Academic journal article Environmental Health Perspectives

Use of Biomonitoring Data to Evaluate Methyl Eugenol Exposure

Academic journal article Environmental Health Perspectives

Use of Biomonitoring Data to Evaluate Methyl Eugenol Exposure

Article excerpt

Methyl eugenol is a naturally occurring material found in a variety of food sources, including spices, oils, and nutritionally important foods such as bananas and oranges. Given its natural occurrence, a broad cross-section of the population is likely exposed. The availability of biomonitoring and toxicology data offers an opportunity to examine how biomonitoring data can be integrated into risk assessment. Methyl eugenol has been used as a biomarker of exposure. An analytical method to detect methyl eugenol in human blood samples is well characterized but not readily available. Human studies indicate that methyl eugenol is short-lived in the body, and despite the high potential for exposure through the diet and environment, human blood levels are relatively low. The toxicology studies in animals demonstrate that relatively high-bolus doses administered orally result in hepatic neoplasms. However, an understanding is lacking regarding how this effect relates to the exposures that result when food containing methyl eugenol is consumed. Overall, the level of methyl eugenol detected in biomonitoring studies indicates that human exposure is several orders of magnitude lower than the lowest dose used in the bioassay. Furthermore, there are no known health effects in humans that result from typical dietary exposure to methyl eugenol. Key words: biomonitoring, exposure assessment, methyl eugenol, risk assessment. Environ Health Perspect 114:1797-1801 (2006). doi:10.1289/ehp.9057 available via http://dx.doi.org/ [Online 12 June 2006]

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Methyl eugenol [1,2-dimethoxy-4-(2-propenyl)benzene (CAS no. 93-15-2), structure shown in Figure 1] is a member of a family of chemicals known as allyl alkoxybenzenes, which include other naturally occurring materials such as isoeugenol, eugenol, estragole, and safrole. All these compounds typically enter the diet via a variety of different food sources, including spices (nutmeg, allspice), herbs (basil, tarragon), bananas (Jordan et al. 2001), and oranges (MacGregor et al. 1974). Many of these compounds are also found as components of natural oils used in perfumes (Smith et al. 2002). In addition there are other potential sources of exposure to methyl eugenol, including agriculture (Vargas et al. 2000), consumption of wine (De Simon et al. 2003), and as part of the ambient background in air and water (Barr et al. 2000).

Given the broad potential for exposure resulting from both dietary and consumer product use and its structural similarity to other carcinogenic allyl alkoxybenzenes, methyl eugenol was nominated for study by the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences. The NTP evaluated methyl eugenol in a rodent bioassay using oral gavage as the route of administration (NTP 2000). Based on the results of the bioassay, the NTP concluded that there was clear evidence of carcinogenicity in F344 rats and B6C3[F.sub.1] mice. This conclusion was based on increases in male and female rats of hepatocellular carcinoma and hepatocholangiocarcinoma, neuroendocrine tumors of the glandular stomach, and the observation of other tumor types in several other tissues, and the primary tumors observed in B6C3[F.sub.1] mice were hepatocellular carcinoma in male and female mice and increased neuroendocrine tumors of the glandular stomach in male mice. Although toxicologic end points have been established in animals, searches of the literature have identified no clinical studies or epidemiology data to provide perspective on whether there are health effects associated with long-term consumption of methyl eugenol by humans.

To provide human exposure data in support of NTP's assessment of methyl eugenol, the Centers for Disease Control and Prevention (CDC) measured methyl eugenol in a non-representative subset of adult serum samples collected as a part of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) (CDC 2004). …

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