Re: Hormesis is central to toxicology, pharmacology and risk ass...

[Guest guest]

Bob,

I read the paper today. Although I don't grasp some of the finer points in great detail, all and all it make MUCH sense to me. I am so glad to see this nonsense go by the wayside from public policy of being able to apply math extrapolations to an acute mechanistic study, add hypothetical threshold numbers pulled out of thin air to the equation (pun intended) and conclude anything of relevance about low dose, chronic, human exposures .

Wish the courts would hurry up and catch on. That would make public policy change even faster from the nonsense that it is scientifically established to be implausible that people experience symptoms of toxicity from exposure to toxins in WDBs.

Hormesis is my favorite word of the day. Gets rid of nonsequitors in the science of toxicology...and eventually the courts. (Steve "Terms" taught me that word "nonsequitor"). LOVE that one, too!

Sharon

Sharon,

It is very interesting that Calabrese authored this article. He has published a number of books on the subject of standard setting and toxicological modeling.

This history makes this paper even more significant because he is highly respected in this area.

Bob

On Apr 9, 2010, at 9:00 AM, SNK1955aol wrote:

Human & Experimental ToxicologyDOI: 10.1177/0960327109363973Hum Exp Toxicol 2010; 29; 249 J CalabreseHormesis is central to toxicology, pharmacology and risk assessmenthttp://het.sagepub.com/cgi/content/abstract/29/4/249

J Calabrese

Department of Public Health, Environmental Health Sciences Division, University of Massachusetts, Amherst, MA, USA, edwardcschoolph (DOT) umass.edu

This paper summarizes numerous conceptual and experimental advances over the past two decades in the study of hormesis. Hormesis is now generally accepted as a real and reproducible biological phenomenon, being highly generalized and independent of biological model, endpoint measured and chemical class/physical stressor. The quantitative features of the hormetic dose response are generally highly consistent, regardless of the model and mechanism, and represent a quantitative index of biological plasticity at multiple levels of biological organization. The hormetic dose-response model has been demonstrated to make far more accurate predictions of responses in low dose zones than either the threshold or linear at low dose models. Numerous therapeutic agents widely used by humans are based on the hormetic dose response and its low dose stimulatory characteristics. It is expected that as low dose responses come to dominate toxicological research that risk assessment practices will incorporate hormetic concepts in the standard setting process.

Key Words: hormesis • hormetic • biphasic • U-shaped • adaptive response • inverted U-shaped

Human & Experimental Toxicology, Vol. 29, No. 4, 249-261 (2010)DOI: 10.1177/0960327109363973

Sharon Noonan Kramer

[Guest guest]

The implication of the hormesis concept is that low-level environmental exposures, even to things known to be harmful in higher doses, can be beneficial (i.e., a low dose of mycotoxin exposure can be a good thing).

The significance of the hypothesis, I think, is that activation of certain epigenetics (switching on of certain genes) can occur at low doses of exposure. The real questions, not addressed by Calabrese, are about what actually happens (causal mechanisms) when various genes are activated due to low-level environmental exposures. Not all such exposures result in a benefit. Some low-level exposures cause (allergic or chemical) sensitization to be induced.

Steve Temes

Sharon,

"Hormesis Defined" article by Mark Mattson where Calabrese is heavily cited is at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248601/

Carl Grimes

Healthy Habitats LLC

-----

Human & Experimental Toxicology

DOI: 10.1177/0960327109363973

Hum Exp Toxicol 2010; 29; 249

J Calabrese

Hormesis is central to toxicology, pharmacology and risk assessment

http://het.sagepub.com/cgi/content/abstract/29/4/249

J Calabrese

Department of Public Health, Environmental Health Sciences Division, University of Massachusetts, Amherst, MA, USA, edwardc@...

This paper summarizes numerous conceptual and experimental advances over the past two decades in the study of hormesis. Hormesis is now generally accepted as a real and reproducible biological phenomenon , being highly generalized and independent of biological model, endpoint measured and chemical class/physical stressor. The quantitative features of the hormetic dose response are generally highly consistent, regardless of the model and mechanism, and represent a quantitative index of biological plasticity at multiple levels of biological organization. The hormetic dose-response model has been demonstrated to make far more accurate predictions of responses in low dose zones than either the threshold or linear at low dose models. Numerous therapeutic agents widely used by humans are based on the hormetic dose response and its low dose stimulatory characteristics. It is expected that as low dose responses come to dominate toxicological research that risk assessment practices will incorporate hormetic concepts in the standard setting process.

