Program Highlights Archive
Project 2: Functional profiling of susceptibility genes
Leaders: Christopher Vulpe and Luoping Zhang
Many people are exposed to a variety of toxic chemicals present in the environment on a daily basis. However, only some people develop disease (get sick) as a result. An individual’s chances depend in part on subtle differences in the genes which comprise the genetic blueprint for each person. Unfortunately, for most toxic chemicals, we don’t know where to look for these important variations because we don’t which of the tens of thousands of genes are important for dealing with each toxic chemical. In this project, we are figuring out which genes are the important ones to focus on by using baker’s yeast. By using yeast, we have been able to check thousands of genes for their importance in an individual’s vulnerability to Superfund chemicals. In the past year, the research group led by Dr. Chris Vulpe found several genes associated with the packaging of DNA in a cell (the chromatin) as key to sensitivity to arsenic. Dr. Luoping Zhang’s group further demonstrated the importance of one of these genes in human cells. Arsenic is an established cause of bladder cancer in humans and these findings suggest that alterations in the way that DNA is packaged into chromatin may affect arsenic’s toxicity and carcinogenicity. In the next year, we plan to look to see if these variations in these genes play a role in the likelihood that a person will develop bladder cancer or other diseases after being exposed to arsenic. Understanding the genetic determinants of chemical susceptibility in humans can help identify groups of people that could be at increased risk of developing disease following exposure to toxic agents, and to design prevention and intervention strategies with the aim of preserving public health.
Core B: Research translation
Leaders: Amy Kyle and James Hunt
The Research Translation Core focused this past year on informing policy and stakeholder audiences about key scientific information and principles related to chemical assessment and characterization and about children’s environmental health, both key areas of research for the group as a whole. The Core conducted several formal and informal workshops for stakeholder groups in San Francisco, Oakland, and in Sacramento. The program advised legislative staff about key scientific concepts in the development of several pieces of legislation. This resulted in the inclusion of the concept of ‘hazard traits’ in California’s newly passed green chemistry legislation (AB 1879 and SB 509). This is important because including a concept of ‘hazard traits’ means that the chemical traits of health concern can be further defined and elucidated after legislation is passed and adapted as scientific knowledge and methods improve.
The engineering component of the Core analyzed data from two groundwater plumes containing chromate in the southeastern corner of California to assess groundwater remediation approaches. The monitoring data were reported in over a hundred wells during site investigation and remediation efforts over a 20 year period. These data reveal that chromium as a soluble contaminant has been retained in the groundwater aquifer up to 50 years after release. The analysis showed that pumping out groundwater has not been an effective remediation tool because the source of concentrated chromate present in trapped brines continues to slowly release chromate into flowing groundwater. Discussion with the Stakeholders involved is on-going.
2007 Program Highlights
Project 3: Arsenic biomarker epidemiology
Leaders: Patricia Buffler and Martyn Smith
Project 3 explores the effects of childhood arsenic exposure and the mechanisms that may confer susceptibility to these effects. The Arsenic Health Effects Research Program led by Dr. Allan Smith has shown that in utero and early childhood exposure to arsenic results in major increases in lung cancer and bronchiectasis mortality in young adults aged 30-49. The program also reported findings of more than a 3-fold increase in mortality from acute myocardial infarction in young adults who had early life exposure to arsenic in drinking water. These findings show that early life environmental exposure to arsenic in drinking water is strongly linked to disease incidence and mortality in adulthood.
Project 5: Nanotechnology-based environmental sensing
Leaders: Catherine Koshland and Donald Lucas
Project 5 made significant progress towards developing a functional arsenic detector in ground water using nanotechnology through the doctoral thesis work of student Martin Mulvihill. Using close-pack arrays of octahedral shaped silver nanocrystals, the chemical sensing of arsenic ions with detection limits as low as 1 part per billion in solution was possible. The sensor is based on surface-enhanced Raman spectroscopy (SERS), where analyte molecules near nanostructured metallic surfaces experience huge enhancements in Raman scattering cross-sections, typically orders of magnitude higher than expected. The nature of vibrational spectroscopy allows for the simultaneous measurement of arsenic in both of its commonly found oxidation states and can discriminate between the two. This is important since the different oxidation states have different toxicities.
The detection is performed directly on the substrate by placing a droplet of the analyte solution onto the nanocrystal monolayer, with no additional sample preparation required. These substrates have been verified to work in the presence of known competing anions, and have been used to accurately characterize the arsenic levels in polluted well water obtained by collaborators in Nevada.
