title: Evaluation of the butter flavoring chemical diacetyl and a fluorochemical paper additive for mutagenicity and toxicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells.
abstract: Diacetyl (2,3-butanedione) is a yellowish liquid that is usually mixed with other ingredients to produce butter flavor or other flavors in a variety of food products. Inhalation of butter flavoring vapors was first associated with clinical bronchiolitis obliterans among workers in microwave popcorn production. Recent findings have shown irreversible obstructive lung disease among workers not only in the microwave popcorn industry, but also in flavoring manufacture, and in chemical synthesis of diacetyl, a predominant chemical for butter flavoring. It has been reported that perfluorochemicals utilized in food packaging are migrating into foods and may be sources of oral exposure. Relatively small quantities of perfluorochemicals are used in the manufacturing of paper or paperboard that is in direct contact with food to repel oil or grease and water. Because of recent concerns about perfluorochemicals such as those found on microwave popcorn bags (e.g. Lodyne P208E) and diacetyl in foods, we evaluated both compounds for mutagenicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells. Lodyne P208E was less toxic than diacetyl and did not induce a mutagenic response. Diacetyl induced a highly mutagenic response in the L5178Y mouse lymphoma mutation assay in the presence of human liver S9 for activation. The increase in the frequency of small colonies in the assay with diacetyl indicates that diacetyl causes damage to multiple loci on chromosome 11 in addition to functional loss of the thymidine kinase locus.
authors.affiliation: Center for Food Safety and Applied Nutrition, Food and Drug Administration, 5100 Paint Branch Parkway, HFS-717, College Park, MD 20740-3835, United States. paul.whittaker@fda.hhs.gov
authors.forename: Paul
authors.initials: P
authors.lastname: Whittaker
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Clarke
authors.forename: Richard H C
authors.initials: RH
authors.lastname: San
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Begley
authors.forename: Virginia C
authors.initials: VC
authors.lastname: Dunkel
mesh_terms: D000782:Aneuploidy; D000818:Animals; D002079:Butter; D045744:Cell Line, Tumor; D005617:Chlorofluorocarbons, Methane / Q000633:toxicity*; D002872:Chromosome Deletion; D003114:Colony-Forming Units Assay; D003931:Diacetyl / Q000633:toxicity*; D005421:Flavoring Agents / Q000633:toxicity*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000633:toxicity*; D007940:Leukemia L5178; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens; D010209:Paper; D017354:Point Mutation / Q000187:drug effects; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: D005617:Chlorofluorocarbons, Methane; D005421:Flavoring Agents; D006845:Hydrocarbons, Fluorinated; C531289:Lodyne P208E; D009153:Mutagens; D002079:Butter; D003931:Diacetyl