Key Words: hormesis • hormetic • biphasic • U-shaped • adaptive response • inverted U-shaped

Human & Experimental Toxicology, Vol. 29, No. 4, 249-261 (2010)

DOI: 10.1177/0960327109363973

[Guest guest]

The implication of the hormesis concept is that low-level environmental exposures, even to things known to be harmful in higher doses, can be beneficial (i.e., a low dose of mycotoxin exposure can be a good thing).The significance of the hypothesis, I think, is that activation of certain epigenetics (switching on of certain genes) can occur at low doses of exposure. The real questions, not addressed by Calabrese, are about what actually happens (causal mechanisms) when various genes are activated due to low-level environmental exposures. Not all such exposures result in a benefit. Some low-level exposures cause (allergic or chemical) sensitization to be induced.Steve Temes

Steve,

It is a misperception that Homesis is about promoting low dose exposures are always beneficial...even though in some instance, I would say that is true in that low dose exposures make one less susceptable. Look a children who go to preschool before kindergarten and who gets sickest in kindergarten. Its those who were not exposed to much beforehand.

I have this whole paper, but don't think I should put it on a discussion board in its entirety. Some of what is in this paper that I find significant is:

A. Defining hormesisIn a broad reading of the general or popularized articleson hormesis, it has often been defined as a lowdose beneficial response to a stressor agent. However,Calabrese and Baldwin proposed that the doseresponse definition of hormesis be decoupled from adecision on whether the response was beneficial ornot. This was done because it had become obviousto us that the low dose hormetic stimulation couldbe either beneficial or harmful, depending on the situation.

B. In the course of our assessment of hormetic dose responserelationships, the question was raised as towhether the threshold dose response was formallyassessed for its capacity to predict below thresholdresponses. While there was the general belief that itmust have been, given the importance of this questionand the universal acceptance of this model within thescientific and regulatory communities, our comprehensiveattempts to find research that had addressedthis issue uniformly failed. Yet, this failure was veryunsettling, for how could the biomedical communityhave built an entire toxicological and drug testing andregulatory framework upon a dose-response modelthat had not been validated? This seemed to beimplausible and therefore could not possibly be true.It most likely meant that our comprehensive attemptswere not really ‘comprehensive’ and that we musthave been missing the obvious.

B. Eventually a disturbing conclusion was reached, thatis, the principal dose-response model upon whichchemical and drug toxicity testing has been based hadnever been validated, but simply accepted as true,being passed down with authoritative conclusionarystatements from textbook to textbook, from professorto student, from regulatory agencies to citizens, acrossgenerations of scientists, creating an illusion ofknowledge and informed guidance.

C. These findings point to a critical and ongoing failureof the scientific and regulatory communities toproperly validate models, especially ones that aredirectly used to affect public health and medical practices.The societal costs of the failure to vet and validatethe threshold dose-response model for the past 75years are unknown. However, one must ask how itwas possible for U.S. federal agencies such as theEPA, FDA, ATSDR, NIEHS, NIOSH, OSHA andothers to never conduct or fund studies that wouldhave addressed this question. The same question maybe asked of private sector funding of toxicological andpharmaceutical research and why this question hasnever been addressed.

[Guest guest]

Sorry for a second post in a row. This is my understanding of hormesis:

Hormesis is the study of chronic low dose exposures. It blows threshold and linear exposure models that are based on acute high dose right out of the water. While threshold & linear models attempt to establish the minimum dose of exposure before effects occur in chronic low exposure (without even including chronic low exposure in the equation); hormesis comes at the problem from the other side of the elephant and attempts to establish a model to determine the maximum chronic low dose exposure before adverse effects occur. It rightfully acknowledges that some exposures in low dose can be beneficial to the immune system. (Personally, I would think that many do)

So..what people are exposed to in WDBs that cause them adverse health effects lays somewhere between the maximum chronic low dose of exposure before its bad for you - that hormesis models could help to establish; and the minimum dose that the garbage of threshold and linear exposure studies have professed to scientifically prove based on using the wrong data.

