Airborne concentrations of benzene and mineral spirits (stoddard solvent) during cleaning of a locomotive generator and traction motor

Mineral spirits (also called Stoddard solvent), a petroleum distillate, is often used as a degreaser or an industrial cleaning agent. Although several studies measured airborne concentrations of mineral spirits in various occupational settings, none have characterized the airborne concentrations of benzene from use of mineral spirits. Recent case reports have suggested that benzene, as a contaminant in mineral spirits, might be responsible for adverse health effects. Because some claims of health effects in the railroad industry have been attributed to potential historical exposures to mineral spirits and little information is available regarding air concentrations in this type of occupational setting, a simulation study was conducted to quantitate historical exposures a railroad worker might have experienced while spraying mineral spirits on locomotive engine parts in the 1970s. To quantitate potential historical exposures, worker tasks were simulated under worst-case exposure conditions by spraying minerals spirits on a locomotive generator and traction motor. The results of both generator and traction motor cleaning events produced concentrations of mineral spirits ranging from 34 to 221 ppm and an average 1-h concentration of 121 ppm, whereas benzene concentrations associated with the spraying and drying tasks were less than the limit of detection (0.002-0.006 ppm). Results indicate that a railroad worker who cleaned a locomotive traction motor and generator with mineral spirits for 2 h each workday under worst-case exposure conditions would be exposed to an 8-h time-weighted average (based on lapel measurements) of 30.4 ppm airborne mineral spirits. On the basis of the conditions under which these concentrations were obtained, the results should be the reasonable maximum values that can be achieved in a modern-era (post-1970) workplace in the United States.     

Benzene Exposures and Risk Potential for Vehicle Mechanics from Gasoline and Petroleum-Derived Products

Benzene exposures among vehicle mechanics in the United States and abroad were characterized using available data from published and unpublished studies. In the United States, the time-weighted-average (TWA) airborne concentration of benzene for vehicle mechanics averaged 0.01–0.05 ppm since at least the late 1970s, with maximal TWA concentrations ranging from 0.03 to 0.38 ppm. Benzene exposures were notably lower in the summer than winter and in the Southwest compared to other geographic regions, but significantly higher during known gasoline-related tasks such as draining a gas tank or changing a fuel pump or fuel filter. Measured airborne concentrations of benzene were also generally greater for vehicle mechanics in other countries, likely due to the higher benzene content of gasoline and other factors. Short-term airborne concentrations of benzene frequently exceeded 1 ppm during gasoline-related tasks, but remained below 0.2 ppm for tasks involving other petroleum-derived products such as carburetor and brake cleaner or parts washer solvent. Application of a two-zone mathematical model using reasonable input values from the literature yielded predicted task-based benzene concentrations during gasoline and aerosol spray cleaner scenarios similar to those measured for vehicle mechanics during these types of tasks. When evaluated using appropriate biomarkers, dermal exposures were found to contribute little to total benzene exposures for this occupational group. Available data suggest that vehicle mechanics have not experienced significant exposures to benzene in the workplace, except perhaps during short-duration gasoline-related tasks, and full-shift benzene exposures have remained well below current and contemporaneous occupational exposure limits. These findings are consistent with epidemiology studies of vehicle mechanics, which have not demonstrated an increased risk of benzene-induced health effects in this cohort of workers. Data and information presented here may be used to assess past, current, or future exposures and risks to benzene for vehicle mechanics who may be exposed to gasoline or other petroleum-derived products.     

AIRBORNE CONCENTRATIONS OF BENZENE AND MINERAL SPIRITS (STODDARD SOLVENT) DURING CLEANING OF A LOCOMOTIVE GENERATOR AND TRACTION MOTOR

