Abstract  Objectives Investigating the role of occupational exposure to solvents in the occurrence of lymphoid neoplasms (LNs) in men. Methods The data were generated by a French hospital-based case-control study, conducted in six centres in 2000–2004. The cases were incident cases aged 18–75 years with a diagnosis of LN. During the same period, controls of the same age and gender as the cases were recruited in the same hospitals, mainly in the orthopaedic and rheumatological departments. Exposure to solvents was assessed using standardised occupational questionnaires and case-by-case expert assessment. Specific quantification of benzene exposure was attempted. The analyses included 491 male patients (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma, 104 of lymphoproliferative syndrome and 56 of multiple myeloma) and 456 male controls. Unconditional logistic regressions were used to estimate OR and 95% CI. Results Solvent exposure, all solvents considered together, was marginally associated with NHL (OR=1.4 (1.0 to 2.0) p=0.06), but not with other LNs. No association with the main chemical series of solvents was observed. There was no trend with the average intensity or frequency of exposure. Exposure to pure benzene was not significantly related to NHL (OR=3.4 (0.8 to 15.0)). The highest maximum intensities of benzene exposure were associated with diffuse large cell lymphoma (OR=2.1 (1.0 to 4.6)). Conclusion The results of the present study provide estimates compatible with the hypothesis that exposures to pure benzene and high benzene intensities may play a role in some NHL. There was no evidence for a role of other organic solvents in the occurrence of LN.

Abstract  A variety of so-called innocuous chemicals can have insidious and long lasting effects on the developing male reproductive system. Developmental exposures of male rabbits to common industrial contaminants in drinking water (a mixture of arsenic, chromium, lead, benzene, chloroform, phenol, and trichloroethylene); alkyl phenols (e.g. octylphenol); water disinfection by-products (e.g. dibromoacetic acid); anti-androgenic pesticides (e.g. pp'-DDT and vinclozolin); and plasticizers (e.g. dibutyl phthalate) produce testicular dysgenesis. The lesions include testicular carcinoma in situ, also called intratubular germ cell neoplasia - the precursor lesion of germ cell tumors in men, and acrosomal dysgenesis - characterized by sharing of a dysplastic acrosome by two or more spermatids resulting in characteristic sperm acrosomal-nuclear malformations. Certain manifestations of testicular dysgenesis arch across environmental agents, and sequelae of intentional developmental exposures of rabbits duplicate what has been encountered in deer, horses, and humans for which the etiology is uncertain. (C) 2007 Elsevier B.V. All rights reserved.

Abstract  A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclin. renal damage. The study included a screening of urinary proteins excreted by SDS-PAGE, and quantitations of the specific urinary proteins ?1-microglobulin and glutathione-S-transferase ? (GST ?) as biomarkers for damage of the proximal tubule and glutathione-S-transferase ? (GST ?) for damage of the distal tubule. The exposures were categorized semiquant. (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathol. protein excretion patterns with the semiquant. ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, esp. those in the higher exposed groups, were confined to pathol. urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tomm-Horsfall protein, a 105 kDa protein marker, was noted. Data on the biomarkers ?1-microglobulin, GST ?, and GST ? consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients obsd. among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Abstract  Samples of mother's milk were collected from Bayonne, NJ; Jersey City, NJ; Pittsburgh, PA; Baton Rouge, LA; and Charleston, WV, and analyzed for volatile (purgeables) and semivolatile (extractable) organics using glass capillary gas chromatography/mass spectrometry/computer. In the volatile fraction, 26 halogenated hydrocarbons, 17 aldehydes, 20 ketones, 11 alcohols, 2 acids, 3 ethers, 1 epoxide, 14 furans, 26 other oxygenated compounds, 4 sulfur-containing compounds, 7 nitrogen-containing compounds, 13 alkanes, 12 alkenes, 7 alkynes, 11 cyclic hydrocarbons, and 15 aromatics were found, including major peaks for hexanal, limonene, dichlorobenzene, and some esters. The levels of dichlorobenzene appeared to be significantly higher in the samples from Jersey City and Bayonne than in samples from other sites. Jersey City samples also appeared to have significantly higher levels of tetrachloroethylene. Charleston and Jersey City samples appeared to have significantly higher levels of chloroform; however, chloroform was observed in the blanks at about 20% of that in the samples. Due to the small sample size and lack of control over the solicitation of sample donors, the data cannot be used to extrapolate to the general population. Fewer semivolatile compounds of interest were found. Polychlorinated naphthalenes, polybrominated biphenyls, chlorinated phenols, and other compounds were specifically sought and not detected (limit of detection about 20-100 ng/mL milk). Polychlorinated biphenyls (PCBs) and DDE were found.

