Abstract  Whereas a lot of marine research work has been done on heavy metals and semivolatile organic compounds, far less attention has been paid to the fate of volatile organic compounds in this area. This work focuses on 13 volatile organic compounds in marine waters and the marine atmosphere. During six campaigns in September 1994−December 1995, simultaneous air and water sampling was carried out in both the southern North Sea area and the Scheldt Estuary. Mean water concentrations for individual compounds were in the 2.2−72.9 ppt range (n = 38), whereas atmospheric concentrations varied between 2.3 and 854 pptv. Samples from the Scheldt Estuary proved to have elevated concentrations of chlorinated compounds. A number of water and air samples showed enhanced concentrations of C2-substituted monocyclic aromatic hydrocarbons, which could not clearly be linked to anthropogenic activities. Back-trajectory calculations showed that a number of over sea atmospheric samples were affected by atmospheric transport from industrial sites, 250−300 km up wind. Fugacity modeling showed that the North Sea acts as a source to the atmosphere, not as a sink. Mean water to air mass transfer rates varied between 0.6−52.7 μg m-2 day-1 for all VOCs. It was statistically shown that water to air exchange rates of tetrachloroethylene, benzene, and toluene were slowed when air masses from continental origin were at the marine sampling sites instead of air masses from remote noncontinental origin.

Abstract  This study examines the applicability of the iron-based degradative solidification/stabilization (DS/S-Fe(II)) process to 1,1,1-trichloroethane (1,1,1-TCA), which is one of common chlorinated aliphatic hydrocarbons (CAHs) of concern at contaminated sites. DS/S-Fe(II) combines contaminant degradation by Fe(II) and immobilization by the hydration reactions of Portland cement. The transformation of 1,1,1-TCA by Fe(II) in 10% Portland cement slurries was studied using a batch slurry reactor system. The effects of Fe(II) dose, pH, and initial concentration of 1,1,1-TCA on the kinetics of 1,1,1-TCA degradation were evaluated. Degradation of 1,1,1-TCA in cement slurries including Fe(II) was very rapid and could be described by a pseudo-first-order rate law. The half-lives for 1,1,1-TCA were measured between 0.4 and 5h when Fe(II) dose ranged from 4.9 to 39.2mM. The pseudo-first-order rate constant increased with pH to a maximum near pH 12.5. A saturation rate equation was able to predict degradation kinetics over a wide range of target organic concentrations and at higher Fe(II) doses. The major transformation product of 1,1,1-TCA in mixtures of Fe(II) and cement was 1,1-dichloroethane (1,1-DCA), which indicates that degradation occurred by a hydrogenolysis pathway. A small amount of ethane was observed. The conversion of 1,1,1-TCA to ethane was better described by a parallel reaction model than by a consecutive reaction model.

Abstract  This paper describes a set of multipathway, multimedia models for estimating potential human exposure to environmental contaminants. The models link concentrations of an environmental contaminant in air, water, and soil to human exposure through inhalation, ingestion, and dermalcontact routes. The relationship between concentration of a contaminant in an environmental medium and human exposure is determined with pathway exposure factors (PEFs). A PEF is an algebraic expression that incorporates information on human physiology and lifestyle together with models of environmental partitioning and translates a concentration (i.e., mg/m3 in air, mg/liter in water, or mg/kg in soil) into a lifetime-equivalent chronic daily intake (CDI) in mg/kg-day. Human, animal, and environmental data used in calculating PEFs are presented and discussed. Generalized PEFs are derived for air → inhalation, air → ingestion, water → inhalation, water → ingestion, water → dermal uptake, soil → inhalation, soil → ingestion, and soil → dermal uptake pathways. To illustrate the application of the PEF expressions, we apply them to soil-based contamination of multiple environmental media by arsenic, tetrachloroethylene (PCE), and trinitrotoluene (TNT).

Abstract  Measures of bronchial responsiveness are widely used for the diagnosis and monitoring of asthma. A vast array of non-specific bronchoconstrictor stimuli is available. Methacholine and histamine cause airflow limitation predominantly through a direct effect on airway smooth muscle. Indirect challenges (adenosine, exercise and hypertonic saline) induce airflow limitation by an action on cells other than smooth muscle cells, with a variety of cells, mediators and receptors being involved in this process. Bronchial responsiveness to a direct stimulus is only weakly related to airway inflammation, whereas indirect airway challenges might better reflect active airway inflammation. Both direct and indirect airway challenges are useful outcome parameters in clinical studies of asthma. For example, an indirect challenge responds to treatment with inhaled steroids within hours to days, whereas improvement in direct responsiveness might take months to years. Bronchial challenges are also an essential step in the development of new anti-asthma treatments, such as adenosine or tachykinin receptor antagonists.

