occur. One week of exposure at 800 p.p.m. caused a statistically significant increase in whole brain dopamine concentration while the noradrenaline concentration was unaffected. Exposure at both exposure levels for 1 week caused a statistically significantly decreased concentration of 5-hydroxytryptamine in whole brain. The reduction was related to the exposure concentration. These changes in neurotransmitter concentrations were normalised after 2 and 3 weeks' exposure. In conclusion, after 3 weeks of exposure the fat:brain:blood concentration coefficients for total white spirit were approximately 250:3:1, and redistribution from fat to brain is possible. As total white spirit behaved similarly to the n-alkanes in blood, brain, and fat tissue, we suggest that the non-n-alkane white spirit components possess toxicokinetic properties similar to the n-alkanes.

Substance abuse through the deliberate inhalation of petrol (petrol sniffing or gasoline sniffing) is prevalent in inner-urban and remote rural communities. Although acute toxic encephalopathy is a well-documented consequence of petrol sniffing, the neurological and cognitive effects of chronic petrol sniffing are unknown. A structured neurological examination and the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess neurological and cognitive function in 33 current-sniffers (individuals who had sniffed petrol for >6 months), 30 ex-sniffers (individuals who had sniffed petrol in the past but had abstained for 6 months) and 34 matched non-sniffers (individuals who had never sniffed petrol). No subject was, or had been, encephalopathic from petrol sniffing and all were residing in their community. Blood lead and hydrocarbon levels and information about petrol sniffing behaviour were obtained from each subject. When compared with non-sniffers, current-sniffers showed higher rates of abnormal tandem gait, rapid alternating hand movements, finger to nose movements, postural tremor, bilateral palmomental reflexes and brisk deep reflexes. Cognitive deficits occurred in the areas of visual attention, visual recognition memory and visual paired associate learning. Ex-petrol sniffers showed higher rates of abnormal tandem gait and bilateral palmomental reflexes and cognitive deficits in the areas of visual recognition memory and pattern-location paired associate learning. Blood lead levels and length of time of petrol sniffing correlated significantly with the magnitude of neurological and cognitive deficits. Blood hydrocarbon levels were not related to neurocognitive deficits, although this may have been due to methodological difficulties in obtaining hydrocarbon levels. These results suggest that subtle neurological and cognitive abnormalities do occur in individuals who abuse petrol but who do not have acute toxic encephalopathy and that the severity of these abnormalities is reduced with abstinence.

A solid-phase microextraction (SPME) protocol was developed for the quantitative analysis of monocyclic aromatic amines from biological fluids. The headspace SPME sampling technique was optimized for extraction and concentration of five target analytes (aniline, o-toluidine, 2-chloroaniline, 2,6-dimethylaniline, 2,4,6-trimethylaniline) from urine, blood, and milk. The temperature, pH, and ionic strength of the matrix sample were modified to allow maximum adsorption of the analytes onto the SPME fiber. This method is rapid yet sensitive and can be completed in 15 min on a 5-mL sample. SPME/GC/MS analysis yielded good reproducibility (RSD > 11%) for each analyte from urine, blood, and milk. Method detection limits for the various biological fluids were determined and ranged from 0.40 ppb for 2,4,6-trimethylaniline in urine to 7.7 ppb for aniline in blood. This SPME sampling protocol can be applied to the biomonitoring of monocyclic aromatic amines from occupational, environmental, and medical exposure.

