Topic: Question Set 1. Question 1. Questions arising from the historical background of toxicology.

Subject: Question Set 1. Question 1. Questions arising from the historical background of toxicology. Posted: Mar-04-02 at 4:05 PM by Kenneth Campbell

1. The idea of causality arose during the middle ages and Renaissance. This builds on careful observation and testing. How might this give rise to the notions of occupational hazards or the nonmystical explanation for oncogenesis?

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Posted: Feb-12-03 at 11:59 AM by Erin Valentine

1. The idea of studying causality through careful observation and testing might give rise to the notion of occupational hazards because certain occupations expose workers to unique risks of exposure. If particular subsets of workers are all experiencing a similar disease or condition, the logical way to explain the symptoms is to carefully observe the working conditions. This would entail sampling the environment in search of the causative agent, or the "toxicon". Potential candidates could then be used in animal or in vitro tests to determine response to various dose levels, site of action and what types of symptoms are observed in the test subjects. They could also undergo biochemical analysis to determine structure/activity relationships. The information gathered could then be used to determine the causative agent and could also be used to infer other potential hazards. This type of testing could then also be used to test other potentially hazardous working environments before workers exhibit symptoms. This would allow for preventative measures to be taken against toxic exposure.

In the case of non-mystical explanation of oncogenesis, the same process applies. In the onset of unexplained cancer, one can carefully observe the afflicted individual's potential exposure to a potential carcinogen. Similar tests to those described above could then be performed to identify the culprit.

Posted: Feb-12-03 at 3:38 PM by Lisa McIntosh

The process of simple observation from occupational or incidental exposures may be suitable for noncarcinogenic effects resulting from acute exposures; however, for chronic adverse effects or carcinogenesis, it is not as easy a matter as to pinpoint the potential culprit. Liver cancer, or heart disease, for example, may result from a lifetime of cumulative effects of numerous causative agents, which may or may not be obvious based on the individual's exposure.

Posted: Feb-13-03 at 10:34 PM by Lisa McIntosh

"Watch and learn" tactics. In the past, people have noted adverse effects associated with exposure to particular substances. Likewise, it was noted that certain occupations had correspondingly higher incidences of diseases (e.g., "Mad Hatters" syndrome, resulting from mercury toxicity (neurotoxicity). Mercury was commonly used by hat makers…..). As for oncogenesis, the same premise holds: exposure to a particular substance eventually initiated the onset of cancer (e.g., the elevated incidence of lung cancer among smokers). One problem with this approach, however, is that a particular type of cancer (or, say, a nonspecific noncancer effect) may correlate with a substance's use, but may not necessarily be directly related to exposure. Simple observation does not take into account confounding factors such as the incidence of background cancer rates, or the numerous other entities in our lives that may also attribute to adverse effects (e.g., diet, acute exposures, etc.)

Posted: Feb-15-03 at 11:30 AM by DINA KATZ

During the Renaissance, the idea of scientific experiments and replicability arose. It became understood that an event can be caused by something non-immediate. The spread of literacy and printed works made it easier for scientists and others to share observations and note patterns, such as the high occurrence of scrotal cancer in chimney sweepers. Likewise it was known that mining and covering building domes with gold leaf (I believe the gold was in a mercury solution) were dangerous occupations, because many of these profesionals died relatively quickly of similar diseases, such as lung problems. While the exact mechanisms of lung injury were not known, the cause-effect relationship was established. Similarly, while initially oncogenesis was attributed to mystical causes, the observation of patterns of lifestyle and environment among victims contributed to the uncovering of certain cause-effect relationships, like the above-mentioned scrotal cancer of chimney sweepers and, more recently, lung cancer and emphysema among heavy smokers.

Posted: Feb-15-03 at 2:59 PM by ERIC FAULKNER

While scientific advancements of the cause and effect relationship of toxicants on the human system did occurred during the Middle Ages, one could say that these were great scientific alchemy experiments than the precusors of government regulatory bodies like OSHA, EPA, and the NIH. One pioneer of the Middle Ages, Catherine de Medici, tested toxic concoctions on men. Now, her horrific crimes can be interpreted to modern toxicology terms such as onset of action, specificity of action, and clinical significant. The fate for her evil ways was execution, but one could argue that her scientific studies are exactly what occurs during Phase I, II, and III clinical trials of new chemical entities therapies. Overall humans have tried to learn from there mistakes and this what has initated governmetal control Back in the 1900's one pharmaceutical company killed 108 children with their cough drop medicine. They had used ethylene gylcol instead of proylene glycol in their formulation. Their medicine was termed the Elixr of death and hence the FDA was then established soon afterwards.