Abstract  As evidenced by the recent report of the Commission of the European Communities (CEEC) project (Detection of Aneugenic Chemicals-CEEC project, 1993), there currently is a great deal of effort towards developing and validating assays to detect aneuploidy-inducing chemicals. In this report, we describe the utility of the Syrian hamster embryo (SHE) cell transformation assay for detecting carcinogens with known or suspected aneuploidy-inducing activity. The following carcinogens were tested: asbestos, benomyl, cadmium chloride, chloral hydrate, diethylstilbestrol dipropionate, and griseofulvin. Thiabendazole, a noncarcinogen, was also tested. Chemicals of unknown or inconclusive carcinogenicity data, colcemid, diazepam, econazole nitrate, and pyrimethamine were also evaluated. All of the above chemicals except thiabendazole induced a significant increase in morphological transformation (MT) in SHE cells. Based on these results as well as those published in the literature previously, the SHE cell transformation assay appears to have utility for detecting carcinogens with known or suspected aneuploidy-inducing ability.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM OCCUPATIONAL TOXICOLOGY

Abstract  Results on 105 cases with histopathologically confirmed non-Hodgkin's lymphoma (NHL) and 335 controls from a previously published case-control study on malignant lymphoma are presented together with some extended analyses. No occupation was a risk factor for NHL. Exposure to phenoxyacetic acids yielded, in the univariate analysis, an odds ratio of 5.5 with a 95% confidence interval of 2.7-11. Most cases and controls were exposed to a commercial mixture of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. Exposure to chlorophenols gave an odds ratio of 4.8 (2.7-8.8) with pentachlorophenol being the most common type. Exposure to organic solvents yielded an odds ratio of 2.4 (1.4-3.9). These results were not significantly changed in the multivariate analysis. Dichlorodiphenyltrichloroethane, asbestos, smoking, and oral snuff were not associated with an increased risk for NHL. The results regarding increased risk for NHL following exposure to phenoxyacetic acids, chlorophenols, or organic solvents were not affected by histopathological type, disease stage, or anatomical site of disease presentation. Median survival was somewhat longer in cases exposed to organic solvents than the rest. This was explained by more prevalent exposure to organic solvents in the group of cases with good prognosis NHL histopathology.

Abstract  The nephrotoxin S-(1,2-dichlorovinyl)-L-cysteine (DCVC) is cleaved in the renal tubules to produce a reactive electrophilic intermediate. If this intermediate is responsible for the toxicity, addition of the nucleophilic scavenger glutathione (GSH) should decrease toxicity, and depletion of tubular GSH should enhance toxicity. GSH was added to isolated rabbit renal tubules simultaneously with, 15 min before, and 15 min after the addition of DCVC. The active accumulation of the organic anion para-aminohippuric acid (PAH) and organic cation tetraethylammonium bromide (TEA) was used as an index of renal toxicity. Incubation of renal tubules with 0.01-1 mM DCVC for 15 min decreased active transport, with complete inhibition at 1 mM. This was accompanied by a 50% decrease in non-protein sulfhydryl concentration. The addition of GSH (6 mM) simultaneously with DCVC completely prevented any decrease in active transport. The addition of GSH (6 mM) to tubules in which active transport was inhibited by DCVC reversed the inhibition to 80% of control. Similar enhancement of active transport occurred when tubules isolated 1 h after in vivo exposure to DCVC at 20-100 mg kg-1 were incubated with GSH (6 mM). Preincubation of renal tubules with GSH (5-15 mM) made them more refractory to the DCVC-induced decreased PAH and TEA transport. The inhibition of active transport by DCVC is enhanced if the tubular non-protein sulfhydryl is first lowered by diethyl maleate or glycidol. Thus, the tubular GSH concentration appears to be an integral component in regulating the alterations in active transport caused by DCVC.