A static capillary gas chromatographic method using three different detectors [photoionization detector (PID), electron capture detector (ECD) and flame ionization detector (FID)] switched in series is presented for the determination of volatile organic compounds (VOCs) in sub microgram l-1 levels. The method was applied for the analysis of selected environmentally and occupationally relevant non-halogenated and chlorinated aromatic hydrocarbons (e.g., benzene, toluene, xylenes, dichlorobenzenes) as well as chlorinated aliphatic hydrocarbons (e.g., trichloroethene, tetrachloroethene) in blood samples. Detailed investigations, in respect to the figures of merit were carried out. For most of the selected VOCs detection limits (calculated as the three-fold standard deviation of low level calibration standards) in the range from 26 (benzene) to 67 ng l-1 (m/p-xylene) were achieved which are comparable with those reported for dynamic headspace techniques in combination with mass spectrometric detection. For the individual VOCs the within-series precision varied from 4 to 19% and the day-to-day precision from 11 to 28%. Regarding PID as well as FID the calibration graphs for all substances were linear up to at least 10 micrograms l-1 while the ECD response was linear up to concentrations of about 0.6 microgram l-1 for the halogenated compounds. Our method is applicable for the quantitative determination of VOCs in blood in the occupationally as well as in the physiologically relevant (normal) concentration range.

A broad range of pollutants such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), polynitrohydrocarbons (PNHs), polychlorinated biphenyls (PCBs) and organochlorine (OCs) insecticides were simultaneously analyzed in spiked soil, water or plasma samples by using gas chromatography-mass spectrometry (GC-MS). Water and plasma samples containing the pollutants were extracted by a solid-phase extraction (SPE) method using florisil columns. The soil samples, fortified with the toxicants, were extracted with water, methanol or dichloromethane (DCM). The water extract was processed by the SPE method. The methanol and DCM samples were dried, dissolved in acetonitrile and subjected to the SPE extraction. The extracted samples were analyzed by GC-MS programmed to monitor selected ions. The deuterium labelled compounds were used as the internal standards. The chromatographic profile of total ions indicated complete separation of some compounds such as isophorone, naphthalene, all PCBs, most OC insecticides and PNHs; high Mr PAHs and some PCHs were partially or incompletely separated. The chromatographic profile of individual ion indicated good separation of each ion. The minimum detection limit ranged from 1 to 4 pg injected when 1 or 2 ions were monitored or from 20 to 200 pg injected when 20 ions were monitored. The SPE method that provided 60-105% recovery of pollutants from water samples, provided only 2-60% recovery from plasma samples. This may be due to the binding of pollutants to plasma proteins. Water recovered 1-30%, while methanol or DCM recovered 65-100% of the pollutants added to the soil samples. The use of internal standards corrected for the loss of pollutants from plasma or soil.

The present study describes quantitative property-property relationships (QPPRs) for the partitioning of organic chemicals between blood and tissue homogenates from both rats and humans. The n-octanol/water partition coefficient (K[ow]) is used as a non-biological descriptor. QPPRs for human tissue-blood partition coefficients (PCs) were derived from a dataset of 24 volatile organic compounds in blood, liver, muscle, fat, kidney and brain tissue homogenates. QPPRs were also derived for the PCs of rat tissues, using a dataset of 42 volatile organic compounds in blood, liver, muscle and fat tissue homogenates. These QPPRs were evaluated using a test set of 10 compounds for human tissues and a test set of 14 compounds for rat tissues. For both human and rat test sets, it was generally observed that most estimated PCs were within a range of 50-200% of their experimental values. The present approach is concluded to offer a rapid means for the estimation of tissue-blood PCs of compounds on the basis of K(ow) values. In addition, indications for a possible role of tissue components other than lipid and water in the tissue-blood partitioning process of compounds were observed from the calibration results of the model.

Volatile organic compounds constitute a group of important environmental pollutants that have been associated with the constellation of symptoms known as sick building syndrome. An understanding of the kinetics of uptake and elimination of volatile organic compounds is important for the proper interpretation of the internal dose concentrations of people exposed to these compounds. Blood concentrations measured before, during, and after exposure of five individuals to a mixture of volatile organic compounds in a controlled chamber are described. Blood concentrations were related directly to air exposure concentrations and appeared to be a function of the blood/air partition coefficient. The half-lives of the internal dose of the volatile organic compounds measured were less than 1/2 h, but the elimination time courses were multiexponential. The complexity of the elimination curve suggested the existence of multiple storage sites within the body. The presence of a long-term exponential in the blood elimination curve suggested that, with repeated exposure, bioaccumulation may occur in humans.

