A dichotomy between lipophilicity and in vivo and in vitro genotoxicity

An analysis of a number of data bases revealed a dichotomy between the lipophilicity of groups of agents capable of inducing genotoxicity in vitro and in vivo. Thus agents with the potential for reacting with cellular DNA, inducing mutations in Salmonella and clastogenicity in cultured cells were characteristically significantly more hydrophilic than agents which did not induce such effects. On the other hand, in vivo inducers of clastogenicity (micronuclei) were significantly more lipophilic than non-inducers. Cellular and systemic toxicants were also more lipophilic than non-toxicants.     

Rationale and Procedures for Using the Tissue-Residue Approach for Toxicity Assessment and Determination of Tissue,Water, and Sediment Quality Guidelines for Aquatic Organisms

This article describes a set of procedures for developing tissue, water, and sediment quality guidelines for the protection of aquatic life by using the tissue-residue approach (TRA) for toxicity assessment. The TRA, which includes aspects of the Critical Body Residue (CBR) approach, associates tissue concentrations of chemicals with adverse biological effects in a dose-response fashion that can be used to determine CBRs. These CBRs can then be used to develop tissue quality guidelines (TQGs), which may be translated into water or sediment guidelines with bioaccumulation factors. Not all toxicants are amenable to this type of analysis; however, some appear to exhibit relatively consistent results that can likely be applied in a regulatory framework. By examining tissue residues, variations in toxicokinetics (temporal aspects of accumulation, biotransformation, and internal distribution) are greatly reduced allowing a greater focus on toxicodynamics (action and potency) of the toxicants. The strongest feature of this approach is causality; hence, guidelines based on tissue concentrations are based on data demonstrating a causal relationship between the acquired dose and the biological effect. Because the TRA has utility for assessing the toxicity of contaminant mixtures, an approach is presented here using toxic unit values that can be used to assess the likelihood of observing toxic effects based on tissue residues.     

Identification of developmental toxicants using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX)

Because growth and development are processes sensitive to the action of many chemicals, bioassays that screen for developmental toxicants may be more indicative of chronic effects than acute toxicity assays. FETAX is a 96 h whole embryo static renewal test employing the embryos of the frog Xenopus laevis. Endpoints are mortality, malformation and growth. Because of the frog's fecundity, its extensive use in basic research and the ability to obtain embryos year-round, it is an ideal organism to use in screening for developmental toxicants. By validating using known mammalian teratogens and the use of rat liver microsomes to stimulate mammalian metabolism, we have extended the use of the system for the prescreening of human developmental toxicants. In past validation work, we have correctly identified the teratogenicity of 15 to 17 compounds used in validation for a predictive accuracy of approximately 88%. In the present study, the ability of FETAX to detect developmental toxicants in groundwater samples taken from an industrial waste dump was evaluated. FETAX showed that it was sensitive enough to detect developmental toxicants in samples without prior concentration. In some samples, less than half the LC50 concentration was required to cause significant malformation. In some cases, a dose-response curve was not obtainable but the test results nonetheless indicated some developmental toxicity. The results of this study indicate that it is necessary to routinely screen for developmental toxicants when establishing water quality criteria for the preservation of species and for human health.     

Newest approaches to quantitative assessment of bioactive organotins

Abstract

New approaches for assessing the toxicity of organotin chemical species have been developed. These approaches are based upon the selective responses of sensitive biodetectors whose chemical and molecular interactions with a wide variety of toxicants have been previously determined and reported. Bioassays capable of quantitating and chemically speciating toxicants for impacts on diverse bacterial sensors are discussed herein. The principal new development is a laser/bacterial bioassay which is capable of differentiating between various toxic chemicals and specifically distinguishing between the different organotin species based on their mechanism of toxic action. The system uses a battery of isogenic Bacillus subtilis strains genetically engineered to respond differentially to specific toxicants. The response is monitored by differential light scattering of a laser which is integrated with a computerized system that collects and analyzes the data. The system routinely generates fully analyzed data within 66 min for most samples. It is capable of making 1,200 measurements on each sample within 2 to 4 seconds, and shows promise as a rapid and inexpensive system to monitor organotins and various other toxicants on site.     