Mineral spirits (also called Stoddard solvent), a petroleum distillate, is often used as a degreaser or an industrial cleaning agent. Although several studies measured airborne concentrations of mineral spirits in various occupational settings, none have characterized the airborne concentrations of benzene from use of mineral spirits. Recent case reports have suggested that benzene, as a contaminant in mineral spirits, might be responsible for adverse health effects. Because some claims of health effects in the railroad industry have been attributed to potential historical exposures to mineral spirits and little information is available regarding air concentrations in this type of occupational setting, a simulation study was conducted to quantitate historical exposures a railroad worker might have experienced while spraying mineral spirits on locomotive engine parts in the 1970s. To quantitate potential historical exposures, worker tasks were simulated under worst-case exposure conditions by spraying minerals spirits on a locomotive generator and traction motor. The results of both generator and traction motor cleaning events produced concentrations of mineral spirits ranging from 34 to 221 ppm and an average 1-h concentration of 121 ppm, whereas benzene concentrations associated with the spraying and drying tasks were less than the limit of detection (0.002-0.006 ppm). Results indicate that a railroad worker who cleaned a locomotive traction motor and generator with mineral spirits for 2 h each workday under worst-case exposure conditions would be exposed to an 8-h time-weighted average (based on lapel measurements) of 30.4 ppm airborne mineral spirits. On the basis of the conditions under which these concentrations were obtained, the results should be the reasonable maximum values that can be achieved in a modern-era (post-1970) workplace in the United States.     

Characterization of cancer risk from airborne benzene exposure

Airborne benzene is a ubiquitous environmental air pollutant. However, research regarding ambient environmental benzene exposures and leukemogenesis is lacking. Alternatively, occupational exposure to significantly elevated levels of benzene is associated with acute myeloid leukemia (AML). This investigation uses ambient air monitoring data from six counties in the state of Florida to characterize the extrapolated cancer risk from airborne benzene concentrations. The study uses both a regulatory and comparative risk analysis methodology to appropriately frame “risk” for the public. Between the years 2003 and 2006, 3794 air samples were collected from 23 monitoring stations distributed in Broward, Duval, Orange, Miami-Dade, Hillsborough, and Pinellas counties. The mean benzene concentrations by site ranged from 0.18 to 3.58 ppb. Extrapolated cumulative lifetime exposures ranged from 0.036 to 0.702 ppm-years. Regulatory risk analysis resulted in cancer risk estimates ranging from 4.37 × 10⁻⁶ to 8.56 × 10⁻⁵, all of which exceed the Florida Department of Environmental Protection acceptable risk of 1 × 10⁻⁶. Comparative analysis with the epidemiologic literature indicates the association between benzene exposure and AML is related to cumulative exposures far in excess of 1 ppm-years, with the likely threshold for benzene-induced leukemogenesis of 50 ppm-years cumulative exposure. Based upon the results of this investigation, it is unreasonable to anticipate AML cases in Florida residents as a result of ambient airborne benzene concentrations.     

Distribution of chromosome breakpoints in benzene-exposed and unexposed AML patients

Results of laboratory studies and investigations of occupationally exposed healthy individuals have been used to develop a mode of action for benzene-induced leukemia that mirrors disease following treatment with chemotherapeutic agents. Recently we have described series of AML and MDS cases with benzene exposure history, and have provided cytogenetic, molecular, and pathologic evidence that these cases differ significantly in many features from therapy-related disease. Here we have extended this work, and describe chromosome breakpoints across 441 identifiable regions, in terms of gains or losses, in 710 AML cases collected during the Shanghai Health Study, which include 75 with a history of benzene exposure. Using FISH and cytogenetic analysis, we developed prevalence information and risk ratios for benzene exposure across all regions with a lesion in at least one exposed and unexposed case. These results indicate that AML following benzene exposure mirrors de novo disease, and supports a mechanism for development of hematopoietic disease that bears no resemblance to therapy-related disease.     

Characterization of cancer risk from airborne benzene exposure

Airborne benzene is a ubiquitous environmental air pollutant. However, research regarding ambient environmental benzene exposures and leukemogenesis is lacking. Alternatively, occupational exposure to significantly elevated levels of benzene is associated with acute myeloid leukemia (AML). This investigation uses ambient air monitoring data from six counties in the state of Florida to characterize the extrapolated cancer risk from airborne benzene concentrations. The study uses both a regulatory and comparative risk analysis methodology to appropriately frame “risk” for the public. Between the years 2003 and 2006, 3794 air samples were collected from 23 monitoring stations distributed in Broward, Duval, Orange, Miami-Dade, Hillsborough, and Pinellas counties. The mean benzene concentrations by site ranged from 0.18 to 3.58 ppb. Extrapolated cumulative lifetime exposures ranged from 0.036 to 0.702 ppm-years. Regulatory risk analysis resulted in cancer risk estimates ranging from 4.37 × 10⁻⁶ to 8.56 × 10⁻⁵, all of which exceed the Florida Department of Environmental Protection acceptable risk of 1 × 10⁻⁶. Comparative analysis with the epidemiologic literature indicates the association between benzene exposure and AML is related to cumulative exposures far in excess of 1 ppm-years, with the likely threshold for benzene-induced leukemogenesis of ⩾50 ppm-years cumulative exposure. Based upon the results of this investigation, it is unreasonable to anticipate AML cases in Florida residents as a result of ambient airborne benzene concentrations.     