Abstract  AP-1/cJun, NF-κB and STAT3 transcription factors control expression of numerous genes, which regulate critical cell functions including proliferation, survival and apoptosis. Sodium arsenite is known to suppress both the IKK-NF-κB and JAK2-STAT3 signaling pathways and to activate the MAPK/JNK-cJun pathways, thereby committing some cancers to undergo apoptosis. Indeed, sodium arsenite is an effective drug for the treatment of acute promyelocytic leukemia with little nonspecific toxicity. Malignant melanoma is highly refractory to conventional radio- and chemotherapy. In the present study, we observed strong effects of sodium arsenite treatment on upregulation of TRAIL-mediated apoptosis in human and mouse melanomas. Arsenite treatment upregulated surface levels of death receptors, TRAIL-R1 and TRAIL-R2, through increased translocation of these proteins from cytoplasm to the cell surface. Furthermore, activation of cJun and suppression of NF-κB by sodium arsenite resulted in upregulation of the endogenous TRAIL and downregulation of the cFLIP gene expression (which encodes one of the main anti-apoptotic proteins in melanomas) followed by cFLIP protein degradation and, finally, by acceleration of TRAILinduced apoptosis. Direct suppression of cFLIP expression by cFLIP RNAi also accelerated TRAIL-induced apoptosis in these melanomas, while COX-2 suppression substantially increased levels of both TRAIL-induced and arsenite-induced apoptosis. In contrast, overexpression of permanently active AKTmyr inhibited TRAIL-mediated apoptosis via downregulation of TRAIL-R1 levels. Finally, AKT overactivation increased melanoma survival in cell culture and dramatically accelerated growth of melanoma transplant in vivo, highlighting a role of AKT suppression for effective anticancer treatment

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  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  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  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  Water-miscible metalworking fluids (MWFs) are capable of causing respiratory symptoms and diseases. Recently, much emphasis has been put on developing new methods for assessing respiratory exposure to MWF emulsions. The air concentrations of ingredients and contaminants of MWF and inhalable dust were measured in 10 metal workshops in southern Finland. Oil mist was determined by infra red spectroscopy analysis after tetrachloroethylene extraction from the filter. Aldehydes were collected on Sep-Pak chemosorbents and analysed by liquid chromatography. Volatile organic compounds (VOCs) were collected on Tenax adsorbents and analysed by gas chromatography with mass spectrometric detection after thermal desorption. Endotoxins were collected on glass fibre filter and analysed by enzyme-based spectrophotometry, and viable microbes were collected on polycarbonate filter and cultured. Inhalable dust was collected on cellulose acetate filter and quantified gravimetrically. Associations between the different exposures were calculated with Spearman's correlations. The mean concentration of oil mist was 0.14 (range <0.010-0.60) mg m(-3). The mean total concentration of aldehydes was 0.095 (0.026-0.38) mg m(-3), with formaldehyde as the main aldehyde. The average total concentration of VOC was 1.9 (0.34-4.5) mg m(-3) consisting mainly of high-boiling aliphatic hydrocarbons. Several potential sensitizing chemicals such as terpenes were found in small quantities. The concentration of microbial contaminants was low. All the measured air concentrations were below the Finnish occupational exposure limits. The exposure in machine shops was quantitatively dominated by volatile compounds. Additional measurements of MWF components such as aldehydes, alkanolamines and VOCs are needed to get more information on the chemical composition of workshops' air. New air cleaning methods should be introduced, as oil mist separators are insufficient to clean the air of small molecular impurities.

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  A wide variety of pharmacological agents, drugs of misuse and environmental pollutants can cause an equally wide variety of renal disease. Consequently, the clinician should always consider these a potential cause for any newly diagnosed case of renal disease. In this contribution we present some of the commoner and more important presentations.