Sharon

[Guest guest]

Steve,I agree but we are still left with the difficulty of determining low and high levels on an individual basis. These are ranges of exposure, not clear-line thresholds. A low level benefit for you may be a harmful high for me, for example. Even the harsh evidence-only advocates are starting to modify their proselytizing because of the unrefutable reality of individual gene expression. Which appears to put classical toxicology as still true but in a much smaller "box" rather than as the only "enchilada."Carl GrimesHealthy Habitats LLC(fm my Blackberry)From: AirwaysEnv@...Date: Sat, 10 Apr 2010 12:56:43 EDTTo: <iequality >Subject: Re: "Hormesis is central to toxicology, pharmacology and risk ass...The implication of the hormesis concept is that low-level environmental exposures, even to things known to be harmful in higher doses, can be beneficial (i.e., a low dose of mycotoxin exposure can be a good thing).The significance of the hypothesis, I think, is that activation of certain epigenetics (switching on of certain genes) can occur at low doses of exposure. The real questions, not addressed by Calabrese, are about what actually happens (causal mechanisms) when various genes are activated due to low-level environmental exposures. Not all such exposures result in a benefit. Some low-level exposures cause (allergic or chemical) sensitization to be induced.Steve Temes Sharon, "Hormesis Defined" article by Mark Mattson where Calabrese is heavily cited is at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2248601/ Carl Grimes Healthy Habitats LLC -----Human & Experimental ToxicologyDOI: 10.1177/0960327109363973Hum Exp Toxicol 2010; 29; 249 J CalabreseHormesis is central to toxicology, pharmacology and risk assessmenthttp://het.sagepub.com/cgi/content/abstract/29/4/249 J Calabrese Department of Public Health, Environmental Health Sciences Division, University of Massachusetts, Amherst, MA, USA, edwardc@... This paper summarizes numerous conceptual and experimental advances over the past two decades in the study of hormesis. Hormesis is now generally accepted as a real and reproducible biological phenomenon , being highly generalized and independent of biological model, endpoint measured and chemical class/physical stressor. The quantitative features of the hormetic dose response are generally highly consistent, regardless of the model and mechanism, and represent a quantitative index of biological plasticity at multiple levels of biological organization. The hormetic dose-response model has been demonstrated to make far more accurate predictions of responses in low dose zones than either the threshold or linear at low dose models. Numerous therapeutic agents widely used by humans are based on the hormetic dose response and its low dose stimulatory characteristics. It is expected that as low dose responses come to dominate toxicological research that risk assessment practices will incorporate hormetic concepts in the standard setting process. Key Words: hormesis • hormetic • biphasic • U-shaped • adaptive response • inverted U-shaped Human & Experimental Toxicology, Vol. 29, No. 4, 249-261 (2010)DOI: 10.1177/0960327109363973

[Guest guest]

Jim,

That was very well stated. I understand and agree with everything you write, with the exception of this one statement:

"There is almost no good science done anymore because our bosses and professors and government agencies will not have their basic assumptions questioned."

I am of the opinion there is some unbelievably skilled science taking place in the private sector, universities and government agencies. It is the science of professionally marketing false concepts into health policy.

The term for this science is "health marketing". It is the science I understand and am educated to understand. Just like you are appalled to see your field of science frequently bastardized, I feel the same way about my field of science.

Mine is the field of science we really need to get control over to allow your field of science to be re-instilled with integrity.

Sharon

[Guest guest]



Sharon

In good science one continually challenges ones assumptions and rechecks to see if they are still true. There is almost no good science done anymore because our bosses and professors and government agencies will not have their basic assumptions questioned. Loyalty to the old ones and the old ways is the greatest good!

I get nowhere with most organizations, especially in government, when I suggest that we often do not even know the right questions to ask and that the probability of getting useful answers goes way down when you do not ask the right questions; like maybe to zero, eh?

