Abstract  This study examined the relationship between birthweight and exposure to emissions of methylene chloride (DCM) from manufacturing processes of the Eastman Kodak Company at Kodak Park in Rochester, Monroe County, New York. County census tracts were categorized as exposed to high, moderate, low or no DCM based on the Kodak Air Monitoring Program (KAMP) model, a theoretical dispersion model of DCM developed by Eastman Kodak Company. Birthweight and information on variables known to influence birthweight were obtained from 91,302 birth certificates of white singleton births to Monroe County residents from 1976 to 1987. No significant adverse effects of exposure to DCM on birthweight were found. Adjusted birthweight in high exposure census tracts was 18.7 g less than in areas with no exposure (95% confidence interval for the difference between high and no exposure - 51.6, 14.2 g). Problems inherent in the method of estimation of exposure, which may decrease power or bias the results, are discussed. Better methods to estimate exposure to emissions from multiple industrial point sources are needed.

Abstract  Dichloromethane dehalogenase from Methylophilus sp. DM11 is a glutathione S-transferase homolog that is specifically active with dihalomethane substrates. This bacterial enzyme and rat liver glutathione S-transferases were purified to investigate their relative reactivity with CH2Cl2 and related substrates. Rat liver alpha class glutathione transferases were inactive and mu class enzymes showed low activity (7-23 nmol/min/mg of protein) with CH2Cl2. theta class glutathione transferase 5-5 from rat liver and Methylophilus sp. dichloromethane dehalogenase showed specific activities of > or = 1 mumol/min/mg of protein. Apparent Kcat/Km were determined to be 3.3 x 10(4) and 6.0 x 10(4) L M-1 S-1 for the two enzymes, respectively. Dideutero-dichloromethane was processed to dideutereo-formaldehyde, consistent with a nucleophilic halide displacement mechanism. The possibility of a GSCH2X reaction intermediate (GS, glutathione; X, halide) was probed using CH2ClF to generate a more stable halomethylglutathione species (GSCH2F). The reaction of CH2ClF with dichloromethane dehalogenase produced a kinetically identifiable intermediate that decomposed to formaldehyde at a similar rate to synthetic HOCH2CH2SCH2F. 19F-NMR revealed the transient formation of an intermediate identified as GSCH2F by its chemical shift, its triplet resonance, and H-F coupling constant consistent with a fluoromethylthioether. Its decomposition was matched by a stoichiometric formation of fluoride. These studies indicated that the bacterial dichloromethane dehalogenase directs a nucleophilic attack of glutathione on CH2Cl2 to produce a halomethylthioether intermediate. This focuses attention on the mechanism used by theta class glutathione transferases to generate a halomethylthioeter from relatively unreactive dihalomethanes.

Abstract  Cytochrome P4502E1 (CYP2E1) is expressed in human peripheral blood lymphocytes (PBLs), and previous reports have suggested the possibility of using this readily available tissue as a reporter of CYP2E1 status. To further explore the relevance of this approach we assessed CYP2E1 expression in PBLs in two contrasting conditions, chronic hepatitis C and insulin-dependent diabetes (IDD), illustrating an organ and a systemic disease, respectively.

Total RNA was isolated from extracted PBLs (hepatitis C patients + IDD) and by percutaneous needle biopsy (hepatitis C patients only). Gene expression for CYP2E1 was determined by real-time reverse-transcription polymerase chain reaction. Histological changes in liver tissue were assessed according to Ludwig's criteria.

In patients with chronic hepatitis C a clear relationship was found between CYP2E1 expression in the liver and the progression of hepatic disease (both lobular inflammation and fibrosis indices), and observed variations were consistent with the preferential distribution of CYP2E1 in the lobular zone. No effect of the liver disease was, however, found at the PBL level. A statistically significant increase in mean CYP2E1 expression level was observed in the lymphocytes from poorly controlled IDD subjects compared to controls.

Taken together, our data indicate that the measurement of CYP2E1 expression in PBLs is not useful in liver diseases. However, in a systemic condition (IDD) this measurement can be proposed for monitoring the CYP2E1 induction in a relatively noninvasive manner. This tool should therefore be further validated in clinical field or experimental studies for CYP2E1 phenotyping purposes.

