EC/US workshop report: assessment of genetic risks associated with exposure to ethylene oxide, acrylamide, 1,3-butadiene and cyclophosphamide

The EC/US Workshop on Risk Assessment: ‘Human Genetic Risks from Exposure to Chemicals, Focusing on the Feasibility of a Parallelogram Approach’ had as its main objective the identification of the methodology, data requirements and mechanistic research to understand the human health impact of germ cell mutagens. Specifically, it represented an evaluation of current knowledge and the identification of future research needs for a more precise assessment of human genetic risks from exposure to mutagenic chemicals. Four chemicals were selected for review at the Workshop and in this Special Issue: ethylene oxide, 1,3-butadiene, acrylamide, and cyclophosphamide. The first three are important industrial chemicals with substantial use worldwide and, therefore, considerable potential for human exposure. The fourth, cyclophosphamide, is a commonly used cancer chemotherapeutic agent. This Special Issue contains the major scientific reports from the workshop. These include four Introductory Papers (on the parallelogram concept, alternative genetic risk assessment approaches, regulatory data needs, and the research background for risk assessment of ethylene oxide), four Working Group Reports on the specific compounds mentioned above and, finally, three Crosscutting Papers pertinent to the issue of germ-line mutagenesis and genetic risk estimation.     

Health risk assessment of volatile organic compounds in urban areas

The atmosphere is the first medium containing hazardous compounds entering the living environment. Metropolitan areas contain many industrial complex areas with high emissions of volatile organic compounds (VOCs), and consequently also large-scale exposure groups. As respiration is the most important part of the human exposure pathway, the atmosphere should be treated with greater importance than other media. It is therefore very important to monitor the emission of hazardous air pollutants (HAPs) and measure the concentration of VOCs in the atmosphere of such areas. It is essential to establish basic measures in order to protect public health as part of overall national safety management. This study utilized the national air pollution monitoring network data from Seoul, Incheon, and Gyeonggi, and investigated the differences in risk levels for humans considering various factors of the receptors, including gender and age. A total of 13 VOCs were categorized into carcinogens and noncarcinogens for risk assessment. The carcinogens 1,3-butadiene and benzene demonstrated a high level of cancer risk, ranging between 10^?4 and 10^?6, respectively. Noncarcinogens did not exceed Hazard Quotient (HQ) 1 in any area. The results will serve as important references for managing urban air environments and setting air quality standards.     

Potential health effects of exposure to carcinogenic compounds in incense smoke in temple workers

Incense smoke is a potential hazard to human health due to various airborne carcinogens emitted from incense burning. This study aimed to evaluate the potential health effects of exposure to benzene, 1,3-butadiene, and polycyclic aromatic hydrocarbons (PAHs) emitted from incense smoke in temple workers. Exposure and health risks were assessed through the measurement of ambient exposure as well as through the use of biomarkers of exposure and early biological effects. Ambient air measurement showed that incense burning generates significantly higher levels of airborne benzene (P<0.01), 1,3-butadiene (P<0.001) and total PAHs (P<0.01) inside the temples, compared to those of the control workplace. Temple workers were exposed to relatively high levels of benzene (45.90 microg/m(3)) 1,3-butadiene (11.29 microg/m(3)) and PAHs (19.56 ng/m(3)), which were significantly higher than those of control workers (P<0.001). The most abundant PAHs were chrysene, B[ghi]P, B[a]P, B[a]F and fluoranthene. Concentrations of B[a]P and B[a]P equivalents in air samples to which temple workers were exposed were 63- and 16-fold, higher, respectively, than those to which control subjects were exposed (P<0.001). Biomarkers of exposure to benzene (blood benzene and the urinary metabolites trans,trans-muconic acid and S-phenylmercapturic acid), 1,3-butadiene (urinary monohydroxy-butenyl mercapturic acid) and PAHs (1-hydroxypyrene) were all significantly higher in temple workers than those in control workers. DNA damage and DNA repair capacity were measured as biomarkers of early biological effects. Temple workers had a significant increase in DNA damage observed as a 2-fold increase in the levels of leukocyte 8-hydroxy-2'-deoxguanosine (8-OHdG) and DNA strand breaks (P<0.001). A significant reduction of DNA repair capacity in temple workers determined by the radiation challenge assay was also observed. These results indicate that exposure to carcinogens emitted from incense burning may increase health risk for the development of cancer in temple workers.     