Problems with benzene in Turkey

Until recently heavy occupational exposures to benzene were frequent in Turkey. Therefore, numerous cases of aplastic anemia associated with chronic exposure to benzene were detected among workers, mostly shoemakers. In addition, there was an increase in the incidence of leukemia among shoeworkers during the period 1967–1975, but the incidence has recently declined, possibly as a result of the phaseout of benzene. Furthermore, apart from leukemia, a frequent association between chronic exposure to benzene and various types of malignancies such as malignant lymphoma, myeloid metaplasia, paroxysmal nocturnal hemoglobinuria, multiple myeloma, and lung cancer has been found and this relationship is discussed.     

Shanghai Health Study (2001–2009): What was learned about benzene health effects?

The Shanghai Health Study (SHS) was a large epidemiology study conducted as a joint effort between the University of Colorado and Fudan University in Shanghai, China. The study was funded by members of the American Petroleum Institute between 2001 and 2009 and was designed to evaluate the human health effects associated with benzene exposure. Two arms of the SHS included: an occupational-based molecular epidemiology study and several hospital-based case control studies. Consistent with historical literature, following sufficient exposure to relatively high airborne concentrations and years of exposure, the SHS concluded that exposure to benzene resulted in an increased risk of various blood and bone marrow abnormalities such as benzene poisoning, aplastic anemia (AA), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). Non-Hodgkin lymphoma (NHL) was not significantly increased for the exposures examined in this study. Perhaps the most important contribution of the SHS was furthering our understanding of the mechanism of benzene-induced bone marrow toxicity and the importance of identifying the proper subset of MDS relevant to benzene. Investigators found that benzene-exposed workers exhibited bone marrow morphology consistent with an immune-mediated inflammatory response. Contrary to historic reports, no consistent pattern of cytogenetic abnormalities was identified in these workers. Taken together, findings from SHS provided evidence that the mechanism for benzene-induced bone marrow damage was not initiated by chromosome abnormalities. Instead, chronic inflammation, followed by an immune-mediated response, is likely to play a more significant role in benzene-induced disease initiation and progression than previously thought.     

Reconstruction of benzene exposure for the Pliofilm cohort (1936-1976) using Monte Carlo techniques

The current cancer slope factor and occupational standards for benzene are based primarily on studies of the rubber hydrochloride (Pliofilm) workers. Previous assessments of this cohort by Rinsky et al. (1981, 1987), Crump and Allen (1984), and Paustenbach et al. (1992) relied on different assumptions about the available industrial hygiene data and workplace practices and processes over time, thereby yielding significantly different estimates of annual benzene exposures for many jobs. Given the inherent limitations and uncertainties involved in estimating historical exposures for this cohort, a probabilistic approach was used to better characterize their likely degree of benzene exposure. Ambient air exposures to benzene were based, in part, on the distribution of air sampling data collected at the Pliofilm facilities and assumptions about how workplace concentrations probably decreased over time as the threshold limit value (TLV) was lowered. The likely uptake of benzene from dermal exposures was estimated based on probability distributions for several exposure factors, including surface area, contact rate and duration, and skin absorption. The assessment also quantitatively accounts for improved engineering controls, extended work hours, incomplete Pliofilm production, and the use and effectiveness of respirators over time. All original data and assumptions are presented in this assessment, as is all new information obtained through additional interviews of former workers. Estimated benzene exposures at the 50th and 95th percentiles are reported as equivalent 8-h time-weighted average (TWA) airborne concentrations for 13 job categories from 1936 to 1965 (Akron I and II facilities) and 1939 to 1976 (St. Mary's facility). Data indicate that estimated equivalent airborne benzene concentrations for St. Mary's workers were highest for four job categories (Neutralizer, Quencher, Knifeman, Spreader), typically ranging from about 50 to 90 ppm during 1939-1946 (lower during 1942-1945), and 10 to 40 ppm during 1947-1976 at the 50th percentile. These estimates are 2-3 times greater than for other jobs in the Pliofilm process, and about 1.5 times less than those estimated at the 95th percentile. Estimates of equivalent airborne benzene concentrations for Akron I and II were about 1.5 times higher than for St. Mary's, but there is less confidence in these estimates, given the lack of industrial hygiene monitoring data for these facilities. Study results suggest that Paustenbach et al. (1992) generally over-estimated exposures for those job categories that had the highest exposure by about a factor of two to four. On the other hand, it was concluded that Rinsky et al. (1981, 1987) under-predicted benzene exposures for most jobs, and Crump and Allen (1984) both under- and overpredicted benzene exposures, depending on the specific job category and time period. The new estimates presented in this analysis incorporate what is considered to be the most likely range of plausible exposure values, and, accordingly, provide a better characterization of the potential workplace exposures for this cohort. These data could be combined with current or future mortality information to calculate a new cancer potency factor or occupational health standard for benzene.     