A purge and trap concentrator with a Tenax trap was coupled to gas chromatography-Fourier transform infrared spectrometry for the identification of volatile organic compounds in blood samples. A styrene-divinyl benzene porous layer capillary column allowed the separation of compounds such as household and medical gases, solvents and alcohol congeners. The identification limits in blood, measured by comparison to an in-house vapour phase spectrum library, generally ranged from 0.05 to 10 mg/l, depending on the analyte structure. Low molecular weight alcohols had identification limits up to 100 mg/l. Six actual casework examples were collected during a 1-year period of routine use to demonstrate the feasibility of the method.

Accurate measures of individual exposure are critical in reducing misclassification and establishing scientifically valid associations between health outcomes and exposures to environmental contaminants. As part of a community health study, the Agency for Toxic Substances and Disease Registry conducted exposure testing for volatile organic compounds (VOCs) in the blood of people residing near an industrial complex. The purposes of the study were to assess recent exposures to VOCs in this community and to assess the utility of conducting blood VOC testing on populations near hazardous waste sites. One hundred blood specimens from the target area and 106 blood specimens from the control area were collected for analysis. The blood VOC levels in the target-area participants were compared to those in the control area and to a national reference population. Of the 31 separate VOCs for which testing was done, only acetone was statistically significantly (p < 0.05) higher in target-area participants (1,636 parts per billion [ppb]) than in control-area participants (1,353 ppb). 1,1,1-Trichloroethane was found at higher geometric mean levels in the control group (0.169 ppb) than in the target group (0.115 ppb) (p = 0.01). Median blood levels of 2-butanone and 1,4-dichlorobenzene were slightly higher in both target- and control-area groups than in the national reference population, but neither area was statistically significantly higher than the national reference population for any contaminant measured. Overall, there appeared to be no association between residing in the target area and elevated blood VOC levels. Based on the results of this study, blood VOC testing should be limited to populations living near sites where environmental testing has shown recent, elevated VOC exposure, or where unusual circumstances of illness may be attributed to VOC exposure.

Objective: In mid 1989, leaded petrol was replaced by unleaded petrol to reduce lead toxicity in petrol sniffers in Maningrida, a remote Aboriginal community in Northern Australia. RETROSPECTIVE REVIEWS: Hospital admissions between 1987 and 1992 due to petrol sniffing were compared for Maningrida and a community using only leaded petrol., Results: Admissions from Maningrida decreased significantly following introduction of unleaded petrol (chi 2 on 2df = 22.25, p < 0.001). Lead and hydrocarbon exposures were also compared for three groups from Maningrida (27 sniffers using only unleaded petrol; 15 exsniffers and 13 nonsniffers) and 24 individuals admitted to hospital for petrol sniffing related illness from other communities using only leaded petrol. Median blood lead levels for hospitalized sniffers (using only leaded petrol). Maningrida sniffers (using only unleaded petrol), exsniffers and nonsniffers were 5.06, 1.87, 1.24 and 0.17 microM/L respectively. There were significant differences between blood lead level, delta-aminolevulinic acid dehydratase activity, and free erythrocyte protoporphyrin for sniffers of leaded and unleaded petrol, whereas these indices were not significantly different for current sniffers and exsniffers in Maningrida. Hydrocarbons were only detectable in the blood of active sniffers (toluene < or = 0.5 micrograms/mL; benzene < or = 0.17 micrograms/mL blood; n-hexane not detected)., Conclusions: The elimination of tetraethyl lead from petrol resulted in a significant decrease in hospitalization of petrol sniffers.

