Few industrial chemicals have received as much attention from occupational health scientists as benzene: evidence of its harmful effects date back nearly 100 years. Today benzene is recognized as a human carcinogen, based on studies showing that exposure to high levels of the chemical causes leukemia in workers. But scientists now recognize that low levels of benzene also may pose a health threat, and attention is being directed at understanding the risks of low-level exposures in both the workplace and the environment.
Benzene is a widely used material: only 15 chemicals are produced in the United States in greater volume. Benzene is an important raw material for the chemical industry and an occasional industrial solvent, as well as a component of crude oil and gasoline. Thus, it is virtually impossible for someone in the United States to avoid low-level environmental exposure to benzene. For example, benzene enters the air through vehicle emissions, so anyone who drives or is caught in traffic is exposed. The chemical can seep into a house from an attached garage, when benzene in gasoline evaporates from the car's hot engine and tank. Drivers filling gas tanks usually get a hefty whiff and end up with the odor of gasoline on their hands. Indoors, some consumer products and furnishings emit small amounts of benzene, and refineries and coke oven plants emit benzene into outdoor air. Benzene is just one of the many hazardous constituents of cigarette smoke. People may also be exposed to benzene while showering when the heat volatilizes benzene present in the water.
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Lance Wallace-- Important sources of exposure are not regulated. |
The combined levels of all indoor and outdoor exposures are very low, says Lance Wallace of the EPA, "averaging only 5 parts per billion in the United States." Wallace was project officer for EPA's Total Exposure Assessment Methodology (TEAM) studies, which measured 24-hour personal exposures to selected chemicals, including benzene. The environmental levels of benzene measured by EPA are far lower than the currently permitted workplace standard of 1 part per million (ppm).
It is the disparity between the typically low environmental levels and the comparatively high workplace exposures that challenges regulators and scientists assessing risks and that concerns the oil and auto industries worried about potentially stricter regulations for the workplace and for motor vehicle fuel and emissions. The key questions center on whether low levels of benzene cause leukemia or other adverse health effects, the mechanism by which benzene causes cancer, and whether the mechanism at high doses is relevant at low doses.
Answering these questions is hampered, say many scientists, by the inability to identify an animal model in which benzene produces leukemia. Nonetheless, researchers are making advances by focusing their efforts on more accurately quantifying exposure, dose, and effects, for example, by evaluating exposure in microenvironments using molecular biology and epidemiologic approaches, target tissue dosimetry, toxicokinetic modeling, and identifying biological markers. Ultimately, their research aims at illuminating the issue of high- to low-dose extrapolation and the controversial issue of how strictly benzene needs to be regulated.
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Eula Bingham-- Benzene is a very dangerous chemical. |
"We recognize that benzene can cause leukemia at high levels of exposure, say 25, 50, or 100 parts per million in the workplace," says Robert Drew of the American Petroleum Institute. "But we disagree that there is a risk of cancer at the lower levels present in the environment." In contrast, nine scientists and health professionals have signed a letter arguing that the current workplace standard for benzene (1 ppm) should be reduced dramatically because "any higher than 0.1 ppm presents a needless and preventable cancer danger." One signer of the letter, which was sent to the American Conference of Governmental Industrial Hygienists (ACGIH), is Eula Bingham, former head of the Occupational Safety and Health Administration during the Carter administration. "We had concerns about benzene when we set the 1 ppm standard in 1978," she says, "and since then the evidence has magnified." "Now," she adds, "we see that benzene is a carcinogen for multiple organs, and we have human experience supporting the conclusion that this is a very dangerous chemical."
A regulatory battle is expected on two fronts: the first, as EPA prepares to regulate motor vehicle fuel and vehicle emissions under the Clean Air Act and the second, as the ACGIH debates a proposal to lower its recommendation for occupational exposures from 1 ppm to 0.1 ppm. The values adopted by ACGIH have regulatory implications because some states (e.g., California) adopt them as workplace standards.
