“Wining” about corked Tylenol

Lot number BCM155 of the 50-caplet product is affected by the October 18th recall.

Things have not been going very well for Johnson & Johnson's McNeil Consumer Healthcare division with regard to their now-closed Fort Washington, PA, manufacturing facility. Last week, they issued another recall for 8-Hour Tylenol products due to a musty smell caused by trace quantities of 2,4,6-tribromoanisole (TBA). I wrote about J&J's issues at this blog's old home back in May when some of our comments were included in a ABC News report by Dan Childs after a recall of 43 different products due to problems with potency, microbial contamination, and particulate matter in liquid dosage formulations. This past week's story was covered extensively around the popular press but I was particularly taken by the article on TIME magazine's Healthland site written last Wednesday by Meredith Melnick, a former fellow at Columbia University's Digital Media program. In general, I've been really impressed with the quality of science writing at Healthland all around, a blog I've been following since an online writer friend, Maia Szalavitz, joined them. Beyond the high quality of her writing, Melnick won points from me in discussing the chemistry of the TBA contamination. The compound is believed to emanate from the wooden pallets upon which the products are stored and shipped. A commonly used wood preservative, 2,4,6-tribromophenol, can be O-methylated to TBA by microorganisms such as the filamentous fungi, Paecilomyces variotii, as detailed in this 1997 paper in the Journal of Food and Agricultural Chemistry.

Cross-section of Quercus suber. Source: Wikimedia Commons

Within her article, Melnick made drew from another field that I had forgotten since my wine writing days. She linked to another Journal of Food and Agricultural Chemistry paper by Chatonnet et al., detailing that TBA is also the compound associated with the musty or "corked" smell of wines that had gone off. Among trained wine tasters, TBA has a sensory limit of detection in wine on the remarkable order of 4 ng/L. The compound does not appear to have any health risks at these concentrations but Dan Miller's CellarNotes states that the musty smell is responsible for the contamination of 3% to 7% of wines, on average. Corks made from the bark of the aptly-named Cork Oak, Quercus suber, are most often associated with the unpleasant aroma of corked wines (hence the term). But just last month the same research group at the EXCELL Laboratorie in Merignac, France had another paper in the Journal revealing that oak barrels used to age wine could be a source of another halogenated anisole, 2,4,6-trichloroanisole (TCA).  These other oaks (the European oaks, Quercus robur Linn. and Q. petrae Liebl., and the American oaks, e.g., Q. alba and macrocarpa L.) have been extensively used in wineries around the world for aging. Chatonnet's group now describes how the oak used for the construction of aging barrels serves as the source of chlorinated anisoles:
Thus, in some cases, contamination of oak wood by 2,3,4,6-tetrachloroanisole (TeCA) and pentachloroanisole (PCA) has been traced back to preventive treatment applied to unbarked logs, or indirect contamination of staves split in industrial premises where pentachlorophenol (PCP) had been used to treat other types of wood (14). Chlorophenols are commonly biomethylated into the corresponding chloroanisoles via the intermediary of an O-phenylmethylase (15). Many microorganisms, particularly molds that develop easily under the conditions in damp, poorly ventilated aging cellars, are capable of this type of reaction.
Indeed, the move to extruded polyethylene wine corks has not completely solved the problem since those stored in high-TBA or TCA environments can still absorb the nasty compounds. This 2003 article from Wine Business Monthly details the problem of TCA in the winery and steps that can be taken to avoid the halogenated anisoles. Interestingly, the winery discussed therein mentioned Pascale Chatonnet as a consultant who was sought regarding the issue. But back to the TBA contamination of the Tylenol bottles. As acetaminophen is not aged in oak where might the TBA be in the recalled products? Insight comes from this passage on wine contamination from Chatonnet in 2004:
Polyethylene- or polyester-based winemaking equipment, vulcanized rubber gaskets, and the silicone bungs used in barrels readily fix pollutants from the air and release them into wine over time. Analysis of the materials in contact with the atmosphere in this winery showed that the wooden roof timbers had been massively impregnated with TBP, which had gradually broken down into TBA due to the action of microflora in the atmosphere. Some of the paints assayed in the same winery also contain TBP as flame retardant or/and fungicide.
Everyone knows that alcohol and acetaminophen don't mix. Here's another problem that links them both. And before anyone thinks that the halogenated phenols and anisoles are simply anthropogenic products, marine algae have been shown to make their own bromophenol by fixing oceanic bromide via the action of peroxidases.

Author: David Kroll

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  1. Are either of these the same chemicals found in the tainted, musty smelling Lipitor? (IIRC, Ed Silverman at Pharmalot reported the Lipitor story recently.) It seems odd that this issue has arisen at two different manufacturers at two different plants this year.

  2. k, you are absolutely correct – if I had prizes I give one to you!

    The cause of the Lipitor recalled earlier this month was also 2,4,6-tribromoanisole. Ed cited this FDA enforcement report – scroll down about a thrid of the way or just do a cntrl-F to look for Lipitor. This recall was for five lots and a total of 4.6 million bottles.