2006 Program Highlights
Project 3: Arsenic biomarker epidemiology
Leaders: Allan Smith and Martyn Smith
Very little evidence exists concerning the possible impairment of children’s intellectual function in relation to arsenic exposure in utero and childhood. Children worldwide are exposed to arsenic in drinking water at concentrations that exceed the standard recommended by the World Health Organization and the U.S. Environmental Protection Agency maximum contaminant level of 10 μg/L. Children are particularly at risk for high exposure in arsenic-affected areas of South Asia such as West Bengal, India.
Acute neurotoxic effects of arsenic in high doses have been well documented. Arsenic poisoning related to occupational exposure causes central nervous system alterations, including impairments of recent memory, learning, and concentration. Children may be particularly susceptible to neurotoxic substances as suggested by findings from studies on the effects of lead, methylmercury, solvents, and PCBs. Experimental animal and petri dish studies, and some limited evidence from the few earlier reports considering children’s intellectual function and arsenic, suggested possible associations between arsenic exposure and neurodevelopment. One recent study of 201 children conducted in Bangladesh, which is neighboring our study region, suggested that current arsenic concentrations in water as low as 10 μg/L were linked to reductions in intellectual functioning in 10-year-old children.
We conducted a cross-sectional study among 351 children aged 5 to 15 years selected from a source population of 7,683 people in West Bengal, India, 2001-2003. Intellectual function was assessed with six subtests from the Wechsler Intelligence Scale for Children, as well as with the Total Sentence Recall test, the Colored Progressive Matrices test and a pegboard test. Arsenic in urine and lifetime water sources including the pregnancy period were assessed using measurements of samples from 409 wells. The test scores were analyzed with linear regressions based on the method of generalized estimating equations incorporating relevant covariates.
This study systematically addresses arsenic exposure from all water sources used over a lifetime (including the pregnancy period), as well as urinary arsenic concentrations, in relation to intellectual function in children. Effects were found for the vocabulary, picture completion, and object assembly tests with reductions between 12% and 20%, but the confidence intervals were broad. Our findings suggest that increased urinary arsenic concentrations reflecting current exposure from all sources, including food, are associated with small decrements in intellectual function testing, whereas little evidence for an effect of long-term arsenic concentrations in drinking water was found.
Our findings suggest that arsenic exposure measured in urine is related to decrements in intellectual function scores, which may be in the range of 10% to 20% for some tests. However, the 95% confidence intervals of these estimates were wide. Whether or not these effects have persisting impact needs further investigation. There was little evidence of an association between arsenic drinking water concentrations alone and intellectual function. Current urine concentrations reflecting exposure from all sources appeared to be more relevant than pregnancy, peak, or cumulative exposure based on measurements of water sources. One possible explanation is that the relationship with current exposure relates only to transient effects. However, it is also possible that the lack of findings with past water concentrations is due to incomplete assessment of past exposure, in particular, exposure originating from food. Although the findings need to be confirmed, they add to the body of evidence of adverse health effects in children resulting from exposure to arsenic.
von Ehrenstein OS, Poddar S, Yuan Y, Mazumder DG, Eskenazi B, Basu A, Hira-Smith M, Ghosh N, Lahiri S, Haque R, Ghosh A, Kalman D, Das S, Smith AH (2006) Children’s Intellectual Function in Relation to Arsenic Exposure. Epidemiology. Jan;18(1):44-51. PMID: 17149142. [Abstract] [Full text]
Project 4: Application of comparative genomics, transcriptomics, and proteomics to optimize microbial reductive dehalogenation
Leaders: Lisa Alvarez-Cohen and Gary Andersen
This project seeks to understand and optimize the microbial detoxification of common Superfund pollutants, perchloroethene (PCE) and trichloroethene (TCE) by focusing on the only genus of bacteria, Dehalococcoides, known to completely reduce PCE and TCE to ethene. A better understanding of the genome, transcriptome and proteome of Dehalococcoides will greatly improve our understanding of the physiology of these difficult to grow organisms, so that their abundance and activity at bioremediation sites can be maximized.
We have determined that Dehalococcoides strain BAV1 diverges from that of D. ethenogenes 195 in several major metabolic pathways. Conversely, we determined that ANA enrichment possesses most of the same genes as D. ethenogenes 195 suggesting significant horizontal gene transfer among species. This has furthered a specific aim of the project to identify important genes that are conserved throughout Dehalococcoides spp. as well as those that vary between strains.
