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Biosensor for direct determination of organophosphate nerve agents using recombinant Escherichia coli with surface-expressed organophosphorus hydrolase. 2. Fiber-optic microbial biosensor.

A fiber-optic microbial biosensor suitable for direct measurement of organophosphate nerve agents was developed. The unique features of this novel microbial biosensor were the recombinant Escherichia coli cells expressing the enzyme organophosphorus hydrolase on the cell surface and the optical detection of the products of enzyme-catalyzed organophosphate hydrolysis. The use of cells with the metabolic enzyme expressed on the cell surface as a biological sensing element provides advantages of no resistance to mass transport of the analyte and product across the cell membrane and low cost due to elimination of enzyme purification, over the conventional microbial biosensors based on cells expressing enzyme intracellularly and enzyme-based sensors, respectively. The use of an optical transducer allows the detection of different organophosphates in a mixture, presently not feasible with acetylcholinesterase-based biosensors. E. coli cells expressing organophosphorus hydrolase (OPH) on the cell surface were immobilized in low melting temperature agarose on a nylon membrane and attached to the common end of a bifurcated fiber-optic bundle. OPH-expressing E. coli cells catalyzed the hydrolysis of organophosphorus pesticides to form stoichiometric amounts of chromophoric products that absorb light at specific wavelengths. The backscattered radiation of the specific wavelength incident light was measured using a photomultiplier detector and correlated to the organophosphate concentration. The best sensitivity and response time were obtained using a sensor constructed with 1.5 mg of cells operating in pH 9, 50 mM HEPES buffer with 100 mM NaCl and 0.05 mM CoCl2 at 30 degrees C. At optimized conditions, the biosensor measured paraoxon, parathion, and coumaphos pesticides with high selectivity against triazine and carbamate pesticides in approximately 10 min. The lower detection limits were 3 microM for paraoxon and parathion and 5 microM for coumaphos. When stored in the buffer at 22 degrees C, the biosensor was stable for over a 1-month period and showed no decline in the response for over 75 repeated usages. The new fiber-optic microbial biosensor is an ideal tool for on-line monitoring of the detoxification process for organophosphate pesticides-contaminated wastewaters but may not be suitable for environmental monitoring.

Aryldialkylphosphatase↗

Mysid crustaceans as potential test organisms for the evaluation of environmental endocrine disruption: a review.

Anthropogenic chemicals that disrupt the hormonal systems (endocrine disruptors) of wildlife species recently have become a widely investigated and politically charged issue. Invertebrates account for roughly 95% of all animals, yet surprisingly little effort has been made to understand their value in signaling potential environmental endocrine disruption. This omission largely can be attributed to the high diversity of invertebrates and the shortage of fundamental knowledge of their endocrine systems. Insects and crustaceans are exceptions and, as such, appear to be excellent candidates for evaluating the environmental consequences of chemically induced endocrine disruption. Mysid shrimp (Crustacea: Mysidacea) may serve as a viable surrogate for many crustaceans and have been put forward as suitable test organisms for the evaluation of endocrine disruption by several researchers and regulatory bodies (e.g., the U.S. Environmental Protection Agency). Despite the long-standing use of mysids in toxicity testing, little information exists on their endocrinology, and few studies have focused on the potential of these animals for evaluating the effects of hormone-disrupting compounds. Therefore, the question remains as to whether the current standardized mysid endpoints can be used or adapted to detect endocrine disruption, or if new procedures must be developed, specifically directed at evaluating hormone-regulated endpoints in these animals. This review summarizes the ecological importance of mysids in estuarine and marine ecosystems, their use in toxicity testing and environmental monitoring, and their endocrinology and important hormone-regulated processes to highlight their potential use in assessing environmental endocrine disruption.

Animals↗

Biologic monitoring of exposure to environmental chemicals throughout the life stages: requirements and issues for consideration for the National Children's Study.