A new approach to investigate the circumstances relating to carbon monoxide intoxication by analysing volatile hydrocarbons in the blood of cadavers is reported. Headspace gas chromatography/mass spectrometry was used to demonstrate the hydrocarbons. The results can be characterized into four categories depending on the compounds detected. In construction fire cases where no accelerants were found at the scene benzene, toluene and styrene were detected in the blood. In cases where gasoline was found in the fire debris surrounding the victim, high levels of benzene, toluene, ethylbenzene, xylene isomers, n-hexane and n-heptane were detected in the blood. In cases where kerosene was found in the fire debris around the victim, benzene, toluene, ethylbenzene, xylene isomers, C9-aromatics(n-propylbenzene, trimethyl-benzene isomers), n-octane, n-nonane and n-decane were detected in the blood. In cases where the victim was found inside a gasoline-fuelled automobile filled with exhaust gas, benzene, toluene, ethylbenzene, xylene isomers, C9-aromatics were found, but no aliphatic hydrocarbons such as components of petroleum. The analyses of the combustion gases of inflammable materials, exhaust gas, gasoline vapours and kerosene vapours were also performed to evaluate the results of the blood analyses. Consequently, some compounds are proposed as indicators to discriminate between inhaled gases i.e. styrene in common combustion gas, n-hexane and n-heptane as well as benzene, toluene and C9-aromatics in gasoline cases, n-nonane and n-octane as well as benzene, toluene and C9-aromatics in kerosene cases, and benzene, toluene, C9-aromatics but no aliphatic hydrocarbons in exhaust gas cases.

Because smoking is a major contributor to the internal dose levels of many volatile organic compounds (VOCs), it is difficult to assess other VOC exposures among smokers. Purge and trap/gas chromatography/isotope-dilution mass spectrometry was used to determine the internal dose of VOCs of smokers and nonsmokers. Median whole blood concentrations of benzene, styrene, and toluene were shown to be approximately two times higher among smokers than among nonsmokers. In addition, smoking elevated the blood levels of ethylbenzene, m-/p-xylene, and o-xylene when the log-transformed data were compared. Smoking also led to greatly increased levels of 2,5-dimethylfuran. These results indicate that blood levels of many VOCs are highly correlated with blood levels of 2,5-dimethylfuran and that this effect is primarily a result of smoking. The smoking confounder to blood levels of VOCs can be removed by including the concentration of blood 2,5-dimethylfuran concentration when evaluating results from a health and exposure evaluation. Determining the blood 2,5-dimethylfuran concentration appears to be an effective means of correcting the confounding influence of smoking and supplies a way of determining lower-level exposures that previously could not have been distinguished from the effects of smoking.

Vacutainers that are routinely used for blood collection contain significant amounts of volatile organic compounds (VOCs). These VOCs interfere with the low parts-per-trillion analysis of VOCs in whole blood either by causing false positives or by masking the presence of VOCs because of high background levels. Benzene, bromoform, ethylbenzene, m/p-xylene, o-xylene, styrene, and various hydrocarbons are the most significant sources of VOC contamination present in the vacutainers. A method of removing VOCs from 10-mL gray-top vacutainers is presented. This method uses a combination of heat and vacuum to reduce the VOCs to levels compatible with low parts-per-trillion analysis of VOCs in whole blood.

The objectives of the present study were (1) to develop an algorithm to predict tissue:blood partition coefficients (PCs) of organic chemicals from n-octanol: water (Ko/w) PC data, and (2) to apply this algorithm to predict the rat tissue:blood PCs of some relatively hydrophilic organics, particularly ketones, alcohols, and acetate esters. The algorithm, developed by modifying a previously published one, involved predicting tissue:blood PCs of chemicals by dividing their partitioning into tissues by the sum of their partitioning into erythrocytes and plasma. The partitioning of a chemical into tissues, erythrocytes, and plasma was expressed as an additive function of its partitioning into neutral lipids, phospholipids, and water contained in them. The muscle, liver, and adipose tissue:blood PCs predicted with the present method were compared with the experimental values obtained from the literature for five ketones, eight alcohols, and eight acetate esters. The predicted muscle:blood and liver:blood PCs for the set of 21 hydrophilic organics were within a factor of 1.01 and 0.99 (on an average), respectively, of the experimental values. However, the predicted adipose tissue:blood PCs of the hydrophilic organics were greater than the experimental values by a factor of 4.13, which improved when vegetable oil:saline (Ko/s) PCs were used instead of Ko/w PCs (factor of 1.51). Overall, the use of the present algorithm should enable the prediction of tissue:blood PCs for organic chemicals for which Ko/w or Ko/s data are available.