We measured the transcriptomic effects of cobalamin (vitamin B12)-limited growth conditions. This stress condition is of particular relevance because cobalamin is a necessary co-factor for reductive dehalogenases but cannot be biosynthesized de novo by this isolate. The findings revealed a cobalamin regulon in this isolate and provided novel genetic targets for monitoring cobalamin stress in Dehalococcoides spp.
Chlorinated solvents are the most common groundwater contaminants at Superfund sites. In situ bioremediation is a promising and cost effective method for remediation of these contaminants. The aim of project 4 is to improve prediction and monitoring which will ultimately optimize system performance at remediation sties.
Work in specific aim 1 involved an enriched anaerobic microbial community (ANAS) that reductively dechlorinates chlorinated ethenes including TCE, cis-dichloroethene (c-DCE) and vinyl chloride (VC). We used whole genome microarrays based upon the chromosome of D. ethenogenes 195 to compare the genomics of strain 195 to those of Dehalococcoides strain BAV1 and the ANAS enrichment. Thus far, we have determined that the genome of strain BAV1 diverges from that of strain 195 in several major metabolic pathway genes including genes typically involved in carbon assimilation, nitrogen fixation, cobalamin usage, hydrogenases, and especially reductive dehalogenases. Conversely, the ANAS enrichment possesses most of the same genes found in strain 195, with the exception of a number of viral inserts containing reductive dehalogenase genes, suggesting significant horizontal gene transfer among species.
As part of specific aim 2, we applied whole-genome microarrays to compare the transcriptome of strain 195 when grown under differing growth conditions. In particular we measured the transcriptomic effects of cobalamin (vitamin B12)-limited growth conditions. This stress condition is of particular relevance because cobalamin is a necessary co-factor for reductive dehalogenases but cannot be biosynthesized de novo by this isolate. The findings revealed a cobalamin regulon in this isolate and provided novel genetic targets for monitoring cobalamin stress in Dehalococcoides spp.
In a related study, we characterized the effects of exposing strain 195 to cell-free supernatants obtained from the ANAS enrichment. To our surprise, the genes that were most strongly down regulated after exposure to the supernatants were involved with cobalamin salvage and recycling, suggesting that members of ANAS biosynthesize additional cobalamin de novo that can be transferred to Dehalococcoides. We intend to further characterize this eco-physiological interaction as it may be crucial for avoiding cobalamin stress and prolonging dechlorination activity in the environment.
Progress on specific aim 3 includes the assembly of defined consortia from combinations of Dehalococcoides and other key species identified in the ANAS enrichment. We were able to grow Desulfovibrio vulgaris Hildenborough (DVH) with strain 195 in syntrophy on a defined medium containing no hydrogen and no sulfate. We will apply qPCR and whole-genome microarrays to compare the transcriptomes of DVH, 195, and the co-culture DVH/195 and to identify genes important in these symbiotic interactions.
With respect to specific aim 5, we have completed the molecular analysis of a microbial community through different phases of enhanced bioremediation at Ft. Lewis East Gate Disposal Yard (Seattle, Washington), a TCE contaminated field site undergoing in situ bioremediation. We applied qPCR to measure the 16S rRNA gene and the three functionally important reductive dehalogenase genes (tceA, bvcA, vcrA) of Dehalococcoides spp. present in the groundwater through different stages of treatment process (biostimulation and bioaugmentation). Quantification of gene concentration and expression suggests that Dehalococcoides spp. were not only present but were physiologically active in the field communities and provided a clear trend of the dynamics of the different strains of Dehalococcoides in response to the manipulations at the site.
Finally, we have expanded our analyses to include application of a whole genome microarray to measure the expression of genes by Rhodococcus sp. RHA1 in response to induction by propane. In these studies we have shown that the propane monooxygenase is inducible and responsible for NDMA degradation by this organism.
2005 Program Highlights
Project 3: Arsenic Biomarker Epidemiology
Leaders: Drs. Allan Smith and Martyn T. Smith
Millions of people are exposed to arsenic-contaminated water in the U.S. and worldwide, and arsenic is ranked first on the most recent priority list of Superfund site hazardous substances. Dr. Allan Smith and the Berkeley Arsenic Health Effects Research Group he leads first identified major potential risks from arsenic in drinking water in a publication in 1992 which has since been cited in the scientific literature more than 300 times (Environmental Health Perspectives, 97:259-267, 1992). Since then, studies by this group and others led the International Agency for Research on Cancer (IARC) in 2002 to classify arsenic in drinking water as an established cause of human bladder cancer, lung cancer, and skin cancer. It is surprising that ingestion of arsenic in drinking water could cause lung cancer, but current evidence suggests that lung cancer is the leading cause of long-term mortality resulting from exposure to arsenic. In Chile, for example, the research group showed that about 1 in 10 persons with high exposure to arsenic in drinking water would eventually die as a result of that exposure (Am J Epidemiol, 147:660-669, 1998). Lung cancer was by far the major contributor to this startling increase in mortality, with smaller contributions from bladder cancer, kidney cancer and skin cancer.