Adverse Health Effects
Leukemia linked to benzene exposure in the workplace has been documented in numerous case reports and epidemiologic studies. For example, in Italy in the 1960s, printing shop workers and shoemakers exposed to benzene were found to have a risk of leukemia 20 times higher than expected. A 1977 study of U.S. rubber workers at Goodyear facilities by Peter Infante and associates at the National Institute for Occupational Safety and Health found a statistically significant increase in deaths from acute myelogenous leukemia among workers exposed to benzene in the range of 10-100 ppm. Finally a recent study of the Swedish Cancer Registry, published in the July/August 1993 issue of the Archives of Environmental Health, found an excess of acute myelogenous leukemia among petrol station attendants.
Strict OSHA standards make it unlikely that large numbers of U.S. workers continue to be exposed to high levels of benzene. Thus, epidemiologists interested in studying the health effects of benzene are turning to other countries that have not yet implemented such strict exposure standards. Since the early-1980s, Yin Song-nian and colleagues at the Chinese Academy of Preventive Medicine have been conducting a massive epidemiologic study of workers exposed to benzene in 12 Chinese cities. In 1989, they reported a statistically significant excess of leukemia and lung cancer, along with possible increases of liver and stomach cancer, and lymphoma. The Yin report states that "leukemia occurred in some workers with as little as 6-10 ppm of exposure."
The National Cancer Institute is now co-sponsoring the research in China and expanding its scope. Richard Hayes and Martha Linet are co-principal investigators on the project. Hayes says the cohort contains shoemakers, spray painters, and workers from many other manufacturing industries, with a recent average exposure of 8 ppm. Hayes reports that paint in China still contains benzene as a solvent in the range of 7-8%.
More work needs to be done to determine which blood-related cancers other than leukemia and which solid tumors are definitely related to benzene exposure. In the judgment of Bernard Goldstein, director of the Environmental and Occupational Health Sciences Institute at Rutgers, and former assistant EPA administrator for research and development, "It is more likely than not that most hematological neoplasms under the heading of lymphoma or acute lymphoblastic leukemia can be caused by benzene." Goldstein says he has no scientific proof, but "I think more likely than not, chronic leukemias and multiple myeloma also can be caused by benzene." Goldstein says the evidence on solid tumors is much weaker. He recommends a meta-analysis (group analysis of studies that may enhance the ability to relate exposure to response) of the epidemiologic database to look at solid tumors.
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Bernard Goldstein-- More likely than not, leukemia can be caused by benzene. |
Although cancer has driven the risk assessment and regulation of benzene, some human evidence links benzene exposure to various blood abnormalities and neurological, immunological, and reproductive effects in exposed workers--all of which need greater scrutiny.
Regulation of Benzene
The International Agency for Research on Cancer has designated benzene as a group 1 carcinogen ("with sufficient evidence of carcinogenicity in humans"). These designations often affect standards-setting policies both in the United States and abroad. In the United States, EPA's regulatory clock is ticking for benzene and other hazardous pollutants in motor vehicle fuels and exhaust. By May 1995, EPA must propose new regulations for these pollutants, under provisions of the 1990 Clean Air Act Amendments. Questions about low-dose effects of benzene will have to be addressed in the regulations.
EPA has already completed a study on motor vehicle-related air toxics, which was also required under the Clean Air Act Amendments. The report says the current average level of benzene in gasoline in the United States is 1.5% and that the fraction of benzene in the exhaust generally runs 3-5%, depending on control technology. EPA may choose to require a reduction in the benzene content of gasoline, as the agency has already done for reformulated gasoline (which has a limit of 1.0% benzene). Benzene also can be produced from engine combustion of other aromatic hydrocarbons present in gasoline. Thus, simply reducing the levels of benzene in fuel will help solve the benzene emission problem. Other regulatory approaches such as alternative fuels and energy sources and vapor recovery may also be necessary.
Such approaches have been used to reduce smog since the 1970s in California, where 4000 gas stations in large cities have had to use vapor recovery systems. Starting in 1987, an additional 1000 gas stations had to install vapor recovery systems to reduce benzene air emissions in response to the California Air Resource Board rules designating benzene as a toxic air contaminant "because of its ability to cause cancer."
Attempts to regulate workplace exposure to benzene have resulted in bitter legal battles--all the way up to the U.S. Supreme Court. In 1978 OSHA issued a regulation reducing the permissible benzene exposure from 10 ppm to 1 ppm over an 8-hour day to protect workers from cancer. OSHA subsequently was sued by both labor unions and by industry (including various chemical, oil, and rubber companies and their trade associations). The Supreme Court later vacated the OSHA standard, stating that OSHA had not shown it would achieve a "substantial reduction in significant risk" by reducing levels from 10 ppm to 1 ppm. The court ordered OSHA to reconsider the standard. In 1987 a new benzene standard, again at 1 ppm, was issued and is now in effect. Employers are required to start monitoring when exposures reach 0.5 ppm.
