From: Mark Probert on
Mike wrote:
> Peter Bowditch wrote:
>> "Jan" <jdrew63929(a)aol.com> wrote:
>>
>>> On Feb 4, 1:16?am, Peter Bowditch <myfirstn...(a)ratbags.com> wrote:
>>>> Mike <m...(a)xyz.com> wrote:
>>>>> Mark Probert wrote:
>>>>>> Mike wrote:
>>>>>>> David Wright wrote:
>>>>>>>> In article <DUPwh.78$yH3.42(a)trndny07>, Mike <m...(a)xyz.com> wrote:
>>>>>>>>> David Wright wrote:
>>>>>>>>>> Children are almost never given TT or Td. he amount of
>>>>>>>>>> thimerosal in
>>>>>>>>>> even the heaviest pediatric HepB dose is less than you'd get
>>>>>>>>>> from a
>>>>>>>>>> tuna sandwich.
>>>>>>>>> It is not so innocuous when you take body weight into account. One
>>>>>>>>> tuna sandwich for a 9 lb infant is like 20 sandwiches for a 180 lb
>>>>>>>>> adult. Actually it is even worse than that because an infant
>>>>>>>>> body is
>>>>>>>>> much weaker, especially for very young children who do not have
>>>>>>>>> blood brain barrier yet.
>>>>>>>> Except that the amount of mercury is even smaller than the doses
>>>>>>>> you
>>>>>>>> seem to be worried about.
>>>>>>> Smaller than what? Pregnant women are advised to avoid tuna
>>>>>>> sandwiches
>>>>>>> to protect their future children, why should the children be getting
>>>>>>> an equivalent of 20 tuna sandwiches?
>>>>>> Do you know the difference between ethyl and methyl mercury? I'll
>>>>>> give
>>>>>> you a hint, it is not just the 'm'.
>>>>> Yes, I do. According to a research on monkeys ethylmercury is MORE
>>>>> toxic
>>>>> for the brain than methylmercury.
>>>>> http://www.safeminds.org/research/library/Burbacher-EHP-Primates-Apri...
>>>>>
>>>> Why am I not surprised to find to find that SafeMinds are telling
>>>> lies?
>>> What lies?
>>
>> How about "ethylmercury is MORE toxic for the brain than
>> methylmercury"? That will do for a start.
>>
> For start, it is hardly a lie. The research showed that more inorganic
> mercury remains in the brain after exposure to ethylmercury than to
> methylmercury. And inorganic mercury stays much longer. That is, after 6
> months from exposure more mercury remains in the brain if the exposure
> was to thimerosal (ethylmercury) than to methylmercury.

However, that does NOT address T O X I C I T Y. Toxicity is NOT a
synonym for "remains in the brain".

For you to support your claim, you would have to show that the levels of
inorganic mercury are toxic, and these levels are more toxic than that
of MeHg.

Nothing you have posted that I have read, so far, shows that.

> Second, it has nothing to do with Safeminds. The quote above
> ("ethylmercury is MORE toxic for the brain than methylmercury") is from
> my posting but I did not quote Safeminds. You can blame me but again,
> this is not a lie.

If Safeminds is promoting the idea that you espouse, then they are lying.
From: mainframetech on


Welp, you see, one of the things that stand out to me is that this
forum is called "misc.health.alternative". That gives me and probably
other folks the idea that here we might hear about and discuss
ALTERNATIVE health solutions. That's 'discuss', not argue or insult,
or pick little logical nits about. The folks that I spoke of so
harshly all seem to berate almost all alternative' treatments, and
seem to swear by anything any med. community follower says. It's
things like that that give the impression that some folks are being
paid by the big drug companies to tout their products and put down the
competition, like supplements, etc. How do they get away from such a
low esteem position in other people's eyes? I guess they have little
choice. Keep doing it hoping to somehow wrest victory from the slime,
or convince someone somewhere that big pharma is the way to go.