OMNIITOX - operational life-cycle impact assessment models and information tools for practitioners

This article is the preamble to a set of articles describing initial results from an on-going European Commission funded, 5th Framework project called OMNIITOX, Operational Models aNd Information tools for Industrial applications of eco/TOXicological impact assessments. The different parts of this case study-driven project are briefly presented and put in relation to the aims of contributing to an operational life cycle-impact assessment (LCIA) model for impacts of toxicants. The present situation has been characterised by methodological difficulties, both regarding choice of the characterisation model(s) and limited input data on chemical properties, which often has resulted in the omission of toxicants from the LCIA, or at best focus on well characterised chemicals. The project addresses both problems and integrates models, as well as data, in an information system- the OMNIITOX IS. There is also a need for clarification of the relations between the (environmental) risk assessments of toxicants and LCIA, in addition to investigating the feasibility of introducing LCA into European chemicals legislation, tasks that also were addressed in the project. Keywords: Case studies; characterisation factor; chemicals; environmental risk assessment; hazard assessment; information system; life cycle impact assessment (LCIA); potentially toxic substances; regulation; risk assessment; risk ranking     

Establishment and Assessment of a New Human Embryonic Stem Cell‐Based Biomarker Assay for Developmental Toxicity Screening

A metabolic biomarker‐based in vitro assay utilizing human embryonic stem (hES) cells was developed to identify the concentration of test compounds that perturbs cellular metabolism in a manner indicative of teratogenicity. This assay is designed to aid the early discovery‐phase detection of potential human developmental toxicants. In this study, metabolomic data from hES cell culture media were used to assess potential biomarkers for development of a rapid in vitro teratogenicity assay. hES cells were treated with pharmaceuticals of known human teratogenicity at a concentration equivalent to their published human peak therapeutic plasma concentration. Two metabolite biomarkers (ornithine and cystine) were identified as indicators of developmental toxicity. A targeted exposure‐based biomarker assay using these metabolites, along with a cytotoxicity endpoint, was then developed using a 9‐point dose–response curve. The predictivity of the new assay was evaluated using a separate set of test compounds. To illustrate how the assay could be applied to compounds of unknown potential for developmental toxicity, an additional 10 compounds were evaluated that do not have data on human exposure during pregnancy, but have shown positive results in animal developmental toxicity studies. The new assay identified the potential developmental toxicants in the test set with 77% accuracy (57% sensitivity, 100% specificity). The assay had a high concordance (≥75%) with existing in vivo models, demonstrating that the new assay can predict the developmental toxicity potential of new compounds as part of discovery phase testing and provide a signal as to the likely outcome of required in vivo tests.     

Rapid screening for soil ecotoxicity with a battery of luminescent bacteria tests

A bacterial test battery, involving i) Microtox, an aquatic test, ii) the Flash assay, a soil-suspension test (with Vibrio fischeri as the test organism), and iii) the Metal Detector assay, a semi-specific aquatic test for heavy metals (with recombinant luminescent Escherichia coli), was used in a combined toxicological and chemical hazard assessment of Estonian soils sampled from a former Soviet military airfield (13 samples) and from traffic-influenced roadsides (5 samples). The soils showed slightly elevated levels of total petroleum hydrocarbons (TPH), but not of heavy metals. In most of the samples, the levels of TPH did not exceed the Estonian permitted limit values set for residential areas. Toxicity testing was performed on both fresh and dried soils, after aqueous extraction for 1 hour and 24 hours. The toxicity results obtained with the Microtox test did not significantly differ in all of the sample treatment schemes; however, it appeared that the drying and sieving of the soils increased the bioavailability of toxicants, probably due to an enlarged reactive soil surface area. According to chemical analysis of the soils and the data from the Microtox test and the Metal Detector assay (performed on aqueous elutriates of the soils), these soils would not be considered to be hazardous. In contrast, the Flash assay performed on soil-water suspensions of dried soils, showed that most of the soils were toxic and thus probably contained undetermined particle-bound bioavailable toxicants. The photobacterial toxicity test (the Flash assay) can be recommended for the rapid screening of soils, as it is sensitive, cheap and inexpensive, and provides valuable information on particle-bound bioavailable toxicants, useful for complementing a chemical analysis and for assessing the risks originating from polluted soils.     