Peter Infante, an epidemiologist with OSHA, argues that the current permissible exposure limit for benzene carries with it a significant risk of leukemia. "Based on cancer data, the benzene level should be stricter than 1 ppm," he contends. "The agency was not able to go lower than 1 ppm because of economic feasibility." Infante believes that a standard based on health risk alone should be no higher than 0.1 ppm, the level proposed by the ACGIH in July 1990. Carl Mackerer of the Mobil Oil Corporation, strongly disagrees. He believes that regulating benzene at levels below 1 ppm is unreasonable: "It would cost billions of dollars, be extremely difficult for industry to meet, and be of questionable positive health impact."
Exposure
Year after year, workplace exposure levels to benzene continue to drop. Exposures early in the century sometimes were as high as 1000 ppm. Several sources say that most major U.S. employers today are trying to keep benzene exposures under 0.5 ppm, the OSHA "action level," which triggers special monitoring requirements. In developing countries, on the other hand, typical benzene exposures are much higher. A joint U.S.-China study, for example, found levels of occupational benzene exposure for workers in 12 Chinese cities averaged 8 ppm in 1987. Workers in the study were primarily involved in spray painting, shoe manufacturing, synthetic rubber production, and adhesive production.
In contrast, EPA says outdoor air levels in the United States are usually well under 5 parts per billion (ppb), often ranging from 1 to 2 ppb. The largest contributors are mobile sources, which EPA says account for approximately 85% of the total ambient air emissions, with the majority coming from exhaust and the rest from evaporative emissions (from hot engines) and refueling emissions (from filling gas tanks). The remaining 15% of benzene emissions come from stationary sources, such as refinery and coke oven operations.
Wallace concludes from the TEAM studies that mobile sources contribute more benzene to 24-hour personal exposures than do industrial emissions. The more time people spend in cars, the more benzene exposure they receive. Some of his other results are significant. First, Wallace found that indoor air usually has higher levels of benzene than outdoor air. "On average," Wallace says, "the outdoor air contributes 2 ppb to your benzene exposure and the indoor air contributes 3 ppb." Wallace attributes much of the higher indoor levels to benzene entering from autos in attached garages and to emissions from consumer products that contain benzene such as paint or adhesives.
Second, Wallace calculated that mainstream cigarette smoke provides a larger dose of benzene to the smoker than all other sources combined. For example, personal exposures during the course of a 24-hour day averaged approximately 5 ppb for a nonsmoker. A smoker received an additional 30 ppb. "Ambient air levels are so low," says Wallace, "that if the person is a smoker, most of his benzene exposure will be from cigarettes." The studies also showed a 50% increase in benzene exposures for spouses and children in the homes of smokers.
In a 1990 article in Risk Analysis, Wallace concluded that EPA's "current environmental regulations and control strategies are misdirected" in that "important sources of exposure are not regulated in any way, whereas unimportant sources are heavily regulated." Environmentalist Ed Rothschild of Citizen Action, in Washington, DC, criticizes these conclusions, arguing that when Congress passed the Clean Air Act Amendments, it asked for regulation of mobile air toxics, not smoking. "No one disagrees that people who smoke get lots of benzene exposure," says Rothschild. "But that can't be used as a rationale for EPA to stop reduction of benzene emissions." Toxicologist Myron Mehlman of the Environmental and Occupational Health Sciences Institute at Rutgers University, argues that smoking and "self-serve" filling of gas tanks are avoidable behaviors, but that exposure to benzene emissions from vehicles must be regulated because it is involuntary. "No one in our society can avoid it," says Myron. Wallace finds the highest peak exposures to benzene when driving and refueling cars. "It takes about 70 seconds to fill a tank," Wallace says. "During that time the exposure goes from 2 ppb to 1000 ppb." Wallace adds, "You can still see a difference in the breath of people 24 hours after they fill their tank with gasoline."