Chris


From: Jan Drew on

"Mark Probert" <markprobert(a)lumbercartel.com> wrote in message
news:mFIxh.1031$Yl3.240(a)trndny09...
> Mike wrote:
>> Peter Bowditch wrote:
>>> "Jan" <jdrew63929(a)aol.com> wrote:
>>>
>>>> On Feb 4, 1:16?am, Peter Bowditch <myfirstn...(a)ratbags.com> wrote:
>>>>> Mike <m...(a)xyz.com> wrote:
>>>>>> Mark Probert wrote:
>>>>>>> Mike wrote:
>>>>>>>> David Wright wrote:
>>>>>>>>> In article <DUPwh.78$yH3.42(a)trndny07>, Mike <m...(a)xyz.com> wrote:
>>>>>>>>>> David Wright wrote:
>>>>>>>>>>> Children are almost never given TT or Td. he amount of
>>>>>>>>>>> thimerosal in
>>>>>>>>>>> even the heaviest pediatric HepB dose is less than you'd get
>>>>>>>>>>> from a
>>>>>>>>>>> tuna sandwich.
>>>>>>>>>> It is not so innocuous when you take body weight into account.
>>>>>>>>>> One
>>>>>>>>>> tuna sandwich for a 9 lb infant is like 20 sandwiches for a 180
>>>>>>>>>> lb
>>>>>>>>>> adult. Actually it is even worse than that because an infant body
>>>>>>>>>> is
>>>>>>>>>> much weaker, especially for very young children who do not have
>>>>>>>>>> blood brain barrier yet.
>>>>>>>>> Except that the amount of mercury is even smaller than the doses
>>>>>>>>> you
>>>>>>>>> seem to be worried about.
>>>>>>>> Smaller than what? Pregnant women are advised to avoid tuna
>>>>>>>> sandwiches
>>>>>>>> to protect their future children, why should the children be
>>>>>>>> getting
>>>>>>>> an equivalent of 20 tuna sandwiches?
>>>>>>> Do you know the difference between ethyl and methyl mercury? I'll
>>>>>>> give
>>>>>>> you a hint, it is not just the 'm'.
>>>>>> Yes, I do. According to a research on monkeys ethylmercury is MORE
>>>>>> toxic
>>>>>> for the brain than methylmercury.
>>>>>> http://www.safeminds.org/research/library/Burbacher-EHP-Primates-Apri...
>>>>> Why am I not surprised to find to find that SafeMinds are telling
>>>>> lies?
>>>> What lies?
>>>
>>> How about "ethylmercury is MORE toxic for the brain than
>>> methylmercury"? That will do for a start.
>>>
>> For start, it is hardly a lie. The research showed that more inorganic
>> mercury remains in the brain after exposure to ethylmercury than to
>> methylmercury. And inorganic mercury stays much longer. That is, after 6
>> months from exposure more mercury remains in the brain if the exposure
>> was to thimerosal (ethylmercury) than to methylmercury.
>
> However, that does NOT address T O X I C I T Y. Toxicity is NOT a synonym
> for "remains in the brain".

Just admit you were wrong.

http://groups.google.com/group/misc.health.alternative/msg/e8fe54c29370d71a
>
> For you to support your claim, you would have to show that the levels of
> inorganic mercury are toxic, and these levels are more toxic than that of
> MeHg.

Your insane need to argue is showing. A quick search answers your question.

http://www.atsdr.cdc.gov/tfacts46.html#bookmark02

http://www.atsdr.cdc.gov/toxpro2.html

http://www.atsdr.cdc.gov/toxprofiles/phs46.html

>
> Nothing you have posted that I have read, so far, shows that.
>
>> Second, it has nothing to do with Safeminds. The quote above
>> ("ethylmercury is MORE toxic for the brain than methylmercury") is from
>> my posting but I did not quote Safeminds. You can blame me but again,
>> this is not a lie.
>
> If Safeminds is promoting the idea that you espouse, then they are lying.

Look who is talking about lying.......

Shall I post your MANY, Many, many lies?

I have better things to do, as we have bought a park model on the lake here.

Absolutely beautiful and much to do.