Some substances that cause lung cancer also cause other types of lung disease. For example, smoking causes emphysema in the lungs, as well as lung cancer. Asbestos causes lung cancer, but also causes asbestosis in the lungs. Since arsenic in water was such a potent cause of lung cancer, the research group thought that perhaps it might also cause other lung effects. Recent findings by the Arsenic Health Effects Research Group provide strong evidence that this is indeed so.
The research team has conducted population-based investigations of the effects of arsenic in drinking water on lung function in West Bengal, India. They recently identified lung function deficits in men consuming high concentrations of arsenic in drinking water (Am J Epidemiol 2005 Sep;162(6):533-41). These impacts were so strong, that in this population they exceeded lung function effects due to smoking. Epidemiologic studies of ingested arsenic to date have been based on respiratory symptoms; this is the first systematic population-based study of arsenic ingestion that objectively measured lung function.
The research team also found that bronchiectasis in the lungs is greatly increased in subjects with arsenic-caused skin lesions (Epidemiology 2005 Nov; 16(6);760-5). This study involved high resolution computed tomography scans (HRCT) with readings by scientists in both India and the Untied States who did not know if the x-rays they were assessing came from persons exposed to arsenic or not. The findings suggested that persons who have high exposure to arsenic in water and develop arsenic-caused skin lesions are about ten times more likely to have evidence of bronchiectasis in the lungs than comparable persons not exposed to arsenic.
The non-cancer effects of arsenic are not just confined to the lungs. The Arsenic Health Effects Research Group has also been studying the effects resulting from exposure to arsenic during pregnancy and childhood. They recently identified a six-fold increase in rates of stillbirth in women with arsenic exposure (Am J Epidemiol, in press).
The results of these studies highlight the importance of investigations into long-term health effects of arsenic. Exposures to arsenic cause multiple effects in different parts of the body, and the research group will be increasingly giving priority to investigating the long-term consequences of exposure to arsenic during childhood.
Project 8: Development of Tools For Monitoring in situ Bioremediation
Leaders: Drs. Lisa Alvarez-Cohen and Mark Conrad
In situ bioremediation uses naturally occurring microorganisms to degrade contaminants in place with the goal of creating harmless chemicals as end products. The technology was developed as a less costly, more effective alternative to the standard pump-and-treat methods used to clean up contaminated groundwater sites. The goal of Project 8 is to develop tools for evaluating the progress of in situ bioremediation in the field.
Lisa Alvarez-Cohen and Mark Conrad, co-leaders of Project 8, made significant progress on both molecular biology and stable isotopic approaches over the past year. They recently developed a rapid test can be used to determine whether key bacteria are producing the appropriate enzymes needed to biodegrade chlorinated solvents, one of the most prevalent groundwater contaminants at Superfund sites. This test is based up the precise quantification of molecules within bacteria that lead to the production of solvent degrading enzymes. Specifically, this technique utilizes an internal standard along with quantitative PCR to enable the precise quantification of gene expression in bacterial communities. This technique has been tested and validated with microbial communities that biodegrade chlorinated solvents. Results demonstrated that losses experienced at each step of the nucleic acid processing prior to qPCR could be quantified and compensated for by the internal standard technique, leading to absolute quantification of molecule copy numbers. Because this technique is more accurate and faster than previous alternatives, it could greatly facilitate site assessment, application design, and bioremediation monitoring, leading to substantial cost savings for application of in situ bioremediation. Further, this technique will facilitate the measurement of a wide variety of gene expression in both environmental and laboratory samples, potentially leading to advances in both fundamental and applied science. This technique has recently been published (1,2).