A Risk-Based Approach to Health Impact Assessment for Input-Output Analysis, Part 1: Methodology (7 pp)

Goal, Scope and Background Incorporation of exposure and risk concepts into life cycle impact assessment (LCIA) is often impaired by the number of sources and the complexity of site-specific impact assessment, especially when input-output (I-O) analysis is used to evaluate upstream processes. This makes it difficult to interpret LCIA outputs, especially in policy contexts. In this study, we develop an LCIA tool which takes into account the geographical variability in both emissions and exposure and which can be applied to all economic sectors in I-O analysis, relying on screening-level risk calculations and methods to estimate population exposure per unit emissions from specific geographic locations. Methods We develop our analytical approach with reference to the case of increasing insulation for new single-family homes in the US. We quantify the public health costs from increasing insulation manufacturing and compare them with the benefits from energy savings, focusing on mortality and morbidity associated with exposure to primary and secondary fine particles (PM2.5) as well as cancer risk associated with exposure to toxic air pollutants. We use OpenLC to estimate the incremental economic outputs induced by increased insulation and reduced fuel consumption and calculate emissions from a sector-specific pollution intensity matrix. We calculate sector-specific intake fractions (dimensionless ratios between the amount of pollutant intake and the amount of a pollutant emitted) using previously-derived regression models and apply these values to the supply chain emissions of fiberglass and fuel sources. We refine the exposure estimates for selected emission sites and pollutants that contribute significantly to total health impacts, running site-specific air dispersion models. We estimate health impacts using concentration-response functions from the published literature and compare the costs and benefits of the program by assigning monetary values to the health risks. In the second part of this paper, we present the results of our case study and consider the implications for incorporating exposure and risk concepts into I-O LCA.     

LCA of Multicrystalline Silicon Photovoltaic Systems - Part 1: Present Situation and Future Perspectives (8 pp)

- Part 1: Present Situation and Future Perspectives Part 2: Application on an Island Economy Goal, Scope and Background Incorporation of exposure and risk concepts into life cycle impact assessment (LCIA) is often impaired by the number of sources and the complexity of site-specific impact assessment, especially when input-output (I-O) analysis is used to evaluate upstream processes. This makes it difficult to interpret LCIA outputs, especially in policy contexts. In this study, we develop an LCIA tool which takes into account the geographical variability in both emissions and exposure, and which can be applied to all economic sectors in I-O analysis. Our method relies on screening-level risk calculations and methods to estimate population exposure per unit of emissions from specific geographic locations. Methods We propose a simplified impact assessment approach using the concept of intake fraction, which is the fraction of a pollutant or its precursor emitted that is eventually inhaled or ingested by the population. Instead of running a complex site-specific exposure analysis, intake fractions allow for the accounting of the regional variability in exposure due to meteorological factors and population density without much computational burden. We calculate sector-specific intake fractions using previously-derived regression models and apply these values to the supply chain emissions to screen for the sectors whose emissions largely contribute to the total exposures. Thus, the analytical steps are simplified by relying on these screening-level risk calculations. We estimate population exposure per unit emissions from specific geographic locations only for the facilities and pollutants that pass an initial screening analysis. We test our analytical approach with reference to the case of increasing insulation for new single-family homes in the US. We quantify the public health costs from increasing insulation manufacturing and compare them with the benefits from energy savings, focusing on mortality and morbidity associated with exposure to primary and secondary fine particles (PM2.5) as well as cancer risk associated with exposure to toxic air pollutants. We estimate health impacts using concentration-response functions from the published literature and compare the costs and benefits of the program by assigning monetary values to the health risks. In the second part of this paper, we present the results of our case study and consider the implications for incorporating exposure and risk concepts into I-O LCA. Conclusions We have presented a methodology to incorporate regional variability in emissions and exposure into input-output LCA, using reduced-form information about the relationship between emissions and population exposure, along with standard input-output analysis and risk assessment methods. The location-weighted intake fractions can overcome the difficulty in incorporation of regional exposure in LCIA.     