Jerry Blancato, a research biologist with EPA's Exposure Monitoring Program in Las Vegas, Nevada, says he would like to see more research to characterize possibly unrecognized sources of benzene exposure inside homes, including a better look at heating and cooking fuels such as natural gas and oil. And although Wallace's research claims negligible benzene intake from food and water, NIEHS researchers Eric Johnson and George Lucier have called for a closer examination of benzene exposure from routes other than air. Johnson and Lucier detected the benzene metabolite muconic acid, found in benzene workers, in the general public, suggesting the possibility that some people may be exposed to more than 1 ppm of benzene, some of it from unknown sources.
The Health Effects Institute of Cambridge, Massachusetts, which is jointly funded by the motor vehicle industry and EPA, held a series of workshops on "Research Priorities for Mobile Air Toxics" in 1992-1993. The HEI report on these workshops contains a lengthy series of research recommendations on benzene. The report suggests that better assessments of the contribution of benzene from attached garages need to be conducted, along with studies of how home construction could be modified "to reduce the transfer of benzene vapors into the living areas." The HEI report also cites the need for mathematical models to assess human indoor exposure.
Exposure Analysis in Risk Assessment
Exposure assessment in epidemiologic studies is an important parameter in the development of risk assessments. The link between exposure levels of toxic chemicals and observed adverse effects is used to determine the risk expected from continued exposure and to set regulations. EPA conducted a risk assessment of benzene in the 1980s and calculated a cancer risk of 2.6 per 100 for someone breathing 1 ppm of benzene in the air over a 70-year lifetime. To calculate that risk, EPA used several epidemiologic studies containing benzene exposure data, including the cohort study of rubber workers by Rinsky and colleagues at NIOSH. The exposure assessment methods in the Rinsky study have become a focus of attention in discussions of benzene's risk assessment in the scientific literature and in the HEI report.
A recent paper in EHP (volume 100) by toxicologist Robert Snyder and colleagues at Rutgers describes the Rinsky/NIOSH study of Goodyear workers as "one of the most thorough retrospective exposure assessments ever done on a cohort of workers." But the Snyder paper also argues that "it appears that NIOSH significantly underestimated the extent of exposure during World War II."
Rinsky says the industrial hygiene measurements at the plants studied were unusually comprehensive for such retrospective studies. Nonetheless, levels of benzene were not measured during all years. Rinsky's approach to estimating exposures was to use all available monitoring data; if none were available for a certain period of time, he chose as the estimated level a point midway between the recorded measurements on either side of that time period. If anything, Rinsky theorizes, his exposures may be overestimated in part because industrial hygienists generally performed sampling in "trouble spots."
This issue is critical to the risk assessment of benzene, particularly to industries that are affected by standards based on these assessments. If the exposures that caused leukemia were higher than Rinsky estimated, for example, then the resulting risk calculations would be lower and standards would not need to be as strict.
The American Petroleum Institute (API) has supported a number of efforts, including those of Dennis J. Paustenbach, vice president of Chem-Risk, Inc., a consulting firm in Alameda, California, to reevaluate the Rinsky exposure assumptions. Paustenbach concluded that almost all workers were exposed to higher levels of benzene than Rinsky had estimated. In his evaluation, for example, Paustenbach concluded that many workers during the war worked longer than 40-hour weeks and thereby received higher exposures. Using Paustenbach's exposure estimates, Mary Burr-Paxton and colleagues at API came up with a somewhat lower estimate of occupational risk than Rinsky.
When referring to the Rinsky study, the HEI report notes the controversy over the exposure estimates. "What is controversial," says Rinsky, "is the way the American Petroleum Institute went after my study after the ACGIH recommended lowering the workplace standard to 0.1 ppm in 1990." Rinsky defends his work as solid, adding that it was based on the sampling data "as it existed, without any attempt to read things into it." He says, "I used a classic epidemiologic approach, whereas the approach used by Paustenbach and colleagues was to do everything they could to maximize the levels of benzene."
Robert Drew of API defends Paustenbach's work and the API's participation in it, arguing that "it was a reasonable effort to show that exposures were actually higher than Rinsky had estimated." Drew says that there is now a reasonable body of evidence suggesting that exposures were higher than EPA had assumed, "hence benzene is not as potent as EPA thinks it is."
