Toxicology Paracelsus

Borzelleca IF. Profiles in toxicology—Paracelsus Herald of modern toxicology. Toxicol Sci 2000 53 2-4. 

We have already seen in earlier chapters that even essential metal ions can be toxic — as the historical father of toxicology, Paracelsus (1493—1541), wrote... 

That a laboratory animal may qualitatively and quantitatively be extrapolated to man is a basic premise of toxicology (Paracelsus, 1493-1541). Paracelsus stated that, "All things are poisons, for there is nothing without poisonous properties it is only the dose which makes a thing poison" ( ). Inherent in this interpretation is the concept that quantitatively there will be an exposure level below which no discernable adverse effects occur. In addition, logical extrapolation of the premise of Paracelsus includes the concept that responses due to chemicals will be qualitatively similar in animals and man. 

Today, the concern is less about the lethal quantity of these relatively benign substances, but rather about pollutants in our food, water, and air. Yet despite our lack of sophistication, my young friends and I weren t actually so far off the mark. We didn t realize it at the time, but we were channeling a sixteenth-century physician, Paracelsus. Considered the father of toxicology, Paracelsus is credited with the first and most important tenet of the field, the idea that the dose makes the poison All things are poison and nothing is without... 

Natural and synthetic chemicals affect every phase of our daily Hves ia both good and noxious manners. The noxious effects of certain substances have been appreciated siace the time of the ancient Greeks. However, it was not until the sixteenth century that certain principles of toxicology became formulated as a result of the thoughts of Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus (1493—1541). Among a variety of other achievements, he embodied the basis for contemporary appreciation of dose—response relationships ia his often paraphrased dictum "Only the dose makes a poison."... 

The basic principle of toxicology, as first noted by the Swiss physician Paracelsus, is that the dose makes the poison. While this principle is easy to understand, the processes used to understand the relationships between dose and biological response, and ultimately to determine what dose of a chemical poses a reasonable certainty of no harm , are much more complicated. 

Toxicology is the study of the noxious effects of chemical and physical agents. The most fundamental concept in toxicology states that there is a relationship between the dose of an agent and the response that is produced in a biological system. The concept was first formalized by Paracelsus (1493-1541 A.D.). 

The dose-response relationship, which reflects the fact that toxicity is a relative phenomenon, was recognized by Paracelsus and is central to toxicology. 

There appear to have been few advances in either medicine or toxicology between the time of Galen (ad 131-200) and Paracelsus (1493-1541). It was the latter who, despite frequent confusion between fact and mysticism, laid the groundwork for the later development of modem toxicology by recognizing the importance of the dose-response relationship. His famous statement— All substances are poisons there is none that is not a poison. The right dose differentiates a poison and a remedy —succinctly summarizes that concept. His belief in the value of experimentation was also a break with earlier tradition. 

Environmental toxicology is based on the premise that the amount of chemical reaching an active site in, or on the surface of, an organism determines whether a compound will exert a specific beneficial or adverse effect or pose an ecological or health risk. This basic toxicological principle is embodied in the expression attributed to Paracelsus that it is "the dose that makes the poison."... 

Much later, Paracelsus, the father of modem toxicology (1493-1541), pronounced a dictum of his own Sola dosis facit veneum, meaning only the dose makes the poison. There is a glorified commonness to these ancient thinkers, neither knowing the other and from different periods of time. 

Paracelsus prescribed chemically defined substances with such success that enemies within the profession had him prosecuted as a poisoner. This was primarily based upon his use of inorganic substances in medicine, because his critics claimed that they were too toxic to be used as therapeutic agents. He defended himself with the thesis that has become axiomatic in pharmacology/toxicology If you want to explain any poison properly, what then isn t a poison All things are poisons, nothing is without poison the dose alone causes a thing not to be poison. ... 

W. C. Krieger, Forword on Paracelsus-Dose Response, in Handbook of Pesticide Toxicology 2nd edn., ed. R. Krieger, Academic Press, San Diego, CA, 2001, Vol. 1-2, p. xxvii. 

The principle of Paracelsus that the dose makes the poison is paramount. It means that all chemicals, from whatever source, human manufacture or natural, are potentially toxic at some dose. This is a fundamental concept which underlies toxicology and is crucial to the assessment of risk from chemicals and their safe use. The coroUary to this principle is that aU chemicals are potentially safe at some, perhaps extremely low, dose and therefore most can be used safely. The relationship between the dose and toxic effects of chemicals wiU be discussed later (see pp. 36-9, 298-301). 

The fundamental principle of toxicology is the concept that the sixteenth century physician Paracelsus articulated in the 1500s sola dosis facit venenum or the dose makes the poison . The modem version of this observation is the dose-response relationship, which is experimentally and theoretically supported through pharmacokinetic and pharmacodynamic experimentation. Pharmacokinetics is concerned with the study of the time course of the disposition of drugs, specifically absorption, distribution, metabolism and elimination, often referred to as ADME. In non-technical terms it can be thought of as what the body does to the chemical. An understanding of the pharmacokinetic (in the case of dmgs) or toxicokinetic (all chemicals) profile is critical to estimate the... 

The central tenet of toxicology was stated by the sixteenth-century physician Paracelsus All substances are poisons. There is none that is not a poison. The right dose differentiates a poison and a remedy. The scope of this chapter includes the toxic effects of several classes of chemicals on the human cardiovascular system (CVS). These include drugs (including those commonly abused, as well as therapeutic), pesticides, other organic chemicals, metals and other... 

Important writings came from Avicenna of Persia ( 1000) and Maimonides, court physician to Saladin and rabbi of Cairo ( 200). These texts exerted an enormous influence for nearly 500 years. Finally, Paracelsus ( 1525), a Swiss physician, made the important declaration that all things are poisons...solely the dose determines that a thing is not a poison. This concept is the cornerstone of modem toxicology. 

Consequently, toxicologists give credit to Paracelsus for this basic tenet of toxicology, dose-dependency. 

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