Local risks and global impacts considering plant-specific functions and constraints: a case study of metal parts cleaning

Background, aim, and scope  

To achieve sustainable development in industrial processes, attributed chemical risks as well as environmental impacts should be managed. Such non-monetary issues have been analyzed by scientific assessment methodologies such as various risk assessment (RA) and life cycle assessment (LCA) procedures. Local risks to be addressed in RA are microenvironments, including the workplace and neighborhood. Although a comprehensive interpretation of such risks is necessitated in industrial decision making, no practical method has been developed to interpret various types of risk with sufficient understandings of plant-specific functions and constraints. Because elaborate model-based approaches are inevitable for practical process development, actual case studies on chemical risks and detailed plant-specific functions and constraints should be performed. Manufacturing processes require that metal parts must be cleaned in preparation for surface treatments or the completion of metal processing. The significant amount of cleansing agents utilized in cleaning processes has become an issue in Japan. Almost all cleaning processes in Japan are carried out by small- and medium-sized enterprises (SMEs). Machinery processes have not been systematically analyzed in terms of chemical risks and, in addition, the environmental management skills of SMEs are generally far behind those of large enterprises. The objective of this study is to reveal the relationships between chemical risks and plant-specific conditions for a practical risk reduction carried out by industrial decision makers. For this purpose, we aimed at the analysis of such relationships in metal-cleaning processes. Through this analysis, the correlation between local risks and global impacts were discussed in terms of plant-specific conditions.     

Use of haemoglobin adducts in exposure monitoring and risk assessment

Many industrial bulk chemicals are oxiranes or alkenes that are easily metabolised to oxiranes in mammalian systems. Many oxiranes may react with DNA and are therefore mutagenic in vitro. Some oxiranes have been shown to be carcinogenic in rodents in vivo as well. Despite the very limited evidence of the carcinogenicity of oxiranes in humans, they should be considered potential human carcinogens. As a consequence, exposure to these compounds should be minimised and controlled. Twenty-five years ago, Ehrenberg and co-workers suggested that exposure to oxiranes might be determined through the measurement of the adducts they form with haemoglobin (Hb). Ten years later, a modification of the Edman degradation was developed at Stockholm University that allowed determination of adducts with the N-terminal valine of Hb by GC-MS. In our laboratory, this methodology was modified and adapted for analysis on an industrial scale. Since 1987, exposure of operators in our facilities to ethylene oxide (EO) has been routinely monitored by determination of N-(2-hydroxyethyl)valine in Hb. Biological monitoring programmes for propylene oxide (PO) and 1,3-butadiene (BD) were developed later. In this review, the methodology and its results are discussed as a tool in human risk assessment of industrial chemicals. Two major advantages of Hb adduct determinations in risk assessment are (1) the qualitative information on the structure of reactive intermediates that may be obtained through the mass spectrometry, which may provide insight in the molecular toxicology of compounds such as BD, and (2) the possibility of reliable determination of exposure over periods of several months with limited number of samples for compounds such as ethylene oxide (EO), propylene oxide (PO) and BD which form stable adducts with Hb. Since good correlations between the airborne concentrations of these chemicals with their respective adducts have been established, Hb adducts can also be used to quantitate airborne exposure which is of paramount importance as exposure assessment is usually one of the weaker parameters in risk assessment.     