A biologically-based algorithm for predicting the tissue: blood partition coefficients (PCs) of organic chemicals has been developed. The approach consisted of (i) describing tissues and blood in terms of their neutral lipid, phospholipid, and water contents, (ii) obtaining data on the solubility of chemicals in n-octanol and water, and (iii) calculating the tissue: blood PCs by assuming that the solubility of a chemical in n-octanol corresponds to its solubility in neutral lipids, the solubility in water corresponds to the solubility in tissue/blood water fraction, and the solubility in phospholipids is a function of solubility in water and n-octanol. The adequacy of this approach was verified by comparing the predicted values with previously published experimental data on human tissue (liver, lung, muscle, kidney, brain, adipose tissue): blood PCs for 23 organic chemicals. In the case of liver, lung, and muscle, the predicted PC values were in close agreement with the higher-end of the range of experimental PC values found in the literature. The predicted brain: and kidney: blood PCs were greater than the experimental PCs in most cases by approximately a factor of two. Whereas the adipose tissue: blood PCs of relatively less hydrophilic chemicals were adequately predicted, the predicted PCs for relatively more hydrophilic chemicals were much greater than the experimentally-determined values. There was a good agreement between the predicted and experimentally-determined blood solubility of the 23 chemicals chosen for this study, indicating that the over-estimation of tissue:blood PCs by the present method is not due to under-estimation of blood solubility of chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred and twenty-two persons employed in an industrial waste incineration plant were examined with respect to organic and inorganic substances which may be produced during the combustion of different waste. The employees were divided into three groups: persons with contact with the incinerator (WI workers, n = 45), periphery workers (n = 54) and management (n = 23). For the evaluation of internal exposure, the levels of lead, cadmium, mercury, benzene, toluene, ethylbenzene and m-xylene in blood, chromium in the erythrocytes, polychlorinated biphenyls, hexachlorobenzene and pentachlorophenol in plasma, and arsenic, chromium, nickel, vanadium, chlorophenols and hydroxypyrene in urine were determined. The internal exposures of the three groups were tested against each other and were compared with the reference values of the general population. Differences between the groups investigated were tested using the U test according to Wilcoxon, Mann and Whitney (P < 0.05). The biological exposure limits valid in Germany (BAT values) were not exceeded in any cases. Compared with the background levels of the German population, certain parameters were exceeded in several employees. Significantly higher levels of the WI workers in comparison to both periphery workers and management were found for toluene in blood (median: 1.1 vs 0.9 vs 0.6 microgram/l). For the lead and cadmium levels in blood and for the urinary excretion of arsenic, 2,4-dichlorophenol and tetrachlorophenols, statistical differences were found only between WI workers and one of the other groups. However, in all cases the elevations were very small and of interest more from the environmental than from the occupational point of view. It must be stressed that this waste incineration plant is very modern in terms of worker health and safety. At older plants without corresponding health and safety measures, higher internal exposure of the employees to hazardous substances may exist.