With regards to the explanation oncgoneiss, the formation of tumors can be enviromentally stimualed as well as genetic inherited. Indeed OSHA is there to protect workers from safety and toxic hazards, but if they were really that concerned why does mining still exist. An occupation were many maligancies have been well document. Maybe humans have not really progessed as much as we have thought. And as far as governmental control, the pharmaceutical company that made the Elixir of death is still in business.

Posted: Feb-15-03 at 4:19 PM by ERIC FAULKNER

(Note: The spell check was not saved from the original response)

While scientific advancements of the cause and effect relationship of toxicants on the human system did occurred during the Middle Ages, one could say that these were great scientific alchemy experiments than the precursors of government regulatory bodies like OSHA, EPA, and the NIH. One pioneer of the Middle Ages, Catherine de Medici, tested toxic concoctions on men. Now, her horrific crimes can be interpreted to modern toxicology terms such as onset of action, specificity of action, and clinical significant. The fate for her evil ways was execution, but one could argue that her scientific studies are exactly what occurs during Phase I, II, and III clinical trials of new chemical entities therapies. Overall humans have tried to learn from there mistakes and this what has initiated governmental control Back in the 1900's one pharmaceutical company killed 108 children with their cough drop medicine. They had used ethylene glycol instead of propylene glycol in their formulation. Their medicine was termed the Elixir of death and hence the FDA was then established soon afterwards.

With regards to the explanation oncogenesis, the formation of tumors can be environmentally stimulated as well as genetic inherited. Indeed OSHA is there to protect workers from safety and toxic hazards, but if they were really that concerned why does mining still exist. An occupation were many malignancies have been well document. Maybe humans have not really progressed as much as we have thought. And as far as governmental control, the pharmaceutical company that made the Elixir of death is still in business.

Posted: Feb-15-03 at 4:38 PM by Michael George

During the Middle Ages and the Renaissance, the beginnings of careful observations and testing began. Looking at the cause and affects of a toxicant/toxin began. For example, Catherine de Medici looked at toxic effects on the poor by noting the rapidity of the toxic response (onset of action), the effectiveness of the compound (potency), the degree of response of the parts of the body (specificity, site of action) and the complaints of the victims (clinical signs and symptoms). As cruel as these experiments were, they were really an early version of the Phase I, II, and III testing. During the Renaissance, Parcellis was the first to look at a toxicant as a chemical entity rather than a mixture of some sort. His 3 concepts were:

1.) Experimentation is Essential in examination of responses to chemicals.

2.) One needs to make a distinction between therapeutic and toxic properties of chemicals.

3.) These properties above are sometimes distinguishable by dose but not always.

4.) One can ascertain a degree of specificity of chemicals and their therapeutic or toxic side affects.

This can really be seen as the beginning of the dose-response relationship. Percellis also looked at the etiology of diseases associated with miners and how to treat/prevent them. Also the hazards of metal working began with the works of Ellenborg warning of toxicity of mercury and lead in goldsmith work. All these lead to looking at the occupational hazards of toxicants and looking at nonmystical explanations for oncogenesis.

Posted: Feb-16-03 at 8:18 PM by Shaun McAuliffe

If one considers simple hunter-gathering an occupation, causality via observation and testing likely developed prior to the middle ages and Renaissance, during early hunting and foraging expeditions. Early man likely encountered poisonous plant, animal and insect species. Tribal leaders likely recorded the species of plant, animal and insect that caused a toxic response in a member; thus establishing early causality. Over time I imagine that unexplained and/or mysterious death previously attributed to mystical causes was later attributed to an exposure to a naturally occuring toxin/species delivering said toxin. Once studied and understood, it is evident from early manuscripts that early man was able to apply this toxicological knowledge to hunting and warfare.

This early study was later refined by persons like Maimonides and Hippocrates who furthered the study of toxins and early toxicants. They and their peers authored papers on poisoning and antidotes. Their work helped to define how most poisons/toxins of the time manifested themselves and establish the notion of bioavailability.

As this study was furthered, individuals like Paracelsus and Ramazzini documented disease trends amongst asbestos workers, miners (radon, dusts), metallurgists, printers, potters, weavers and end users of products and/or resources. Like the early hunter-gatherers and their peers furthering the study of poisons and antidotes, I image that individuals like Ellenbog, Paracelsus, and Ramazzini desired to further establish the causal relationships between occupation and disease. Once established and like Maimonides and Hippocrates, Ellenbog, Paracelsus, and Ramazzini worked to develop treatment and prevention strategies.