Cancer risk assessment for 1,3-butadiene: data integration opportunities

The US Environmental Protection Agency recently released its new guidelines for carcinogen risk assessment together with supplemental guidance for assessing susceptibility from early-life exposure to carcinogens. In particular, these guidelines encourage the use of mechanistic data in support of dose-response characterization at doses below those at which an increase in tumor frequency over background levels might be detected. In this context of the utility of mechanistic data for human cancer risk assessment, the International Life Sciences Institute (ILSI) has developed a human relevance framework (HRF) that can be used to assess the plausibility of a mode of action (MoA) described for animal models operating in humans. The MoA is described as a sequence of key events and processes that result in an adverse outcome. A key event is a measurable precursor step that is in itself a necessary element of the MoA or is a bioindicator for such an element. A number of cellular and molecular perturbations have been identified as key events whereby DNA-reactive chemicals can produce tumors. These include DNA adducts in target tissues, gene mutations and/or chromosomal alterations in target tissues and enhanced cell proliferation in target tissues. This type of data integration approach to quantitative cancer risk assessment can be applied to 1,3-butadiene, for example, using data on biomarkers in exposed Czech workers [1]. For this study, an extensive range of biomarkers of exposure and response was assessed, including: polymorphisms in metabolizing enzymes; urinary concentrations of several metabolites of 1,3-butadiene; hemoglobin adducts; HPRT mutations in T-lymphocytes; chromosomal aberrations by FISH and conventional staining procedures; sister chromatid exchanges. Exposure levels were monitored in a comprehensive fashion. For risk assessment purposes, these data need to be considered in the context of how they inform the MoA for leukemia, the tumor type reported to be increased in synthetic rubber workers exposed to 1,3-butadiene. Also, for the HRF it is necessary to establish key events for a MoA in rodents for the induction of tumors by 1,3-butadiene. There is clearly a species difference in sensitivity to tumor induction, with mice being much more sensitive than rats; key events need to explain this difference. For butadiene, the MoA is DNA-reactivity and subsequent mutagenicity and so following the EPA's cancer guidelines, a linear extrapolation is used from the point of departure (POD), unless additional data support a non-linear extrapolation. For the present case, the human bioindicator data are not informative as far as dose-response characterization is concerned. Mouse chromosome aberration data for in vivo exposures might be used for establishing a POD, with linear extrapolation from this POD. The available cytogenetic data from rodent studies appear to be sufficiently extensive and consistent for this to be a viable approach. This approach of using MoA and key events to establish the human relevance can lead to the development of specific informative bioindicators of response that can be used as surrogates to predict the shape of the tumor dose response curve at low doses. Truly informative predictors of tumor responses should be able to provide estimates of human tumor frequencies at low, environmental exposures to 1,3-butadiene.     

Cancer and non-cancer health risk assessment associated with exposure to non-methane hydrocarbons among roadside vendors in Delhi,India

Abstract

This study estimates the cancer and non-cancer health risk among the roadside vendors in Delhi, the capital city of India. Air samples of selected NMHCs and their derivatives were collected from four different sites (one traffic intersection, one industrial, and two residential) in Delhi and were analyzed on Gas Chromatograph (GC) to obtain their atmospheric concentrations. At each site, a survey among the roadside vendors was also conducted to obtain information about their bodyweight and exposure to outdoor ambient air. The study reveals that hazard quotient of 1,3-butadiene is greater than one at all the sites, with its maximum value occurring at the industrial site. The major contributors to the workplace cancer risk (WCR) are found to be 1,3-butadiene and chloroform. The overall WCR is observed to be the highest (9.4?×?10^?4) at the traffic intersection site, followed by the industrial site (7.0?×?10^?4). Cancer incidence data and the population data are also used to estimate the growth of cancer risk in Delhi from 2009 to 2016. Comparison of the WCR values of the four sites with the cancer risk estimated from the cancer incidence data shows that NMHCs and their derivatives are significant contributors to the overall cancer risk in Delhi. Our results suggest that NMHCs and their derivatives need to be given due consideration in the National Cancer Control Programme of India.     