From: Jan Drew on


Comparison of Blood and Brain Mercury Levels in
Infant Monkeys Exposed to Methylmercury or
Vaccines Containing Thimerosal
Thomas M. Burbacher, Danny D. Shen, Noelle Liberato,
Kimberly S. Grant, Elsa Cernichiari, and Thomas Clarkson
doi:10.1289/ehp.7712 (available at http://dx.doi.org/)
The National Institute of Environmental Health Sciences
National Institutes of Health
U.S. Department of Health and Human Services
ehponline.org
Online 21 April 2005
Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing Thimerosal
Thomas M. Burbacher, Ph.D.a,c,d*, Danny D. Shen, Ph.D.b, Noelle Liberato,
B.S. a,c,d,
Kimberly S. Grant, Ph.D.a,c,d, Elsa Cernichiari, M.S. e, and Thomas
Clarkson, Ph.D. e
Departments of Environmental and Occupational Health Sciences,a
School of Public Health and Community Medicine,
Departments of Pharmacy and Pharmaceutics b, School of Pharmacy,
Washington National Primate Research Center,c and
Center on Human Development and Disability,d
University of Washington, Seattle, Washington 98195 USA
Department of Environmental Medicinee , University of Rochester School of
Medicine,
Rochester, New York 14642 USA
Tables: 4
Figures: 7
*To whom all correspondence should be addressed:
Department of Environmental and Occupational Health Sciences
1705 NE Pacific Street
Health Sciences Building (F555)
School of Public Health and Community Medicine
University of Washington
Seattle, Washington 98195
Phone: (206) 685-1862
FAX: (206) 685-4696
e-mail address: tmb(a)u.washington.edu
2
Running Title: Thimerosal and blood and brain mercury
Key words: thimerosal, methylmercury, ethylmercury, brain and blood
distribution,
elimination half-life, infant nonhuman primates
Acknowledgments
The authors wish to thank the staff of the Infant Primate Research
Laboratory for their
cooperation during this study and Dr. David Blough for his assistance with
statistical
analyses. The authors would also like to thank Dr. John Treanor from the
University of
Rochester for supplying the vaccines used in the study. This project was
supported by
funds from the National Institutes of Health, Grants RO1ES03745, P51HD02274,
P51RR00166, P30ES07033 and NO1-A1-25460. The authors declare they have no
competing financial interests.
3
Abstract
Introduction
Methods
Subjects
Mercury Dosing Schedule
Blood Draw Schedule
Sacrifice Schedule
Blood and Brain Hg Measurement
Kinetic Analysis
Results
Infant Growth and Health Status
Oral Methylmercury Kinetics
Intramuscular Thimerosal Kinetics
Discussion
4
Abstract
Thimerosal is a preservative that has been used in manufacturing vaccines
since the
1930s. Reports have indicated that infants can receive ethylmercury (in the
form of
thimerosal) at or above the Environmental Protection Agency (EPA) guidelines
for
methylmercury (MeHg) exposure, depending on the exact vaccinations,
schedule, and
size of the infant. This study compared the systemic disposition and brain
distribution of
total and inorganic mercury in infant monkeys following thimerosal exposure
with
infants exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or
vaccines
containing thimerosal (via i.m. injection) at birth and 1, 2, and 3 weeks of
age. Total
blood mercury (Hg) levels were determined 2, 4 and 7 days after each
exposure. Total
and inorganic brain Hg levels were assessed 2, 4, 7 or 28 days after the
last exposure.
The initial and terminal half-life of Hg in blood following thimerosal
exposure was 2.1
and 8.6 days, which are significantly shorter than the elimination half-life
of Hg
following MeHg exposure at 21.5 days. Brain concentrations of total Hg were
significantly lower by ~3-fold for the thimerosal-exposed infants when
compared to the
MeHg infants, while the average brain-to-blood concentration ratio was
slightly higher
for the thimerosal-exposed infants (3.5�1.0 vs. 2.5�0.6). A higher
percentage of the total
Hg in the brain was in the form of inorganic mercury for the
thimerosal-exposed infants
(34% vs 7%). The current study indicates that MeHg is not a suitable
reference for risk
assessment from exposure to thimerosal derived Hg. Knowledge of the
toxicokinetics
and developmental toxicity of thimerosal is needed to afford a meaningful
assessment of
the developmental effects of thimerosal-containing vaccines.
5
Introduction
Public perception of the safety and efficacy of childhood vaccines has a
direct impact on
immunization rates (Biroscak et al. 2003, Thomas et al. 2004). The current
