FW: Intraspecies Variability

arie at no.mail.thanks.nl arie at no.mail.thanks.nl
Mon May 31 13:48:08 EST 1999

Dear James, as Beata Lisek seems to have 'quoted' me by repeating a
message of mine, I will try to answer to your question.

On Wed, 26 May 1999 09:40:18 -0400, "James Stanley Smith, Jr., Ph.D."
<jssmith at oak-creek.net> wrote:

>Your post is quite intriguing.  Can you supply me with a reference(s) to your
>statement that "exposure to mercury from amalgams can be a lot higher than the
>amount that corresponds to 0.3 ug/m^3?"

That probably was my statement indeed, so I will give you a reference:

>For comparison purposes, only 0.01 percent of elemental mercury is absorbed in
>the gut following oral ingestion (US EPA Mercury Study Report to Congress,

Well, the above statement mentioned only 'exposure' which is different
from 'absorption'. So this explains away one intriguing aspect :)
In the report mentioned above, the mean (averaged over 17,351
subjects!) 'exposure' via oral ingestion was below 21 ug/day for only
30 % of the subjects. 

And as the amount that corresponds to 0.3 ug/m^3 equals 0.3 ug/m^3 *
20 m^3/day = 6 ug/day and 21 ug/day > 6 ug/day, I think my statement
still holds. (I'm not yet talking about absorption here.)

For a further 40% of the subjects, the daily 'exposure' (intake) is
below 44 ug/day. So about 30% have an intake above these 44 ug/day.
3.5% above 128 ug/day (as if these 3 digits are all significant), and
1.9% above 171 ug/day.

Further, I don't know yet whether I can agree with this figure 0.01 %
absorption. Is this a general figure, applicable to all ways to ingest
all forms of mercury?
In what form was the mercury ingested? Was it in the exremely small
particle size (high area-to-volume ratio => high absorption rate, high
methylation rate by bacteriae in the oral cavity as well as in the
gut) as in when the mercury is 'dissolved' in the saliva? Or was it
one big 'blob' of mercury? Please help me to get a grip on this
intriguing question.
To me it looks extremely low (well, to be honest: it *is* extremely
low), even too low to be accepted by me without viewing the report and
evaluating the research methodology and the measurement setup that
lead to this figure. Would you please be so kind to (let someone) send
me a copy of this report? For this please leave your e-mail address in
order that I can contact you to arrange this.

>  In contrast, nearly all (100 percent) of the inhaled elemental mercury
>is thought to be absorbed in the lung.  Combine this with an assumed respiration
>rate of 20 m^3/day (US EPA default value used in risk assessment, 1989) and one
>would have to ingest 600 ug/day (0.3 ug/m^3 x 20 m^3/day = amount absorbed via
>inhalation, then multiply by 100 to get the presumed equivalent oral dose
>ingested) to have an equivalent exposure to 0.3 ug/m^3. This calculation is, of
>course, crude 

Very crude indeed, as you seem to state that from the mercury only
0.01% is absorbed, where you seem to calculate as if it was 1%.
Calculating with these 0.01% would lead to an 'equivalent oral
ingestion' of 60 mg, which is obviously ridiculously high.

>and may not represent any particular reality, but it does provide
>a point of departure for discussing the relative exposure to mercury in dental

Which is a very interesting topic indeed, deserving a lot of research.

>I hope that you will respond similarly, by sharing your knowledge in this area.
>I look forward to a meaningful discussion of this issue.

I hope I did respond according to your wishes. Now I'd really be very
happy if you could provide me with the US EPA report that leads to the
0.01% absorption factor, as I've provided you with the terrific report
that led me to the conclusion that "exposure to mercury from amalgams
can be a lot higher than the amount that corresponds to 0.3 ug/m^3?"

kind regards,
arie sstt (and for all *not* a senator :)