Abstract  The present study focused on monitoring the concentration of 14 halogenated volatile organic compounds in surface waters, including sea, estuarine, river water and industrial effluents in order to determine the most ubiquitous compounds and their concentration levels, which were used to establish their geographical and temporal distribution. EPA Method 502, based on purge and trap techniques, was used. In this method volatile organic pollutants are extracted (purged) from the water sample by bubbling inert gas through the aqueous sample. Purged sample components are trapped in a cartridge containing the polymeric sorbent Tenax and, thereafter, the cartridge is heated and backflushed with helium to desorb the trapped sample components directly into a gas chromatograph with electron capture detector (GC-ECD). The linearity range of the method varied from 0.1 to 4 microg L(-1) with a limit of detection at the low microg L(-1) level. The present study consisted of a monthly monitoring of 46 points throughout Portugal, during 14 months. Chloroform was found in 50% of the samples analyzed, its presence being correlated to both agricultural and industrial activities. Other compounds detected were tetrachloroethylene, trichloroethylene, carbon tetrachloride and 1,2,4 trichlorobenzene, which were present in 10-20% of the samples at concentrations up to 18 microg L(-1). 1,1,2,2-Tetrachloroethane and its degradation product 1,1,2-trichloroethane were found in 5% of the samples, the levels of the latter being higher than those of the parent compound in most samples. Sporadic high concentrations of some volatile halogenated organic compounds were attributed to local uses as solvents.

Abstract  A new module of membrane-assisted solvent extraction (MASE) with miniaturized membrane bags was applied to the determination of seven volatile organic compounds (VOCs): chloroform, 1,1,1-trichloroethane, trichloroethylene, 1,1,2-trichloroethane, tetrachloroethene, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane with boiling points between 61 and 147 degrees C in aqueous samples. Different from the known procedure the new, shortened membrane bags were filled with 100 microl of an organic solvent. The membrane bags were placed in a 20 ml headspace vial and filled with 15 ml of the aqueous sample. The vial was transferred into an autosampler where it was stirred for a definite time at elevated temperature. After the extraction, 1 microl of the organic extract was transferred into the spilt/splitless injector of a GC system equipped with an electron-capture detector. This work included optimization of the membrane device, the determination of the optimized extraction conditions such as stirring rate, extraction time and the impact of salt addition. The validation of the method involved repeatability, recovery and detection limit studies, followed of its application towards real water samples. The repeatability, expressed as the relative standard deviation of the peak areas of six extractions was below 10%. The detection limits (LODs) were between 5 ng/l (tetrachloroethene) and 50 ng/l (chloroform). Calibration was performed in a range from 5 ng/l to 150 microg/l, since the concentration in the aqueous samples was expected quite various in this concentration range. Five river water samples of Bitterfeld, Saxony-Anhalt, Germany were analyzed with miniaturized-MASE and the results were compared with those obtained with Headspace-Analysis. The method can be fully automated and moreover, it allows the simultaneous determination of volatile and semi volatile compounds.

Abstract  Risk assessment procedures can be improved through better understanding and use of tissue dose information and linking tissue dose level to adverse outcomes. For volatile organic compounds, such as toluene and trichloroethylene (TCE), blood and brain concentrations can be estimated with physiologically based pharmacokinetic (PBPK) models. Acute changes in the function of the nervous system can be linked to the concentration of test compounds in the blood or brain at the time of neurological assessment. This set of information enables application to a number of risk assessment situations. For example, we have used this approach to recommend duration adjustments for acute exposure guideline levels (AEGLs) for TCE such that the exposure limits for each exposure duration yield identical tissue concentrations at the end of the exposure period. We have also used information on tissue concentration at the time of assessment to compare sensitivity across species, adjusting for species-specific pharmacokinetic differences. Finally this approach has enabled us to compare the relative sensitivity of different compounds on a tissue dose basis, leading to expression of acute solvent effects as ethanol-dose equivalents for purposes of estimating cost-benefit relationships of various environmental control options. © 2005 Elsevier B.V. All rights reserved.