Several researchers using linear dose extrapolations from the Rinsky data have ended up with estimates of environmental leukemia risk comparable to EPA's. In contrast, according to the HEI report, a recent assessment by Louis Cox of Cox Associates in Denver, Colorado, and Paolo Ricci of Ricci and Molton in Berkeley, California, using a nonlinear approach to the dose-response relationship and information from physiologically based pharmacokinetic models, ended up with a risk estimate much lower than the previous assessments. Since 1992, the journal Risk Analysis has carried an ongoing series of articles and letters between these authors and others concerned about benzene's cancer risk assessment.
Animal Bioassays
Benzene is an example of a chemical that caused cancer in humans before it was found to be an experimental carcinogen. The chemical causes blood abnormalities and aplastic anemia in most animal species exposed. It is also a potent carcinogen at many different sites in rats and mice, although no animal species has been identified that consistently develops leukemia after exposure to benzene.
The first successful animal work on benzene's carcinogenicity was conducted in 1982 by Caesare Maltoni and his colleagues in Bologna, Italy. In mice and rats, Maltoni was able to produce tumors in the Zymbal gland (a small external gland behind the ear of a mouse or rat), oral and nasal cavities, skin, forestomach, and mammary glands, as well as angiosarcomas of the liver, hemolymphoreticular neoplasms, lung cancer, and possibly hepatomas.
The largest animal study ever conducted on benzene was done by the National Toxicology Program and the NIEHS. The bioassay of rats and mice found benzene-induced cancers in the oral cavity, skin, Zymbal gland, lung, Harderian gland, preputial gland, hematopoietic system (lymphoma), skin, mammary gland, and probably forestomach. Based on the bioassay, toxicologist James Huff of NIEHS says, "I predicted in the late 1980s that we would start to see humans with different types of cancer from benzene in addition to leukemia; already we are beginning to see other cancers in the Yin study from China." He adds, "If someone dies from leukemia, they are not likely to have an autopsy, so you will never know if they had other tumors."
Many scientists strongly recommend research "to develop an animal model for benzene-induced leukemia in humans." The HEI report concludes that "in the absence of proper models, it is impossible to study the mechanism of benzene-induced leukemia." The report also recommends further work on benzene metabolism in monkeys and chimpanzees to see if those species could serve as models for leukemia.
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Michele Medinsky--Searching for animal models is expensive--so is setting very low exposure standards. |
Several investigators believe that it is possible to place too much emphasis on the need for the perfect animal model. "We don't need an expensive monkey model, we already have the best model in the world," says Mehlman. "It's the human." Michele Medinsky, a toxicologist at the Chemical Industry Institute of Toxicology, argues that it may be expensive to test monkeys or keep searching for an animal model in which to produce leukemia, but "it is also expensive to set a very low exposure standard." Medinsky adds that her work on pharmacokinetic modeling of benzene is hampered by the lack of a good animal model, which results in uncertainty about which toxic metabolites are important in leukemia.
Mackerer, of Mobil Oil's environmental sciences laboratory, which conducts research on benzene metabolism and biomarkers, urges evaluating the Zymbal gland's utility in helping to understand benzene's mechanism, suggesting that the gland might serve as a potential model. The Zymbal gland is a consistent site of tumor in the rodent studies. In fact, Huff points out it is the only organ in which cancer has been produced in both sexes of both species. Mackerer suggests looking at whether chromosomal changes occurring in the Zymbal gland tumor cells are "analogous to the changes we see in bone marrow leukemia."
Snyder is not convinced. "I still don't think Zymbal gland tumors, even in culture, are a model for benzene-induced leukemia," he says. "We'd like the tumor to be the kind of cancer we see in people."
Metabolism and Physiologically Based Pharmocokinetic Models
Benzene undergoes many changes when it is inhaled. For example, many different metabolites are formed by the liver via several metabolic pathways involving several different enzyme systems. "Benzene can go from the lungs to the liver where enzymes metabolize it," says Medinsky. For example, one enzyme metabolizes benzene to phenol, and the same enzyme metabolizes benzene to hydroquinone. Then the metabolites are sent out of the liver to the bone marrow, where some research suggests they are metabolized to a different reactive metabolite which may be actively responsible for the toxicity.