Abstract  Despite the very wide recognition that carbon monoxide (CO) is a significant neurotoxicant, the level at which subtle effects occur, and the existence of sensitive periods in development for such toxicity, has been undetermined. In terms of risk to the fetus, a potentially susceptible sub-population, there is concern, first, that the level of exposure at which neurotoxicity occurs may be different from the adult, and second, that the site of toxic action and subsequent neurotoxic effects of CO may be different in the immature and mature brain. The investigator studied the susceptibility of the developing brain to moderate levels of CO maintained chronically through the period of neuronal proliferation, and into the period of synapse formation. Carbon monoxide may be thought of as both a prototypical hypoxic agent, and a significant public health hazard in its own right. Carbon monoxide is a ubiquitous toxic agent that accounts for large numbers of deaths and significant morbidity in human populations. Subtle neurotoxic effects of this agent may be even more common, but they may go largely undetected, or fail to be associated with CO exposure. We have shown that prenatal CO exposure at moderate levels can produce significant neurotoxic effects in rats. The data obtained from the cerebellum and neostriatum, in particular, suggest that chronic, moderate perinatal CO exposure may disrupt neuronal proliferation and, perhaps, may disrupt certain markers for neurochemical transmission.

Abstract  The purpose of this study of 3211 cellulose-fiber production workers was to evaluate earlier findings of excess biliary tract and liver cancer in a similarly exposed cohort reported in 1990. Mortality from biliary tract and liver cancer was not increased in this study population, and there was no excess mortality from pancreatic cancer. Mortality was not elevated for cancers of the lung or liver, sites at which tumors were induced in experimental animals exposed to methylene chloride. Men with 20 or more years of employment exhibited increased mortality from prostate cancer, whereas women who also had 20 or more years of employment experienced higher-than-expected mortality from cervical cancer. Although these apparent increases in mortality are difficult to interpret biologically and are not consistent with previous studies, they require further investigation.

Abstract  Some cytochrome P450 catalyzed reactions show atypical kinetics, and these kinetic processes can be grouped into five categories: activation, autoactivation, partial inhibition, substrate inhibition, and biphasic saturation curves. A two-site model in which the enzyme can bind two substrate molecules simultaneously is presented which can be used to describe all of these observed kinetic properties. Sigmoidal kinetic characteristics were observed for carbamazepine metabolism by CYP3A4 and naphthalene metabolism by CYPs 2B6, 2C8, 2C9, and 3A5 as well as dapsone metabolism by CYP2C9. Naphthalene metabolism by CYP3A4 and naproxen metabolism by CYP2C9 demonstrated nonhyperbolic enzyme kinetics suggestive of a low Km, low Vmax component for the first substrate molecule and a high Km, high Vmax component for the second substrate molecule. 7, 8-Benzoflavone activation of phenanthrene metabolism by CYP3A4 and dapsone activation of flurbiprofen and naproxen metabolism by CYP2C9 were also observed. Furthermore, partial inhibition of 7, 8-benzoflavone metabolism by phenanthrene was observed. These results demonstrate that various P450 isoforms may exhibit atypical enzyme kinetics depending on the substrate(s) employed and that these results may be explained by a model which includes simultaneous binding of two substrate molecules in the active site.

Abstract  Mortality ascertainment was extended through 1990 for a cohort of 1271 workers involved in the production of cellulose triacetate fiber at a plant in Rock Hill, South Carolina. Each subject was employed for at least three months between 1 January 1954 and 1 January 1977 in jobs that entailed exposure to the highest concentrations of methylene chloride. Median exposures in 1977 ranged from 140 to 745 ppm (8-h time-weighted average). The observed numbers of deaths from specific causes were compared with the expected numbers of deaths computed from rates in York County, South Carolina. For most causes of death, there was little if any association with employment. Among causes of particular interest, no new deaths were observed from cancer of the liver and biliary tract, although the excess from the earlier study persisted (4 observed, 1.34 expected). No excess mortality was observed for cancer of the pancreas (2 observed, 2.42 expected) or for ischemic heart disease (43 observed, 47.8 expected).

Abstract  The objective of this study was to compare the human immunodeficiency virus (HIV) viral load (VL) and CD4 counts in patients infected with HIV with and without cervical cancer. The authors hypothesized that HIV-positive women with cervical cancer would have a greater risk of immune suppression.