The death of a 'preconception of great understanding' goes through the many stages of grief, as does the death of a friend or spouse or child. The first stage is denial.

Jim H. White System Science Consulting

Re: "Hormesis is central to toxicology, pharmacology and risk ass...

In a message dated 4/10/2010 1:00:31 P.M. Pacific Daylight Time, AirwaysEnvcs writes:

The implication of the hormesis concept is that low-level environmental exposures, even to things known to be harmful in higher doses, can be beneficial (i.e., a low dose of mycotoxin exposure can be a good thing).The significance of the hypothesis, I think, is that activation of certain epigenetics (switching on of certain genes) can occur at low doses of exposure. The real questions, not addressed by Calabrese, are about what actually happens (causal mechanisms) when various genes are activated due to low-level environmental exposures. Not all such exposures result in a benefit. Some low-level exposures cause (allergic or chemical) sensitization to be induced.Steve Temes

Steve,

It is a misperception that Homesis is about promoting low dose exposures are always beneficial...even though in some instance, I would say that is true in that low dose exposures make one less susceptable. Look a children who go to preschool before kindergarten and who gets sickest in kindergarten. Its those who were not exposed to much beforehand.

I have this whole paper, but don't think I should put it on a discussion board in its entirety. Some of what is in this paper that I find significant is:

A. Defining hormesisIn a broad reading of the general or popularized articleson hormesis, it has often been defined as a lowdose beneficial response to a stressor agent. However,Calabrese and Baldwin proposed that the doseresponse definition of hormesis be decoupled from adecision on whether the response was beneficial ornot. This was done because it had become obviousto us that the low dose hormetic stimulation couldbe either beneficial or harmful, depending on the situation.

B. In the course of our assessment of hormetic dose responserelationships, the question was raised as towhether the threshold dose response was formallyassessed for its capacity to predict below thresholdresponses. While there was the general belief that itmust have been, given the importance of this questionand the universal acceptance of this model within thescientific and regulatory communities, our comprehensiveattempts to find research that had addressedthis issue uniformly failed. Yet, this failure was veryunsettling, for how could the biomedical communityhave built an entire toxicological and drug testing andregulatory framework upon a dose-response modelthat had not been validated? This seemed to beimplausible and therefore could not possibly be true.It most likely meant that our comprehensive attemptswere not really ‘comprehensive’ and that we musthave been missing the obvious.

B. Eventually a disturbing conclusion was reached, thatis, the principal dose-response model upon whichchemical and drug toxicity testing has been based hadnever been validated, but simply accepted as true,being passed down with authoritative conclusionarystatements from textbook to textbook, from professorto student, from regulatory agencies to citizens, acrossgenerations of scientists, creating an illusion ofknowledge and informed guidance.

C. These findings point to a critical and ongoing failureof the scientific and regulatory communities toproperly validate models, especially ones that aredirectly used to affect public health and medical practices.The societal costs of the failure to vet and validatethe threshold dose-response model for the past 75years are unknown. However, one must ask how itwas possible for U.S. federal agencies such as theEPA, FDA, ATSDR, NIEHS, NIOSH, OSHA andothers to never conduct or fund studies that wouldhave addressed this question. The same question maybe asked of private sector funding of toxicological andpharmaceutical research and why this question hasnever been addressed.

[Guest guest]

Sharon

Linear approximations to performance are almost always wrong, if only at the very low and very high end.

In mechanics, the amount of torque needed to get things going is quite large (the 'stick' region) and then, once motion starts, the minimum level of friction goes way down. Until that was modeled, may control systems were continually getting assemblies in the 'bang-bang' performance regime and as unstable as hell. The Canadarm control system always used a stick-slip model of the joints and worked well from the beginning; everyone 'knew' that it was too complicated but it worked really well and was not revised back to where control theory was then (in the dark ages, really).

The theory of health effects was always overly-simplistic because so many (nearly all) doctors and even medical researchers had taken no science and little if any statistics. The hens are coming home to roost and it is a great day ahead!

Jim H. White SSC

Re: "Hormesis is central to toxicology, pharmacology and risk ass...

