About concentration and bioactivity

In previous activities you have learned that some chemicals migrate into food and drinks from food contact materials. These are called “non intentionally added chemicals” This VIDEO will show you that these chemicals can have negative effects on human health. You will learn about the importance of concentration and how low quantities of unwanted chemicals can disturb our internal balance called homeostasis. Some chemicals are highly toxic and dangerous for living organisms. We call them poisons and they cause severe organ damage or death if ingested, breathed in, absorbed through the skin or injected into the body. Some poisons are very natural chemical substances, thus it is wrong to think “chemical means poison”.

Poisons are harmful at low doses, act very fast and upon one single exposure. For example, botulinum toxin, cobra venom toxin, tetrodoxin, methanol, arsenicum, etc… Poisons of natural origin are known and, obviously, they are strictly controlled and therefore absent in food and packaging. Long ago, the medieval physician Paracelsus said that no substance is completely safe for our body, and everything that is in excess can be poisonous. He did not have the knowledge and technology we have today, but his idea was quite right and today we have many examples to support that thesis. For example, glucose, essential for our life, if excessive can lead to obesity or diabetes. Even CO2 and water – very natural chemicals, can be harmful when in excess.

The concept of dose is related to the concept of CONCENTRATION, that is the quantity of substance per unit of volume. Or if you prefer, the density of molecules. In biological systems the concentration of the substance is more important than just its quantity. As we can see the same quantity of substance dispersed in different volumes lead to different (higher or lower) concentrations. Similarly, different quantities of substance dispersed in different volumes can give rise to the same concentration. In the illustration that you see here on the right, half of the quantity dispersed in two times less volume creates exactly the same concentration.

In our body the concentration of a substance is what really matters … Concentration is the combination of the dose with body weight. To activate some response and become bioactive a minimal concentration needs to be reached, this is called threshold. The dose of the substance required to achieve bioactive concentration is different for a mouse and an elephant, for the same reason that the dose of a medicine we take is different if we are children or adults. But we must remember that even positively working medicine consumed in excess may lead to serious conditions or even death. The concentration in our body depends on absorbed amount, body size, and how the organism retains or discards substances.

Every organism is a semi-open system and the content of exogenous substances is the result of the balance between intake, consumption and excretion. If the intake and excretion are balanced then the concentration maintains a constant level, as you see here. However, when the intake is higher than excretion, then the substance is accumulated inside the body and reaches higher concentration, as you see here. If the excretion is very low or absent, even a very low intake can cause accumulation of the substance within the body and the result is a concentration that exceeds the bioactivity limit, as you see in this case.

Bioactivity limit in not a property of the substance itself but mostly depends on the TOLERANCE, and this is specific for each organism.

Two examples : Cobra venom is terrible for us and many other animals, but NOT for the mongoose…So the mongoose has high tolerance. Not the venom, but the mongoose The muscarine and falloidine contained in some poisonous mushrooms can be FATAL to us, but snails can feed on them with no effects. So, the snail has high tolerance, not the venom. To indicate the concepts that we just showed you, in the field of toxicology we talk about Maximum Tolerated Dose, that is the highest dose of a substance that does not cause unacceptable negative effects … and the Threshold of Toxicological Concern, that means the level of exposure for all chemicals below which there would be no appreciable risk to human health.

You may remember from previous activities that FCM can release chemicals into food and drinks. Cans used for drinks have an inner coating made of other chemicals, some of which can migrate. The quantities of package-derived chemical are very low, but we are exposed to them almost constantly. The process of chemicals migration from FMC occurs when ..we store liquids, and in particular those with acidic pH .. or when we store food for a long time, such as preserved or canned food .. or when we heat food inside plastic containers. Heat is an accelerator of migration. All the chemicals that migrate into food or drink are not considered poisons and we don’t see any immediate negative effects.

However, epidemiology and laboratory sciences tell another story. Plastic containers, wraps or kitchenware contain low doses of unbound chemicals - plasticizers and additives - used in the manufacturing process. Chemi-joe tells us that some of them have similarities to natural hormones which regulate physiology and metabolism. For example, the famous BPA - bisphenol A - is slightly similar to estradiol, a sex hormones. BPA can interfere with the biological processes regulated by estradiol. Research-Ann tells us that estradiol is a steroid hormone that play a critical role in hypothalamus pituitary gonadal axis, the significant biochemical regulatory pathway responsible, for example, for the regulation of fertility and maturation in females. Since BPA can interfere with these hormones, it is considered an Endocrine Disrupting Chemical, or EDC.

We will talk about them later. In our body, the production, secretion and activity of hormones are strictly controlled. This is important to maintain our internal balance, that we call homeostasis. Hormones are secreted in regulated quantities and in response to specific signals. Their action is usually limited and directed to specific target cells. On the other hand, intake of endocrine disrupting chemicals is beyond any regulation. They can get into our body with consumed food, but they can be also inhaled with air or absorbed through the skin. Their absorption is not a response to specific condition or signal and it can last for a long time Their activity area is not limited, they can influence every single cell of the body.

Very often there is no mechanism for their degradation or excretion and they can accumulate inside organisms to relevant concentration. If the rain falls for a long time, many tiny drops can cause massive floods. Due to specificity of food industry and ubiquity of plastics, the exposure of endocrine disrupting chemicals is almost constant. Therefore, their concentration in our bodies can easily exceed Maximal Tolerated Dose, become bioactive and interfere with natural hormones. Please note that the bioactive limit of a hormone in our body is very low, so it is very easy to exceed this limit.

To summarize, the intake of very low doses of some chemicals for long times does not cause poisoning but can lead to subtle disturbances of the delicate endocrine system and negatively influence our health. We call these chemicals Endocrine Disrupting Chemicals, or EDCs. Here you see some of the negative effects of EDCs, contributing to obesity, type-2 diabetes, hypertension and metabolic problems … … or thyroid problems, sexual maturation problems, reduced male fertility, even prostate and breast cancer … …some even claim that EDCs are implicated in neurodevelopmental and cognitive disorders. You will know more on the documented effects of EDCs on our body in coming activities. Plastics create more problems than just environmental pollution.

In next week you will learn that we are exposed to many chemicals although at low doses. Plastics are ubiquitous and it is difficult to imagine to quickly eliminate them from our surroundings or rapidly find substitutes. So, considering that we cannot change our body, perhaps we should work on the exposure.