Biomonitoring of exposure is a useful tool for assessing environmental exposures. The matrices available for analyses include blood, urine, breast milk, adipose tissue, and saliva, among others. The sampling can be staged to represent the particular time period of concern: preconceptionally from both parents, from a pregnant woman during each of the three trimesters, during and immediately after childbirth, from the mother postnatally, and from the child as it develops to 21 years of age. The appropriate sample for biomonitoring will depend upon matrix availability, the time period of concern for a particular exposure or health effect, and the different classes of environmental chemicals to be monitored. This article describes the matrices available for biomonitoring during the life stages being evaluated in the National Children's Study; the best biologic matrices for exposure assessment for each individual chemical class, including consideration of alternative matrices; the analytical methods used for analysis, including quality control procedures and less costly alternatives; the costs of analysis; optimal storage conditions; and chemical and matrix stability during long-term storage.

Adolescent↗

Environmental health physics: 50 years of progress.

Environmental health physics is an interdisciplinary field, involving study of the release, transport, and fate of radioactive material in the environment. Further, it addresses the interaction of humans with radioactive materials within the ambient (outdoor) environment and with the environments associated with modern technology and lifestyles. It also involves both naturally occurring and artificially produced radionuclides with the former generally being by far the highest source of exposure. In fact, doses from naturally occurring radionuclides are increasingly being used as a benchmark for the establishment of dose rate limits for people. Because of the pioneering work of early environmental health physicists, models exist today that can be used to assess the potential impacts of new nuclear facilities prior to their operation. In fact, these people represent the branch of the health physics profession who conducted environmental monitoring programs and performed the associated research studies that led to the identification of the principal radionuclides of interest, the major pathways and mechanisms through which they expose people, and the doses that may result from radioactive materials in the natural and technologically enhanced environments. One of their most important contributions was the identification and quantification of many of the key parameters that serve as input to such models. Monitoring of nuclear weapons development facilities used during and after World War II was the initial stimulus for the establishment of environmental health physics programs. Thereafter, these programs were expanded both nationally and globally, as a result of the atmospheric weapons testing programs of nations such as France, the People's Republic of China, the former Soviet Union, the United Kingdom, and the United States. Additional stimuli were provided by the development of the commercial nuclear power industry. Current environmental programs, particularly within the U.S., focus on decontamination and decommissioning of dormant facilities from these earlier defense and commercial programs. The range of the environmental health physics aspects of these activities is the subject of this paper. Presented at the end of the paper is a summary of some of the more important lessons that have been learned. As will be noted, this is an exciting field that will present challenges to health physicists for years to come.

Background Radiation↗

Radionuclides in the terrestrial ecosystem near a Canadian uranium mill--Part II: Small mammal food chains and bioavailability.

Food chain transfer through the soil-vegetation-small mammal food chain was measured by concentration ratios (CRs) for uranium, 226Ra, 210Pb, and 210Po at three sites near the Key Lake uranium mill in northern Saskatchewan. Plant/soil CRs, animal carcass/GI tract CRs, and animal/soil CRs were depressed at sites impacted by mill and tailings dusts relative to a nearby control site. Thus, radionuclides associated with large particulates in tailings and/or ore dusts may be less bioavailable to terrestrial plants and animals than natural sources of radioactive dust. These results show that reliance on default food chain transfer parameters, obtained from uncontaminated terrestrial ecosystems, may overpredict impacts at uranium mine and mill sites. Given the omnivorous diet of small mammals and birds, animal/soil CRs are recommended as the most cost-effective and robust means of predicting animal concentrations from environmental monitoring data at uranium mill facilities.

Animals↗

[Origin, structure and distribution of dioxins].