A case-control study was conducted that included all HIV-positive patients who were seen at the authors' institution from January 1, 1995 to April 20, 2006 with invasive cervical cancer (cases) and without invasive cervical cancer (controls). Patients were included only if they had a CD4 count recorded<6 months before or<3 months after their diagnosis of invasive cervical cancer (cases) or at their last gynecologic examination (controls). Controls were matched to cases on a 4:1 ratio according to current smoking history. Patients were considered immunocompetent if they had both a CD4 count>200 cells/microL and a VL<10,000 copies/mL.

In total, 15 cases and 60 controls were identified. The median CD4 count for cases was 208 cells/microL (range, 18-1102 cells/microL) compared with 445 cells/microL (range, 20-1201 cells/microL) for controls (P=.03). The median VL was 16,918 copies/mL (range, 50-214,915 copies/mL) for cases compared with 1430 copies/mL (range, 50-571,000 copies/mL) for controls (P=.15). Only 1 of 14 cases (7%) was immunocompetent compared with 35 of 55 controls (64%; odds ratio, 0.04; 95% confidence interval, 0-0.37; P<.001). This significance was maintained after adjusting for other factors (P=.002).

Women with HIV who were diagnosed with invasive cervical cancer appeared to have a much greater degree of immunosuppression than women with HIV without invasive cervical cancer.

Abstract  More than a million workers are at risk for methylene chloride exposure. Aerosol sprays and paint stripping may also cause significant nonoccupational exposures. After methylene chloride inhalation, significant amounts of carbon monoxide are formed in vivo as a metabolic by-product. Poisoning predominantly affects the central nervous system and results from both carboxyhemoglobin formation and direct solvent-related narcosis. In this report, we describe a case of methylene chloride intoxication probably complicated by exogenous carbon monoxide exposure. The worker's presentation of intermittent headaches was consistent with both methylene chloride intoxication and carbon monoxide poisoning. The exposures and symptoms were corroborated by elevated carboxyhemoglobin saturations and a workplace inspection that documented significant exposures to both methylene chloride and carbon monoxide. When both carbon monoxide and methylene chloride are inhaled, additional carboxyhemoglobin formation is expected. Preventive efforts should include education, air monitoring, and periodic carboxyhemoglobin determinations. Methylene chloride should never be used in enclosed or poorly ventilated areas because of the well-documented dangers of loss of consciousness and death.

Abstract  Pairs of forward and reverse primers and TaqMan probes specific to each human cytochrome P450 isoform were prepared. Analysis of the mRNA level of each CYP isoform in total RNA from pooled specimens of various human organs was performed by real-time reverse transcription PCR using an ABI PRISM 7700 sequence detector system. The expression of CYP3A4 mRNA was similar to that of CYP3A7 mRNA in the fetal liver, and CYP3A4 mRNA levels in the fetal liver were about 0.1 times lower than in the adult liver. CYP2E1 showed the highest level of mRNA expression in the liver. The mRNA expression of 30 CYP isoforms (CYP1A1, 1A2, 1B1, 2A6, 2A7, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2J2, 3A4, 3A5, 3A7, 4A11, 4F2, 4F3, 5A1, 7B1, 8A1, 8B1, 17, 26A1, 27, 27B1, 39A1, 46, and 51) in the liver was successfully detected by this method. CYP2F1, 4B1, 4F8, 11s (11A, 11B1, and 11B2), 19, and 24 mRNA levels were the highest in the lung, lung, prostate, adrenal gland, placenta, and kidney, respectively; however, the mRNA expression of these eight CYP isoforms in the liver was not detected by this method. The mRNA levels of the CYP isoforms determined in various human tissues were in good agreement with previously reported data. The method described here has the advantages of high specificity and excellent quantification over a wide range of mRNA concentrations, making it suitable for the evaluation of a large number of samples in the assessment of the expression profile of drug-metabolizing enzymes.