Gas chromatographic determination of 3-butene-1,2-diol in urine samples after 1,3-butadiene exposure

1,3-Butadiene is an important industrial chemical and a common environmental contaminant. Because of its suspected carcinogenicity butadiene-related research has gained high activity. The obvious lack of knowledge so far has been that a biomonitoring method that can detect at least one of the metabolites of butadiene from body fluids or excretas does not exist. In this communication we describe a robust and simple analytical method which can be applied for biomonitoring purposes. We have developed a method that can detect 3-butene-1,2-diol in urine samples of rats inhalation-exposed to various concentrations of 1,3-butadiene. The method is based on liquid–liquid extraction and subsequent gas chromatographic analysis. The extraction efficiency of 3-butene-1,2-diol at a concentration of 2.2 μg/ml was 95% (SD=±3%, n=3) and was achieved by using sodium chloride saturation and isopropanol as an extracting solvent. The standard deviation of the gas chromatographic analysis was ±2% (n=12), the limit of detection was 0.08 μg/ml, the limit of quantitation was 0.11 μg/ml (SD=±4.8%, n=3) and the analysis was observed to be linear from 0.11 to 486 μg/ml (R=0.9987). Animals exposed to 1,3-butadiene showed a linear excretion of 3-butene-1,2-diol into urine as a function of butadiene exposure. During the exposure saturation of metabolism or accumulation of 1,3-butadiene or 3-butene-1,2-diol into the body was not observed in any exposure levels used.     

Micronuclei, DNA single-strand breaks and DNA-repair activity in mice exposed to 1,3-butadiene by inhalation

We investigated single-strand breaks and endonuclease III-sensitive sites in DNA along with gamma-irradiation-specific DNA-repair activity in hepatocytes and frequencies of micronuclei in polychromatic bone-marrow erythrocytes of male NMRI mice (2 months old, weight 30-35 g) during sub-acute inhalation exposure to 1,3-butadiene (28 days, 500 mg/m3) and up to 28 days after the exposure. Concentrations of 1,3-butadiene in blood, an indicator of internal exposure, moderately increased during the exposure period. The most interesting finding was that gamma-irradiation-specific DNA-repair activity gradually increased during exposure, being significantly higher compared with control levels on days 7 and 28 of exposure (P = 0.005 and 0.035, respectively), reaching a maximum on day 1 after the termination of exposure (P = 0.003) and then returning to control levels. A significant correlation between gamma-irradiation-specific DNA-repair activity and the concentration of 1,3-butadiene in blood (R = 0.866, P = 0.050) supports a possible induction of DNA-repair activity by the exposure to 1,3-butadiene and formation of its metabolites. The initial increase in micronucleus frequency (micronuclei per 1000 cells) in the exposed mice continuously decreased from 20.4 +/- 5.1 (day 3) to 15.1 +/- 3.2 (day 28) within the exposure period, and subsequently from 12.4 +/- 5.1 to 4.6 +/- 1.6 in the period following termination of the 1,3-butadiene exposure, while micronucleus frequencies in control animals were significantly lower (from 1.7 +/- 1.5 to 4.2 +/- 0.8).     

Spatial Assessment of Heavy Metals in Surface Soil from Klang District (Malaysia): An Example from a Tropical Environment

Heavy metals (Al, Cd, Co, Cr, Cu, Fe, Pb, Zn) in surface soil of Klang district were determined and multivariate analysis was used to understand their potential sources. The total and bioavailability of concentrations were used in identifying the potential risks to the ecology and human health. The means for the total heavy metal concentrations were found to be in the order of Fe > Al > Zn > Pb > Cu > Cr > Co > Cd, while the means for the bioavailability concentrations were found to be in the order of Al > Fe > Zn > Cu > Co > Cd > Pb > Cr. Principal Component Analysis showed Principal Component 1 as being of natural origin whereas Principal Components 2, 3, and 4 were associated with mixed anthropogenic sources, such as traffic and industrial emissions, organic matter, and granulometric fractions. Potential ecological risk assessment indicated an overall low ecological risk. Spatial assessment of non-carcinogenic risks showed that the Hazard Index values were more than one in Johan Setia, due to biomass burning of peat swamps exploited for agricultural development. While for spatial assessment of carcinogenic risks, the Lifetime Cancer Risk values were in the limit (1 × 10^?5), indicating low cancer inducing risks. Nevertheless, with intense development pressure in the Klang district could overlap pollution inputs in the future.     