debate
linking the use of thimerosal in vaccines to autism and other developmental
disorders
(IOM 2001, 2004) has led many families to question whether the potential
risks
associated with early childhood immunizations may outweigh the benefits
(Blaxill et al.
2004; http://www.SafeMinds.org). Thimerosal is an effective preservative
that has been
used in the manufacturing of vaccines since the 1930s. Thimerosal is
comprised of 49.6
% mercury by weight and breaks down in the body to ethylmercury and
thiosalicylate
(Tab and Parkin 2000). Recent reports have indicated that some infants can
receive
ethylmercury (in the form of thimerosal) at or above the Environmental
Protection
Agency (EPA) guidelines for methylmercury (MeHg) exposure, depending on the
exact
vaccinations, schedule, and size of the infant (Ball et al. 2001). Clements
et al. (2000)
calculated that children receive 187.5 micrograms of ethylmercury from
thimerosal
containing vaccines given over the first 14 weeks of life. According to the
authors, this
amount approaches or, in some cases, exceeds the EPA guidelines for MeHg
exposure
during pregnancy (0.1 �g/kg/day). Other estimates (Halsey 1999) have
indicated that the
schedule could provide repeated doses of ethylmercury from approximately 5
to 20 �g/kg
over the first 6 months of life. Studies in preterm infants indicate that
blood levels of
mercury following just one vaccination (hepatitis B) increase by over
10-fold to levels
above the EPA guidelines (Stajich et al. 2000).
EPA guidelines for MeHg are based on several decades of studies of humans
and
animal models of developmental toxicity (Burbacher et al. 1990; National
Research
Council 2000). Since little data exist for ethylmercury, the use of the MeHg
guidelines
would seem appropriate if the two compounds have similar toxicokinetic
profiles and
neurodevelopmental effects. The results from the few studies that have
provided a direct
comparison of these two compounds have been summarized recently in a review
article
by Magos (2003), who concluded that:
� Mercury clears from the body faster after the administration of
ethylmercury than after the administration of MeHg
� The brain-to-blood mercury concentration ratio established for MeHg will
6
overestimate mercury in the brain after exposure to ethylmercury
� Because ethylmercury is decomposed faster than MeHg, the risk of brain
damage is less for ethylmercury than for MeHg.
These conclusions are based on only a few studies, none of which included
measurements
of both blood and brain mercury levels in infant subjects.
The current study was initiated to provide a direct comparison of the blood
and
brain levels of mercury in infant nonhuman primates exposed orally to MeHg
or via i.m.
injections of vaccines containing thimerosal. Nonhuman primates have been
used
extensively in previous studies of MeHg toxicokinetics and developmental
neurotoxicity
(Stinson et al. 1989; Vahter et al. 1994, 1995; Burbacher et al. 1986, 1990;
Gunderson et
al. 1986, 1988; Rice and Gilbert 1982, 1990, 1995). The routes of
administration (oral
for MeHg and i.m. injection for thimerosal-containing vaccines) were chosen
to mimic
the two routes of mercury exposure for humans. The dosages and schedule of
administration of mercury were chosen to be comparable to the current
immunization
schedule for human newborns, taking into consideration the faster growth
(approximately
4 to 1) of the macaque infant (Gunderson and Sackett 1984). The results of
this study
provide important new information regarding the comparative toxicokinetics
of these two
compounds in newborns and infants.
Methods
Subjects: Forty-one infant Macaca fascicularis born at the Washington
National Primate
Research Center�s Infant Primate Research Laboratory were used in the study.
The birth
weights of the infants were within the normal range for this species; the
average birth
weight was 341 grams (range 255 to 420 grams). Infants were weighed daily
throughout
the study and any clinical problems were recorded.
Mercury Dosing Schedule: The mercury-dosing schedule is shown in Table 1.
Infants were assigned to 1 of 3 exposure groups at birth. Seventeen infants
assigned to
the thimerosal group were given the typical schedule of vaccines for human
infants (see
Table 1). Thimerosal (Omicron Quimica S.A.), dissolved in saline, was mixed
with
thimerosal-free vaccines to yield a final concentration of 4, 8, or 20 �g/ml