Mice exposed in utero to low concentrations of benzene exhibit enduring changes in their colony forming hematopoietic cells

Pregnant Swiss-Webster mice were exposed to either 0, 5, 10, or 20 ppm benzene from days 6 through 15 of gestation. Hematopoietic progenitor cell assays were performed on fetal, neonatal and adult progeny of the exposed dams. All concentrations of benzene employed induced marked changes in the numbers of the more differentiated erythroid colony forming cells, the CFU-E. Granulocytic colony forming cells (GM-CFU-C) were affected by the 2 higher exposure concentrations. When mice previously exposed in utero to 10 ppm benzene were re-exposed as adults, marked depressions in the numbers of CFU-E and GM-CFU-C were observed. Thus, in utero exposures to concentrations of benzene at the current occupational exposure limit induce alterations of the murine hematopoietic system which persist into adulthood.     

State-of-the-Science Review of the Occupational Health Hazards of Crystalline Silica in Abrasive Blasting Operations and Related Requirements for Respiratory Protection

Excessive exposures to airborne crystalline silica have been known for over 100 years to pose a serious health hazard. Work practices and regulatory standards advanced as the knowledge of the hazards of crystalline silica evolved. This article presents a comprehensive historical examination of the literature on exposure, health effects, and personal protective equipment related to silica and abrasive blasting operations over the last century. In the early 1900s, increased death rates and prevalence of pulmonary disease were observed in industries that involved dusty operations. Studies of these occupational cohorts served as the basis for the first occupational exposure limits in the 1930s. Early exposure studies in foundries revealed that abrasive blasting operations were particularly hazardous and provided the basis for many of the engineering control and respiratory protection requirements that are still in place today. Studies involving abrasive blasters over the years revealed that engineering controls were often not completely effective at reducing airborne silica concentrations to a safe level; consequently, respiratory protection has always been an important component of protecting workers. During the last 15–20 yr, quantitative exposure-response modeling, experimental animal studies, and in vitro methods were used to better understand the relationship between exposure to silica and disease in the workplace. In light of Occupational Safety and Health Administration efforts to reexamine the protectiveness of the current permissible exposure limit (PEL) for crystalline silica and its focus on protecting workers who are known to still be exposed to silica in the workplace (including abrasive blasters), this state-of-the-science review of one of the most hazardous operations involving crystalline silica should provide useful background to employers, researchers, and regulators interested in the historical evolution of the recognized occupational health hazards of crystalline silica and abrasive blasting operations and the related requirements for respiratory protection.     

United States Voluntary Children's Chemical Evaluation Program (VCCEP) risk assessment for children exposed to benzene

As part of the Voluntary Children's Chemical Evaluation Program (VCCEP) program, a risk assessment was performed to evaluate the risks to children from environmental benzene exposures. This paper summarizes this risk assessment. Risk was characterized using two distinct methods: USEPA's default type of risk assessment, which used the Reference Dose (RfD) and Cancer Slope Factor (CSF) to characterize non-cancer and cancer risks, as well as a Margin of Safety (MOS) approach that utilized a point of departure (POD). The exposures for most scenarios evaluated in this VCCEP risk assessment are lower than both the cancer and non-cancer PODs by several orders of magnitude, indicating a large MOS and corresponding low potential for toxicity at these exposures. The highest benzene exposures likely experienced by children, associated with the lowest MOS, are from cigarette smoke. In addition, the potential for age-related differences in the sensitivity towards benzene-induced toxicity was investigated. In general, this risk assessment does not indicate that children are likely to be at a elevated risk of AML or hematopoietic toxicity associated with environmental exposures to benzene.     