Abstract  In the human liver, the major rise of the cytochrome P-450 isoform content occurs during the first months following birth (e.g., the high vulnerability period to sudden infant death syndrome (SIDS), a syndrome frequently associated with viral infection and drug hypersensitivity. We examined the expression of individual P-450 isoforms in liver samples collected postmortem from SIDS infants and compared values with those of control adults and children of the same age suffering from various pathologies. Hepatic microsomes were prepared and examined for their content in total P-450, the level of individual isoforms (CYP1A2, CYP2E1, CYP4A, CYP3A, and CYP2C) determined with specific antibodies and for their enzymatic activities. Total RNA was extracted and probed with several CYP cDNAs and oligomers. The overall hepatic P-450 content was not modified in SIDS infants. Among cytochrome P-450 isoforms, only CYP2C was markedly increased. This rise resulted from an accumulation of RNA encoding CYP2C and was associated with a stimulation of diazepam demethylation. The precocious expression of CYP2C in SIDS could result in a higher production of epoxyeicosatrienoic acids in the neonate, believed to act as relaxant of pulmonary smooth muscles. Its consequence might be the induction of fatal apnea in SIDS.

Abstract  Various groups including the Occupational Safety and Health Administration, Environmental Protection Agency, and Consumer Product Safety Commission have expressed concern over methylene chloride and its possible effects on human health. A group of employees exposed to relatively high levels of methylene chloride (average = 475 ppm 8-hour time-weighted average) for greater than 10 years were compared to a similar nonexposed group of employees for selected health parameters. All were participants in an employee health monitoring program. Selected questions evaluating cardiac and neurologic health effects revealed no differences between the two groups. Likewise, hematologic assessment also revealed no clinically significant differences between the two groups for SGOT(AST), SGPT(ALT), total bilirubin, and hematocrit. Therefore, it appears that chronic exposure to even high levels of methylene chloride produces no difference in symptoms or adverse health effects in this population as judged by selected liver, cardiac, and neurologic health parameters.

Abstract  An electrochemically active multiwalled carbon nanotube (MWNT) filter is observed to be effective toward the adsorptive removal and electrochemical oxidation of the aqueous dyes, methylene blue and methyl orange, and the oxidation of the aqueous anions, chloride and iodide. In the absence of electrochemistry, the MWNT filter completely removed all dye from the influent solution until a near monolayer of dye molecules adsorbed to the MWNT filter surface. Electrochemical filtration at 2 V resulted in > 98% oxidation of the influent dye during a single pass through the 41 mu m thin porous MWNT network with a <= 1.2 s residence time. The electrochemical MWNT filter was also able to oxidize aqueous chloride and iodide with minimal overpotential. However, the oxidation of these anions was limited by the number of electrochemically active MWNT surface sites. These results show the potential of an electrochemical MWNT filter for the adsorptive removal and oxidative degradation of aqueous contaminants.

Abstract  Methylene chloride (dichloromethane) is used in a variety of industrial applications. To date, there has been no formal assessment of immunotoxicity attributed to methylene chloride. Studies were undertaken to examine whether methylene chloride has any potential to influence the integrity of immune function. For this purpose, Sprague-Dawley rats of both genders were exposed by inhalation to a single high dose (5000 ppm) of methylene chloride for 6 h/d, 5 d/wk for 28 d. This was considered the relevant route of administration, as not only is inhalation a primary route for human exposure to methylene chloride, but, also, the chemical is absorbed rapidly via the lungs. Under these conditions of exposure, methylene chloride failed to influence absolute or relative thymus weights in either gender and produced a significant reduction in relative, but not absolute, spleen weight in female rats only. Immunocompetence was measured as a function of the ability of treated animals to mount immunoglobulin M (IgM) antibody responses to sheep red blood cells (SRBC) as determined by enzyme-linked immunosorbent assay (ELISA). Exposure to methylene chloride did not affect antibody production. Evidence indicates that under these conditions of exposure, methylene chloride did not compromise immune function.

Abstract  The report assesses the risk of exposure to tetrachloroethylene. The study is part of a program to identify the sources of and evaluate exposure to 129 priority pollutants. The analysis is based on available information from government, industry, and technical publications assembled in July of 1980. The assessment includes an identification of releases to the environment during production, use, or disposal of the substance. In addition, the fate of tetrachloroethylene in the environment is considered; ambient levels to which various populations of humans and aquatic life are exposed and reported. Exposure levels are estimated and available data on toxicity are presented and interpreted. Information concerning all of these topics is combined in an assessment of the risks of exposure to tetrachloroethylene for various subpopulations.

Abstract  Maternal smoking is a known risk factor for orofacial clefts. We investigated whether risk is greater among offspring who lack the genetic capacity to produce glutathione S-transferase enzymes relevant to detoxification of chemicals in cigarette smoke.

