*** Q. My only real question regarding the homework for this week is how to compute the effect from exposure when multiple routes of intake occurs. A grave digger will have intake via dermal contact, inhalation, and ingestion. Will the sum of the intake from the three routes (for example 50 mg/kg day) effect the body the same as the amount of intake from just one route (for example 50 mg/kg day from just dermal contact)?
A. Usually you just add the three exposure routes. However: There are three major routes of exposure: Ingestion, Inhalation, and Dermal. Each of those has an entry organ: mouth and upper GI, upper respiratory, and skin. If the "target organ" is the same as one of the entry organs, then that exposure needs to be considered separately. This is rare, however, for environmental exposures, but more common for workplace exposures.
***Q. It appears from what I have read that the average body weight used 15kg.
However what age are they basing this body weight (1-6years old; 1-18?). If
you have a 30 year exposure to some contaminant starting from infancy would
you use the adult body weight or the child body weight or some combination of
both? If children are more sensitive than wouldn't you want to take those years
into account differently than years spent as an adult?
A. These defaults are very general. But if lead was an issue, for example, because it is very toxic to the very young, you have to do special calculations. When you rationalize inhalation rate per body weight, the numbers come out about the same. In general, little enough is known about the effects in adults, when you look at the details.
***Q. There seem to be so many assumptions and generalities made that the Intake is merely a ballpark figure. How can this number be trusted?
A. Yes, it is a very rough estimate, at best.
***Q. n the uncertainty factor for subchronic studies, how do you know to use 10? You said to use 10 if it was a non-chronic study, is that the only value you can use? How do you know what your uncertainty factor would be for the MF?
A. "You" don't get to do that. The EPA, or whoever generated the "official" toxicity study, determines that. It is then published.
***Q. So it appears from the submodule 6b notes, that a contaminant can have both a reference concentration for inhalation and a RfD for non-inhalation pathways?
A. Yes, one for each exposure route: Inhalation (RfC), Dermal, and Ingestion (RfD). As a practical matter, the dermal route is seldom there. Most environmental risk assessments the exposure is much greater from inhaling or ingesting dust than dermal. However for workplace exposures, dermal is often a major hazard.
***Q. I also do not see how the inhalation rate discriminates between time spent indoors and time spent outdoors. Also, what about days of the year when the soil may be snow covered and not stirred up into dust?
A. You account for this in Exposure Frequency, the number of days per year.
***Q. The definition of AT for non-carcinogens in the Guidance for Conducting
Risk Assessments is a little unclear. Does AT = EF*ED or does AT = 365*ED?
A. You need to go back to the toxicology information, IRIS, and see how the RfD was derived and what the effects were. In general, for non-carcinogens, the assumption is that their effects either happen or don't during the exposure. So if exposure is only during the summer, the EF is 90 days.
Q. In the equations when we are calculating for the INTAKE for a child then we considering his/her age as 15 years. But when we are taking ED=70 or 30 years are we taking into fact that the age of the same child will increase?
A. You calculate for adults as well, and the grown kids are automatically included. You always look at children separately, for residential exposures. For industrial exposures you do not consider children.
Q. I do not understand why (even after sub module 6a and 6b) the AT for a carcinogen is 70 years x 365 days and for a non-carcinogen it is the exposure duration. Is there a distinct reason?
A. The averaging time is related to the toxicology studies and inferred biological processes. The general assumption is that non-carcinogens either cause an effect or they don't, and that they have a threshold below which there is no effect. What you see is what you get. Carcinogens are assumed to cause a bio-chemical effect, mutations, even at the smallest doses, but other mutations are needed before there is an observable effect. Hence the bio-chemical effect is averaged over a lifetime.
Q. You noted that the active portion of DNA has the adduct bonded and then must have replication without repair to possibly have a mutation that might possibly have an effect. By active DNA, do you mean the portion of DNA that is expressed in that cell?
A. Not well put by me. In any given cell, the vast majority of the DNA is sequestered, rolled up and put away, and less likely to be exposed to the electrophiles. Most of the DNA that is "active" is being expressed. Some of the known targets, sites of mutations, that are associated with cancer, are housekeeping genes that are usually being expressed, albeit at a low rate. I overreached because have never read that the sequestered DNA is immune to electrophilic attach. Also during the replication process, the entire DNA is out and about.
Q. Maybe this is outside the realm of this class, but it seems that expressing
a numerical amount for the RfD in 0.00033mg/kg-day seems a very small number
that is very difficult to communicate to a non-technical audience. How would
one describe this "specific" dose to someone that just wants to what
that means in a way that will mean something other than an ambiguous number?
A. A major difficulty, handling numbers with non-technical audiences. We will talk about this soon.
Q. My concern is about direct exposure through blood. In most cases it could
be neglected. But speaking of little kids
At least I remember when I was
a kid I always was decorated with all sorts of scratches, cuts and abrasions.
A. These are a great concern with microorganisms, bacteria, entering this way, because once in the body they multiply. Chemicals on the other hand, it is the amount transferred into the body that is important. The material transfer is not necessarily higher through a scrape.
Q. The generic formula for the Intake Rate was quite
generic. By looking
at just a few of available data there seems to be an opportunity to get caught
up in the amount of data generated from all of the different variables: where
does it end? How does one in a professional setting where the stakes are more
important than a classroom decide what data is acceptable and what data is not?
A. If these things really came to fruition, the answer would be "professional judgment." As it is, the answer is still "professional judgment" but the judgment regards what the public, politicians and the regulators want. In a contested matter, you could argue about each and every parameter in each model. See later module on probabilities and uncertainties.
Q. How would we go about calculating the intake rate for someone that has inhaled,
absorbed and digested a chemical. For example, someone working at a lead mine
where the company had inadequate heath standards to such a point where workers
were inhaling lead because of inadequate breathing aparateses, they were absorbing
the lead through their skin because of the lack of use of adequate gloves and
clothing and digesting the lead because the workers where not washing their
hands before eating after working with inadequate gloves. There would be a cumulative
amount of lead in the person, but is it as simple as just adding up the three
A. See elsewhere in closure module. It is "simple" but not necessarily "easy."
Q. Have you found out anything about creating a web-page with the jpg-image
within the page so that when I save the page, the image is saved within the
page instead of requiring me to save the image separate to the page?
A. I'll have to check on that. Usually, sites that do that send a folder with the images in it. I am working on a plan to set up an FTP site, so you can download the whole course.
Q. The Exposure Factor Handbook has a big disclaimer not to quote or cite. Plus, some of the equations seem incomplete. I guess that's why you suggested we use the DoE's equations, but refer to this for some of the factors?
A. There are a number of EPA guidance documents, including RAGS, that never seem go final. They remain stuck in interim status forever.
Q. The Exposure Factor Handbook goes to great detail to defining Ve, E, H,
and VQ but nowhere (can I see) are these terms directly related to terms in
the equation for Average Daily Dose (ADD).
A. Got me.
Q. In your example about the blueberries, how can you justify using 70 years
as an exposure duration for kids? They are only kids for what 16-18 years? (Well,
some of us take a little longer to grow up
A. How old do you have to be to dislike blueberries?
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