Assessing and managing methylmercury risks associated with power plant mercury emissions in the United States

Until the Clean Air Mercury Rule was signed in March 2005, coal-fired electric utilities were the only remaining, unregulated major source of industrial mercury emissions in the United States. Proponents of coal-burning power plants assert that methylmercury is not a hazard at the current environmental levels, that current technologies for limiting emissions are unreliable, and that reducing mercury emissions from power plants in the United States will have little impact on environmental levels. Opponents of coal-burning plants assert that current methylmercury exposures from fish are damaging to the developing nervous system of infants, children, and the fetus; that current technology can significantly limit emissions; and that reducing emissions will reduce exposure and risk. One concern is that local mercury emissions from power plants may contribute to higher local exposure levels, or "hot spots." The impact of the Mercury Rule on potential hot spots is uncertain due to the highly site-specific nature of the relationship between plant emissions and local fish methylmercury levels. The impact on the primary source of exposure in the United States, ocean fish, is likely to be negligible due to the contribution of natural sources and industrial sources outside the United States. Another debate centers on the toxic potency of methylmercury, with the scientific basis of the US Environmental Protection Agency's (EPA's) recommended exposure limit questioned by some and defended by others. It is likely that the EPA's exposure limit may be appropriate for combined exposure to methylmercury and polychlorinated biphenyls (PCBs), but may be lower than the available data suggest is necessary to protect children from methylmercury alone. Mercury emissions from power plants are a global problem. Without a global approach to developing and implementing clean coal technologies, limiting US power plant emissions alone will have little impact.     

Future directions in butadiene risk assessment and the role of cross-species internal dosimetry

The 2005 International Symposium on the evaluation of butadiene and chloroprene health risks provided the opportunity to consider the past, present and future state of research issues for 1,3-butadiene. Considerable advancements have been made in our knowledge of exposure, metabolism, biomarkers of exposure and effect, and epidemiology. Despite this, uncertainties remain which will impact the human health risk assessment for current worker and environmental exposures. This paper reviews key aspects of recent studies and the role that biomarkers of internal dosimetry can play in addressing low to high exposure, gender, and cross-species differences in butadiene toxicity and metabolism. Considerable information is now available on the detection and quantification of protein adducts formed from the mono-, di- and dihydroxy-epoxide metabolites of butadiene. The diepoxide metabolite appears to play a key role in mutagenesis. Species differences in production of this critical metabolite are reflected by the diepoxybutane-specific hemoglobin adduct, pry-Val. To date, the pry-Val adduct has not been quantifiable in human blood samples from workers with cumulative occupational exposures up to 6.3 ppm-weeks; whereas, the pry-Val was quantifiable in the blood of mice and rats with similar cumulative exposures. Levels in mice were much higher than in rats. Further improvements in analytical sensitivity for the pyr-Val adduct are on the horizon. Epidemiology studies are also described and ongoing efforts promise to help bridge our understanding of past and future risks.     

Risk Assessment Applications Beyond Baseline Risks and Clean-Up Goals

Historically, the phrase “Risk Assessment” brought to mind a thick Superfund-type baseline risk assessment or clean-up goal derivation document filled with pages of tables with endless seemingly unrelated algorithms and numbers. Over the last decade, the principles of risk and exposure assessment have gained wide-reaching acceptance and are increasingly utilized to help solve other environmental impact, occupational health, or risk mitigation design problems. The typical objective of the classic risk assessment is the evaluation of current or future risks from exposure to contaminated media within the framework of a regulatory waste management or remediation program. Risk-based techniques are increasingly being used on a voluntary basis (i.e., outside of the standard regulatory arena) to demonstrate the presence, absence, or extent of environmental or health-related concerns in specific exposure circumstances. Likewise, a risk or exposure evaluation may be useful in determining the need for, or the legitimacy of, a public health advisory, alone or in conjunction with remedial or mitigative actions. Finally, risk-based techniques often find their way into the courtroom. Three case studies are presented in which riskbased solutions were employed to assist in resolving environmental or health-related issues: (1) a reversal of a fish consumption advisory; (2) an evaluation of arsenic in soil on and adjacent to a school facility; and (3) a challenge to a case of alleged methyl bromide exposure in a litigation context. In each case, the use of risk assessment principles was employed beyond the classic baseline risk assessment to address an applied problem of toxicological significance.     