mercury,
depending on the vaccine and the age of the infant. The total dose of
mercury
7
administered via the vaccines was 20 �g/kg on day 0 and at 7, 14, and 21
days of age. A
dose of 20 �g/kg was chosen based on the range of estimated doses received
by human
infants receiving vaccines during the first 6 months of life.
Seventeen infants assigned to the MeHg group were given MeHg hydroxide
(MeHgOH, 97% pure, Alfa Aesar, Johnson Matthey Co., Ward Hill, Massachusetts
USA) dissolved in water to a concentration of 20 �g Hg/ml. MeHg was
administered to
infants via oral gavage at a dose of 20 �g/kg on their day of birth (day 0)
and at 7, 14,
and 21 days of age.
Seven infants were assigned to a control group. These infants did not
receive
any gavages or i.m. injections. Infants were assigned to the three groups on
a semirandom
basis, in order to balance gender ratios and average birth weights across
groups.
Blood Draw Schedule: Blood was drawn from the saphenous vein of all infants
at birth (prior to any Hg exposure). Blood was also drawn 2, 4, and 7 days
after the
initial Hg exposure (day 0) and after subsequent exposures on days 7 and 14.
Depending
on the sacrifice group (see below) blood was drawn up to 28 days after the
final
exposure on day 21 to further characterize the washout kinetics of Hg (see
Table 1).
Sacrifice Schedule: Infants were sacrificed 2, 4, 7 or 28 days after their
last Hg
exposure on day 21 (see Table 1). Infants were sedated with an i.m.
injection of
ketamine (10mg/kg) and atropine (0.4 mg/kg) and then given an intravenous
overdose of
Nembutal (20 mg/kg). Autopsy personnel from the Primate Center drew blood
and
removed the brain and other organs for analysis. The autopsy typically
lasted
approximately 1 hour.
The number of infants at each sacrifice day for both the MeHg and thimerosal
groups was Day 2=4, Day 4=4, Day 7=5, and Day 28=4. The 7 control infants
were
assigned sacrifice days as follows Day 2=3, Day 4=1, Day 7=2, and Day 28=1
(see
Table 1). Infants were assigned to sacrifice groups at birth on a
semi-random basis that
balanced gender ratios and average birth weights across groups.
Blood and Brain Hg Measurement: Blood samples were prepared for Hg
analysis by diluting them with an equal volume of 1 % w/v NaCl solution.
Aliquots were
removed for mercury determination without digestion. One drop of antifoam
reagent was
added to the aliquot at the time of the analysis.
8
Half brain samples were fixed in formaldehyde prior to analysis. Samples of
the
fixative were analyzed to check for mercury content. The tissue was removed
from the
jar and blotted dry. A homogenate of the brain in 1% NaCl was prepared using
a
Polytron homogenyzer PT 10-35 ( Brinkmann Instruments, Westbury, NY) while
keeping
the sample in an ice slurry. An aliquot of the homogenate was digested with
1 ml of 1%
w/v cysteine and 2 ml of 45 % NaOH by heating at 950C for 10 to 15 minutes.
Digest
was allowed to cool and then diluted to volume by addition of 7 ml of 1% w/v
NaCl. The
digests were kept in an ice slurry until analysis. Aliquots were removed for
mercury
determination. One drop of antifoam was added to the aliquot at the time of
the analysis.
Total Hg concentrations in blood and total and inorganic Hg concentrations
in
brain were measured using a procedure adapted from Greenwood et al. (1977).
The
method determines total mercury and its inorganic fraction (Magos and
Clarkson 1972).
Cadmium chloride in the presence of stannous chloride at high pH breaks the
mercurycarbon
bond with the subsequent reduction of Hg2+ to Hg0, the latter is then
measured by
cold vapor atomic absorption at 254 nm with a Model #1235 mercury monitor
from
Laboratory Data Control (Thermo Separation Products). Inorganic mercury is
determined by the addition of stannous chloride in the absence of cadmium
chloride.
Concentration of organic Hg was calculated from the difference between the
measured
total and inorganic Hg concentrations. The original concentration of SnCl2
used for the
Magos method (1972) was modified to prevent the decomposition of the
ethylmercury
during assay (Magos et al. 1985). To measure mercury in aqueous solution of
thimerosal
the amount of SnCl2 was reduced from 100 �g to 50 �g per aliquot analyzed.
For tissue
homogenate samples, 500 �g of SnCl2 was added to each aliquot. All reagents
used for
preparation and analysis of the samples were of analytical grade.