1) Johnson D R, Lee PKH, Holmes VF, Alvarez-Cohen L (2005) Transcriptional Expression of the tceA Gene in a Dehalococcoides-Containing Microbial Enrichment. Applied and Environmental Microbiology, 71: 7145-7151. PMID: 16269753. [Abstract] [Full text]
2) Johnson DR, Lee PKH, Holmes VF, Alvarez-Cohen L (2005) An Internal Reference Technique for Accurately Quantifying Specific mRNAs by Real-Time PCR with Application to the tceA Reductive Dehalogenase Gene. Applied and Environmental Microbiology, 71:3866-3871. PMID: 16000799. [Abstract] [Full Text]
2004 Program Highlights
Project 1: Biomarkers of chemical exposure and leukemia risk
Leaders: Drs. Martyn T. Smith and Patricia A. Buffler
Benzene is a ubiquitous environmental contaminant. It has been found at over half of the National Priorities List sites identified by the Environmental Protection Agency, and we are all routinely exposed to benzene via second-hand cigarette smoke, automobile emissions and gasoline vapors. Benzene is one of the most frequently used chemicals in American industry as it is used as a solvent and to make plastics, resins, adhesives, synthetic fibers, lubricants, dyes, detergents, drugs, and pesticides. Workers in shipping, automobile repair, shoe manufacture, and refining/transportation of oil and gasoline are routinely exposed to benzene fumes. U.S. occupational guidelines limit benzene exposure to one part per million (ppm), but workers in developing countries are thought to be exposed to much higher levels of benzene.
While it is well documented that long-term exposure to high levels of benzene reduces white blood cell counts and can cause leukemia in people, the impacts of exposure at levels below 1 ppm in the air are uncertain. Dr. Martyn Smith, Program Director of the University of California-Berkeley SBRP, and Dr. Stephen Rappaport, of the University of North Carolina-Chapel Hill SBRP, are collaborating with researchers from the National Cancer Institute and the Chinese Center for Disease Control to study the impacts of long-term exposure to low levels of benzene.
They conducted a cross-sectional study in a region near Tianjin, China including 250 shoe workers exposed to benzene-containing glues and 140 unexposed age- and sex-matched controls who worked in 3 clothes-manufacturing factories. They conducted extensive exposure assessments for 16 months, testing air samples in the factories as well as at each worker’s home. Using blood and urine samples, the researchers linked individual air-monitoring data to end-points including white blood cell and platelet counts, lymphocyte subsets and progenitor cell colony formation.
As expected, workers exposed to benzene at levels of 1 ppm and higher had fewer total white blood cells, granulocytes, lymphocytes, B cells, and platelets than did unexposed workers. The researchers also found that compared to controls, workers exposed to less than 1 ppm benzene had significantly decreased numbers of all types of white blood cells and platelets. On average, these workers had 15% to 18% fewer granulocytes and B cells than unexposed workers, even after controlling for smoking and other potential confounding factors.
Because benzene affected nearly all blood cell types, the researchers suspected that benzene is toxic to progenitor cells – the unspecialized “parent” cells from which all other blood cells develop. They cultured samples from exposed workers and controls using colony-forming assays to measure the proliferative potential of progenitor cells. The scientists observed highly significant, dose-dependent decreases in colony formation of progenitor cells from exposed workers. Further, benzene caused a greater proportional decrease in colony formation than in levels of differentiated white blood cells and granulocytes, suggesting that early progenitor cells are more sensitive than mature cells to the toxic effects of benzene. This is the first study to find that benzene exposure affects the ability of progenitor cells to grow and multiply in humans.
The researchers then examined the influences of genetic variation in 3 enzymes responsible for activating and detoxifying benzene. They found that exposed subjects with variation in 2 enzymes (MPO and NQO1) were especially susceptible to benzene-induced lowering of white blood cell counts.
The results of this study highlight the importance of investigations into long-term health effects, including increased occurrence of blood diseases such as leukemia, in workers exposed to low levels of benzene.
Lan Q, Zhang L, Li G, Vermeulen R, Weinberg RS, Dosemeci M, Rappaport SM, Shen M, Alter BP, Wu Y, Kopp W, Waidyanatha S, Rabkin C, Guo W, Chanock S, Hayes RB, Linet M, Kim S, Yin S, Rothman N, Smith MT (2004) Hematotoxicity in workers exposed to low levels of benzene. Science 306(5702):1774-6.