Polychlorinated dibenzo-para-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) are generated as unintentional by-products in a number of thermal and chemical-industrial processes. Biogenic formation through dimerization of chlorinated precursors, such as chlorophenols, is know but does not play a major role in national dioxin release inventories and in most cases is not quantified. PCDD/PCDF are semi-volatile substances and undergo long-range transport; they are persistent and accumulate in the environment and organismus; and they are toxic. They have become a global environmetnal problem. At the international level this issue is addressed by the Stockholm Convention on Persistent Organic Pollutants, a legally binding instrument to eliminate PCDD/PCDF through step-wise implementation of reduction measures. Within the Stockholm Convention, Parties have to develop national or regional dioxin inventories. First results show that in most industrialized countries, incineration of municipal solid waste does no longer represent the largest dioxin source; instead, certain processes in the metallurgical industry have become largest emitters. In developing countries, the situation is very different: open burning processes such as forest and grassland fires, burning of agricultural residues either before or after harvest as well as fires in waste dumps or the private fires to dispose of municipal waste represent the largest dioxin sources. First steps for a global environmental monitoring program under the Stockholm Convention have been initiated.

Dioxins↗

Neurodevelopmental toxicity of 2-(Methylthio)benzothiazole (MTBT) in zebrafish: Insights into PTGS2- associated dysregulation of the neuroactive ligand-receptor interaction pathway.

2-(Methylthio)benzothiazole (MTBT), an important derivative of benzothiazoles, has extensive applications in industrial processes, pharmaceuticals, and environmental monitoring. It can enter aquatic environments through surface runoff and has been detected at relatively high concentrations in various environmental systems. However, studies investigating the aquatic toxicity of MTBT remain limited. In this study, zebrafish embryos were exposed to MTBT at concentrations of 0, 10, 100, and 1000 μg/L for 144 h to evaluate its developmental and neurotoxic effects. MTBT exposure significantly reduced the survival rate, hatching rate, spontaneous movement, and body length of zebrafish larvae. MTBT also impaired locomotor behavior, reduced fluorescence of Tg(huc:eGFP) larvae in the central nervous system and inhibited motor neuron axonal development. Protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that MTBT-induced neurotoxicity may be associated with disruption of the neuroactive ligand-receptor interaction pathway. Further validation experiments revealed that MTBT induced oxidative stress, inflammation, and apoptosis, suggesting that these adverse effects may underlie its neurodevelopmental toxicity. Collectively, these findings provide biological evidence that MTBT induces neurodevelopmental toxicity in zebrafish larvae and suggest that dysregulation of the PTGS2-related neuroactive ligand-receptor interaction pathway may be involved in this process.

2-(Methylthio)benzothiazole (MTBT)↗

Biochemical responses as indicators of toxic effects of chemicals in ecosystems.

Biochemical responses of animals to environmental chemicals (biochemical biomarkers) can give measures of exposure, and sometimes also toxic effect. They are particularly valuable where they can be used to measure the toxic effects of chemicals in the field, employing non-destructive sampling methods. Measurements of exposure are useful in the case of non-persistent chemicals (e.g. organophosphorus, carbamate, or pyrethroid insecticides) which are difficult or impossible to detect by chemical analysis. They can also be useful to provide an integrated measure of the level of exposure to a group of related chemicals. Biochemical biomarkers are likely to provide a measure of toxic effect, where they are based upon a molecular mechanism which underlies toxicity. A widely-used biochemical biomarker is cholinesterase depression, which may involve destructive sampling (brain acetylcholinesterase) or non-destructive sampling (serum butyrylcholinesterase). For genotoxic chemicals, techniques which measure DNA damage (e.g. detection of DNA adducts) provide a powerful tool in measuring environmental effects. The detection of biochemical changes caused by anticoagulant rodenticides (e.g. abnormal levels of clotting proteins in blood) provides another example of this approach. In general, the development of simple, sensitive, and specific assays that are 'user-friendly' would open the way for much wider use of biochemical biomarkers in environmental monitoring.

Animals↗

Responses to long-term divergent selection for eight-week body weight in chickens.