Using a population-based case-control design, we genotyped 423 California infants with an isolated cleft and 294 nonmalformed controls for null variants of the glutathione S-transferases GSTT1 and GSTM1.

If a mother smoked during pregnancy and her fetus was homozygous null for GSTT1, the risk of isolated cleft lip with or without cleft palate was tripled (odds ratio = 2.9; 95% confidence interval = 1.2-7.2). For fetuses who were homozygous null for GSTM1 and whose mothers smoked >/=20 cigarettes per day, we found nearly a 7-fold increased risk (6.8; 0.82-57). Combined absence of GSTM1 and GSTT1 enzymes among the offspring of smoking mothers was associated with a nearly 6-fold increased risk for cleft lip (6.3; 1.3-42). A similar increased risk for cleft palate was associated with absence of GSTM1, but not for absence of GSTT1.

Maternal smoking during pregnancy increases risks for clefts among fetuses lacking enzymes involved in the detoxification of tobacco-derived chemicals.

Abstract  The objective of this study was to characterize recovered soil fines from construction and demolition (C&D) waste recycling facilities for trace organic pollutants. Over a period of 18 months, five sampling trips were made to 14 C&D waste recycling facilities in Florida. Screened soil fines were collected from older stockpiles and newly generated piles at the sites. The samples were analyzed for the total concentration (mg/kg) of a series of volatile organic compound (VOCs) and semi-volatile organic compounds (semi-VOCs). The synthetic precipitation leaching procedure (SPLP) test was also performed to evaluate the leachability of the trace organic chemicals. During the total analysis only a few volatile organic compounds were commonly found in the samples (trichlorofluoromethane, toluene, 4-isopropyltoluene, trimethylbenzene, xylenes, and methylene chloride). A total of nine VOCs were detected in the leaching test. Toluene showed the highest leachability among the compounds (61.3-92.0%), while trichlorofluoromethane, the most commonly detected compound from both the total and leaching tests, resulted in the lowest leachability (1.4-39.9%). For the semi-VOC analysis, three base-neutral semi-VOC compounds (bis(2-ethylhexyl)phthalate, butyl benzyl phthalate, and di-n-butyl phthalate) and several PAHs (acenaphthene, pyrene, fluoranthene, and phenanthrene) were commonly detected in C&D fines samples. These compounds also leached during the SPLP leaching test (0.1-25%). No acid extractable compounds, pesticides, or PCBs were detected. The results of this study were further investigated to assess risk from land applied recovered soil fines by comparing total and leaching concentrations of recovered soil fines samples to risk-based standards. The results of this indicate that the organic chemicals in recovered soil fines from C&D debris recycling facilities were not of a major concern in terms of human risk and leaching risk to groundwater under reuse and contact scenarios.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Pure cultures of aerobic and anaerobic bacteria capable of oxidation and reductive dehalogenation of chloroethylenes, and aerobic bacteria involved in biodegradation of polychlorinated biphenyls (PCBs) were screened for their ability to cometabolize the persistent pollutant 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE). Bacterial cultures expressing methane monooxygenase (Methylosinus trichosporium), propane monooxygenase (Mycobacterium vaccae) and biphenyl 2,3-dioxygenase enzymes (Pseudomonas fluorescens and Rhodococcus globerulus), as well as bacteria reductively dechlorinating chloroethylenes (Acetobacterium woodii and Clostridium butyricum) could not degrade DDE. Cell-free extracts of M. trichosporium, M. vaccae, P. fluorescens and R. globerulus were also unable to transform DDE, indicating that cell wall and membrane diffusion barriers were not biodegradation limiting. These studies suggest that these bacteria can not degrade DDE, even when provided with cosu