Medinsky has developed one of the physiologically based pharmocokinetic models for benzene, which is like a computerized mathematical road map to predict how much benzene gets to the bone marrow (the "target dose") after differing exposures. Medinsky says her model considers how much benzene is inhaled and the rate of respiration, along with the chemical's solubility in the blood and bone marrow and the rate at which blood circulates through the body to transfer the material from the lung to the liver to the bone marrow.
Target tissue dosimetry is an important issue, says Medinsky. "What you want to be able to predict is, given exposure to 300 ppm of benzene, what is the time course for the benzene metabolites to be in the bone marrow? And given exposure to 1 ppm, what does that time course look like?" She argues that because so many different metabolites are formed, what happens at a high dose to people may not be the same as what happens at a low dose--a crucial issue with respect to benzene-related cancers at environmental levels.
Toxicologist Rogene Henderson says there are some surprises about high doses versus low doses when studying the metabolic and detoxification pathways of benzene. An important issue, she says, is how much of the internal benzene dose becomes the biologically effective dose. In her work at Lovelace Inhalation Toxicology Laboratory in Albuquerque, New Mexico, in collaboration with Lucier of NIEHS and Linda Birnbaum of EPA, Henderson found that proportionately more of the (putative) toxic metabolites are formed at lower doses of benzene than at higher doses. "What this means for risk assessment," she says, "is if you extrapolate from high-dose animal studies to predict low-dose effect, you may underestimate the risk."
More research is still needed to identify with certainty which of the many metabolites of benzene may be toxic, or whether there is only one toxic metabolite. The HEI report recommends studies to characterize the mixture of metabolites delivered from the liver to the bone marrow, with particular attention on the relationship between metabolite concentration and cell damage.
Marrow Aplasia and Leukemia
Case reports show that workers with prolonged exposure to high levels of benzene have developed pancytopenia, a blood disorder characterized by decreased red and white blood cells and platelets, the worst form of aplastic anemia.
Several researchers, including Snyder, contend that aplastic anemia or some other form of myelodysplasia (blood marrow abnormalities) may be a necessary step in the development of leukemia after benzene exposure. According to Snyder, the progression is from bone marrow damage to aplastic anemia to myelodysplasia and then leukemia. "To go through this process," says Snyder, "the person must be exposed to substantial levels of benzene, definitely above 0.1 ppm, maybe above 1 ppm, maybe even above 10 ppm." The HEI report suggests this issue deserves further investigation to determine "whether or not these mechanisms apply at low environmental levels." Goldstein, on the other hand, believes it's unreasonable to suggest that aplastic anemia is a necessary step in developing leukemia, but he agrees that we need to know more about whether myelodysplasia is an independent event or is related to leukemia.
The HEI report suggests that more research is needed into whether "slight decreases in circulating cells, resulting from mild bone marrow damage, can be indicative of a risk of eventual leukemia." Medinsky says this is an area of research calling for an animal model to test the linkage.
Biomarkers of Exposure and Effect
Several types of biomarkers, including muconic acid in urine, are being evaluated as possible biological markers of benzene exposure for both occupationally exposed workers and the general population. Historically, simple blood counts have been used as markers of adverse effects to benzene. More sophisticated cytogenetic tests are now being evaluated, although with few exceptions, studies attempting to show mutagenic activity of benzene in vitro have been negative. Benzene and its metabolites have been shown to cause damage or breaks in the genetic material, as well as chromosomal aberrations. For example, Mackerer reports that in Mobil Oil's laboratory, researchers have found micronuclei in Zymbal gland tumor tissue from animals exposed to low doses of benzene.
NIEHS has been conducting studies of adult leukemia patients and analyzing bone marrow for evidence of chromosomal abnormalities. According to investigator Dale Sandler, leukemia patients with ras oncogene mutations were more likely to report exposure to benzene or unspecified organic solvents. Sandler and colleagues are also conducting a case-control study of 600 leukemia patients, in which an association between loss of chromosome 7 and solvent exposure appears to be confirmed. Again, the solvent exposures were self-reported, but many solvent products were verified to contain benzene when NIEHS investigators obtained classified data and information from the manufacturers.