2003 Program Highlights
Project 6: Historical Exposure Assessment
Investigator: James R. Hunt
Preliminary results from this project are assisting the US Navy and the US EPA in efforts to reach closure on a site remediation plan for the former Alameda Naval Air Station, a Superfund site with significant contamination of estuarine sediments. Contaminants in freshwater and marine sediments are a challenge at many U.S. and international sites. Sediments accumulate contaminants from many sources over long time periods. Radioisotopic tracers arising from natural sources and from atmospheric nuclear weapons testing are being applied at the former Alameda Naval Air Station where additional radioisotopic tracers were added by the use of radium in luminescent paints. Sediment cores collected in November 2002 are being gamma counted and reveal a very detailed record of sediment contamination during and immediately following World War II. Sediment analysis at a one-centimeter interval has demonstrated annual variations in sediment levels of contaminants and tracers. The sediment profile has maintained the chronology of sediment contamination likely due to the anaerobic conditions that precluded sediment mixing by benthic organisms. These results are being shared with the US EPA and the US Navy in their joint efforts to reach a remedial decision. This effort is providing greater spatial coverage than was possible during routine site characterization and utilizes one of the contaminants, radium, as a tracer for sediment dispersal and deposition. This site-specific tracer has the potential to greatly limit the need for trace metal analysis if other contaminants are strongly correlated with the radium levels. It is likely that the US EPA program manager for the joint project will be working with the University researchers to develop additional site-specific data.
Sediment cores from the former military base are also being analyzed for their detailed spatial distribution of trace metals using x-ray fluorescence in undisturbed cores. The approach uses frozen sediments subjected to an intense x-ray beam at Advance Light Source at the Lawrence Berkeley National Laboratory. The method is being developed as a quantitative tool using standard reference materials representative of an estuarine sediment matrix and then actual estuarine sediments from contaminated sites in the San Francisco Bay Area. These data are providing a means for estimating the three dimensional distribution of contaminants as is needed in site characterization and our modeling efforts. Extending from point measurements to a three dimensional representation will be done through tools developed in geostatistics for mineral and groundwater resource evaluation.
2002 Program Highlights
UC Berkeley is proud to have been involved in the NIEHS Superfund Basic Research Program since its inception. In 1987, Dr. Martyn T. Smith, Professor of Toxicology in the School of Public Health, assembled a distinguished research team of biomedical scientists spanning three institutions, UC Berkeley, UC San Francisco, and the California Department of Health Services. For the past 15 years, the UC Berkeley Superfund Basic Research Program has continued to strive for scientific breakthroughs that lead to demonstrable innovations in human health protection and toxic waste remediation.
The highly collaborative atmosphere of the UC Berkeley Superfund research program has led to considerable scientific progress – some notable advances are as follows:
1) Drs. Kent Udell and James Hunt and showed that liquid solvents trapped in soils are able to move towards ground water supplies via a process called dense vapor migration. They also demonstrated that steam injection effectively removes these trapped solvents from soils at hazardous waste sites. Initial SBRP funding lead to a very successful full-scale demonstration of Steam Enhanced Extraction at Lawrence Livermore National Laboratory and then to a showcase industrial application at the Visalia Pole Yard in Visalia, California one of the first sites placed on the National Proiority List. That project is considered a break-through application of remediation technology, thus earning an EPA Remediation Technology Development Award for “for technical excellence in the development of in situ thermal treatment technologies”. The application of Steam Enhanced Extraction at that site decreased the financial liability of the site by $85 million for a cost of about $15 million, showing a clear financial incentive for publicly owned corporations to take a more aggressive approach to environmental restoration. This advance is further highlighted below.
2) Dr. Catherine Koshland’s group identified key conditions for toxic byproduct production in combustion and waste incineration, showing that at sub-optimal temperatures relatively innocuous compounds such as ethyl chloride can be converted into highly hazardous chemicals such as vinyl chloride. The group went on to develop an in situ real time technique for detecting and monitoring chlorinated hydrocarbons in incinerators that has since been extended to ammonia and several metals.
3) Dr. Allan Smith led a study of lung and bladder cancer patients who were exposed to naturally occurring arsenic in drinking water. His population-based studies in Nevada and Chile uncovered a high incidence in bladder cancers from arsenic exposure, and he showed that methylation does not protect from arsenic-related carcinogenesis at low levels of exposure. Using a novel micronucleus assay developed in the laboratory of Dr. Martyn Smith, the researchers were the first to demonstrate that concentrations of arsenic in drinking water at the US standard of 50 ppb produced increased levels of genetic damage in bladder epithelial cells of humans who drank the water. They went on to perform an intervention study that showed a decrease in genetic damage in the bladder following a reduction in arsenic exposure. This work on arsenic has reduced uncertainty in the risk assessment process and had a profound effect on arsenic environmental regulation. It is further highlighted below as a notable advance.
4) Drs. Buffler, Smith and Wiencke have produced new insights into the natural history and environmental etiology of childhood leukemia. Their study, based in Northern California, aims to enroll up to 1,000 cases and incorporates molecular cytogenetic characterization of the cases. They sequenced various specific DNA changes found in childhood leukemia in 56 patients and showed that these rearrangements could be commonly detected in the neonatal blood spots (Guthrie cards) of the cases. These findings show that most childhood leukemias begin in utero and that maternal and peri-natal exposures are likely to be critical. Indeed, the investigators also found that exposure to indoor pesticides during pregnancy and the first year of life raises leukemia risk, but that later exposures do not.
