The Half Decent Pharmaceutical Chemistry Blog

We’re having a bit of a problem with the heating system in the lab. On Monday, the technical office of the university kindly listened to our complains and decided we were freezing sufficiently to turn the heat on in the whole department. Predictably, though, there’s now a sort of tropical climate in the rooms because the heating works very simply: if it’s off, no matter how cold it’s, you’ll carry out your assays wearing your raincoat; when it’s on, it’s simply on, you can’t set a temperature, so the building turns into a fireball.

This seems to be particularly disappointing when you set up a western blotting and, right at the beginning, you prepare your SDS-page. Plainly, yesterday it was so hot that the resolving (a.k.a. running) gel wouldn’t polymerize. First, however, my supervisor told me to make a new acrylamide/bisacrylamide solution, because the one we were using was pretty old and it could be an issue. As it turned out, that wasn’t the problem, because, again, it didn’t polymerized, until we opened the windows in the room (with the heating on…what a great way of saving money and the planet!) and let cold air in to cool down the environment.

While weighing the acrylamide, however, I was warned to be extra-careful. That’s because the monomer, not the acrylate polymer, is a vicious neurotoxin. Acrylamide causes axonopathy, a type of CNS toxicity in which either axon and myelin degenerate, whereas the soma is undamaged and still metabolically active: in fact, it begins to synthesise myofibrils as a response to the injury. Histologically, this gives a bulb onion-shape to the neuron, as myofibrils tend to accumulate upstream the first, damaged site.

Characteristically, the first symptom of an acrylamide axonopathy is the loss of mechanical and thermal sensitivity, at first limited to fingers, but then progressively affecting arms and legs. This is all very worrying, but you may think it’s something that has to do only with chemists and biologists, or some kind of workers (poly-acrylamide is utilized in a pretty wide range of industries, from petroleum industry to water purification). Thing is, acrylamide can be found in carbohydrates-rich foods, cooked at high temperature, such as potatoes and, obviously, pasta.

So, to sum up, most of what you eat contains a substance which has been proved to be a neurotoxin to human beings, a genotoxic carcinogen to rats. The question is: how much of this killing substance do we eat on a daily basis?

Fortunately, not much and, in particular, much less than the so-called NOEL (non-observed effect level), which means children, given the poor activity of their detoxifying enzymes and, if you think about it, the high quantity of backed carbohydrates present in their diet, are immune to the dramatic effects of an exposure to acrylamide. This is a case of ALARA (as low as reasonably achievable): we can’t get rid of acrylamide, but we can determine statistically a level of total safety (which is called, anyhow, virtual safety dose). In this case, the NOEL are (because one is for axonopathy and one for genotoxicity) 0.5 mg/kg and 2 mg/kg. The daily intake for a baby is estimated to be 0.3 – 0.8 μg/kg.
To sum up, we can go on eating our beloved spaghetti and French-fries.
Still, there are a few concerns about the long-term consequences of an exposure to low levels of acrylamide, regarding carcinogenesis. What’s more, although it’s been proposed for acrylamide the same mechanism demonstrated for hexane, which reacts with ammines (yielding pyrroles) and cytoskeleton proteins and yields derivatives (such as 2,5 – hexandione), the exact molecular action of acrylamide is yet to be determined.