Reevaluation of benzene exposure for the Pliofilm (rubberworker) cohort (1936-1976).

The Pliofilm cohort is the most intensely studied group of workers chronically exposed to benzene. Information on this cohort has been the basis for regulations and/or guidelines for occupational and environmental exposure to benzene. Rinsky et al. (1986, 1987) and Crump and Allen (1984) developed different approaches for reconstructing the exposure history of each member of the group. The predicted levels of exposure, combined with the data on the incidence of disease, have been used to estimate benzene's carcinogenic potency. In this paper, recent information from worker interviews and historical records from the National Archives and elsewhere were used to evaluate the accuracy of prior exposure estimates and to develop better ones for the cohort. The following factors were accounted for: (1) uptake of benzene due to short-term, high-level exposure to vapors, (2) uptake due to background concentrations in the manufacturing building, (3) uptake due to contact with the skin, (4) morbidity and mortality data on workers in the Pliofilm process, (5) the installation of industrial hygiene engineering controls, (6) extraordinarily long work weeks during the 1940s, (7) data indicating that airborne concentrations of benzene were underestimated due to inaccurate monitoring devices and the lack of adequate field calibration mated due to inaccurate monitoring devices and the lack of adequate field calibration of these devices, and (8) likely effectiveness of respirators and gloves. Our estimates suggest that Crump and Allen (1984) overestimated the exposure of workers in some job classifications and underestimated others, and that Rinsky et al. (1981, 1986) almost certainly underestimated the exposure of nearly all workers. Airborne concentrations of benzene at the St. Marys facility during the years of its operation were found (on average) to be about half those of the two Akron facilities. Our analysis indicates that short-term, high-level exposure to benzene vapors and dermal exposure significantly increased (by about 25-50%) the total absorbed dose of benzene for some workers. One of the key findings was that, unlike prior analyses, the three facilities probably had significantly different airborne concentrations of benzene, especially during the 1940s and 1950s.     

State-of-the-science review of the occupational health hazards of crystalline silica in abrasive blasting operations and related requirements for respiratory protection

Excessive exposures to airborne crystalline silica have been known for over 100 years to pose a serious health hazard. Work practices and regulatory standards advanced as the knowledge of the hazards of crystalline silica evolved. This article presents a comprehensive historical examination of the literature on exposure, health effects, and personal protective equipment related to silica and abrasive blasting operations over the last century. In the early 1900s, increased death rates and prevalence of pulmonary disease were observed in industries that involved dusty operations. Studies of these occupational cohorts served as the basis for the first occupational exposure limits in the 1930s. Early exposure studies in foundries revealed that abrasive blasting operations were particularly hazardous and provided the basis for many of the engineering control and respiratory protection requirements that are still in place today. Studies involving abrasive blasters over the years revealed that engineering controls were often not completely effective at reducing airborne silica concentrations to a safe level; consequently, respiratory protection has always been an important component of protecting workers. During the last 15-20 yr, quantitative exposure-response modeling, experimental animal studies, and in vitro methods were used to better understand the relationship between exposure to silica and disease in the workplace. In light of Occupational Safety and Health Administration efforts to reexamine the protectiveness of the current permissible exposure limit (PEL) for crystalline silica and its focus on protecting workers who are known to still be exposed to silica in the workplace (including abrasive blasters), this state-of-the-science review of one of the most hazardous operations involving crystalline silica should provide useful background to employers, researchers, and regulators interested in the historical evolution of the recognized occupational health hazards of crystalline silica and abrasive blasting operations and the related requirements for respiratory protection.     