5) Our outreach program, the Children’s Environmental Health Network has played a key role in the emergence of pediatric environmental health as a credible and recognized field of research. They have created a national “network” of health professionals, researchers, policy makers and advocates addressing children’s environmental health. In addition, they have defined a national research agenda on children’s environmental health by convening national conferences at which researchers can share their findings, raise new research questions, and together craft a child focused national research agenda.
NOTABLE ADVANCE 1
Technology Transfer of Steam Injection for Soil and Groundwater Cleanup
Project Investigator: Kent S. Udell
A decade of NIEHS support of scientific research, process development and technology transfer has paid large dividends for the national and international remediation community. The support of the fundamental science of thermal remediation at the University of California at Berkeley has generated new national and international industry, and a solid technical basis for EPA policy on source removal for soil and groundwater cleanup. It is now clear that many sites previously considered as untreatable can be remediated with reasonable cost and acceptable certainty using thermal remediation techniques. Thermal techniques have been used by several industries and in many countries to provide a permanent solution to problems that would otherwise persist for centuries. Prior arguments that there is not technology capable of removing heavier than water liquids from the subsurface have been negated, giving fresh impetus to the push for aggressive environmental cleanup by regulatory agencies.
The Berkeley research, under NIEHS funding, lead to a very successful full scale demonstration of Steam Enhanced Extraction at Lawrence Livermore National Laboratory and then to a showcase industrial application at the Visalia Pole Yard in Visalia, California one of the first sites placed on the National Proiority List. That project has been considered to be a break-through application of remediation technology, thus earning the first and only EPA Remediation Technology Development Award for “for technical excellence in the development of in situ thermal treatment technologies”. The application of Steam Enhanced Extraction at that site decreased the financial liability of the site by $85 million for a cost of about $15 million, showing a clear financial incentive for publicly owned corporations to take a more aggressive approach to environmental restoration.
The transfer of NIEHS supported thermal technology has continued with growing applications at Superfund sites and other sites of National interest. Specifically, the use of Steam Enhanced Extraction was included as the selected cleanup remedy in the record of decision for Wyckhoff Superfund site adjacent to Eagle Harbor near Seattle. A pilot test of the technology, consisting of about 10 injection and 10 extraction wells is now underway. The technology is also being considered for the remediation of the Baxter and McCormick Superfund site near Stockton, California with a full scale design completed in sufficient detail for costing purposes. The project now is under funding consideration by EPA. This site is one on the largest wood treating chemical spills in the country and defies all other techniques for remediation in any reasonable time frame.
Steam injection was also applied at Cape Canaveral at Launch Complex 34. This site is particularly important in that the steam technology is the third technique to be demonstrated in adjacent plots. The use of steam injection at that site is also unique in its application through the co-injection of air with the steam. This approach, first considered by researchers at the University of Stuttgart in Germany for the removal of semi-volatile non-aqueous phase liquids in the vadose zone, was extended for application to volatile non-aqueous phase liquids found in the saturated zone through NIEHS funding. That research developed the theoretical underpinning of the value of air co-injection with the steam in the elimination of accumulation of the non-aqueous phase liquid at the steam condensation front. Such accumulation has been shown to be the requisite step leading to uncontrolled downward migration of the non-aqueous phase liquid during thermally enhanced cleanup operations. In principal, the co-injection of air provides conditions where the NAPL vapors do not condense with the steam at the condensation front. Instead, the non-aqueous phase liquid vapors remain in the gaseous phase to percolate upward into the vadose zone where they are pulled to vapor extraction wells. In all cases, including controlled two dimensional laboratory experiments, the simultaneous injection of air and steam increases the NAPL compound removal rate beyond that which could be achieved by either pure steam injection or pure air sparging.
Of near equal importance is a project initiated at Loring Air Force Base in Maine where steam is to be injected into fractured rock which is contaminated by non-aqueous phase liquids trapped in the fractures. This is a large project where both State of Maine and EPA are actively engaged in the application and evaluation of the potential of steam enhanced extraction to remediate fractured geologies. NIEHS contributes to that project through the transfer of the steam injection technology expertise to the multi-agency consortium of stakeholders to ensure that the most current engineering knowledge is applied to the contaminants and media of interest at that site.