Thirty-six generations of divergent selection for body weight at 8 wk of age resulted in approximately an eightfold difference between the high (HWS) and low (LWS) lines for this trait. In both White Plymouth Rock lines, selection intensities declined over generations, with responses about five times greater during the first 18 than the last 18 generations of selection in Line HWS and about two times greater in Line LWS. Also, responses to selection were more irregular in the later than in earlier generations. Sexual dimorphism of body weight (male:female) was greater for Line LWS than HWS. A randombred control line (AC) maintained concurrently with the selected lines did not exhibit environmental trends across generations. Relaxed lines, established at different generations of selection, were used to evaluate effectiveness of selection and monitor environmental changes over short periods.

Animals↗

Aspergillus terreus infections in haematological malignancies: molecular epidemiology suggests association with in-hospital plants.

During a three-year period nine patients with haematological diseases after myeloablative chemotherapy died from invasive fungal infections caused by Aspergillus terreus. The hospital inanimate environment was monitored and A. terreus was cultured from potted plants in the vicinity of the patients. The patients (N = 14) and the environmental isolates (N = 2) were fingerprinted by RAPD-PCR with four different primers. Based on RAPD patterns the patients' isolates were differentiated into five different types; the environmental isolates represented two types. The isolates of four patients were identical to those found in the environment. Five additional patients were infected by RAPD types not found in the environment. One patient was infected with two different types. The data indicate a hospital-acquired infection in many of the patients and underline the need for careful environmental monitoring of units in which high-risk patients are housed.

Aspergillosis, Allergic Bronchopulmonary↗

Rapid assays for environmental and biological monitoring.

Rapid, inexpensive, sensitive, and selective enzyme-linked immunosorbent assays (ELISAs) now are utilized in environmental science. In this laboratory, many ELISAs have been developed for pesticides and other toxic substances and also for their metabolites. Compounds for which ELISAs have recently been devised include insecticides (organophosphates, carbaryl, pyrethroids, and fenoxycarb), herbicides (s-triazines, arylureas, triclopyr, and bromacil), fungicides (myclobutanil), TCDD, and metabolites of naphthalene and toluene. New rapid assays have been developed for mercury.

Antifungal Agents↗

Environmental health physics-50 years of progress.

Environmental health physics is an interdisciplinary field, involving study of the release, transport, and fate of radioactive material in the environment. Further, it addresses the interaction of humans with radioactive materials within the ambient (outdoor) environment and with the environments associated with modern technology and lifestyles. It also involves both naturally occurring and artificially produced radionuclides with the former generally being by far the highest source of exposure. In fact, doses from naturally occurring radionuclides are increasingly being used as a benchmark for the establishment of dose rate limits for people. Because of the pioneering work of early environmental health physicists, models exist today that can be used to assess the potential impacts of new nuclear facilities prior to their operation. In fact, these people represent the branch of the health physics profession who conducted environmental monitoring programs and performed the associated research studies that led to the identification of the principal radionuclides of interest, the major pathways and mechanisms through which they expose people, and the doses that may result from radioactive materials in the natural and technologically enhanced environments. One of their most important contributions was the identification and quantification of many of the key parameters that serve as input to such models. Monitoring of nuclear weapons development facilities used during and after World War II was the initial stimulus for the establishment of environmental health physics programs. Thereafter, these programs were expanded both nationally and globally, as a result of the atmospheric weapons testing programs of nations such as France, the People's Republic of China, the former Soviet Union, the United Kingdom, and the United States. Additional stimuli were provided by the development of the commercial nuclear power industry. Current environmental programs, particularly within the U.S., focus on decontamination and decommissioning of dormant facilities from these earlier defense and commercial programs. The range of the environmental health physics aspects of these activities is the subject of this paper. Presented at the end of the paper is a summary of some of the more important lessons that have been learned. As will be noted, this is an exciting field that will present challenges to health physicists for years to come.

Background Radiation↗

Human biomonitoring to optimize fish consumption advice: reducing uncertainty when evaluating benefits and risks.