Quality control was assured by analysis of reference samples prior to each
assay
run. Fisher Mercury Reference Solutions (SM114-100, certified 1000 ppm + 1%)
was
used as a stock solution. Working standards of 30 and 10 ng Hg/ml were made
daily from
appropriate dilutions of the stock solution. In addition, the following
certified reference
materials were analyzed daily prior to analysis of the samples: Trace
Elements in Whole
Blood (Seronorm Trace Elements, Accurate Chemical & Scientific Corporation,
Certified
Reference Material #201605, 6.8-8.5 �g/L), and Trace Elements in Human Hair
9
(Commission of the European Communities, Certified Reference Material #397:
12 �g/g
+/- 0.5). The detection limit of the instrument was estimated to be 0.75 ng
Hg per aliquot
used for analysis.
Data Analysis: The mean total blood Hg concentration data from both the oral
MeHg and i.m. thimerosal groups (N=17 in each) were subject to analysis
using the
compartmental module of the pharmacokinetic modeling software SAAM II (SAAM
Institute, Seattle, WA).
The accumulation and washout of total blood Hg concentration-time data from
the
MeHg infants were well described by a one-compartment model featuring a
first-order
absorption process. Regression fit of the data to the model yielded
estimates of the
absorption rate constant (ka), elimination rate constant (K), and an
apparent volume of
distribution (V/F, F is the implicit bioavailability term). Half- lives
(T1/2) corresponding
to each of the rate constants were calculated by dividing ln 2 by the rate
constant
estimate. Blood clearance (Cl/F) was derived from the product of K and V/F.
A one-compartment model failed to provide a satisfactory fit of the mean
total
blood Hg concentration-time data from the thimerosal infants. The model
over-predicted
the blood concentration during accumulation; at the same time, it
under-predicted the
blood concentration during washout rate (i.e., over-predicted washout rate).
Further
examination of a scatter-plot of the individual monkey data suggested a
biphasic pattern
in the washout of Hg from the blood following the last dose. Accordingly, a
regression
fit of the mean total blood Hg concentration data with a two-compartment
model was
attempted. This yielded a much better visual fit of the data, with minimal
change in the
objective function and Akaike Information Criterion (AIC). The
two-compartment
parameter estimates from the regression analysis included the absorption
rate constant
(ka), rate constants for Hg transfer from the central to the peripheral
compartment (k12)
and the return from the peripheral to the central compartment (k21), the
elimination rate
constant from the central compartment (k10), and the apparent volume of the
central
compartment (Vc/F). From these primary parameters, we further estimated the
apparent
distribution volume at steady-state (Vss/F), and the peripheral volume
referenced to
blood concentration (i.e., Vp=Vss � Vc). The initial and terminal rate
constants and halflives
(T1/2,a and T1/2,�) for the biexponential decline of total blood Hg
concentration were
10
estimated by standard formulae (Gibaldi and Perrier 1982). Blood clearance
was
computed by the product of Vc and k10. For both the MeHg and thimerosal
model fits, a
fractional standard deviation of 0.1 was used as the weighting scheme.
The washout half-life of total and organic Hg in the brain of both the oral
MeHg
and i.m. thimerosal groups were estimated by regression fit to a
monoexponential model
using the WinNonlin software (Pharsight Corp., Mountain View, CA). One of
the Day
28 brain samples from the MeHg exposure group had a spuriously high total Hg
concentration; i.e., a concentration of 151 ng/g, which is more than 50%
higher than the
other samples obtained on Day 28 (71-90 ng/ml) and higher than those
observed at the
earliest sacrifice time at Day 2 (75 to 129 ng/g). The unreasonably high
concentration is
most likely due to contamination of the sample. Therefore, data from this
brain and its
corresponding blood were excluded from the regression analysis. The average
brain-toblood
concentration ratio was also calculated using data from the earliest
sacrifice
duration (2 days). Because of different washout half-lives in blood and the
brain, brainto-
blood concentration ratio is expected to vary with the duration of washout.
Samples at
Day 2 offered the best measure of the extent of uptake of Hg species into
the brain that