Abstract  This research determined the removal and fate of 11 selected RCRA compounds in a pilot‐scale activated sludge system with a 4‐day SRT and 7.5‐hour HRT. Screened and degritted raw wastewater from a Cincinnati, OH, wastewater treatment plant was used for this study at the U.S. EPA's Test and Evaluation (T&E) Facility. A continuous feed of spike toxic cocktail of 0.25 mg/L each of acetone, methyl ethyl ketone, cyclohexanone, tetrahydrofuran, carbon tetrachloride, 1,1,1‐trichloroethane, 1,1,2‐trichloroethane, trichloroethylene, tetrachloroethylene, chlorobenzene, and ethylbenzene was used to produce an acclimated biomass. The test was run for 7 weeks. Volatilization losses in primary sedimentation exceeded 10% for carbon tetrachloride, 1,1,1‐trichloroethane, 1,1,2‐trichloroethane, and tetrachloroethylene. Sorption of the 11 compounds to primary and secondary sludge ranged from 0.6 to 5.1%. Nine of the 11 test compounds were removed >94% with estimated biodegradation ranging from 0 to 93.4%.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Incineration of dilute mixtures of volatile organic compounds (VOCs) in air was studied in an externally heated quartz tube reactor. A dilute stream of ozone (O3) in air was injected into the flowing VOC-in-air stream at various molar ratios of O3 of VOCs. A number of trials were made to determine the degree of enhancement of the destruction of several VOCs-heptane, isopropanol, chlorobenzene, and trichloroethylene. Temperatures studies for heptane destruction ranged from 637ˆ C to 687ˆ C and residence times varied from 0.26 to 0.84 seconds. It was shown that O3 definitely increased the rate of destruction of n-heptane, but apparently had no effect on the other organics tested. At the residence times and temperatures studied, both organic intermediates and CO persisted. The results for n-heptane using O3 were compared with results previously reported for n-heptane using hydrogen peroxide.

Abstract  Some of the most frequent drinking water contaminants are halogenated hydrocarbons formed, in part, by the chlorination of water. This study involves the gas-chromatographic analysis of water samples from the water supply of different cities in Galicia (Spain): La Coruna, Ferrol, Lugo, Orense, Pontevedra and Vigo. The compounds investigated were: bromochloromethane, bromodichloromethane, chlorobenzene, chloroform, dibromochloromethane, 1,2-dichloroethane, dichloromethane, tetrachloroethylene, carbon tetrachloride and trichloroethylene. A total of 400 samples were analyzed. The results obtained showed that the range of concentrations is between 160.9-1.3-mu-g.l-1 for bromochloromethane, 79.5-2.0-mu-g.l-1 for chloroform, 53-1.5-mu-g.l-1 for dichloromethane, 58.7-1.5-mu-g.l-1 for tetrachloroethylene, 39.5-1.5-mu-g.l-1 for carbon tetrachloride, 44.6-2-mu-g.l-1 for bromodichloromethane, 22-2-mu-g.l-1 for 1,2 dichloroethane and 11.6-1.0-mu-g.l-1 for trichloroethylene. Dibromochloromethane and chlorobenzene were not detected.