Sorry for a second post in a row. This is my understanding of hormesis:

Hormesis is the study of chronic low dose exposures. It blows threshold and linear exposure models that are based on acute high dose right out of the water. While threshold & linear models attempt to establish the minimum dose of exposure before effects occur in chronic low exposure (without even including chronic low exposure in the equation); hormesis comes at the problem from the other side of the elephant and attempts to establish a model to determine the maximum chronic low dose exposure before adverse effects occur. It rightfully acknowledges that some exposures in low dose can be beneficial to the immune system. (Personally, I would think that many do)

So..what people are exposed to in WDBs that cause them adverse health effects lays somewhere between the maximum chronic low dose of exposure before its bad for you - that hormesis models could help to establish; and the minimum dose that the garbage of threshold and linear exposure studies have professed to scientifically prove based on using the wrong data.

Sharon

[Guest guest]

As a computer circuit designer type, this kind of nonlinear stimulus response

curve is normal, the kind of thing I started seeing sophomore year in college as

we looked at basic mathematical models of transistors.

Looks like there are five zones in this curve:

1. dose too low for any reaction at all

2. dose high enough to trigger the adaptive response by the body

3. asymptomatic dose above (after) the trigger, and up to

4. dose at which symptoms appear, and up to

5. dose at which toxicological sensitization occurs

Note that each of these doses is individual. (I remember having this

conversation with my father, after his 2 year political appointment as head of

policy for OSHA, and him describing his discomfort with one size fits all

permitted exposure levels).

Note also that sensitization could occur lower down the chart. My own guess is

sensitization is a probability distribution which itself depends on the body's

genetics, past exposures, and current state.

Steve Chalmers

stevec@...

>

> Sorry for a second post in a row. This is my understanding of hormesis:

>

>

> Hormesis is the study of chronic low dose exposures. It blows threshold and

> linear exposure models that are based on acute high dose right out of the

> water. While threshold & linear models attempt to establish the minimum

> dose of exposure before effects occur in chronic low exposure (without even

> including chronic low exposure in the equation); hormesis comes at the

> problem from the other side of the elephant and attempts to establish a model

to

> determine the maximum chronic low dose exposure before adverse effects

> occur. It rightfully acknowledges that some exposures in low dose can be

> beneficial to the immune system. (Personally, I would think that many do)

>

> So..what people are exposed to in WDBs that cause them adverse health

> effects lays somewhere between the maximum chronic low dose of exposure before

> its bad for you - that hormesis models could help to establish; and the

> minimum dose that the garbage of threshold and linear exposure studies have

> professed to scientifically prove based on using the wrong data.

>

> Sharon

>

[Guest guest]

Steve

This is the sort of thing we should be looking at; the looking should be done by a group with a wide range of backgrounds and interests. It is only in groups who have many skills and concerns (including the vested interests but not controlled by them) that there is the chance of producing a really good consensus on how such complex does-response matters can be properly redefines. By consensus I do not mean 100% agreement, since that will be impossible if all of the affected parties are involved, but it does mean that a majority agrees that what is produced is the best that can be done with the information available. That is a good target for humans; perfect is for angels!

Let us hope that, with the new concerns from above, a significantly-improved approach can be developed by the powers that be.

Thanks for your input; Lord knows your are deeply interested in this and can focus well enough to make a real contribution.

Jim H. White System Science Consulting (Helping you find the right question)

Re: "Hormesis is central to toxicology, pharmacology and risk ass...