Abstract  Total suspended particulate matter was collected in a German anthropogenically influenced agricultural area and in a Finnish forest. The occurrence of water-soluble compounds leftover by a traditional dichloromethane (DCM)-extraction technique was investigated using an additional water-extraction and analyzing the corresponding trimethylsilyl derivatives by GC-MS. The organic carbon content of the samples and extracts was also measured. The additional extraction with water recovered more than 20% of total organic carbon, which is comparable to the 31% extracted with DCM. The fraction of water-extractable organic carbon that eluted was <10%, but the employed GC-MS approach proved to be useful in the identification and quantification of polar water-soluble organics containing hydroxyl groups. Concentrations and size distributions of polyhydroxymono- and dicarboxylic acids, polyols, and sugars were obtained. The German meadow presented the highest levels of sugars and acidic compounds, whilst polyols were the most abundant class in the Finnish forest. The major compounds of these classes were malic acid, mannitol, arabitol, glucose and sucrose. Levoglucosan was also detected in the water-extract. Acidic compounds occurred mainly in fine particles. Polyols and most sugars presented size distributions with variable fine or coarse maximum. Possible primary and secondary sources of polyhydroxylated compounds are discussed.

Abstract  Flexible polyurethane foams were prepared using naturally-derived materials as alternatives to conventional auxiliary blowing agents. This research was based on the concept held by some that natural chemicals are better as a part of industrial ecology. The authors have attempted to define the foam manufacturing suitability of natural chemicals, but have not defined or defended the policy implications of such choices. Natural chemicals are often less suitable than those refined from petroleum and may then need some environmental credit related to greater discharge to be viable substitutes. Modest decreases in density (relative to foams without any auxiliary blowing agent) were obtained with the addition of solid CO2, but other physical properties were not measured. It is unclear whether the reduction in density is a result of the phase change of CO2 from solid to liquid within the polyurethane cell matrix or simply a bubbling effect of CO2 in solution causing voids within the final product. Although it was anticipated that the high boiling point of limonene, from citrus peels, would negate effectiveness as an auxiliary blowing agent, there were analogous decreases in foam density. The observed effect might be rationalized by the significant vapor pressure of limonene at temperatures lower than the boiling point. The limonene may be swept from the foam system coincident with the loss of in situ generated CO2. Isoprene, naturally emitted from deciduous vegetation as well as from the combustion of carbonaceous fuels, provides a useful, if not complete, range of foam densities and may then be a partial substitute for halogenated auxiliary blowing agents. Switching from methylene chloride to isoprene as the auxiliary blowing agent of choice would immediately decrease organic emissions from polyurethane foam plants by 20 percent (molecular weight effect). Regulation as a VOC and the residual acrid odor may be potential drawbacks to commercial utilization of isoprene.

Abstract  Wild female and male white sucker (Catostomus commersoni) inhabiting an area receiving pulp mill effluent had reduced hepatic levels of retinol, didehydroretinol, retinyl esters, and didehydroretinyl esters, while vitamin F levels were unaffected. This disruption of the retinoid system led us to test methanol and dichloromethane extracts from the effluent of 11 pulp mills from across Canada for their ability to bind to rainbow trout (Oncorhynchus mykiss) retinoic acid receptors (RARs) from the gill and retinoid X receptors (RXRs) from the liver. Concentrated extracts of the final effluent from 6 of the 11 pulp mills were able to displace greater than 25% of the receptor-bound [3H]all-trans retinoic acid (RA) or [3H]9-cis RA from trout RARs and RXRs, respectively. The ability of the extracts to displace retinoic acid did not appear to be linked to the pulping or treatment processes. Moreover, extracts with the greatest activity came from thermomechanical mills, suggesting the compounds may originate from the wood furnish. In addition, extracts prepared from wood furnish (wood chips: white spruce [50%], lodgepole pine [47%], and balsam fir [3%]) from one mill were able to displace [3H]RA from the RARs and RXRs. The 4-hydroxy RA, a metabolite of RA that has been shown to be generated in greater quantities in fish exposed to P450-inducing xenobiotics, was able to displace [3H]all-trans RA from trout RARs as effectively as unlabeled all-trans RA. These results suggest that pulp mill effluent may impact the retinoid system of fish at multiple sites, either by decreasing hepatic retinoid stores or through contributing additional ligands (from the wood furnish) that can bind to RA receptors.

Abstract  Hazardous air pollutants are plausible candidate exposures for autism spectrum disorders. They have been explored in recent studies for their role in the development of these disorders.

