In the past several years, pharmaceutical companies have recalled some of their products due to the presence of a musty, moldy,
earthy odor (1–5). When a consumer opens a product container and smells an unusual odor, it indicates that the product has
been compromised. Subsequent analysis of the recalled products determined that 2,4,6-tribromanisole (TBA) caused the odor.
TBA has been found to cause odor problems in the past. Whitfield and coworkers identified TBA as a possible source for a musty
odor in sultanas that were packaged in polyethylene bags (6). They demonstrated that when these food packages were stored
in the presence of TBA-contaminated fiberboard, the food could acquire the off odor or off flavor after only one week.
Chatonnet and colleagues also identified TBA as the compound responsible for a musty off odor in wine (7). The compound was
present in wines that had a musty character during tasting. The wine acquired this flavor from being stored in an atmosphere
contaminated with TBA.
TBA belongs to a group of organic compounds called haloanisoles, which are extremely powerful and can add musty, moldy, or
earthy odors to many materials, such as food, beverages, and packaging. Haloanisole compounds contain at least one halogen
atom (i.e., fluorine, chlorine, bromine, or iodine) as part of their chemical composition.
Other haloanisole compounds, such as 2,4,6-trichloroanisole (TCA), 2,3,4,6-tetrachloroanisole, and pentachloroanisole have
similar odor characteristics and have been associated with cork taint in wine (8). They are extremely aromatic and have low
odor-threshold concentrations i.e., (the minimum amount necessary for the compound to be smelled by the majority of people).
The minimum concentration necessary to produce the characteristic off odor of TBA and TCA is approximately 30 parts per quadrillion
(9). These haloanisole compounds are a byproduct of microbial metabolism in products that have been treated with halophenols.
The biomethylation process is performed by various types of filamentous fungi primarily as a biochemical self-defense mechanism.
Figure 1 shows the chemical reaction during which the hydrogen of the hydroxyl group is replaced with a methyl group. The
fungi convert the usually toxic halophenol compounds into less toxic haloanisole compounds.
Figure 1: Biomethylation reaction where 2,4,6-tribromophenol is converted to 2,4,6-tribromoanisole. (ALL FIGURES ARE COURTESY
OF THE AUTHORS)
Haloanisoles can be present in many manufacturing and shipping areas. Trichlorophenol can be formed when chlorine reacts with
the natural phenolic compounds found in wood and water. Cleaning or sanitizing materials are a possible source of chlorine.
Tribromophenol (TBP) can be used as a flame retardant in brominated plastics, papers, and textiles. The compound also is used
as a fungicide, a wood preservative, and an antiseptic agent.
TBP is also a synthetic intermediate used for producing many types of brominated flame retardants (10). In some parts of the
world, TBP continues to be used as a fungicide and wood preservative. The compound is not a registered pesticide with the
Environmental Protection Agency, and its use as a fungicide has been banned in the United States, Canada, and Europe (11).
For contamination to occur, TBP and the filamentatous fungi must be present. As the fungi consume the TBP, the local concentration
of TBA increases as a function of time. Only after the odor-threshold concentration for TBA is exceeded does the characteristic
odor of TBA become apparent.