Scientists like Percival Pott were able to build upon the foundation that Paracelsus and Ramazzini had established. Armed with a broader depth and understanding of biological and chemical science, scientists like Pott were able to establish that specific occupational exposures led to the development of organ and/or tissue specific disease and/or manifestations.

In summary, it is clear that man's pursuit to understand causality has led to our present understanding of occupational disease and oncogenesis. Perhaps as we further broaden our base of knowledge, man will not only be able to prevent the incidence of occupational disease but also repair the damage that an accidental exposure has caused.

Posted: Feb-18-03 at 3:15 PM by Diana Esshaki

The idea of causality seems to have developed around the introduction of the physician-alchemist, Paracelsus. He promoted the idea of a dose-response relationship. Looking at the relation of cause (i.e. "toxicon" exposure) and effect (i.e. disease, death) parallels Paracelsus' studies of how chemical entities can elicit various responses in individuals- both neg. and positive.

The idea/doctrine that "all things" have a cause definitely give rise to the notions of occupational hazards and nonmystical explanations for oncogenesis. For example, exposure to mercury and lead (cause; high dose)leads to disease (effect; response). Also, in the field of oncology, the role of soot in scrotal cancer demonstrated that the cause of disease was nonmystical (moving away from antiquity beliefs). As the book noted (the big picture), the idea of causality has improved medical practices, given a greater understanding to the broader fields of biology and chemistry, developed the beginnings of the scientific method (Campbell), and aided in prevention as well.

Posted: Feb-18-03 at 10:25 PM by Ivana Djuretic

I would just point out again the Age of Enlightment and the Industrial Revolution as major breakpoints in human history as far as toxicology is concerned. Throughout most of the history, including the Middle Ages, concern about the toxic effects of chemicals has been focused on poisons which act quickly and result in death. Socrates ingested hemlock to commit sucide. Infamous Toffana made many young married women wealthy widows by her arsenic containg cosmetics. Since exposure to these chemicals was not common and the risks were well known there was little public concern about these poisons.

Gradually we became more concerned with poisons, especially those that cause adverse effects after long periods of exposure. Industrial revolution has led to new and increased uses of known chemicals and the synthesis and widespread use of newly developed chemicals which has started a greater awareness of possible adverse health effects of chemicals other than lethality. More recently, increase in the average human life span due to cures and treatments for infectious diseases has made chronic non-infectious diseases more common and opened up a whole new area of research for toxicology.

Posted: Feb-20-03 at 0:17 AM by Ivana Djuretic

Referenced from:

www.iet.msu.edu/tox_for_public/riskasmt.htm

Old

Joanne:

February 19, 2002

1) The idea of casuality would potentially give rise to the notions of occupational hazards and/or the nonmystical explanations for oncogenesis by one's observing and posing a plausible causal relationship between the environment (work or otherwise) and an adverse (cancer promoting ..etc) reaction in the exposed individual. Instead of attributing ailments to superstitious beliefs, they had begun to establish the fundamental beginnings of the scientific method.

Allison:

February 19,2002

1. Occupational hazards associated with metal working were recognized during the 15th century. Paracelsus published a major piece of work addressing the etiology of miner's disease, along with treatment and prevention strategies.

Occupational diseases and causuality increased during the Industrial Revolution. The recognition of the basis behind scrotal cancer among chimney sweeps was the first reported example of polyaromatic hydrocarbon carcinogenity. These findings led to improved medical practices and prevention. Through careful observation, diseases that were prevelant among

a certain group of workers or people led to testing and experimenting on metals, plants, and minerals that they might be exposed to or using in their daily activity. This led to the understanding and further development of determination of how workers were becoming ill and the specific cause of these diseases.

Neetu:

February 19,2002

1. The occupational hazards and causalities were very commonly occuring in olden days.

People were perhaps, exposed to many chemicals and other hazardous material in their work

environment due to ignorance or they simply did not have any other choice. They had to work in

the environment they were working in bceause there were not many jobs and because they had

to provoide living for themselves and their families. After the industrial revolution, people started	becoming educated and taking more precautions, which made the working environments safer. With the advanced type of technology, and medical techniques, conditions are much better now than they were during industrial revolution. Learning, understanding and taking precautions while working, definately helped prevent occupational hazards.