Preface

In former times, when toxicologists wanted to find out whether a hazardous substance was suitable to trigger a certain health damage they were forced to review so-called “toxicological profiles” to learn whether this health damage was listed there as typical effect of a toxicity with this hazardous substance.

For a long time it was unknown whether, and if so, how these listed health disorders or health damages that differed extremely with regard to their point of action in the organism were causally linked to each other.

The toxicologists were never sufficiently confident that a concrete health damage could definitely be ascribed to a certain exposure to a hazardous substance.

That changed with the discovery of the aryl hydrocarbon receptor by Poland (and others) in 1972 and the relevant findings that have been continuously increasing to date. Over the decades, the receptor toxicology has established itself as individual and independent human-toxicological area of expertise.

In plain language, the signalling pathway of the Ah receptor presents a knock-on effect that principally triggers the same reactions after a suitable hazardous substance, e.g., dioxin or the softening agent bisphenol-A has docked to the receptor.

One of these always identical reactions causes a certain gene sequence in the cell to be transcribed, which entails an increased production of a certain enzyme (CYP450). The more toxic a hazardous substance, the higher the activity of the CYP450 enzyme. This basic principle is applied in every examination of food or consumer goods suspected of being contaminated with dioxins.

On the basis of this principle, the same neurological and cardiovascular health impairments develop after a correspondingly strong activation of the Ah receptor. The same applies to changes of the immune and detoxification systems (glutathione-S-transferase) that can be diagnosed by laboratory tests, and to pathological organ changes, primary target organs: heart, liver, brain, and lungs.

Although each of these diagnoses is listed as typical damage effect in the internationally recognized toxicological profiles of these hazardous substance groups (polycyclic / aromatic halogen hydrocarbons), the causal relation between exposure and health damage has been questioned or denied by the interested parties.

The findings connected with the discovery of the aryl hydrocarbon receptor signalling pathway can put an end to this situation.

The causal relation between cause (hazardous substance) and effect (health damage) could doubtlessly be broken down to the last detail with the help of this basic principle ‘AhR signalling pathway’.

Hereinafter, we will try to describe the partly rather complicated AhR signalling pathway in a most general and comprehensive way, subdivided in stages.