Toxicity vesus Sensitization as a factor in building construction an...

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Barb:

I read the “References”

(and that's a LOOSE term here):

A. The Dose Makes the Poison—Or Does It?

by Trautmann

1. She doesn’t say that dose does not make the poison. She

indicates that the dose-response curve may be broader than how it is typically

applied.

My Response: True enough, but we can’t protect everyone from

everything, it all goes back to acceptable risk. If you drive a car, you have

defacto accepted a high risk.

2. She makes a point about low dose response of hormones as defying

dose-response. She is incorrect. She mixes one dose-response curve for one

endpoint and presume it is applied to another endpoint. I’d call that

poor toxicology and poor science.

B. Does 'the dose make the poison?'

by Pete Myers, Ph.D. and Hessler

1. I loved the

“As doses rise above 100 ppb, estradiol becomes overtly

toxic to the cell and the system stops responding completely, dropping even

below the control level. “

But that means it does become more toxic as the dose gets

higher. Kinda defeats their point.

2. They also ignore that dose-response curve is for a single end

point.

3. They do touch on hormesis, which surprises me because it does

indicate a different dose-response curve (one being rejected by EPA). But the

dose still makes the poison, just a different kinda curve.

4. They cover sensitization, which is a shift in the dose-response

curve, one for induction and one for elicitation (but she can’t see that

aspect apparently).

5. As for HCB, it is a different dose-response curve but still the

dose makes the response. This is one that a good tox person looks for in the

dosing regime applied and in the biological aspects of the response to check

for changes in ADME to different pathways. It is not overlooked, just not

relevant in most cases. I just spoke of this aspect on methamphetamine, making

sure the low-dose response is consistent with the high-dose response.

6. These aren’t the Classical forms of response, but they are

considered in reviewing acceptable levels today (except hormesis - which would

suggest low levels are good for you and no one seems to want to be realistic

but rather apply the “[precautionary principal”

C. As for Theo, I’m familiar with Theo and not impressed.

D. Does " the dose make the poison? "

CHE

1. ‘“The dose makes the poison " is taken to mean

that the higher the dose, the greater the effect.’

My Response: Classically yes, modern era Nope - see above.

2. “One may be simply that few scientists looked. Driven by

" the dose makes the poison, " toxicologists would perform experiments

at higher doses and work down the dose-response curve until they found a level

at which no response was detectable. Experiments at doses 1/10th to 1/100th of

that no-response level made no sense. But without experiments at much lower

doses, the low-dose effects of NMDRCs could not be detected. “

My Response: If this process was followed for Bis A (the example

shown), then the dose response curve as shown would be found I the process, so

what's the problem?.

As for not seeing these effects, we have a lot of data on a lot

of chemicals and this response is rare, but still a dose-based response.

3. The one thing this “article” could have pointed out

was that we can’t just do toxicology with numbers, we need to look at

mechanisms as well. Maybe that’s why the Bradford Hill criteria

includes:

Plausibility:

This refers to biological plausibility of the observed

association. There should be some biologically acceptable or relevant reason

for the cause to produce a certain effect. But biological plausibility is

reflection of available knowledge as of now; it may change with time.

Coherence:

Coherence implies that the association does not conflict with

current knowledge about the disease (its natural history, biology, etc.). For

example, the knowledge that smoking damages bronchial epithelium is compatible

with the association between smoking and lung cancer.

Analogy:

A previous experience can be used as an analogy to make a causal

inference. Hill uses the example of thalidomide; since we know it causes

congenital anomalies, it not difficult to appreciate another drug causing

anomalies.

E. Final Comments

1. The Precautionary Prinicipal has several faults

Starr, The Precautionary Principle Versus Risk Analysis, Risk Anal, 23,

1, 1-3, 2003

2. Can you cite any peer-reviewed

references?

Or am I supposed to believe

that 3 non-peer reviewed web references are indicative of the general field of

toxicology and risk assessment

3. Oh - yeh, I’m still

waiting for those peer-reviewed references on the last post you made.

.......................................................................

" Tony " Havics, CHMM, CIH, PE

pH2, LLC

5250 E US 36, Suite 830

Avon, IN

46123

www.ph2llc.com

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fax

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90% of Risk Management is knowing where to place the decimal point...any

consultant can give you the other 10%(SM)

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