Effect of repeated benzene inhalation exposures on benzene metabolism, binding to hemoglobin, and induction of micronuclei

Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1 mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were exposed to 600 ppm, 14C-labeled benzene for 6 hr. Individual benzene metabolites in urine collected for 24 hr after the exposure were analyzed. There was a significant decrease in the respiratory rate of mice (but not rats) pretreated with benzene which resulted in lower levels of urinary [14C]benzene metabolites. The analyses indicated that the only effects of benzene pretreatment on the metabolite profile in rat or mouse urine were a slight shift from glucuronidation to sulfation in mice and a shift from sulfation to glucuronidation in rats. Benzene pretreatment also had no effect, in either species, on formation of [14C]benzene-derived hemoglobin adducts. Mice and rats had similar levels of hemoglobin adduct binding, despite the higher metabolism of benzene by mice. This indicates that hemoglobin adduct formation occurs with higher efficiency in rats. After 1 week of exposure to 600 ppm benzene, the frequency of micronucleated, polychromatic erythrocytes (PCEs) in mice was significantly increased. Exposure to the same level of benzene for an additional 2 weeks did not further increase the frequency of micronuclei in PCEs. These results indicate that repeated exposures to benzene, such as might be encountered by humans as a result of occupational or environmental exposures, are not likely to change or increase benzene metabolism.     

Analysis of OSHA's short-term-exposure limit for benzene

A review of the data cited by OSHA in its final standard for exposure to benzene provides no clear scientific basis for a short-term-exposure limit (STEL). While leukemia and bone marrow toxicity were related to cumulative exposures of benzene received by workers, no evidence was presented that the rate of exposure at a given cumulative exposure contributed to the effects. Likewise, animal experiments suggested that exposures of several hours duration at a given level of benzene induced more bone-marrow toxicity when administered 3 rather than 5 days/week but did not indicate that the rate of exposure over shorter time scales played any role. The toxicokinetics of benzene in humans were also studied to determine whether nonlinear dose-rate effects would be likely to result from peak exposures associated with an exposure dose of 8 ppm-hr, which is allowed under the permissible exposure limit. This led to three conclusions. First, the concentration of benzene in the bone marrow should be sufficiently damped that the impact of a peak exposure should be minimal. Second, the peak concentration of benzene in the liver should be within the capacity of the cytochrome P450 system to maintain first-order metabolism. And finally, the maximum blood concentration of metabolites should be well below levels which have been shown to induce toxic effects in vitro. Taken together, the toxicokinetic relationships and the absence of clear experimental dose-rate effects suggest that the current STEL for benzene is unwarranted, assuming that 8-hr average exposures are kept below 1 ppm. While the argument can be made, on the basis of health considerations, that the existing 8-hr limit for benzene is too high, the rate of exposure during short periods appears to be irrelevant. Thus, we recommend that health professionals focus upon long-term exposures to benzene received by large numbers of workers rather than devote scarce resources to evaluate transient air levels.     

Application of oligonucleotide microarray technology to toxic occupational exposures

Microarray technology has advanced toward analysis of toxic occupational exposures in biological systems. Microarray analysis is an ideal way to search for biomarkers of exposure, even if no specific gene or pathway has been identified. Analysis may now be performed on thousands of genes simultaneously, as opposed to small numbers of genes as in the past. This ability has been put to use to analyze gene expression profiles of a variety of occupational toxins in animal models to classify toxins into specific categories based on response. Analysis of normal human cell strains allows an extension of this analysis to investigate the role of interindividual variation in response to various toxins. This methodology was used to analyze four occupationally related toxins in our lab: oxythioquinox (OTQ), a quinoxaline pesticide; malathion, an organophosphate pesticide; di-n-butyl phthalate (DBP), a chemical commonly found in personal care and cosmetic items; and benzo[a]pyrene (BaP), an environmental and occupational carcinogen. The results for each exposure highlighted signaling pathways involved in response to these occupational exposures. Both pesticides showed increase in metabolic enzymes, while DBP showed alterations in genes related to fertility. BaP exposure showed alterations in two cytochrome P450s related to carcinogenicity. When used with occupational exposure information, these data may be used to augment risk assessment to make the workplace safer for a greater proportion of the workforce, including individuals susceptible to disease related to exposures.     