Abstract  A thermal desorption-gas chromatography (GC) system was developed for use with commercial adhesive plasters used for monitoring exposure of hands to common solvents. The efficiency of solvent adsorption on the activated carbon pads located on the plasters was determined for acetone, trichloroethylene, D-limonene, methanol, ethyl methyl ketone, toluene, tetrachloroethylene and m-xylene. The degree of solvent recovery for the system was also investigated for each solvent, as was its sensitivity and reproducibility. All solvents exhibited > 90% adsorption on the pads at spiking levels of 100-200 ng for each solvent, except for m-xylene and d-limonene. Solvent recovery was dependent on the volatility of the solvent at spiking volumes of about 1 microliter per pad with solvents with boiling points above 110 degrees C showing recoveries of < 75%. Increasing primary desorption times and temperatures increased these values. The precision was good with RSD < 5% for all solvents over the range 0.5-5.0 microliters of applied solvent. It was possible to detect 15-60 ng of each solvent component within solvent mixtures on the pads with the exception of D-limonene. It is concluded that all solvents tested except D-limonene can be determined on the pads under the conditions for thermal desorption-GC analysis described. The pads were used under protective gloves with six workers using xylene isomers as solvent in the workplace, when apparent solvent breakthrough through their gloves was observed.

Abstract  We tested the impact of three features of a job-exposure matrix on risk estimates in a case-control study that evaluated the association of methylene chloride and astrocytic brain cancer. These features were probability of use of the agent; the consideration of decade of predominant use of methylene chloride within each occupation; and the use of a more specific industrial-occupational coding system. We compared the risk estimates obtained with and without these features. The introduction of each feature had a striking effect on the estimate of relative risk. The odds ratio ranged from 1.47 with none of these features, to 2.47 with high probability of exposure within industry and occupation, to 4.15 with high probability of exposure and specific industrial-occupational coding, to 6.08 with the three features together. These results indicate that the degree of exposure misclassification can be reduced by the introduction of these features into the job-exposure matrix.

Abstract  Dichloroacetate (DCA) is a by-product of drinking water chlorination. Administration of DCA in drinking water results in accumulation of glycogen in the liver of B6C3F1 mice. To investigate the processes affecting liver glycogen accumulation, male B6C3F1 mice were administered DCA in drinking water at levels varying from 0.1 to 3 g/l for up to 8 weeks. Liver glycogen synthase (GS) and glycogen phosphorylase (GP) activities, liver glycogen content, serum glucose and insulin levels were analyzed. To determine whether effects were primary or attributable to increased glycogen synthesis, some mice were fasted and administered a glucose challenge (20 min before sacrifice). DCA treatments in drinking water caused glycogen accumulation in a dose-dependent manner. The DCA treatment in drinking water suppressed the activity ratio of GS measured in mice sacrificed at 9:00 AM, but not at 3:00 AM. However, net glycogen synthesis after glucose challenge was increased with DCA treatments for 1-2 weeks duration, but the effect was no longer observed at 8 weeks. Degradation of glycogen by fasting decreased progressively as the treatment period was increased, and no longer occurred at 8 weeks. A shift of the liver glycogen-iodine spectrum from DCA-treated mice was observed relative to that of control mice, suggesting a change in the physical form of glycogen. These data suggest that DCA-induced glycogen accumulation at high doses is related to decreases in the degradation rate. When DCA was administered by single intraperitoneal (i.p.) injection to naïve mice at doses of 2-200 mg/kg at the time of glucose challenge, a biphasic response was observed. Doses of 10-25 mg/kg increased both plasma glucose and insulin concentrations. In contrast, very high i.p. doses of DCA (> 75 mg/kg) produced progressive decreases in serum glucose and glycogen deposition in the liver. Since the blood levels of DCA produced by these higher i.p. doses were significantly higher than observed with drinking water treatment, we conclude that apparent differences with data of previous investigations is related to substantial differences in systemic dose and/or dose-time relations.