>"Lisek, Beata" wrote:
>> -----Original Message-----
>> From: arie at no.mail.thanks.nl [mailto:arie at no.mail.thanks.nl]
>> Sent: Wednesday, May 19, 1999 6:42 PM
>> To: toxicol at net.bio.net
>> Subject: Re: Intraspecies Variability
>> What do you mean to say? That the US EPA lowest allowable dose of
>> mercury intake is in every individual larger than the real intake of
>> mercury from amalgams? So that health problems due to amalgam are
>> impossible? Is this what you suggest by
>> "however, even this small population's sensitivity is limited" and
>> "as you can see there can be a lot of additional uncertainty taken
>> into account in the derivation of the level of a compound that is
>> deemed "safe" and thought to be unlikely to cause adverse effects over
>> a lifetime of exposure."
>> ?
>> The exposure to mercury from amalgams can be a lot higher than the
>> amount that corresponds to 0.3 ug/m^3, for instance by ingestion.
>> kind regards,
>> arie
>> On Wed, 19 May 1999 09:26:24 -0400, "James Stanley Smith, Jr., Ph.D."
>> <jssmith at oak-creek.net> wrote:
>> >You are correct to assume that a small percentage of the populace may be
>> more
>> >sensitive to mercury intoxication than the general populace, however, even
>> >this small population's sensitivity is limited.  US EPA and other human
>> health
>> >organizations typically use an uncertainty factor (UF) of 10 (no
>> information)
>> >or 3 (limited information) to account for variability in human sensitivity.
>> >This UF is in addition to UFs that are typically used to account for a
>> limited
>> >data base (10), interspecies extrapolation (10), extrapolation from
>> subchronic
>> >to chronic study results (10), and extrapolation from a low observed
>> adverse
>> >effect level (LOAEL) to a no observed adverse effect level (NOAEL).  When
>> >appropriate, these UFs are multiplied together (UF product) and used to
>> lower
>> >the lowest amount of mercury shown to have an effect in the most sensitive
>> >animal species (LOAEL) or to lower the NOAEL, defined as the dose below a
>> >LOAEL at which no adverse effect occurs.  As you can see there can be a lot
>> of
>> >additional uncertainty taken into account in the derivation of the level of
>> a
>> >compound that is deemed "safe" and thought to be unlikely to cause adverse
>> >effects over a lifetime of exposure.
>> >
>> >For elemental mercury such as that used in amalgam, the US EPA
>> ><http://www.epa.gov/ngispgm3/iris/subst/0370.htm> uses a UF product of 30;
>> 10
>> >was used for the protection of sensitive human subpopulations (including
>> >concern for acrodynia) and 3 was used for the lack of a sufficent data
>> base,
>> >particularly developmental and reproductive studies.
>> >
>> >Current scientific studies suggest that an UF of 10 is adequate and in fact
>> >very likely to be overprotective of the most sensitive human population.
>> >Consequently, there is little concern for adverse health effects developing
>> in
>> >humans from chronic exposure to elemental mercury vapor that does not
>> exceed
>> >0.3 micrograms per cubic meter air (ug/m3).
>> >
>> >Finally, I do not want to suggest absolutely that some people are not
>> affected
>> >by chronic exposure to lower concentrations of elemental mercury vapor, but
>> I
>> >am not aware of any scientific evidence in support of their health claims.
>> >
>> >arie at no.mail.thanks.nl wrote:
>> >
>> >> I wonder if this would apply to mercury.
>> >> It's often said that only a small portion of the population (2 - 3 %)
>> >> suffers from detrimental health effects due to the chronical low dose
>> >> intoxication from mercury leaking from amalgam fillings. This could
>> >> mean that the other part has much more resistance.
>> >>
>> >> arie
>> >>
>> >> On Mon, 17 May 1999 11:52:46 -0400, toddh at brownvm.brown.edu (Todd)
>> >> wrote:
>> >>
>> >> >We often use a 10-fold uncertainty factor when considering the
>> >> >intraspecies variability in reactions to a particular chemical.  I am
>> >> >currently interested in looking at cases where that 10-fold factor may
>> >> >understate the true variability in the population.  I would be greatly
>> >> >appreciative if somebody could either give me examples or point me in
>> the
>> >> >direction of a good resource to find examples where this may be the
>> case.
>> >> >Human variation in reactions to Prozac would be one example.  Again, I'd
>> >> >appreciate any help that you could lend.  Thank you very much!
>> >> >
>> >> >Todd

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