California’s decision to set a safe maximum limit of 29mcg on a compound found in caramel color, 4-methylimidazole (4-MEI or 4-MI), was largely based on a study in mice carried out by the NTP, which found that the compound was carcinogenic at high doses – although another study in rats did not find this link.
NTP associate director Dr. John Bucher told FoodNavigator-USA that the program’s studies usually form part of a larger database of information.
“This is really the first stage of the risk assessment process,” he said. “Unfortunately there’s lots and lots of chemicals that fall into this bracket…and the regulatory agencies need to make a decision.”
He said that in order to more accurately assess a chemical’s safety, among other factors, it would be necessary to have information about how it is metabolized in humans.
“We don’t generally work in human metabolism,” he said.
4-MEI forms in some caramel color production processes and is found in colas, coffee and some beers, as well as baked goods, breads and molasses. Its safety in caramel coloring used for colas in particular has stirred up controversy after California included the compound on its list of potential human carcinogens, with warning labels required at much lower levels than those found in common colas on the market.
New approach
Bucher said that “often in absence of information”, safety data may be oversimplified – but he is hopeful that a new kind of testing will emerge to allow for more certainty about chemicals that may pose human health risks.
“We are working on developing a new approach – a high throughput screening process that uses automated robotics,” he said.
“It allows you to test thousands of chemicals across chemical space, if you will…So you would be able to compare how a chemical works in animal cells and in human cells and then take suspect chemicals into animal studies. That’s the future. Unfortunately at the moment we are working the other way around.”
Assuming a linear relationship
The Center for Science in the Public Interest (CSPI) has called on the FDA for a complete ban of caramel colors that contain the chemical at levels that exceed the Californian threshold.
According to the information from the NTP’s mouse study, about a third of the mice developed tumors at very high dosage levels of 4-MEI. When CSPI extrapolated this in a linear manner to account for likely maximum intake of the chemical in human diets, it said the suggested 4-MEI could be responsible for seven cancers in every million Americans.
“Toxicologists assume a linear relationship (unless there is reason to think otherwise) between dose and effect,” CSPI executive director Michael Jacobson said.
However, the Food and Drug Administration (FDA) has refuted claims that the amounts of caramel color in colas carry a cancer risk, and the European Food Safety Authority (EFSA), after conducting its own safety review, concluded that 4-MEI is not of concern.
Avoidable addition
CSPI is standing by its position that 4-MEI in caramel colorings should be banned, on the basis that coloring is an avoidable addition to products – and non-4-MEI and low-4-MEI alternatives are available, although they may be more expensive or present functional challenges for manufacturers.
“Governments should insist that only 4-MI-free caramel colorings be permitted,” Jacobson said.
Thresholds of response
Bucher added that high throughput screening may also help to develop more reliable ways to extrapolate dosage risk from animal data to humans.
“We use 15 dose response curves, so you can see if there are thresholds of response much more easily,” he said.
4-MEI is not the only chemical formed during high temperature cooking that has been linked to cancer in animals. Researchers and manufacturers have developed a variety of options for reducing levels of acrylamide, for example, in foods such as baked goods and French fries.
“This is probably prudent,” Bucher said.
Meanwhile, despite controversy over 4-MEI, the CSPI has said that the sugar content of cola beverages “presents a greater health risk than the ammonia sulfite process caramel”.