Exposure to certain volatile organic compounds (VOCs) commonly occurs in industrialized countries. We developed a method for measuring 32 VOCs in 10 mL of whole blood at low concentration. We used this method to determine the internal dose of these compounds in 600 or more people in the US who participated in the Third National Health and Nutrition Examination Survey. From our study results, we established a reference range for these VOCs in the general population of the US. We found detectable concentrations of 1,1,1-trichloroethane, 1,4-dichlorobenzene, 2-butanone, acetone, benzene, chloroform, ethylbenzene, m,p-xylene, styrene, tetrachloroethane, and toluene in most of the blood samples of nonoccupationally exposed persons. The accuracy of VOC evaluations depends on the ability of investigators to make sensitive and reproducible measurements of low concentrations of VOCs and to eliminate all sources of interference and contamination.

Carbohydrate poisoning is among serious children intoxications, made possible by inadequate stocking; boys, one to five years old, are particularly at risk in a series of 43 children examined and admitted in Hôtel-Dieu de France Hospital over a 10-year period. Outcome is constantly good, after a short hospital care; clinical exam and chest X-ray are of particular value on admission. Some cases may need home care, whereas others should undertake hospital day care; treatment is discussed and long-term follow-up is being stressed on.

Certain complications of pregnancy, e.g., threatened spontaneous abortion, toxemia, emesis, and anemia, were studied in pregnant women living in industrial areas contaminated by smelters and the petrochemical industry. Exposure to lead or aromatic hydrocarbons was assessed in parallel by the determination of these agents or their metabolites in blood and urine. Comparison of respective exposure levels was made between women with normal pregnancies and those with complications. Significantly higher levels of lead in blood and increased excretion of the metabolic products of organic solvents were found in women with complicated pregnancies compared to those with normal pregnancies. Threatened spontaneous abortion, toxemia, and anemia were associated with higher lead exposure in the vicinity of smelters. In these patients, evidence of disturbances of blood glutathione equilibrium and increased lipid peroxidation were found indicating a decreased ability to compensate for the effects of exposure. Styrene exposure in a petrochemical industrial area was associated mainly with late toxemia and nephropathy. Patients with these complications also had a tendency to elevated exposure to other aromatic hydrocarbons. It is suggested that complications of pregnancy may be induced by environmental agents at levels lower than those that result in pregnancy loss or preterm birth.

A linear model relating levels of volatile organic chemicals (VOCs) in exhaled breath to personal exposures at environmental (parts per billion) levels has been developed and evaluated in a chamber study of four human volunteers. The purpose of the model is to allow estimation of VOC concentrations in the body from measurements of exposure, or conversely to estimate previous exposure from a measurement of exhaled breath. The model differs from previous models in considering long-term inhalation at low or moderate concentrations rather than instantaneous intake (as in drug administration) or intermittent exposure at high concentrations (as in occupational situations). The model is based on a mass balance approach using one or more compartments to represent distribution of the chemical in the body. The main observable parameters in the model are the residence times tau 1 in the compartments, their "capacities" Ai, and the fraction f of the parent compound that is exhaled under equilibrium conditions. The basic equations for the one-, two-, three-, and n-compartment cases are derived. Solutions to these equations for the cases of a sudden constant high exposure, a sudden constant low exposure, and a linearly increasing exposure are provided. These solutions can be readily applied to more complex exposure scenarios. The chamber study suggests residence times on the order of a few minutes in the blood and 1-2 hr in the vessel-rich group of tissues. The design of the chamber study did not allow an estimate of the model parameters for fat; a subsequent chamber study has provided initial estimates of 50-100 hr. Field studies of personal exposures and breath concentrations of several hundred persons suggest values of f ranging from 0.1 for xylenes and ethylbenzene to about 0.9 for tetrachloroethylene.

Methods for the biological monitoring of aromatic hydrocarbons and their metabolites in the human blood and urine are reviewed. For the determination of the unchanged aromatic hydrocarbon in blood, gas chromatographic head-space analysis is recommended. The metabolites can be monitored by photometric, thin-layer chromatographic, high-performance liquid chromatographic and gas chromatographic methods. For the assessment of health risks caused by aromatic hydrocarbons, reference values and occupational limit values, expressed as biological tolerance values and biological exposure indices, have to be considered.