Genotoxicity of heat-processed foods

Gene-environment interactions include exposure to genotoxic compounds from our diet and it is no doubt, that humans are regularly exposed to e.g. food toxicants, not least from cooked foods. This paper reviews briefly four classes of cooked food toxicants, e.g. acrylamide, heterocyclic amines, nitrosamines and polyaromatic hydrocarbons. Many of these compounds have been recognised for decades also as environmental pollutants. In addition cigarette smokers and some occupational workers are exposed to them. Their occurrence, formation, metabolic activation, genotoxicity and human cancer risk are briefly presented along with figures on estimated exposure. Several lines of evidence indicate that cooking conditions and dietary habits can contribute to human cancer risk through the ingestion of genotoxic compounds from heat-processed foods. Such compounds cause different types of DNA damage: nucleotide alterations and gross chromosomal aberrations. Most genotoxic compounds begin their action at the DNA level by forming carcinogen-DNA adducts, which result from the covalent binding of a carcinogen or part of a carcinogen to a nucleotide. The genotoxic and carcinogenic potential of these cooked food toxicants have been evaluated regularly by the International Agency for Research on Cancer (IARC), which has come to the conclusion that several of these food-borne toxicants present in cooked foods are possibly (2A) or probably (2B) carcinogenic to humans, based on both high-dose, long-term animal studies and in vitro and in vivo genotoxicity tests. Yet, there is insufficient scientific evidence that these genotoxic compounds really cause human cancer, and no limits have been set for their presence in cooked foods. However, the competent authorities in most Western countries recommend minimising their occurrence, therefore this aspect is also included in this review.     

Endocrine regulation of the reproduction in crustaceans: Identification of potential targets for toxicants and environmental contaminants

Progress in ecotoxicological research documents that crustaceans are highly vulnerable to diverse chemicals and toxicants in the environment. In particular, pollutants affecting endocrine homeostasis in crustaceans (i.e., endocrine disruptors) are intensively studied, and serious reproductive disorders have been documented. In this review, current knowledge about the endocrine regulation of the crustacean reproduction is put together with the published ecotoxicological data with an attempt to summarize the potential of xenobiotics to affect crustacean reproduction. Following gaps and trends were identified: (1) Studies are required in the field of neurohormone (serotonin and dopamine) regulation of the reproduction and possible modulations by environmental toxicants such as antidepressant drugs. (2) Molting-related parameters (regulated by ecdysteroid hormones) are closely coordinated with the development and reproduction cycles in crustaceans (cross-links with methyl farnesoate signalling), and their susceptibility to toxicants should be studied. (3) Other biochemical targets for xenobiotics were recently discovered in crustaceans and these should be explored by further ecotoxicological studies (e.g., new information about ecdysteroid receptor molecular biology). (4) Some sex steroid hormones known from vertebrates (testosterone, progesterone) have been reported in crustaceans but knowledge about their targets (crustacean steroid receptors) and signalling is still limited. (5) Determination of the sex in developing juveniles (affecting the sex ratio in population) is a sensitive parameter to various xenobiotics (including endocrine disruptors) but its modulation by general environmental stress and non-specific toxicity should be further studied.     

Utilization of juvenile animal studies to determine the human effects and risks of environmental toxicants during postnatal developmental stages