Kinetics of granulocytic and erythroid progenitor cells are affected differently by short-term,low-level benzene exposure

In previous work, we determined that granulocytic (CFU-GM) and erythroid (CFU-E) progenitor cell populations exhibited disparate responses to short-term benzene exposures. We now report on work investigating possible mechanisms for these observed disparate responses. Mice were exposed to either air or 10 ppm benzene for 6 h/d X 5 d. Immediately after the last exposure, mice were injected, i. v., with either saline or hydroxyurea (HU). The dose of HU was sufficient to kill hematopoietic cells in or near S-phase of the cell cycle and sufficient to synchronize the surviving populations of hematopoietic cells. Three days after benzene exposure, CFU-E numbers had declined to 50% of control values while CFU-GM numbers were equal to control values at this time. The benzene exposures were sufficient to double the percentage of CFU-E in S-phase but produced no such increase among CFU-GM. During 3 days of recovery from benzene exposure and HU treatment, the CFU-E population expanded 30-fold while the CFU-GM population expanded less than 3-fold. Following benzene exposure and HU treatment, both progenitor cells produced elevated numbers of their respective progeny. When CFU-E from benzene-exposed mice were cultured with varying concentrations of erythropoietin (EPO), the response at maximal EPO concentration was 66% of the response by control CFU-E. This strongly suggests that the CFU-E populations from benzene-exposed mice had been depleted of cells in or near S-phase. The results indicate that CFU-GM respond to low-level benzene exposure by increasing their rate of differentiation but not their rate of proliferation, while CFU-E respond by increasing both their rates of differentiation and proliferation. We speculate that it is the increase in CFU-E proliferation that renders these cells more susceptible to benzene than their granulocytic counterparts, especially those CFU-E at or near the S-phase of the cell cycle.     

NQO1, MPO, CYP2E1, GSTT1 and GSTM1 polymorphisms and biological effects of benzene exposure--a literature review

BACKGROUND: Benzene is a ubiquitous toxic environmental pollutant. Biological effects have been detected as a result of low-level environmental exposures, suggesting that a large proportion of the population may potentially suffer ill health effects. Polymorphisms in genes involved in benzene metabolism are thought to influence individual susceptibility to various levels of benzene exposure. METHODS: Medline literature database search for articles relating to benzene exposure and polymorphisms in genes known to be involved in benzene metabolism (NQO1, CYP2E1, GSTT1, GSTM1 and MPO). Twenty-two reports were included in this review. RESULTS: A modest effect of the studied gene polymorphisms on the analyzed biomarkers was observed. GSTM1 and GSTT1 showed some consistent associations with both biomarkers of exposure and effect. CONCLUSION: Genetic polymorphisms on the benzene metabolism pathway should be taken into account when studying the biological effects of benzene exposure. Unique combinations of genetic polymorphisms may increase susceptibility of individuals and/or population subgroups. However, gene-gene interactions, and the biological effects of long-term and low-level exposure to benzene are not yet analyzed with well-designed studies that incorporate multiple biological end-points and multiple genes.     

The Design,Construction, and Operation of a Whole-Body Inhalation Chamber for Use in Avian Toxicity Studies

Environmental risk assessments are broadening to include evaluations of avian species exposed to gaseous and particulate materials (; ; ). Since the avian respiratory tract is fundamentally different from the respiratory tract of rodents, the effects of gaseous materials on birds cannot validly be extrapolated from data derived from rodent exposure studies (; ). To address the lack of avian-specific lowest observable effect levels used to calculate reference concentrations for airborne pollutants, a system was designed to facilitate research on inhalation toxicology in small birds. Birds have long been used as early indicators of poor air quality (), and various chambers have been designed for head only exposures of larger birds (). Smaller birds with short tracheal lengths and hooked beaks however require less restrictive exposure apparatus, thus warranting the proposed design. The chamber described in this article was designed to accommodate a small falcon, the American kestrel, a species frequently used in toxicological risk assessments (Wiemeyer & Lincer, 1987a; ; ; ). To accomplish this, a 41-L closed inhalation system capable of exposing 12 adult American kestrels was constructed primarily of galvanized steel, polyvinyl chloride, and copper tubing. Humidified air was passed over the birds and subsequently decontaminated by an activated carbon filter and released to a HEPA filtration system. The proposed inhalation chamber was successfully used in 2005 and 2006 to expose a total of 55 male American kestrels to benzene and toluene. Measurements of various biochemical endpoints associated with benzene and toluene toxicity allowed us to study the effects of airborne pollutants on small nondomesticated birds in a controlled laboratory setting.