Abstract  BACKGROUND: There is limited evidence on the association between paternal occupational exposure during preconception and infant mortality and deaths due to congenital malformation. This retrospective cohort study was conducted to determine if such an association existed among male workers employed in an electronics factory. METHODS: We linked the databases of labor insurance, birth registration, and national death registry, identified 7,202 male workers ever employed in this factory with 13,592 liveborn children and 81 deaths in the first year after, excluding 861 children with potential maternal exposure from the same workplace. Fathers employed in this factory during their preconceptional periods (3 months prior to the conception) were considered as exposed compared with those not employed during the same periods. Poisson regression models were constructed to adjust for potential confounding by child's sex, parity, multiple births, year of birth, parental age at delivery, and educational levels. RESULTS: Based on 24 exposed cases, the rate ratios (RRs) of infant mortality were increased to 5.06 (95% CI: 2.33-11.00) and 2.81 (95% CI: 1.44-5.51) among liveborn children whose fathers worked for >10 and 1-10 years, respectively, in this factory during preconception. Maternal delivery age less than 20 years, fathers with less than 10 years of education, and multiple births were associated with increased risks of infant mortality. When limited to 28 deaths with congenital malformation, Poisson regression model showed an increased risk for exposed pregnancies (RR = 3.75; 95% CI: 1.29-10.94), especially among cardiac defects (RR = 5.06; 95% CI: 1.58-16.19). CONCLUSIONS: Our study suggests that paternal occupational exposures, possibly to organic solvents during preconception, might increase infant mortality and deaths due to congenital malformation, especially for cardiac defects. However, the small numbers of this study limited the generalization of its findings.

Abstract  In the last decade, more than half of U.S. children were born to working mothers and 65% of working men and women were of reproductive age. In 2004 more than 28 million women age 18-44 were employed full time. This implies the need for clinicians to possess an awareness about the impact of work on the health of their patients and their future offspring. Most chemicals in the workplace have not been evaluated for reproductive toxicity, and where exposure limits do exist, they were generally not designed to mitigate reproductive risk. Therefore, many toxicants with unambiguous reproductive and developmental effects are still in regular commercial or therapeutic use and thus present exposure potential to workers. Examples of these include heavy metals, (lead, cadmium), organic solvents (glycol ethers, percholoroethylene), pesticides and herbicides (ethylene dibromide) and sterilants, anesthetic gases and anti-cancer drugs used in healthcare. Surprisingly, many of these reproductive toxicants are well represented in traditional employment sectors of women, such as healthcare and cosmetology. Environmental exposures also figure prominently in evaluating a woman's health risk and that to a pregnancy. Food and water quality and pesticide and solvent usage are increasingly topics raised by women and men contemplating pregnancy. The microenvironment of a woman, such as her choices of hobbies and leisure time activities also come into play. Caregivers must be aware of their patients' potential environmental and workplace exposures and weigh any risk of exposure in the context of the time-dependent window of reproductive susceptibility. This will allow informed decision-making about the need for changes in behavior, diet, hobbies or the need for added protections on the job or alternative duty assignment. Examples of such environmental and occupational history elements will be presented together with counseling strategies for the clinician.

Abstract  In a search for evidence for the existence of threshold levels below which chemical carcinogens do not induce cancer, it is essential to consider all aspects of the carcinogenic process. We should not confine our thoughts solely to the generally accepted stages of carcinogeneis: initiation, promotion, and progression.

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  Most rheumatic diseases are complex disorders for which pathogenetic mechanisms are poorly understood. Nonetheless, increasing evidence suggests that many of these illnesses result from one or more specific environmental exposures in genetically susceptible individuals. Although much progress has been made over the past few decades in advancing our knowledge of the genetics of rheumatic diseases, few studies have assessed environmental features and understanding of which exposures are important in pathogenesis remains limited. In this article, we review the difficulties inherent in deciphering the interacting environmental and genetic risk factors for rheumatic diseases, the current state of knowledge of infectious and noninfectious risk factors, possible mechanisms by which environmental exposures might induce pathologic processes and future directions. The advances in technologies and statistical approaches, development of collaborating consortia and focused resources that have resulted in the explosion of genetic information must now be applied to environmental studies so we can eventually interrupt pathogenesis before the onset of disease and transform the practice of medicine from curative to pre-emptive paradigms.

