TR-491: Data

TR-491 Methyl Eugenol

Methyleugenol is a natural constituent of a large number of essential oils including rose, basil, hyacinth, pimento, citronella, anise (400 ppm), nutmeg, mace, and cinnamon and laurel fruits and leaves. The chemical has also been identified in bananas, and black pepper.

Methyleugenol was given GRAS (generally recognized as safe) status in 1965 and is approved by the FDA for use in food (21CFR 121.1164). It is used as a flavoring agent in jellies (52 ppm), baked goods (13 ppm), nonalcoholic beverages (10 ppm), chewing gum, candy (11 ppm), pudding, relish and ice cream (4.8 ppm) . The council of Europe has listed the acceptable daily intake as 5 mg/kg/day. It is also used as a fragrance in perfumes 0.3%-0.8%, creams and lotions (0.01%-0.05%), and soaps and detergents (0.02%-0.2%). One of the major uses for methyleugenol is as an insect attractant. It was used in California in 1982, in combination with malathion, to control an outbreak of oriental fruit flies.

Toxicity and carcinogenicity studies were conducted in rats and mice by administering the chemical by gavage once daily, five days per week for up to 2 years. Additionally a stop exposure study was conducted in rats to determine whether the rodents can recover from the effects of the chemical. Toxicokinetic and metabolism studies in rats and mice as well as in vitro DNA adduct formation studies using rat and human liver slices were also conducted.

Serum from volunteers consuming ginger snaps will be analyzed to determine the bioavailability of this agent in people who consume foods containing methyleugenol. The information obtained from this study will be used for evaluating the health risk to humans from normal exposure to this chemical based on comparisons with blood levels in rodents from the NTP toxicology studies.

The NTP assembles a Pathology Working Group (PWG) to review every study and to resolve any differences between the study laboratory and quality assessment pathology evaluations. It should be noted that in determining final conclusions, the NTP assesses a broad array of information that takes into account all data obtained from the NTP evaluation of each agent and that of the historical controls plus relevant published literature. In addition, all study data are subject to an NTP retrospective audit and the interpretation may be modified based on these findings.

However, in its mandate to keep the public informed in a timely manner of current National Toxicology Program (NTP) study results, summary pathology tables are made available for distribution by mail and are also posted on this NTP website as the PWG reviews are completed. All of the study data for methyleugenol are currently under evaluation and a technical report is being prepared for presentation to the NTP Board of Scientific Counselors' Peer Review Subcommittee on October 30, 1998.

Pathology Tables - Rats

• P03 - Incidence Rates of Non-Neoplastic Lesions - 27 Week Interim Sacrifice

   

• P03 - Incidence Rates of Non-Neoplastic Lesions - 52 Week Interim Sacrifice

   

• P03 - Incidence Rates of Non-Neoplastic Lesions - Core Study + 300 Mg/Kg Stop Study

   

• P04 - Neoplasms by Individual Animal - 27 Week Interim Sacrifice

   

• P04 - Neoplasms by Individual Animal - 52 Week Interim Sacrifice

   

• P04 - Neoplasms by Individual Animal - Core Study + 300 Mg/Kg Stop Study

   

• P05 - Incidence Rates of Neoplasms by Anatomic Site (systemic lesions abridged) - 27 Week Interim Sacrifice

   

• P05 - Incidence Rates of Neoplasms by Anatomic Site (systemic lesions abridged) - 52 Week Interim Sacrifice

   

• P05 - Incidence Rates of Neoplasms by Anatomic Site (systemic lesions abridged) - Core Study + 300 Mg/Kg Stop Study

   

• P08 - Statistical Analysis of Primary Tumors - Core Study

   

• P08 - Statistical Analysis of Primary Tumors - Stop Study

   

• P09 - Non-Neoplastic Lesions by Individual Animal - 27 Week Interim Sacrifice

   

• P09 - Non-Neoplastic Lesions by Individual Animal - 52 Week Interim Sacrifice

   

• P09 - Non-Neoplastic Lesions by Individual Animal - Core Study + 300 Mg/Kg Stop Study

   

• P10 - Statistical Analysis of Non-Neoplastic Lesions - 27 Week Interim Sacrifice

   

• P10 - Statistical Analysis of Non-Neoplastic Lesions - 52 Week Interim Sacrifice

   

• P10 - Statistical Analysis of Non-Neoplastic Lesions - Core Study

   

• P10 - Statistical Analysis of Non-Neoplastic Lesions - Stop Study

   

• P11 - Statistical Analysis of Survival Data - Core Study

   

• P11 - Statistical Analysis of Survival Data - Stop Study

   

• P17 - Neoplasms by Individual Animal (systemic lesions abridged) - 27 Week Interim Sacrifice

   

• P17 - Neoplasms by Individual Animal (systemic lesions abridged) - 52 Week Interim Sacrifice

   

• P17 - Neoplasms by Individual Animal (systemic lesions abridged) - Core Study + 300 Mg/Kg Stop Study

   

• E41 - Mean Body Weights and Survival Table - Core Study + 300 Mg/Kg Stop Study

Pathology Tables - Mice

• P03 - Incidence Rates of Non-Neoplastic Lesions

   

• P04 - Neoplasms by Individual Animal

   

• P05 - Incidence Rates of Neoplasms by Anatomic Site (systemic lesions abridged)

   

• P08 - Statistical Analysis of Primary Tumors

   

• P09 - Non-Neoplastic Lesions by Individual Animal

   

• P10 - Statistical Analysis of Non-Neoplastic Lesions

   

• P11 - Statistical Analysis of Survival Data

   

• P17 - Neoplasms by Individual Animal (systemic lesions abridged)

   

• E41 - Mean Body Weights and Survival Table

Growth and Survival Curves - Rats

• E40 - Rat Growth Curves for Stop & Chronic Study

   

• P40 - Rat Survival Curves for Stop Study

   

• P40 - Rat Survival Curves for Chronic Study

   

Growth and Survival Curves - Mice

• E40 - Mice Growth Curves for Chronic Study

   

• P40 - Mice Survival Curves for Chronic Study