Topic: Question Set 3. Question 4. Time, dose, shielding.

Subject: Question Set 3. Question 4. Time, dose, shielding. Posted: Mar-07-02 at 3:15 AM by Kenneth Campbell

4. In radiation protection there are three cardinal rules for minimizing radiation exposure:

1. minimize time of exposure to the source

2. maximize distance from the source to minimize dose delivered

3. optimize the amount and type of shielding used to minimize dose delivered.

Can these be translated into considerations in toxicant exposure? What are the analogs of time, dose, and shielding for chemical exposures? Are there any differences among routes of exposure or nature of toxicant that need to be considered?

Posted: Feb-12-03 at 12:12 PM by Erin Valentine

4. These three cardinal rules can definitely be translated into considerations in toxicant exposure. The analog of time in chemical exposure is the duration and frequency of exposure. This includes the concepts of acute, subchronic and chronic exposure. The analog of dose is the applied amount of the toxic agent (mg agent/ kg test subject) that an individual is exposed to or more specifically the concentration of the agent at the target site. The analogs for shielding for chemical exposure include mechanisms for preventing absorption, presystematic elimination by biotransformation at exposure sites (lungs, stomach, skin), and prevention of agent's function through inhibitory binding. Shielding could also come in the form of protective gear specific to the route of exposure for the particular toxicant. The nature of the toxicant needs to be considered if the effect of the toxicant is increased by certain conditions. If the delivery of the toxicant were facilitated within the system, then the dosage amounts would be increased. Also if the toxicant were held in an inactive state after exposure until particular conditions released it, then the timing of exposure would also be altered.

Posted: Feb-13-03 at 6:53 PM by Ivana Djuretic

Depending on the route of exposure biological responses to a toxicant will differ/its toxicity changes. A chemical may be severely toxic by inhalation but not toxic by oral or dermal exposure. Differences in toxicity arise due to several factors:

-Rate of absorption- this will depend on the nature of the toxicant. Main sites of absorption are GI tract, lungs, and skin. Lungs are generally more penetrable for volatile compounds such as gases, vapors and aerosols. Skin is impermeable to many chemicals but not to nerve gases, carbon tetrachloride etc. GI tract absorbs a range of molecules:lipophilic molecules by simple difffusion and hydrophilic molecules by active transport or by passing through aqueous pores at the tight junctions.

-Availability of sites- because of a large surface area (size of a tennis court ) lungs are generally the most available site of adsorption)

-Presence of degradative enzymes-liver detoxifies many chemicals so LD50 for a given toxicant decreases if given via portal circulation (goes to liver) than via inhalation (systemic circulation). Degradative enzymes are also present in stomach and intestine. For instance snake venom is much less toxic if given orally rather than IV because it is broken down by digestive enzymes in the GI tract.

-Extreme conditions- newborns have a higher pH in their GI tract which allows for conversion of nitrates to nitrites and leads to a condition called methemoglobinemia (defect in oxygen transport)

-Rate of transit through the body- the slower the movements of the GI tract the more absorption.

Posted: Feb-13-03 at 10:40 PM by Lisa McIntosh

In terms of toxicant exposure, these same three rules likewise hold:

1. Minimize the time of exposure to the source. If you reduce your exposure frequency and duration, you reduce your risk of harm.

2. Maximize the distance from the source to minimize the dose delivered. In other words, avoid exposure, if possible. No exposure is equivalent to no toxicity.

3. Optimize the amount and type of shielding used to minimize dose delivered. We can reduce exposures further by wearing protective equipment (e.g., gloves, respirators, goggles) or by other measures such as washing exposed surfaces following contact.

When working with radioactive materials, dermal penetration of rays is probably one of the greater concerns; however, a radioactive compound, as with any compound, can enter the body through various routes of exposure-ingestion, inhalation, via injection, etc.

Posted: Feb-15-03 at 4:14 PM by ERIC FAULKNER

As ionizing radiation passes through a substance it will lose energy, due to the fact it produces an electron and a positively charged atom residue. When humans are exposed to radiation for certain periods of time, DNA synthesis becomes disrupted as the radiation breaks apart the precursors of DNA replication (purines and pyrimidines molecules). The following cardinal rules for minimizing exposure to radiation can be translated into considerations to toxic exposure because they somewhat pertain to an individual dose response curve (1) Deficiency and Toxicity will occurs with no protection from the radiation source and (2) Region of Homeostasis will occur with protection form the radiation source.

The analogies or similarities that exist would be time is to the frequency of exposure to radiation, the dose would be considered the intensity (delivered dose) of the radiant rays from the distance you stood from the energy source (closer you are the greater the intensity), and shielding exposures would be the protective garments worn to protect the skin and mucosa from absorption and distribution to the target site (DNA). Differences need to be consider among the nature of the toxicant rather than the routes of exposure. There are four main types of radiation, due to; alpha particles, electrons, gamma rays, and X-rays (Klassen). While the frequency and dose of radiation given to take pictures of teeth and broken bones is suitable to patients for X-rays, it would be determinantal to patients if gamma rays were used.

