ME and My Shadow: Everyone Exposed to Methyleugenol.

Everyone Exposed to Methyleugenol Whether you intend to or not, chances are you will consume approximately 6 micro-grams of methyleugenol (ME) today, according to a report in this month's issue by Dana B. Barr and colleagues of a study designed to measure ME in human blood _ serum [EHP 108:323-328]. ME is a compound that occurs naturally in a variety of spices and herbs, including clove oil, nutmeg, allspice, and walnuts. In both its natural and synthetic forms, it is an FDA-approved additive , and it is widely used as a flavoring agent in desserts, condiments, and cigarettes , as an attractant in insecticides, and as a fragrance in perfumes and soaps. Because of its structural similarity to other flavorants that are known to be carcinogenic such as safrole and estragole, ME has come under suspicion of carcino-genicity. Recent research, some of which was conducted by the National Toxicology Program at the NIEHS, has shown clearly that ME causes cancer in laboratory rodents and suggests that it may be a human carcinogen as well. To accurately evaluate the level of risk associated with a compound, both toxicologic and human exposure data are required. The investigators-collaborating teams from the ational Center for Environmental Health at the Centers for Disease Control FIavor fears. New information reveals widespread exposure to methyleugenol, a flavoring agent that may well be carcinogenic to humans. and Prevention and from the NIEHS-used extremely sophisticated tools and carefully planned methodologies to arrive at the conclusion that low-level exposure to ME is virtually ubiquitous in the U.S. adult 4 population. They analyzed serum sam-fl ples from 206 adults who had participated in the Third National Health* and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994. With the U sensitivity and accuracy afforded by isotope dilution gas chromatography high resolution mass spectrometry, they detected ME in 98% of the samples. They then used pertinent questionnaire data from NHANES III to analyze the laboratory results for statistical significance among a wide variety of variables. Unfortunately, none of those demographic and lifestyle variables were statistically significant markers of ME exposure. The fact that there were no clear "smoking guns" correlating to ME exposure led the authors to conclude that it comes from a variety of sources, including air, water, and foods containing naturally occurring ME. They also believe these findings are a good indicator of the prevalence and expected serum concentrations …

rettes, as an attractant in insecticides, and as a fragrance in perfumes and soaps. Because of its structural similarity to other flavorants that are known to be carcinogenic such as safrole and estragole, ME has come under suspicion of carcinogenicity. Recent research, some of which was conducted by the National Toxicology Program at the NIEHS, has shown clearly that ME causes cancer in laboratory rodents and suggests that it may be a human carcinogen as well. To accurately evaluate the level of risk associated with a compound, both toxicologic and human exposure data are required.
The investigators-collaborating teams from the ational Center for Environmental Health at the Centers for Disease Control FIavor fears. New information reveals widespread exposure to methyleugenol, a flavoring agent that may well be carcinogenic to humans. and Prevention and from the NIEHSused extremely sophisticated tools and carefully planned methodologies to arrive at the conclusion that low-level exposure to ME is virtually ubiquitous in the U.S. adult 4 population. They analyzed serum sam-fl ples from 206 adults who had participated in the Third National Health* and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994. With the U sensitivity and accuracy afforded by isotope dilution gas chromatography-high resolution mass spectrometry, they detected ME in 98% of the samples. They then used pertinent questionnaire data from NHANES III to analyze the laboratory results for statistical significance among a wide variety of variables. Unfortunately, none of those demographic and lifestyle variables were statistically significant markers of ME exposure. The fact that there were no clear "smoking guns" correlating to ME exposure led the authors to conclude that it comes from a variety of sources, including air, water, and foods containing naturally occurring ME. They also believe these findings are a good indicator of the prevalence and expected serum concentrations that are likely to be encountered in the U.S. population. So, like it or not, most adults in America are probably exposed to this suspected carcinogen every day and probably have no way of avoiding the compound altogether. Barr and colleagues also point out that children are likely to have higher concentrations of ME, given their smaller size and the nature of some of the identified commercial sources of ME, such as candy, ice cream, chewing gum, and other sweets.
,Therefore, they say, ME exposure and risk assessment in children is a rucial area in which to focus future studies.
The authors are cautious to draw no further conclusions beyond what their data warrant-that the appropriate information is now in place to allow more comprehensive assessment of the risk associated with human exposure to ME. However, it seems clear that the end result of that assessment could be the eventual elimination of ME from the commercial marketplace. That would at least remove the possibility of ME exposure from avoidable sources, substantially reducing the overall prevalence of the compound in the population and the level of risk it poses to human health. -Ernie Hood

Smoking-induced Leukemia
How Much Is Benzene to Blame?
Benzene, known to cause leukemia, is present in cigarette smoke. However, although smokers are one-and-a-half to two times more likely to develop leukemia than nonsmokers, the degree to which the risk of leukemia can be attributed to the low doses of benzene in cigarette smoke is uncertain. Also uncertain is the validity of linear models of dose-response with respect to benzene and leukemia, particularly at doses lower than those encountered in the workplace (and studied) in the past. Some scientists have been concerned that linear models-which link an increase in benzene exposure to a corresponding increase in disease-may overestimate the risk of leukemia.
In this month's issue, Jeffrey E. Korte and colleagues from the University of North Carolina at Chapel Hill compared published eidemiological data to their own risk assessment predictions to determine the proportion of all types of leukemia and acute myeloid leukemia (AML) attributable to benzene in cigarette smoke . They used linear models and one quadratic model to formulate their predictions, which allowed them to test linear models' ability to accurately predict occupational and nonoccupational risk from benzene exposure. This may be important to the future of setting exposure limits in facilities where benzene is used.
The researchers determined the proportion of smokinginduced leukemia deaths caused by benzene by following a fivestep process in which they calculated the lifetime leukemia risk from smoking, determined the potency of benzene in causing leukemia, estimated the benzene dose from smoking, characterized the low-dose risk of leukemia from benzene, and compared the predicted lifetime risk of leukemia from benzene in cigarettes with the observed risk due to smoking. The applied their calculations to light (20 cigarettes daily) and heavy (40 or more cigarettes daily) smokers, with comparisons to those who never smoked.