Studies of DNA adducts have not yielded consistent results in animal or human studies. Questions about whether benzene exposure causes DNA damage are being considered in two molecular epidemiology studies of workers in Shanghai, China, being conducted by Nathaniel Rothman, an epidemiologist with the Occupational Studies section of the National Cancer Institute, and Martyn Smith, a toxicologist at the University of California at Berkeley. Rothman and Smith are conducting a case-control study of the workers diagnosed for compensation purposes as having been "benzene poisoned" (defined as having evidence of benzene exposure and specific blood abnormalities). This study is considering the issue of genetic susceptibility to benzene poisoning. According to Rothman, "We are looking at the impact of variation in enzyme activity among different workers on the risk of having an episode of benzene poisoning."
The cross-sectional study looks at workers currently exposed to an average of 30 ppm of benzene. Smith says the goal of this study is to determine the level and persistence of benzene-induced micronuclei and chromosome damage and to detect and identify DNA adducts to help characterize the risk. Rothman adds that the study has prompted some Chinese factories with heavily exposed workers to consider ways to reduce the levels of benzene, such as substituting less toxic solvents and providing better ventilation.
The HEI report recommends expanding the tools of molecular biology to develop sensitive and specific markers of exposure to identify susceptible populations if they exist and to permit better characterization of benzene's cancer effects. These biomarker studies in China may ultimately provide the first reliable data on the dose-response relationship of benzene exposure and chromosomal effects.
Research Recommendations
The most thorough recent review of research issues involving risk assessment for benzene is found in the HEI report. Some top-priority issues on benzene in the report's final conclusions include exposure in microenvironments, whether benzene causes solid tumors, development of a suitable animal model and dose-response models, and refinement of molecular biology tools. The report also names as priorities research to develop a better understanding of benzene's mechanisms and research on the link between chromosomal changes and leukemia. Lucier, who chaired the HEI benzene working group, stresses the need for multidisciplinary teams of researchers, including epidemiologists, mathematicians, molecular biologists, and toxicologists. "We need solid scientific data at each of these levels," he said, "to fill knowledge gaps that create uncertainty in current risk assessments for benzene."
Andrea Hricko
Andrea Hricko has previously written for EHP about arsenic.
Toxic Taipei Traffic
Even to a visitor from Los Angeles, the air in Taipei in late August seems heavy and polluted. As one walks around the congested city, vehicle exhaust appears to be a main contributor to the air pollution. And it is not just from cars; two-stroke motorcycles are a very popular form of transportation in Taipei. During rush hour, every intersection is jammed with motorcycles jostling for position with nearby cars and buses. Many riders don face masks in the false hope of preventing exposure to tailpipe emissions.
Gas mask. Benzene in exhaust is forcing commuters to don protective gear.
Researchers at National Taiwan University have studied students commuting to school on motorcycles and compared them to students commuting by bus to determine possible health risks of breathing volatile organic compounds (VOCs) from vehicle emissions. Their results, published in September 1993 in the Journal of the Air and Waste Management Association, show that the average on-motorcycle VOC concentrations during rush hour were about two times higher than the in-bus VOC concentrations. As for benzene, the mean concentrations were 128 parts per billion (ppb), many times higher than most state levels for motorcycles in the United States, and 56 ppb for buses. The article reports that the mean benzene levels for motorcycle commuters in Taipei are eight times higher than for car commuters in Los Angeles (which were reported in 1989 as 10-16 ppb); for bus commuters in Taipei, levels are three times higher than for car commuters in Los Angeles.
Author Chang-Chuan Chan blames the high benzene concentrations partly on the lack of strict government regulations on car and motorcycle emissions and partly on the fuel production process in Taiwan. "The typical gasoline currently used in Taiwan is two to five percent benzene, compared to one to two percent in the U.S.," Chan said. "Most of the gasoline used in Taiwan is produced by the China Petroleum Cooperative, a government monopoly, and only one of its two refineries uses BTX [benzene-toluene-xylene] extraction," he added. BTX is a process that removes these organics from the gasoline during the refining process.
Besides advocating improved public transportation and stricter emission controls, the article by Chan and colleagues recommends a large reduction of aromatic compounds in gasoline to improve the air quality of Taipei. Ironically, the city is currently experiencing even worse traffic jams than normal--and will for several more years--because of disruption caused by construction of a new multimillion-dollar subway system.
Andrea Hricko |
Last Update: August 28, 1998