BACKGROUND: Toxicology studies utilizing animals and in vitro cellular or tissue preparations have been used to study the toxic effects and mechanism of action of drugs and chemicals and to determine the effective and safe dose of drugs in humans and the risk of toxicity from chemical exposures. Testing in animals could be improved if animal dosing using the mg/kg basis was abandoned and drugs and chemicals were administered to compare the effects of pharmacokinetically and toxicokinetically equivalent serum levels in the animal model and human. Because alert physicians or epidemiology studies, not animal studies, have discovered most human teratogens and toxicities in children, animal studies play a minor role in discovering teratogens and agents that are deleterious to infants and children. In vitro studies play even a less important role, although they are helpful in describing the cellular or tissue effects of the drugs or chemicals and their mechanism of action. One cannot determine the magnitude of human risks from in vitro studies when they are the only source of toxicology data. METHODS: Toxicology studies on adult animals is carried out by pharmaceutical companies, chemical companies, the Food and Drug Administration (FDA), many laboratories at the National Institutes of Health, and scientific investigators in laboratories throughout the world. Although there is a vast amount of animal toxicology studies carried out on pregnant animals and adult animals, there is a paucity of animal studies utilizing newborn, infant, and juvenile animals. This deficiency is compounded by the fact that there are very few toxicology studies carried out in children. That is one reason why pregnant women and children are referred to as "therapeutic orphans." RESULTS: When animal studies are carried out with newborn and developing animals, the results demonstrate that generalizations are less applicable and less predictable than the toxicology studies in pregnant animals. Although many studies show that infants and developing animals may have difficulty in metabolizing drugs and are more vulnerable to the toxic effects of environmental chemicals, there are exceptions that indicate that infants and developing animals may be less vulnerable and more resilient to some drugs and chemicals. In other words, the generalization indicating that developing animals are always more sensitive to environmental toxicants is not valid. For animal toxicology studies to be useful, animal studies have to utilize modern concepts of pharmacokinetics and toxicokinetics, as well as "mechanism of action" (MOA) studies to determine whether animal data can be utilized for determining human risk. One example is the inability to determine carcinogenic risks in humans for some drugs and chemicals that produce tumors in rodents, When the oncogenesis is the result of peroxisome proliferation, a reaction that is of diminished importance in humans. CONCLUSIONS: Scientists can utilize animal studies to study the toxicokinetic and toxicodynamic aspects of drugs and environmental toxicants. But they have to be carried out with the most modern techniques and interpreted with the highest level of scholarship and objectivity. Threshold exposures, no-adverse-effect level (NOAEL) exposures, and toxic effects can be determined in animals, but have to be interpreted with caution when applying them to the human. Adult problems in growth, endocrine dysfunction, neurobehavioral abnormalities, and oncogenesis may be related to exposures to drugs, chemicals, and physical agents during development and may be fruitful areas for investigation. Maximum permissible exposures have to be based on data, not on generalizations that are applied to all drugs and chemicals. Epidemiology studies are still the best methodology for determining the human risk and the effects of environmental toxicants. Carrying out these focused studies in developing humans will be difficult. Animal studies may be our only alternative for answering many questions with regard to specific postnatal developmental vulnerabilities.     

SH-SY5Y and LUHMES cells display differential sensitivity to MPP+, tunicamycin,and epoxomicin in 2D and 3D cell culture

SH-SY5Y and LUHMES cell lines are widely used as model systems for studying neurotoxicity. Most of the existing data regarding the sensitivity of these cell lines to neurotoxicants have been recorded from cells growing as two-dimensional (2D) cultures on the surface of glass or plastic. With the emergence of 3D culture platforms designed to better represent native tissue, there is a growing need to compare the toxicology of neurons grown in 3D environments to those grown in 2D to better understand the impact that culture environment has on toxicant sensitivity. Here, a simple 3D culture method was used to assess the impact of growth environment on the sensitivity of SH-SY5Y cells and LUHMES cells to MPP+, tunicamycin, and epoxomicin, three neurotoxicants that have been previously used to generate experimental models for studying Parkinson's disease pathogenesis. SH-SY5Y cell viability following treatment with these three toxicants was significantly lower in 2D cultures as compared to 3D cultures. On the contrary, LUHMES cells did not show significant differences between growth conditions for any of the toxicants examined. However, LUHMES cells were more sensitive to MPP+, tunicamycin, and epoxomicin than SH-SY5Y cells. Thus, both the choice of cell line and the choice of growth environment must be considered when interpreting in vitro neurotoxicity data.     