We used a prevalent case-control design to screen perinatal exposure to 35 hazardous air pollutants for further investigation in autism etiology. We included 383 children with autism spectrum disorders and, as controls, 2,829 children with speech and language impairment. All participants were identified from the records-based surveillance of 8-year-old children conducted by the Autism and Developmental Disabilities Monitoring Network in North Carolina (for children born in 1994 and 1996) and West Virginia (born in 1992 and 1994). Exposures to ambient concentrations of metal, particulate, and volatile organic air pollutants in the census tract of the child's birth residence were assigned from the 1996 National Air Toxics Assessment annual-average model. We estimated odds ratios (ORs) for autism spectrum disorders and corresponding 95% confidence intervals (CIs), comparing across the 20th and 80th percentiles of log-transformed hazardous air pollutant concentration among the selected controls, using semi-Bayes logistic models and adjusting for sampling variables (surveillance year and state), a priori demographic confounders from the birth certificate and census, and covarying air pollutants.

We estimated many near-null ORs, including those for metals, established human neurodevelopmental toxicants, and several pollutants that were elevated in a similar study in California. Hazardous air pollutants with more precise and elevated OR estimates included methylene chloride, 1.4 (95% CI = 0.7-2.5), quinoline, 1.4 (1.0-2.2), and styrene, 1.8 (1.0-3.1).

Our screening design was limited by exposure misclassification of air pollutants and the use of an alternate developmental disorder as the control group, both of which may have biased results toward the null. Despite these limitations, methylene chloride, quinoline, and styrene emerged (based on this analysis and prior epidemiologic evidence) as candidates that warrant further investigation for a possible role in autism etiology.

Abstract  The levels and distribution of 55 volatile organic compounds (VOCs) were determined by purge and trap GC-MS on water samples from 30 sites within the urban rivers and estuaries of Osaka, a populated industrialized city of Japan. Forty of 55 target VOCs listed in the US EPA Method 524.2 were detected. Dichloromethane (DCM) was found at higher levels at all of the sampling sites. The distribution of dominant VOCs followed four different patterns. First, the most common VOCs (DCM, toluene, trichloroethene and tetrachloroethene) showed concentration maxima in the river segments, and the sites of maximum concentration fluctuated due to irregular large spills and/or loadings. Second, one VOC (cis-1,2-dichloroethene) was evenly distributed in particular rivers due to fixed loadings. Both of these patterns were found in the upper and middle reaches. Third, some of VOCs (1,2,3-trichloropropane and benzene) were specific to a single industrial site and truceable to those sources. Finally, some VOCs showed no concentration maxima along the rivers and entered from multiple sources (chloroform and bromadichloromethane). Diurnal variations of VOCs at the border of the city area, receiving domestic and industrial discharges, provided information to interpret their observed downstream distribution and possible sources. (C) 1997 Elsevier Science Ltd.

Abstract  Epidemiologic evidence on the relationship between organic solvents and cancer is reviewed. In the 1980s, more than a million persons were potentially exposed to some specific solvents in the United States; in Canada, 40 percent of male cancer patients in Montreal had experienced exposure to solvents; in the Finnish population, one percent was regularly exposed. There is evidence for increased risks of cancer following exposure to: trichloroethylene (for the liver and biliary tract and for non-Hodgkin's lymphomas); tetrachloroethylene (for the esophagus and cervix--although confounding by smoking, alcohol, and sexual habits cannot be excluded--and non-Hodgkin's lymphoma); and carbon tetrachloride (lymphohematopoietic malignancies). An excess risk of liver and biliary tract cancers was suggested in the cohort with the high exposure to methylene chloride, but not found in the other cohorts where an excess risk of pancreatic cancer was suggested. 1,1,1-trichloroethane has been used widely, but only a few studies have been done suggesting a risk of multiple myeloma. A causal association between exposure to benzene and an increased risk of leukemia is well-established, as well as a suggested risk of lung and nasopharynx cancer in a Chinese cohort. Increased risks of various gastrointestinal cancers have been suggested following exposure to toluene. Two informative studies indicated an increased risk of lung cancer, not supported by other studies. Increased risks of lymphohematopoietic malignancies have been reported in some studies of persons exposed to toluene or xylene, but not in the two most informative studies on toluene. Occupation as a painter has consistently been associated with a 40 percent increased risk of lung cancer. (With the mixed exposures, however, it is not possible to identify the specific causative agent[s].) A large number of studies of workers exposed to styrene have evidenced no consistent excess risk of all lymphohematopoietic malignancies, although the most sensitive study suggested an excess risk of leukemia among workers with a high exposure.

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.