Posted: Feb-16-03 at 3:37 PM by DINA KATZ

The radiation exposure rules can definitely be translated into toxicant exposure rules. For chemical exposure, time of radiation exposure is analogous tob the amount of chemical one is being exposed to, since the more time one spends exposed to radiation, the more particles have the potential to hit the body. The dose is analogous to the toxicity of the chemical, the relative speed and amount of damage done at target sites, or possibly route of exposure, since that will control how much of the chemical will get inside the body. Shielding can be compared to either the effectiveness of detoxification processes in the body or the physical barriers preventing the toxicant reaching the target site.

Since toxins and toxicants are so different from each other in their mechanisms of toxicity, any of the three above variables may be the crucial step in preventing the most damage. For example, for highly toxic materials that do not easily detoxify in the body, 'shielding' takes on a much greater importance. For chemicals of relatively low toxicity, limiting the 'time' or concentration factor may prevent major damage.

Posted: Feb-16-03 at 5:02 PM by Michael George

Yes, these can be translated into consideration in toxicant exposure.

1.) Minimize time of exposure to the source-if you can reduce the amount of time you are exposed to a toxicant you can possibly avoid toxicant effects since your body may be able to eliminate the toxicant in small doses.

2.) Maximize distance from source, if you can avoid the toxicant than no toxic effect will be produced.

3.) Optimize the amount of shielding to minimize dose-using goggles, face masks, gloves, etc. can minimize the amount of toxicant received.

Yes there are differences among routes of exposure or the nature of the toxicant that need to be considered. In radiation there are basically just one way of exposure, via x-ray exposure through the skin. In toxicant exposure there are a number of different routes that need to be considered, ie. Subcutaneous, intravenous, inhalation, etc. Toxicants can be a a number of different forms also, ie solid, powder, liquid, gas.

Old

Posted: Mar-11-02 at 12:07 PM by allison gold

The three cardinal rules for minimizing radiation exposure can be translated in toxicant exposure. Minimization of time for toxicant exposure reduces the time available to act on the toxicant's targets and primiary molecules. The ability of the toxicant to bind and act on targets is minimized by minimizing time, as in radiation exposure as well. Maximizing distance of a toxicant relates to dose/potency/concentration. By maximizing distance from source of toxicant the dose/potency/concentration are minimized. Intensity of toxicant is inversely proportional to the distance squared. Toxicants can be minimized by optimizing sheilding. This includes limiting the routes of exposure available to the toxicant. Vaccines may also act as an internal shield, which will optimize endogenous barriers or repair processes (Campbell, Lecture 3/7/02).

Posted: Mar-11-02 at 2:32 PM by Kenneth Campbell

Please elaborate on your last comments.

Posted: Mar-14-02 at 6:19 AM by joanne vannah

Analogs in chemical exposure:

1) (minimizing time) Decrease in time allotted for binding on targets, we had recently discussed the GI tract and how toxic effects occur only after they are absorbed, by limiting the time factor, one decreases the degree of absorption, thereby lessening the toxicity effect.

2)(maximizing distance) Since the intensity of the toxicant is inversely proportional to the distance squared. The increase in distance of the toxicant from its target cell will certainly have a compromised effect in terms of potency and concentration.

3)(shielding) This may be accomplished by limiting the amount/dose, limiting the exposure routes, dilution may be helpful in some cases and interaction with other chemicals may decrease the effect.

Posted: Mar-11-02 at 12:10 PM by allison gold

(con't)

There are also differences among route of exposure or nature of toxicant that need to be considered in minimizing toxicant exposure because limiting access to one route of exposure that is known to be a risk for toxicants may make another route of exposure more accessible to the toxicant after chronic response.

Posted: Mar-12-02 at 1:57 PM by neetu kainth

#4

yes, these rules can be translated into considerations in toxicant exposure. Minimizing time means loweing the time od toxicant to interact with its target molecule. Dose/Potency/ Concentration can be a analog of dose and limiting routes of exposures via vaccines; optimize endogenous barrier of repair processes can be analog of shielding for chemical exposure. Well just like with any other toxicant; you want to choose a route of exposure that will not take a long time to eliminate that toxicant. You also want to choose a toxicant that can be easily discarded by the body. Here, we are talking about radiation, therefore, we have to be little more careful than if we are talking about some kind of drug because radiation can cause mutations rapidly and thereore, can cause developmental defects. Also, depending on the nature of the toxicant, you want to choose the route of exposure taht is limited and will easily eliminate the toxicant. For example, if the toxicant can be degraded in liver, you wnat to choose the route of exposure that is limited to liver only.