Abstract  BACKGROUND: The availability of geographic information from cancer and birth defect registries has increased public demands for investigation of perceived disease clusters. Many neighborhood-level cluster investigations are methodologically problematic, while maps made from registry data often ignore latency and many known risk factors. Population-based case-control and cohort studies provide a stronger foundation for spatial epidemiology because potential confounders and disease latency can be addressed. METHODS: We investigated the association between residence and colorectal, lung, and breast cancer on upper Cape Cod, Massachusetts (USA) using extensive data on covariates and residential history from two case-control studies for 1983-1993. We generated maps using generalized additive models, smoothing on longitude and latitude while adjusting for covariates. The resulting continuous surface estimates disease rates relative to the whole study area. We used permutation tests to examine the overall importance of location in the model and identify areas of increased and decreased risk. RESULTS: Maps of colorectal cancer were relatively flat. Assuming 15 years of latency, lung cancer was significantly elevated just northeast of the Massachusetts Military Reservation, although the result did not hold when we restricted to residences of longest duration. Earlier non-spatial epidemiology had found a weak association between lung cancer and proximity to gun and mortar positions on the reservation. Breast cancer hot spots tended to increase in magnitude as we increased latency and adjusted for covariates, indicating that confounders were partly hiding these areas. Significant breast cancer hot spots were located near known groundwater plumes and the Massachusetts Military Reservation. DISCUSSION: Spatial epidemiology of population-based case-control studies addresses many methodological criticisms of cluster studies and generates new exposure hypotheses. Our results provide evidence for spatial clustering of breast cancer on upper Cape Cod. The analysis suggests further investigation of the potential association between breast cancer and pollution plumes based on detailed exposure modeling.

Abstract  By means of a stepwise selection procedure, mutants capable of growing in the presence of relatively high multiplicities of a bacteriocin from Streptococcus mutans GS-5 were obtained from a sensitivie strain of Streptococcus pyogenes. Mutacin-neutralizing activity of cell extracts containing receptor protein was examined in one variant that adsorbed 1/6 the amount of bacteriocin adsorbed by the parent strain under conditions equivalent to "saturation." Partially purified receptor protein from both parent and mutant cells neutralized an equivalent amount of bacteriocin on a weight-to-weight basis, indicating that in vitro there was no significant difference in affinity for the mutacin between the respective receptor fractions. Cell extracts from the mutant, solubilized by treatment with trichloroacetic acid, neither neutralized mutacin activity nor interfered with receptor protein-mediated mutacin neutralization in vitro. The mutant phenotype may thus represent a cell surface density of receptor protein which results in the adsorption of sublethal amounts of mutacin. The mutant retained its sensitivity to other mutacins, e.g., those produced by strains LM-7 and BHT of S. mutans, and did not differ from wild-type cells with respect to either detergent sensitivity (sodium lauryl sulfate and Triton X-100) or to inhibition by penicillin, rifampin, bacitracin, erythromycin, and tetracycline.

Abstract  The disinfection of water, required to make it safe for human consumption, leads to the presence of halogenated organic compounds. Three of these carcinogenic 'disinfection by-products', dichloroacetic acid (DCA), trichloroacetic acid (TCA) and chloral hydrate (CH) have been widely evaluated for their potential toxicity. The mechanism(s) by which they exert their activity and the steps in the etiology of the cancers that they induce are important pieces of information that are required to develop valid biologically-based quantitative models for risk assessment. Determining whether these chemicals induce tumors by genotoxic or nongenotoxic mechanisms (or a combination of both) is key to this evaluation. We evaluated these three chemicals for their potential to induce micronuclei and aberrations as well as mutations in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells. TCA was mutagenic (only with S9 activation) and is one of the least potent mutagens that we have evaluated. Likewise, CH was a very weak mutagen. DCA was weakly mutagenic, with a potency (no. of induced mutants/microgram of chemical) similar to (but less than) ethylmethanesulfonate (EMS), a classic mutagen. When our information is combined with that from other studies, it seems reasonable to postulate that mutational events are involved in the etiology of the observed mouse liver tumors induced by DCA at drinking water doses of 0.5 to 3.5 g/l, and perhaps chloral hydrate at a drinking water dose of 1 g/l. The weight-of-evidence for TCA suggest that it is less likely to be a mutagenic carcinogen. However, given the fact that DCA is a weak mutagen in the present and all of the published studies, it seems unlikely that it would be mutagenic (or possibly carcinogenic) at the levels seen in finished drinking water.