National fish consumption advisories that are based solely on assessment of risk of exposure to contaminants without consideration of consumption benefits result in overly restrictive advice that discourages eating fish even in areas where such advice is unwarranted. In fact, generic fish advisories may have adverse public health consequences because of decreased fish consumption and substitution of foods that are less healthy. Public health is on the threshold of a new era for determining actual exposures to environmental contaminants, owing to technological advances in analytical chemistry. It is now possible to target fish consumption advice to specific at-risk populations by evaluating individual contaminant exposures and health risk factors. Because of the current epidemic of nutritionally linked disease, such as obesity, diabetes, and cardiovascular disease, general recommendations for limiting fish consumption are ill conceived and potentially dangerous.

Adolescent↗

An evaluation of proposed frameworks for grouping polychlorinated biphenyl (PCB) congener data into meaningful analytic units.

BACKGROUND: Polychlorinated biphenyls (PCBs) have been associated with a variety of health outcomes. Enhanced laboratory techniques can provide a relatively large number of individual PCB congeners for investigation. However, to date there are no established frameworks for grouping a large number of PCB congeners into meaningful analytic units. METHODS: In a case-control study of serum PCB levels on breast cancer risk, measured levels of 56 PCB congener peaks were available for analysis. We considered several approaches for grouping these compounds based on 1) chlorination, 2) factor analysis, 3) enzyme induction, 4) enzyme induction and occurrence, and 5) enzyme induction, occurrence, and other toxicological aspects. The utility of a framework was based on the mechanism of biologic actions within each framework, lack of collinearity among congener groups, and frequency of detection of PCB congener groups in measured serum levels of 192 healthy postmenopausal women. RESULTS: Most participants had detectable levels for the proposed PCB congeners groups, using degree of chlorination as a grouping framework. In addition, the previously proposed grouping approach based on enzyme induction, occurrence, and other toxicological aspects was an applicable alternative to the crude approach of grouping by degree of chlorination. Grouping these congeners with respect to P450 enzyme induction activity, and the previously proposed framework based on enzyme induction and occurrence, did not fit these data as well, because only a small proportion of participants had detectable levels for the congener groups with the greatest toxicological potential. Statistical grouping did not result in an interpretable and meaningful clustering of these exposures. CONCLUSIONS: In these data, grouping with respect to degree of chlorination and the previously proposed framework based on enzyme induction, occurrence, and other toxicological aspects were the most useful approaches to reducing a large number of PCB congeners into meaningful analytic units. Factors affecting the utility of the proposed grouping frameworks are discussed.

Aged↗

Environmental health science research and human risk assessment.

Environmental health science research, with its focus on fundamental science and disease prevention, is important for the development of rational and cost-effective public health and regulatory policies related to environmental protection. Environmentally related diseases are preventable, yet they impose a major burden on society in terms of human suffering and costs related to health care. Similarly, the expenditure of hundreds of billions of dollars for regulatory compliance is a major economic concern. There is considerable debate regarding current regulatory risk assessment practices for environmental agents. Implicit in all risk assessment schemes is the need to extrapolate from high-exposure studies to low-exposure situations and from known risks in rodents to probable risks in people. Both extrapolations are fraught with uncertainties. These uncertainties are accommodated in risk-assessment schemes by the incorporation of arbitrary "safety factors" and other default approaches. Since these factors are not derived experimentally, they may overestimate or under estimate actual risks. Risk-assessment methodology, its relevance to the human condition, and its use in protecting human health will greatly improve when our expanding knowledge of the basic biology of environmental effects is incorporated into toxicological testing and risk-assessment schemes. Moreover, exciting opportunities now exist to advance our understanding of the environmental and genetic bases of many common diseases and to design effective prevention and intervention strategies to combat their development. This report discusses some of the current opportunities and challenges.

Cell Communication↗

The impact of low technology lead hazard reduction activities among children with mildly elevated blood lead levels.