Are zebra mussels restricted by toxicant levels in the River Meuse? a review

This paper questions if chemical barriers prevent the occurrence of benthic invertebrates in the river Meuse. To this purpose an ecotoxicological analysis is presented, using published observations on the zebra musselDreissena polymorpha, a tolerant species that maintains populations in the river. Zebra mussels collected or exposed at the Belgian-Dutch border contained high levels of several groups of toxicants, and mixture toxicity is likely to occur. A recently developed bio-assay, using the filtration rate of the zebra mussel, demonstrated strong inhibitory effects of water from the river Meuse. To determine which (combination of) toxicants cause such effects, laboratory experiments with toxicant mixtures were carried out. It was demonstrated that in a mixture of five metals (Cu, Zn, Ni, Cd, Pb) the metals contributed to the toxicity of the mixture below the No Observed Effect Concentrations (NOEC) for these metals when tested individually. The average concentration of Cu, Zn and possibly Pb in Meuse water exceed the NOEC values for filtration rate. Thus, it seems likely that joint effects of different (groups of) toxicants in the river Meuse cause the overall toxicity of the water for the zebra mussel, explaining the marginal populations at the test site, while other river species are absent there. It is suggested that toxicants in the river Meuse restrict the recolonisation of the river by invertebrate species more sensitive than the zebra mussel. This will be studied using invertebrates of different sensitivities (molluscs, arthropods), enabling the assessment of toxicity at different stages of water quality improvement of the river Meuse.     

Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective

Abstract

Manufacturers have developed prototype cigarettes yielding reduced levels of some tobacco smoke toxicants, when tested using laboratory machine smoking under standardised conditions. For the scientific assessment of modified risk tobacco products, tests that offer objective, reproducible data, which can be obtained in a much shorter time than the requirements of conventional epidemiology are needed. In this review, we consider whether biomarkers of biological effect related to oxidative stress can be used in this role. Based on published data, urinary 8-oxo-7,8-dihydro-2-deoxyguanosine, thymidine glycol, F₂-isoprostanes, serum dehydroascorbic acid to ascorbic acid ratio and carotenoid concentrations show promise, while 4-hydroxynonenal requires further qualification.     

Xenotransplantation Models to Study the Effects of Toxicants on Human Fetal Tissues

Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human‐relevant mechanistic data on the many tissue‐level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development     

The Concept of Hormesis in Developmental Toxicology

Animal bioassay experiments are frequently conducted to assess the toxicity of chemicals on the developing fetus. Experiments are normally conducted at dosage levels that are much higher than human exposure levels to elicit the toxic reproductive effect of the chemical in a limited number of litters. Recently there has been much discussion on the fact that some chemicals may have beneficial effects at low doses and become toxic at high doses. This concept, known as chemical hormesis, has been the focus of attention in many investigations. Here, we consider the prevalence of hormesis in developmental toxicology and show that current design of developmental toxicity testing does not accommodate the study of hormesis. If it can be proved that some developmental toxicants may have stimulatory low dose effects, then design and analysis of developmental toxicity experiments need to be revised by the scientific community and the regulatory agencies. Using a thorough analysis of an experimental data set, we further demonstrate that in order to establish the possible hormetic effects of a chemical in reproduction, often a multiple replication of the experiment may be necessary to examine such effects. Using a trend test, we illustrate that while it is possible that one replicate of a developmental toxicity experiment with a known teratogen shows strong evidence of hormesis, other replicates may show no sign of beneficial effects at low doses.     

A Hypothetical Application of the Pollution-Induced Community Tolerance Concept in Megafaunal Communities Found at Contaminated Sites

The purpose of our paper is to suggest a novel, hypothetical and yet untested use of the pollution-induced community tolerance concept (PICT). Historically, PICT has been applied to determine whether toxicants are deleterious in microfaunal aquatic and terrestrial communities. We hypothesize that it may be possible to apply PICT to megafaunal organisms (e.g., vertebrates). In doing so, researchers could (1) identify which toxicant, in a complex mixture of toxicants, is harmful since only those contaminants that exert selection pressure are biologically relevant and will result in changes in community structure and (2) determine the transfer of toxicants across trophic levels found within that community. We suggest that community tolerance could be measured in megafaunal communities by measuring biomarkers of exposure and effect in either a number of individuals that make up different populations of animals comprising a community, or in the community as a whole. In this article we discuss the theoretical suitability of our megafaunal PICT approach to the assessment of contaminated sites and some of the potential pitfalls associated with its use. Our intention is that this paper will generate debate and commentary surrounding PIGT and its potential uses in the future. Whether this potential approach is feasible remains to be determined.     