International application has also been gaining momentum. Expertise from NIEHS funded work has been applied to a PCE and kerosene site in Denmark with success, and Steam Enhanced Extraction is being used routinely in the Czech Republic, including the first successful remediation of a fractured bedrock site. Also of interest is the successful pilot demonstration of the technology at the Pancevo site in the former Yugoslavia, now Serbia, which experienced a catastrophic release of millions of pounds of the highly toxic chemical, 1,2 DCA due to the NATO bombings in 1999.
Activities funded in part by NIEHS technology transfer money included participation in the expert panel to set the future research agenda for the SERDP program. That agenda now includes expanded consideration of the science and applicability of thermal remediation technologies – thermally enhanced extraction processes in particular. Additional input to the national policy debate on appropriate technologies for source removal has been solicited and provided to EPA. That effort was documented in a expert panel recommendation report completed in September, 2002.
NOTABLE ADVANCE 2
Arsenic is a major environmental carcinogen
Project Investigator: Allan H. Smith
The revelation that arsenic is a major environmental carcinogen is largely due to the work of epidemiologist Dr. Allan Smith’s group at Berkeley, whose research provided definitive evidence that arsenic in drinking water causes bladder, lung, and other internal cancers. Their arsenic research activities began more than ten years ago with a risk assessment focusing mainly on cancer. This work, on which Superfund Director Dr Martyn Smith was also a co-author led to the conclusion that the cancer risks from inorganic arsenic in drinking water were potentially very high. The Arsenic Health Effects Research Program was then started with funding from the Superfund Basic Research Program to study the health risks from exposure to inorganic arsenic (Project 3 in this program). Currently it involves international research projects including studies and investigations in Argentina, Chile, India, Bangladesh as well as projects in California and Nevada in the United States.
Employing novel biomarkers developed in Dr. Martyn Smith’s laboratory (Project 1), the research team showed effects on bladder epithelium occur at or around the U.S. drinking water standard of 50 ppb. The Superfund-sponsored epidemiological studies in Nevada, Argentina, and Chile, made clear the need for better understanding of arsenic-related cancers, and led to the award of R01 support to investigate the dose-response relationship in greater detail. Dr. Allan Smith and Dr. John Wiencke (also of Project 1) both serve on the National Academy of Sciences Subcommittee on Arsenic in Drinking Water set up by the Board on Environmental Studies and Toxicology, National Research Council. Dr. Smith has also served as a Consultant to the World Health Organization on the Arsenic problems in Bangladesh including five visits to Bangladesh and preparation of three reports.
The following is a list of accomplishments:
• Provided definitive evidence (from studies conducted in Argentina and Chile) that arsenic is a potent cause of human bladder cancer.
• Provided definitive evidence (from studies conducted in Argentina and Chile) that arsenic in drinking water is a potent cause of human lung cancer.
• Demonstrated that epidemiological and experimental human data do not support that arsenic methylation protects from low dose effects.
• Showed that with exposure to water containing around 600 ug/L, 1 in 10 adult deaths may be due to arsenic-caused cancers, the highest environmental cancer risk ever reported.
• Identified a dose-response relationship between arsenic exposure and bladder cell micronuclei, a genotoxic biomarker of early effect.
• Identified a preliminary dose-response relationship between arsenic concentration in well water in India and the occurrence of keratoses and hyperpigmentation.
• Studies currently underway in India, Chile and the US, will allow projection of cancer risks with individual exposure data.
• Studies are currently underway to identify nutritional and genetic suceptibility to arsenic effects.
This research has reduced uncertainty in the risk assessment for arsenic and impacted the regulation of this important environmental contaminant.
Adding air during steam injection prevents downward spreading of toxic contaminants
Project Investigator: Kent S. Udell
Basic research on coupled thermo-fluid interactions of toxic liquid/water and gas phases in soils being heated to the boiling point of water has lead to a finding that air added to steam which is being injected into contaminated soils can eliminate the potential of downward spreading on the toxic liquid during thermal remediation operations. This finding served as the foundation for divergent research into the basic mechanisms responsible for this positive result, leading to the development of basic theory to predict the optimum air/steam ratio. With this basic understanding, steam injection projects currently in planning stages were modified to operate with air co-injection . Four projects benefited greatly from this simple modification and a new generation of thermal remediation technologies came into being. This change has eliminated the most problematic feature of steam injection and has revolutionized the remediation industry. The range of contaminated sites that can be cleaned-up has grown substantially, and the EPA has aggressively promoted this new incarnation of thermally enhanced remediation technology.