Spatial and temporal trend evaluation of ambient concentrations of 1,3-butadiene and chloroprene in Texas

This paper provides information on 1,3-butadiene (BD) and chloroprene as atmospheric pollutants in Texas and reviews available emission estimates and monitoring data. Ambient BD concentrations in most areas of Texas are predominantly influenced by on-road and off-road vehicular emissions or biomass burning, since BD is a product of combustion. However, large industrial point sources of BD emissions in Texas locally influence ambient concentrations. Total industrial BD emissions to the atmosphere in Texas for 2003 were estimated at 695 tonnes per year (TPY), approximately 70% of the total reported national industrial BD air emissions. Since 1998, there have not been any large industrial sources of chloroprene emissions in Texas, and total industrial chloroprene emissions for 2003 was estimated at only 0.09 TPY. Chloroprene was never detected at air monitoring sites. In 2003, the Texas Commission on Environmental Quality (TCEQ) monitored BD ambient air concentrations at 57 sites, some of which have been operational since 1992. These air monitors provide information on ambient BD concentrations in Texas and allow spatial and temporal trend evaluation. In 2003, annual average concentrations at monitoring sites in Texas ranged from less than the reporting limit of 0.01 to 3.2 parts per billion by volume (ppbv) with an overall average of 0.2 ppbv. This overall average is reduced to 0.1 ppbv if BD data from monitoring sites in Port Neches and Milby Park in Houston, which are located downwind of significant point sources of BD, are excluded. Ambient air monitoring has been conducted in Port Neches and in Milby Park in Houston since 1996 and 1999, respectively. At the Port Neches monitor, trend evaluation indicates that ambient concentrations of BD have declined since 1996 due to cooperative agreements with industries emitting BD. Annual average BD concentrations at the Port Neches monitor decreased from 8.3ppbv in 1996 to 1.3 ppbv in 2003, giving an 8-year average of 3.8 ppbv. Annual average BD concentrations at the Milby Park monitor varied between 2.1 and 4.4 ppbv from 1999 through 2003, giving a 5-year average of 3.1 ppbv. The results of cancer cluster studies based on Cancer Registry 1995-2001 incidence data and 1993-2002 mortality data conducted by the Texas Department of State Health Services for zip codes 77017/77012 (Houston) and 77651 (Port Neches) will be presented.     

Potential Importance of Inhalation Exposures for Wildlife Using Screening-Level Ecological Risk Assessment

Ecological risk assessments (ERAs) have largely ignored exposure to wildlife via inhalation on the assumption that it is negligible compared to the ingestion route of exposure. The assessment of inhalation risk also has been limited due to a paucity of relevant ecotoxicity data. This article presents toxicity reference values (TRVs) for small mammals based on chronic or subchronic exposure studies for a range of organic and trace metal contaminants and ecologically relevant inhalation endpoints. Potential risk to small mammals due to ingestion and inhalation exposure were compared in two hypothetical air emission scenarios for a point source (incinerator) and non-point source emissions (vehicular emissions). Using two screening-level ERAs, we conclude that it may now be time to reconsider inhalation risk to wildlife in the case of atmospheric emissions of some metals and volatile organic compounds (VOCs). In the case of birds, the toxicological database remains too small to assess risks via this pathway. However, for mammals, we suggest that inhalation exposures to contaminants such as cadmium, benzene, and other VOCs could be important.     