As a computer circuit designer type, this kind of nonlinear stimulus response curve is normal, the kind of thing I started seeing sophomore year in college as we looked at basic mathematical models of transistors.Looks like there are five zones in this curve:1. dose too low for any reaction at all2. dose high enough to trigger the adaptive response by the body3. asymptomatic dose above (after) the trigger, and up to4. dose at which symptoms appear, and up to5. dose at which toxicological sensitization occursNote that each of these doses is individual. (I remember having this conversation with my father, after his 2 year political appointment as head of policy for OSHA, and him describing his discomfort with one size fits all permitted exposure levels).Note also that sensitization could occur lower down the chart. My own guess is sensitization is a probability distribution which itself depends on the body's genetics, past exposures, and current state.Steve Chalmersstevecsurewest (DOT) net>> Sorry for a second post in a row. This is my understanding of hormesis:> > > Hormesis is the study of chronic low dose exposures. It blows threshold and > linear exposure models that are based on acute high dose right out of the > water. While threshold & linear models attempt to establish the minimum > dose of exposure before effects occur in chronic low exposure (without even > including chronic low exposure in the equation); hormesis comes at the > problem from the other side of the elephant and attempts to establish a model to > determine the maximum chronic low dose exposure before adverse effects > occur. It rightfully acknowledges that some exposures in low dose can be > beneficial to the immune system. (Personally, I would think that many do)> > So..what people are exposed to in WDBs that cause them adverse health > effects lays somewhere between the maximum chronic low dose of exposure before > its bad for you - that hormesis models could help to establish; and the > minimum dose that the garbage of threshold and linear exposure studies have > professed to scientifically prove based on using the wrong data.> > Sharon>

[Guest guest]

the number of chemicals receptors in cells are limited. so it makes sense that after a certain dose, the toxic nature of a chemical would change drastically.

-----Original Message-----From: iequality [mailto:iequality ]On Behalf Of Jim H. White SSCSent: Sunday, April 11, 2010 11:16 AMTo: iequality Subject: Re: "Hormesis is central to toxicology, pharmacology and risk ass...

Sharon

Linear approximations to performance are almost always wrong, if only at the very low and very high end.

In mechanics, the amount of torque needed to get things going is quite large (the 'stick' region) and then, once motion starts, the minimum level of friction goes way down. Until that was modeled, may control systems were continually getting assemblies in the 'bang-bang' performance regime and as unstable as hell. The Canadarm control system always used a stick-slip model of the joints and worked well from the beginning; everyone 'knew' that it was too complicated but it worked really well and was not revised back to where control theory was then (in the dark ages, really).

The theory of health effects was always overly-simplistic because so many (nearly all) doctors and even medical researchers had taken no science and little if any statistics. The hens are coming home to roost and it is a great day ahead!

Jim H. White SSC

Re: "Hormesis is central to toxicology, pharmacology and risk ass...

Sorry for a second post in a row. This is my understanding of hormesis:

Hormesis is the study of chronic low dose exposures. It blows threshold and linear exposure models that are based on acute high dose right out of the water. While threshold & linear models attempt to establish the minimum dose of exposure before effects occur in chronic low exposure (without even including chronic low exposure in the equation); hormesis comes at the problem from the other side of the elephant and attempts to establish a model to determine the maximum chronic low dose exposure before adverse effects occur. It rightfully acknowledges that some exposures in low dose can be beneficial to the immune system. (Personally, I would think that many do)

So..what people are exposed to in WDBs that cause them adverse health effects lays somewhere between the maximum chronic low dose of exposure before its bad for you - that hormesis models could help to establish; and the minimum dose that the garbage of threshold and linear exposure studies have professed to scientifically prove based on using the wrong data.

Sharon

[Guest guest]

Actually, the number and types of chemical receptors that can be created by the adaptive immune system is pretty much unlimited.

That's why people can become hypersensitive to celery, mustard, carrots, tomatoes, common solvents, fragrance chemicals, etc., etc.

The right question to ask is, "Why are receptors created by the adaptive immune system to produce an inflammatory response to these "non-toxic", non-self substances?" That is, what causes sensitization to be induced?

Steve Temes

the number of chemicals receptors in cells are limited. so it makes sense that after a certain dose, the toxic nature of a chemical would change drastically.

Re: "Hormesis is central to toxicology, pharmacology and risk ass...

Sharon

Linear approximations to performance are almost always wrong, if only at the very low and very high end.

In mechanics, the amount of torque needed to get things going is quite large (the 'stick' region) and then, once motion starts, the minimum level of friction goes way down. Until that was modeled, may control systems were continually getting assemblies in the 'bang-bang' performance regime and as unstable as hell. The Canadarm control system always used a stick-slip model of the joints and worked well from the beginning; everyone 'knew' that it was too complicated but it worked really well and was not revised back to where control theory was then (in the dark ages, really).