Abstract  This article addresses the evidence that trichloroethylene (TCE) or its metabolites might mediate tumor formation via a mutagenic mode of action. We review and draw conclusions from the published mutagenicity and genotoxicity information for TCE and its metabolites, chloral hydrate (CH), dichloroacetic acid (DCA), trichloroacetic acid (TCA), trichloroethanol, S-(1, 2-dichlorovinyl)-l-cysteine (DCVC), and S-(1, 2-dichlorovinyl) glutathione (DCVG). The new U.S. Environmental Protection Agency proposed Cancer Risk Assessment Guidelines provide for an assessment of the key events involved in the development of specific tumors. Consistent with this thinking, we provide a new and general strategy for interpreting genotoxicity data that goes beyond a simple determination that the chemical is or is not genotoxic. For TCE, we conclude that the weight of the evidence argues that chemically induced mutation is unlikely to be a key event in the induction of human tumors that might be caused by TCE itself (as the parent compound) and its metabolites, CH, DCA, and TCA. This conclusion derives primarily from the fact that these chemicals require very high doses to be genotoxic. There is not enough information to draw any conclusions for trichloroethanol and the two trichloroethylene conjugates, DCVC and DCVG. There is some evidence that DCVC is a more potent mutagen than CH, DCA, or TCA. Unfortunately, definitive conclusions as to whether TCE will induce tumors in humans via a mutagenic mode of action cannot be drawn from the available information. More research, including the development and use of new techniques, is required before it is possible to make a definitive assessment as to whether chemically induced mutation is a key event in any human tumors resulting from exposure to TCE

Abstract  Reductive dechlorination of 2,4,6-trichlorophenol (2,4,6-TCP) was conducted with Zn and Zn bimetals, Pd/Zn, Ni/Zn, Cu/Zn, Pt/Zn. Zn showed relatively low reaction rate toward 2,4,6-TCP, while Pd/Zn had dramatically increased reactivity and other bimetals had higher reaction rates than that of plain zinc. Phenol and less chlorinated phenols were found as dechlorination products. Pd/Zn produced cyclohexanone which is a product of aromatic ring reduced. Surface area normalized kinetic constants and second metal contents normalized kinetic constants were calculated and compared. Two mechanisms, mainly catalytic activation and enhanced corrosion, were proposed for the reactivity enhancement.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. The series of study about the effect of environmental pollutants on cell functions, the influence of several volatile halocarbons (trichloroethylene, tetrachloroethylene, trichloroethanol, bromodichlomethane, chlorodibromomethane and bromoform) and styrene on calcium ionophore (A-23187) or thrombin induced activation of washed rabbit platelets has been examined. Platelet activation was measured by thromboxane B2 synthesis. As a result, tetrachloroethylene and trichloethanol inhibited both A-23187 and thrombin induced platelet activation significantly. Bromoform had an inhibitory action at its highest concentration (10uM) against A-23187 induced platelet activation. Styrene and bromoform revealed a strong inhibitory action against thrombin induced platelet activation. There seemed to be no concentration dependent inhibition of these compounds against platelet activation induced by both agonists. When platelet was pretreated with these compounds, all compounds except tri

Abstract  Peroxisome proliferator-activated receptor alpha (PPARalpha) is responsible for peroxisome proliferator-induced pleiotropic responses, including the development of hepatocellular carcinoma in rodents. However, it remains to be determined whether activation of PPARalpha only in hepatocytes is sufficient to induce hepatocellular carcinomas. To address this issue, transgenic mice were generated that target constitutively activated PPARalpha specifically to hepatocytes. The transgenic mice exhibited various responses that mimic wild-type mice treated with peroxisome proliferators, including significantly decreased serum fatty acids and marked induction of PPARalpha target genes encoding fatty acid oxidation enzymes, suggesting that the transgene functions in the same manner as peroxisome proliferators to regulate fatty acid metabolism. However, the transgenic mice did not develop hepatocellular carcinomas, even though they exhibited peroxisome proliferation and hepatocyte proliferation, indicating that these events are not sufficient to induce liver cancer. In contrast to the transgenic mice, peroxisome proliferators activate proliferation of hepatic non-parenchymal cells (NPCs). Thus, activation of hepatic NPCs and/or associated molecular events is an important step in peroxisome proliferators-induced hepatocarcinogenesis.