are least confounded by differences in their clearance rate.
Between-group statistical comparisons of the rate of washout of total Hg in
blood,
as well as total and organic concentrations in the brain, were accomplished
through
multiple regression analysis as implemented in the PROC GLM subroutine in
SAS
(version 9.1, SAS Institute, Gary NC). PROC GLM performs multiple regression
within
the framework of General Linear Models, and can accommodate missing data or
sparse
sampling and confounding from correlations between repeated measures. Hence,
it is
able to provide tests of hypotheses for the effects of time and group using
blood and brain
data obtained from sacrifice of individual animals at varying times during
washout. Log
transformed blood or brain Hg concentrations in animals from both the MeHg
and
thimerosal groups were entered as the dependent variable. The independent
variables
consisted of sampling time, group (MeHg=0, thimerosal=1), and a
time-by-group
interaction. Once the overall significance of the regression model was
verified, the
significant sources of variation (i.e., time, group and time-by-group) were
identified. A
difference in the rate of washout of Hg in blood or brain between groups was
indicated by
11
a significant regression coefficient for time-by-group interaction. If there
was no
evidence for interaction, a significant decline in blood or brain Hg
concentration over
time for each group was assessed by the t-statistic associated with the
estimated
regression coefficient for time.
The following statistical comparisons of the washout rate of Hg were also
undertaken: total Hg in blood versus total Hg in brain, total Hg in blood
versus organic
Hg in the brain, and total Hg versus organic Hg concentration in the brain.
The
difference between the pair of log transformed Hg concentrations for each
animal
sacrificed at the various times was calculated. Individual difference values
in both
groups were then entered as the dependent variable in the regression model.
The
independent variables were time, group and time-by-group interaction. A
significant
regression coefficient for the time variable indicates that the paired-log
concentration
difference (or the concentration ratio) varied with time; i.e., the two
concentration
measures (e.g. blood and brain) declined in parallel with time.
Results
Infant Growth and Health Status: The weights of infants during the study are
shown in Figure 1. There were no significant differences in the weight gain
across the 3
groups (p>0.10, all comparisons). The average weight gain during the first
23 days of
life was 135 grams. The brain weights at sacrifice and brain-to-body weight
ratios are
shown in Table 2. There were no significant differences in the brain weights
or brain-tobody
weight ratios across the 3 groups (p>0.10, all comparisons). There were no
serious
medical complications for any of the infants.
Oral MeHg Kinetics: The total blood Hg concentrations at 2 days (observed
peak) following the first dose ranged from 8 to 18 ng/ml across the infants,
i.e., a 2-fold
variation. Progressive accumulation of total blood Hg was observed over the
three
subsequent doses of MeHg, such that the peak total blood Hg concentrations
after the
fourth dose were about 3-fold higher (30-46 ng/ml). The inter-animal
variation in blood
Hg concentrations remained at about 2-fold during accumulation. Blood Hg
persisted
through the entire period of washout, and was readily measurable in all 4
infants in the 28
day sacrifice group (16-21 ng/ml). This is consistent with previous reports
of a greater
12
than 20 day elimination T1/2 of methymercury in adult M. fascicularis
(Stinson et al.
1989; Vahter et al. 1994, 1995) and explains the minimal decline (<20%) in
blood
mercury concentrations during the weekly intervals between MeHg doses.
The time course of total blood Hg was fitted to a one-compartment model.
Figure
2 shows the excellent regression fit of the mean blood concentration-time
data. Table 3
presents parameter estimates from the one-compartment model fit of the mean
blood Hg
concentration-time data. The distribution volume of total mercury following
MeHg
administration is estimated to be 1.7 L/kg, or about 20 times the blood
volume (~8%).
This means that only 1/20th of the body burden of mercury is confined to the
vascular
space. This is consistent with the known extensive extravascular
distribution of Hg
following methymercury exposure in primates and agrees with previous
