As the American whiskey market grows—particularly the single-malt style—more distillers are beginning to recognize a concern that’s been flying under the regulatory radar in the United States: glycosidic nitrile, a carcinogen precursor.
Often referred to as GN, glycosidic nitrile is a compound produced in certain varieties of malting barley. It’s commonly found in domestic varieties, but it’s regulated in Canada and Europe and rarely found in newer varieties there. (Beloved historic varieties such as Maris Otter are, unfortunately, GN producers.)
Because the brewing industry dominates the domestic supply of malting barley, GN hasn’t had the attention of U.S. growers and breeders until fairly recently. (Brewing with malt that contains GN results in a beer that contains negligible levels in the final product, but distillation can concentrate GN and help to catalyze it into more dangerous substances.) In consumables such as whiskey, the European Union caps the amount of ethyl carbamate—the carcinogenic compound that results from GN—at 150 parts per billion. In the United States, the federally recommended limit is 125 parts per billion, but it’s not enforced. However, GN and ethyl carbamate may eventually land on the government’s radar as a higher priority, and the regulations in Britain, Canada, and Europe can create issues for distillers who export.
The Risks of Glycosidic Nitrile
The growth in American whiskey production has added urgency to the GN issue for distillers, and it’s not only an issue for single-malts.
Bourbon producers also have reported the occurrence of GN in whiskeys that include up to 10 percent malted barley, according to Harmonie Bettenhausen, director of the Center for Craft Food and Beverage at Hartwick College in Oneonta, New York. While GN doesn’t occur in rye, she says, there is a lack of data on other types of grain.
The International Agency for Research on Cancer lists ethyl carbamate as a Group 2B substance, “possibly carcinogenic to humans.” Bettenhausen says this category includes “lots of things you find in plants,” such as acetaldehyde. The U.S. Environmental Protection Agency lists potential health hazards in humans with acute exposure, including liver and kidney damage; but no health hazards for humans are listed for chronic exposure. Animal testing has indicated dangers of tumors, fetal abnormalities, and issues with the nervous system.
As part of an ongoing effort to raise awareness of the issue, Bettenhausen recently delivered a presentation on GN to the American Malting Barley Association. She explains that GN is technically not just one compound but a group of them. However, in the barley and malting realms, people often use the term as shorthand for epiheterodendrin (EPH), the primary type of GN that occurs in barley.
These compounds are cyanogenic glycosides that can be catalyzed into the carcinogen ethyl carbamate (EC), also known as urethane. In the barley plant, EPH works as a natural pesticide. The EPH reacts with the betaglucosidase enzyme that’s stored separately in the plant, combining when the stalk or leaves get chewed on by a predator—or when the malting process activates betaglucosidase and other glucanases—thus allowing the cyanide compound to be produced.
How It Ends Up in Spirits
There are various pathways to producing glycosides such as GN in beverages. Low levels can be found in most or all fermented beverages and spirits, but they’re often higher in brandies made from stone fruits because of the presence of another cyanogenic glycoside, amygdalin, in the pits of the fruits.
In malting barley, GN is found in the acrospire of the germinating seed. Its presence partly depends on variety, with different malting barleys categorized as nonproducers (less than 0.5 grams per metric ton), low producers (0.5 to 1.5 grams), or high producers (more than 1.5 grams).
Environmental conditions during the barley plant’s growth and the malting process can increase or decrease the amount of GN found in malt. Then, distillery practices can impact how much of it catalyzes into EC and how much of that ends up in the final product. Ultimately, Bettenhausen says, there are too many environmental and malthouse variables for distillers to rely on low-GN varieties.
Because GN is a component of the acrospire, higher proportions of it are correlated to smaller grains of barley because the acrospire constitutes a larger percentage of the whole compared to larger, plumper kernels. Malthouse decisions that optimize grain for full modification and high-enzyme packages—the exact profile that distillers typically want—also increase the level of GN in the malt. These factors include longer germination time, more moisture, and overall higher levels of metabolic processes. Pushing the upper limits of germination and enzyme production means pushing up the production of GN.
Even after malting, EC can still catalyze in the mash; in fermentation, as yeast introduce new betaglucosidase through arginine; and during distillation.
The volatility of different compounds can be a factor in whether EC winds up in the final product. When exposed to heat, GN forms isobutyraldehyde cyanohydrin and then hydrogen cyanide. When exposed to copper and ethanol, the hydrogen cyanide then will produce EC. The distiller can take advantage of the fact that EC is less volatile than water, so any amount that is catalyzed before distillation or in the pot will be left behind. However, hydrogen cyanide is more volatile than ethanol, so unreacted hydrogen cyanide can carry over as vapor and be condensed, winding up in the final spirit.
Distillers can leverage this by bringing wash or spirit into contact with copper early in distillation, allowing the progressively more toxic intermediary compounds leading to ethyl carbamate to react and drop out with the stillage. Ensuring that any copper surfaces in the pot are clean will help to maximize the amount of EC that can be catalyzed, reducing the amount of hydrogen cyanide that’s allowed to escape into the spirit.
Toward Zero-GN
The mutation that led to the first zero-GN—or GN0—cultivar was an accident of breeding that likely occurred in the 1960s in combination with a targeted, desired change in barley. However, researchers didn’t recognize it until the 1980s, and GN0 became a topic of research in Europe in the late 1980s and early 1990s.
For now, there aren’t many GN0 options for distillers. Full Pint barley, a public cultivar released by Oregon State University (OSU) in 2014, was the first known zero-GN variety developed in the United States. Odyssey and Genie are the most-used GN0 varieties currently on AMBA’s recommended varieties list (although the data show Genie is technically an ultra-low GN producer, Bettenhausen says).
Because the genetic package that causes barley’s GN production is large, it’s not a candidate for deletion or transformation through modern gene-editing technology, such as CRISPR. For now, the only way forward is through breeding.
Thus, breeding efforts and AMBA breeding recommendations have pivoted toward GN0 varieties. Rahr Malting recently released a new zero-GN malt, while OSU announced seed availability for two new publicly available GN0 genotypes: the winter varieties Top Shelf and DH170472—the latter preliminarily named Vivar, after longtime grain researcher Hugo Vivar.
While many public breeders are on their way to creating GN0 varieties, and they will hit the market in years to come, it will not be a rapid pivot. The developmental pipeline for new barley varietals—from initial breeding to selection, field trials, and eventually convincing farmers to gamble on a new, unknown variety—is a decade-long process, even when successful.
Alongside the health and regulatory factors, this lends further urgency to the developmental and educational efforts around GN.
Says Bettenhausen: “The time has sort of passed for us to bury our heads in the sand.”