Abstract  Pollutants in groundwater can be a source of exposure to residents of houses overlying contaminated aquifers. Volatile compounds may migrate through soil gas and enter below-grade basements under negative pressure. A three-dimensional apparatus was built to simulate intrusion of volatile organics from groundwater into residence basements. Three reference soil materials were used to fill the model, each with different air permeabilities and organic matter contents. A simulated basement was equipped with holes in the floor, which were sealed in three configurations to represent different size cracks. Experiments were run on each soil, with each hole configuration, at several levels of depressurization. Soil permeability was found to be the overriding factor controlling advective TCE intrusion into basements. Soil porosity as well as particle size and shape distribution will dictate the diffusive migration of TCE through the soil profile and toward the building superstructure. Basement crack size does not appear to be a significant variable, and degree of depressurization is only significant in terms of dilution at higher rates of flow. The experiments also served to verify previous hypotheses proposed by mathematical models and field experiments.

Abstract  The mechanisms responsible for ethanol-mediated teratogenesis have not been resolved. However, possible etiologies include the local formation of the teratogen acetaldehyde or oxygen radicals by fetal ethanol-oxidizing enzymes. As alcohol dehydrogenases are expressed at very low concentrations in human embryonic tissues, the ethanol-inducible P450 enzyme, CYP2E1, could be the sole catalyst of fetal ethanol oxidation. With this in mind, we examined the expression of this P450 in liver samples from fetuses ranging in gestational age from 16 to 24 weeks. Immunoblot analysis of fetal liver microsomes revealed the presence of a protein immunoreactive with CYP2E1 antibodies that exhibited a slightly lower molecular weight than that found in adult liver samples. Embryonic CYP2E1 expression was further confirmed by the reverse transcriptase reaction with RNA from a 19-week gestational fetal liver used as template. Catalytic capabilities of human fetal microsomes were assessed by measurement of the rate of ethanol oxidation to acetaldehyde, which were 12-27% of those exhibited by adult liver microsomes. Immunoinhibition studies with CYP2E1 antibodies revealed that the corresponding antigen was the major catalyst of this reaction in both fetal and adult tissues. We then assessed whether embryonic CYP2E1 was, like the adult enzyme, inducible by xenobiotics. Treatment of primary fetal hepatocyte cultures with either ethanol or clofibrate demonstrated a 2-fold increase in CYP2E1 levels compared with untreated cells. Collectively, our results indicate that CYP2E1 is present in human fetal liver, that the enzyme is functionally similar to CYP2E1 from adults, and that fetal hepatocyte CYP2E1 is inducible in culture by xenobiotics, including ethanol. Because fetal CYP2E1 mediates ethanol metabolism, the enzyme may play a pivotal role in the local production of acetaldehyde and free radicals, both of which have potential deleterious effects on the developing fetus.

Abstract  The Hazardous Air Pollutant Exposure Model, version 5 (HAPEM5) User’s Guide is designed to assist exposure analysts with running and interpreting results from HAPEM5. Throughout the User’s Guide, the input file names and file types are in lowercase italics and program names are in all uppercase letters for easier identification. Likewise, model variables are presented in bold italics. When presented, input and output data and program source codes will be presented in a single lined box, indicating that the text inside the box is shown exactly as it exists in its electronic form. In addition, shaded text boxes appear throughout the document providing useful information and tips to users.

Abstract  Potential risk factors in renal cell carcinoma (RCC) were studied in a case-control study of 315 RCC cases and 313 hospital and 336 population controls. Risk factors included medical history, radiation exposure, predominant lifetime occupation, exposure to high-risk industries, and summary of important risk factors by a linear logistic regression model based on the comparison of RCC cases and controls selected from hospitals and the general population for 33 variables. A significant increase in urologic, cardiovascular, malignant, digestive, and metabolic disease was observed among cases over population controls. Exposure to radiation increased the risk, especially in females. A predominant lifetime occupation as a professional decreased the risk, whereas work as an operative increased the risk significantly. Work in petroleum-related and dry-cleaning industries were associated with elevated risk. Multivariate analysis comparing cases with each of the control groups for males and females identified obesity as the most important risk factor in RCC. Weight control at an early age might help to prevent the occurrence of a significant proportion of this rare but increasing malignant disease.