This prospective environmental intervention study was conducted to determine the impact of low-technology lead hazard reduction activities among children with mildly elevated blood lead levels. Children whose homes had severe lead hazards were automatically assigned to the intervention group. Children whose homes had lesser hazards were randomly assigned to the intervention group or comparison group. The one-time intervention focused mainly on cleaning and repainting window areas and educating caregivers to maintain effective housekeeping techniques. Changes in blood lead and dust lead loading levels were observed following the interventions. Analysis of covariance was used to adjust comparisons of postintervention levels for preintervention levels and other variables. The lead hazard reduction activities were associated with a modest decline in blood lead levels among children with severe hazards. The magnitude of the decline depended on the confounder that was controlled; the majority ranged from-1.1. to-1.6 microgram/dL. A moderate reduction in window well dust lead loading levels was also observed. While low-technology lead hazard reduction measures appeared to be an effective secondary prevention strategy among children with severe household lead hazards, larger studies are needed to confirm these results.

Boston↗

The contribution of lead-contaminated house dust and residential soil to children's blood lead levels. A pooled analysis of 12 epidemiologic studies.

In 1992, the U.S. Congress passed the Residential Lead-Based Paint Hazard Reduction Act, which requires the promulgation of health-based dust lead and soil lead standards for residential dwellings to prevent undue lead exposure in children. Unfortunately, the levels of lead in house dust and soil that are associated with elevated blood lead levels among U.S. children remain poorly defined. This pooled analysis was done to estimate the contributions of lead-contaminated house dust and soil to children's blood lead levels. The results of this pooled analysis, the most comprehensive existing epidemiologic analysis of childhood lead exposure, confirm that lead-contaminated house dust is the major source of lead exposure for children. These analyses further demonstrate that a strong relationship between interior dust lead loading and children's blood lead levels persists at dust lead levels considerably below the U.S. Department of Housing and Urban Development's current postabatement standards and the Environmental Protection Agency's guidance levels. Finally, these analyses demonstrate that a child's age, race, mouthing behaviors, and study-site specific factors influence the predicted blood lead level at a given level of exposure. These data can be used to estimate the potential health impact of alternative health-based lead standards for residential sources of lead exposure.

Child, Preschool↗

Health surveillance in the population living in a methyl mercury-polluted area over a long period.

It is important to follow up on the health status of inhabitants living in the methyl mercury-polluted area surrounding Minamata City, paying particular attention to diseases not only of the central nervous system but also of other organs. We have been carrying out such concentric studies for more than 10 years. We have previously studied the cause-specific standard mortality ratios in Minamata disease patients and reported that the SMRs for liver disease and renal disease were significantly raised in male and female patients, respectively. It was also found that complications arising from diabetes could be due to the large number of old people among the autopsy cases. The next step was to clarify the actual prevalence and incidence of liver disease, renal disease, and diabetes mellitus epidemiologically among the population in this area. The aim of this study was to determine the actual prevalence of these diseases and complaints, and to investigate the contribution of various risk factors to these diseases in this area. The study was a population-based cross-sectional mass screening survey. A case-control study was designed to estimate the role of various risk factors including methyl mercury exposure for these diseases. A mass multiple health examination survey was performed in 1500 subjects aged 40 years and older in Tsunagi Town, neighboring Minamata City, every summer since 1984. Tsunagi Town is located in a methyl mercury-polluted area and there are 36.9 certified Minamata disease patients per 1000 population. Data concerning liver disease, renal disease, and diabetes mellitus were collected on the basis of urine, hematological, physical, and ultrasonographic examinations. Data on risk factors and subjective complaints were collected by interview and other measures. The prevalence of these diseases was not higher in this methyl mercury-polluted area compared with other areas in Japan, contrary to what was expected based on standard mortality ratios and pathological findings. There were no positive correlations between those diseases and methyl mercury exposure. On the other hand, the population in the polluted area had more and a greater variety of complaints than those in the nonpolluted area. It is possible that not only neurological subjective complaints but also nonspecific complaints of the population in the polluted area might be influenced by past methyl mercury exposure. This health surveillance in the population living in a methyl mercury-polluted area must be maintained in the future.

Aged↗