Urinary biomarkers of 1,3-butadiene in environmental settings using liquid chromatography isotope dilution tandem mass spectrometry

Although, 1,3-butadiene is a known human carcinogen emitted from mobile sources, little is known about traffic-related human exposure to this toxicant. This pilot study was designed to characterize traffic-related environmental exposure to 1,3-butadiene and evaluate its urinary mercapturic acids as biomarkers of exposure in these settings. Personal air samples and multiple urine samples were collected on two separate occasions from three groups of individuals that differed by spatial proximity as well as intensity of traffic: (i) toll collectors, (ii) urban-weekday and (iii) suburban-weekend group. Air samples were analyzed using thermal desorption followed by GC/MS and urine samples were analyzed using isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) for two mercapturic acids of 1,3-butadiene: monohydroxy-3-butenyl mercapturic acid (MHBMA) and 1,2-dihydroxybutyl mercapturic acid (DHBMA). Exposure differed between groups (p<0.05) with median values of 2.38, 1.62 and 0.88 microg/m(3) for toll collectors, the urban-weekday group and the suburban-weekend group, respectively. A refined ID-LC-MS/MS method enabled detection of MHBMA, previously detected only in occupational settings, with high frequency. MHBMA and DHBMA were detected in 95 and 100% of urine samples at levels (mean+/-S.D.) of 9.7+/-9.5, 6.0+/-4.3 and 6.8+/-2.6 ng/mL for MHBMA and 378+/-196, 258+/-133 and 306+/-242 ng/mL for DHBMA for the three different groups, respectively. Mean biomarker levels were higher among the toll collectors compared to the other two groups, however, the differences were not statistically significant (p>0.05). This study is the first to evaluate 1,3-butadiene biomarkers for subtle differences in environmental exposures. However, additional research will be required to ascertain whether the lack of statistical association observed here is real or attributable to unexpectedly small differences in exposure between groups (<1 microg/m(3)), non-specificity of the biomarker at low exposure, and/or small sample size.     

N-Nitrosodimethylamine (NDMA) in Food and Beverages: A Comparison in Context to Drinking Water

Human exposure to N-nitrosodimethylamine (NDMA) from foods and beverages was modeled and upper-bound cancer risks were predicted for the United States and Canada. Approximately 0.5 (0–10.8) cancer incidents per million population from lifetime exposure to NDMA in drinking water were estimated. Lifetime exposure to NDMA from the major exogenous sources may result in 49.6 (range: 17.7–171.7) cancer incidents per million population, while meat products contribute the most (15.9/million) followed by milk products (10.9/million). Drinking water may contribute approximately 1% to the exogenous cancer risk and holds the 10th position among 10 exogenous sources. The sum of the cancer risks from the major exogenous sources (e.g., 49.6/million) is higher than the permissible limits (1–10/million) of several regulatory agencies. Thus, NDMA in exogenous sources can pose a significant source for cancer risk. Cancer risk from the exogenous sources was estimated to be much lower than that of the NDMA in the endogenous source (<1%).     

Cancer risk from chronic exposures to chemicals and radiation: a comparison of the toxicological reference value with the radiation detriment

This article aims at comparing reference methods for the assessment of cancer risk from exposure to genotoxic carcinogen chemical substances and to ionizing radiation. For chemicals, cancer potency is expressed as a toxicological reference value (TRV) based on the most sensitive type of cancer generally observed in animal experiments of oral or inhalation exposure. A dose–response curve is established by modelling experimental data adjusted to apply to human exposure. This leads to a point of departure from which the TRV is derived as the slope of a linear extrapolation to zero dose. Human lifetime cancer risk can then be assessed as the product of dose by TRV and it is generally considered to be tolerable in a 10^–6–10^–4 range for the public in a normal situation. Radiation exposure is assessed as an effective dose corresponding to a weighted average of energy deposition in body organs. Cancer risk models were derived from the epidemiological follow-up of atomic bombing survivors. Considering a linear-no-threshold dose-risk relationship and average baseline risks, lifetime nominal risk coefficients were established for 13 types of cancers. Those are adjusted according to the severity of each cancer type and combined into an overall indicator denominated radiation detriment. Exposure to radiation is subject to dose limits proscribing unacceptable health detriment. The differences between chemical and radiological cancer risk assessments are discussed and concern data sources, extrapolation to low doses, definition of dose, considered health effects and level of conservatism. These differences should not be an insuperable impediment to the comparison of TRVs with radiation risk, thus opportunities exist to bring closer the two types of risk assessment.