Background and overview of current sediment toxicity identification evaluation procedures

Laboratory bioassays can provide an integrated assessment of the potential toxicity of contaminated sediments to aquatic organisms; however, toxicity as a sole endpoint is not particularly useful in terms of identifying remedial options. To focus possible remediation (e.g., source control), it is essential to know which contaminants are responsible for toxicity. Unfortunately, contaminated sediments can contain literally thousands of potentially toxic compounds. Methods which rely solely on correlation to identify contaminants responsible for toxicity are limited in several aspects: (a) actual compounds causing toxicity might not be measured, (b) concentrations of potentially toxic compounds may covary, (c) it may be difficult to assess the bioavailability of contaminants measured in a sediment, and (d) interactions may not be accounted for among potential toxicants (e.g., additivity). Toxicity identification evaluation (TIE) procedures attempt to circumvent these problems by using toxicity-based fractionation procedures to implicate specific contaminants as causative toxicants. Phase I of TIE characterizes the general physio-chemical nature of sample toxicants. Phase II employs methods to measure toxicants via different analytical methods, and Phase III consists of techniques to confirm that the suspect toxicants identified in Phases I and II of the TIE actually are responsible for toxicity. These TIE procedures have been used to investigate the toxicity of a variety of samples, including sediments. Herein we present a brief conceptual overview of the TIE process, and discuss specific considerations associated with sediment TIE research. Points addressed include: (a) selection and preparation of appropriate test fractions, (b) use of benthic organisms for sediment TIE work, and (c) methods for the identification of common sediment contaminants.     

A Critical Review of Procedures and Approaches Used for Assessing Pollution-Induced Community Tolerance (PICT) in Biotic Communities

Pollution-induced community tolerance (PICT) is used for the detection of minor effects of toxicants in biotic communities. Organisms survive in toxic environments only if they are tolerant to the chemicals present in their habitat. In the selection phase, toxicants hinder the success of sensitive individuals and species and replace them by more tolerant ones. The resulting increase in community tolerance is quantified in the detection phase by short-term toxicity tests. In this way PICT can establish causal linkages between contaminants and effects. An increase in community tolerance compared to the baseline tolerance at reference sites suggests that the community has been adversely affected by toxicants. PICT has been used in aquatic and terrestrial environments with communities of periphyton, phytoplankton, bacteria, nematodes and insects. A variety of methods have been used for quantification of community tolerance including photosynthesis, sulfolipid synthesis, respiration, thymidine and leucine incorporation, survival, and substrate utilisation patterns. PICT has been observed for copper, zinc, nickel, mercury, cadmium, arsenate, monomethylarsonic acid, diuron, tributyl tin, 4,5,6-trichloroguaiacol, irgarol 1051, seanine 211, atrazine, and trinitrotoluene. It is necessary to validate PICT, at least by showing that it is related to the preexposure concentration of the toxicants and that it is coupled to a toxicant-induced succession (TIS) in the community. Care must also be taken to ascertain that PICT interpretation is not confounded by co-tolerance or bioavailability differences. Co-tolerance patterns, which are indicative of the specificity of PICT, have only been investigated for arsenate, diuron and a few metals. For the further improvement of PICT methodology special attention should be given to co-tolerance patterns and development of new integrating short-term tests for quantification of tolerance. It is also important to broaden the scope of organisms and toxicants used. Properly validated, PICT is a powerful tool for detection of community effects and its use in monitoring and site-specific risk assessment should be encouraged.     

Recombinant microorganisms as environmental biosensors: pollutants detection by Escherichia coli bearing fabA'::lux fusions.

A set of genetically engineered Escherichia coli strains was constructed, in which the promoter of the fabA gene is fused to Vibrio fischeri luxCDABE either in a multi-copy plasmid or as a single copy chromosomal integration. The fabA gene codes for beta-hydroxydecanoyl-ACP dehydrase, a key enzyme in the synthesis of unsaturated fatty acids, and is induced when fatty acid biosynthesis pathways are interrupted. A dose-dependent and highly sensitive bioluminescent response to a variety of chemicals was controlled by the fadR gene. A tolC mutant E. coli host displayed generally lower detection threshold for toxicants. A chromosomal integration of a single copy of the fabA'::lux fusion led to a markedly lower background luminescence, but did not yield an improvement in overall performance. It is proposed that these or similarly constructed reporters of fatty acid biosynthesis inhibition may serve as novel microbial toxicity biosensors.