The theory of health effects was always overly-simplistic because so many (nearly all) doctors and even medical researchers had taken no science and little if any statistics. The hens are coming home to roost and it is a great day ahead!

Jim H. White SSC

Re: "Hormesis is central to toxicology, pharmacology and risk ass...

Sorry for a second post in a row. This is my understanding of hormesis:

Hormesis is the study of chronic low dose exposures. It blows threshold and linear exposure models that are based on acute high dose right out of the water. While threshold & linear models attempt to establish the minimum dose of exposure before effects occur in chronic low exposure (without even including chronic low exposure in the equation); hormesis comes at the problem from the other side of the elephant and attempts to establish a model to determine the maximum chronic low dose exposure before adverse effects occur. It rightfully acknowledges that some exposures in low dose can be beneficial to the immune system. (Personally, I would think that many do)

So..what people are exposed to in WDBs that cause them adverse health effects lays somewhere between the maximum chronic low dose of exposure before its bad for you - that hormesis models could help to establish; and the minimum dose that the garbage of threshold and linear exposure studies have professed to scientifically prove based on using the wrong data.

Sharon

[Guest guest]

Oh my goodness. It is mostly going to take me six months of reading to even come close to grasping what you all are talking about. The only thing I know for certain of the matter is that one cannot take some data from an acute exposure rat study, apply some hypothetical bells and whistles and profess to scientifically prove that the microbial toxins do not harm - and then mass market this via teaching hospitals, medical associations and the US Chamber of Commerce.

I reached the threshold of exposure to this scientific fraud in health marketing long ago before it caused my stomach to turn.

What do you think, Governo? Do you still remember your password?

Sharon

Actually, the number and types of chemical receptors that can be created by the adaptive immune system is pretty much unlimited.That's why people can become hypersensitive to celery, mustard, carrots, tomatoes, common solvents, fragrance chemicals, etc., etc.The right question to ask is, "Why are receptors created by the adaptive immune system to produce an inflammatory response to these "non-toxic", non-self substances?" That is, what causes sensitization to be induced?Steve TemesIn a message dated 4/20/2010 9:20:39 AM Eastern Daylight Time, alice.freundmssm (DOT) edu writes:

the number of chemicals receptors in cells are limited. so it makes sense that after a certain dose, the toxic nature of a chemical would change drastically.

-----Original Message-----From: iequality [mailto:iequality ]On Behalf Of Jim H. White SSCSent: Sunday, April 11, 2010 11:16 AMTo: iequality Subject: Re: "Hormesis is central to toxicology, pharmacology and risk ass... SharonLinear approximations to performance are almost always wrong, if only at the very low and very high end. In mechanics, the amount of torque needed to get things going is quite large (the 'stick' region) and then, once motion starts, the minimum level of friction goes way down. Until that was modeled, may control systems were continually getting assemblies in the 'bang-bang' performance regime and as unstable as hell. The Canadarm control system always used a stick-slip model of the joints and worked well from the beginning; everyone 'knew' that it was too complicated but it worked really well and was not revised back to where control theory was then (in the dark ages, really). The theory of health effects was always overly-simplistic because so many (nearly all) doctors and even medical researchers had taken no science and little if any statistics. The hens are coming home to roost and it is a great day ahead! Jim H. White SSC

Re: "Hormesis is central to toxicology, pharmacology and risk ass... Sorry for a second post in a row. This is my understanding of hormesis: Hormesis is the study of chronic low dose exposures. It blows threshold and linear exposure models that are based on acute high dose right out of the water. While threshold & linear models attempt to establish the minimum dose of exposure before effects occur in chronic low exposure (without even including chronic low exposure in the equation); hormesis comes at the problem from the other side of the elephant and attempts to establish a model to determine the maximum chronic low dose exposure before adverse effects occur. It rightfully acknowledges that some exposures in low dose can be beneficial to the immune system. (Personally, I would think that many do) So..what people are exposed to in WDBs that cause them adverse health effects lays somewhere between the maximum chronic low dose of exposure before its bad for you - that hormesis models could help to establish; and the minimum dose that the garbage of threshold and linear exposure studies have professed to scientifically prove based on using the wrong data. Sharon

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Sharon Noonan Kramer