estimates of Hg
distribution volume in adult M. fascicularis (Stinson et al. 1989). The
elimination T1/2 of
total blood Hg is 21.5 days, which agrees with reported estimates in adult
M. fascicularis
(Stinson et al. 1989; Vahter et al. 1994, 1995). The blood clearance is
estimated at 46.1
ml/day/kg, well within the range of clearance values observed earlier in
adult M.
fascicularis (Stinson et al. 1989). It appears that the systemic disposition
kinetics of
MeHg are the same between infant and adult M. fascicularis, i.e., no change
during
development.
A plot of the blood and brain total Hg concentration data from the infants
sacrificed at various times during the washout period is shown in Figure 3.
There was a
significant decrease in total Hg from the blood during the washout period
(p< 0.01). The
apparent T1/2 for total Hg in blood is 19.1�5.1 days (�standard error of
regression
estimate). The decrease in total Hg in the brain over time was marginally
significant (p<
0.07), with an apparent T1/2 of 59.5�24.1 days. The T1/2 for total Hg in
brain was
significantly longer than the T1/2 for total Hg in blood (p= 0.05) for the
MeHg-exposed
infants. The T1/2 for total Hg in brain (59.5�24.1 days) is also longer than
the previously
reported washout T1/2 from the brain for adult M. fascicularis (37 days,
Vahter et al.
1994, 1995). It should be noted that the relatively high standard error of
the half-life
estimates for the brain reflects the large inter-animal variation in Hg
concentrations at
each sampling time, limited number of data points, and the short duration of
sacrifice
relative to the washout half-life. The concentration of total Hg in the
brain is 1.7 to 3-
13
fold higher than in the blood (mean�SE = 2.5�0.3) 2 days after the last MeHg
dose. This
brain-to-blood concentration ratio increased as the duration between the
last dose and the
sacrifice lengthened. The ratio ranged from 3.9 to 7.4 at 28 days after the
last exposure.
The time-dependence for the brain-to-blood ratio is primarily due to the
difference in the
washout T1/2 between total Hg in the blood and brain (p=0.06). The average
brain-toblood
ratio for these infants at Day 2 after the last MeHg dose (2.5�0.3) is
slightly lower
than previously reported values (3 to 5) for adult macaque and squirrel
monkeys over
various durations of washout (Stinson et al. 1989; Vahter et al. 1994;
Berlin et al. 1975).
Although the cited differences in brain uptake and clearance of MeHg between
adult and
infant monkeys may be attributed to the effects of postnatal brain growth
and
development, it may also be related to variation in exposure regimen between
studies.
A plot of the organic and inorganic Hg concentrations in the brain of
MeHgexposed
infants sacrificed at various times during the washout period is shown in
Figure
4. The decrease in organic Hg in the brain over time was not statistically
significant (p=
0.17). The apparent T1/2 for the washout of organic Hg from the brain was
58.4�25.0
days, close to the T1/2 for total Hg. The concentration of inorganic Hg in
the brain
samples was below the quantifiable limit of the assay (7 ng/ml) in 8 of 17
MeHg-exposed
infants. The average concentration of inorganic Hg for those infants with
values above
the detection limit (N=10) did not change significantly over 28 days of
washout and was
approximately 7 to 8 ng/ml (see Figure 5). Inorganic Hg represented only 6%
to 10% of
total Hg in the brain. These values are consistent with previously reported
data in adult
M. fascicularis (Vahter et al. 1994, 1995).
Intramuscular Thimerosal Kinetics: The initial total Hg concentrations in
the
day 2 blood samples, which ranged from 6 to 14 ng/ml, are comparable to the
concentrations observed in the oral MeHg group. These blood levels are also
similar to
those reported in preterm infants receiving 12.5 �g of mercury from a
hepatitis b vaccine
(Stajich et al. 2000). Blood Hg concentrations declined relatively rapidly
(by >50%) in
between doses. As a result, there was minimal accumulation in blood Hg
concentrations
during weekly dosing. Also, blood Hg concentrations dropped below the
detection limit
of the assay in some animals by day 10 after the last vaccine injection.
The time course of total blood Hg concentrations was best described by a
two14
compartment model; i.e., the disposition kinetics is biphasic, with a rapid
initial phase
followed by a slower terminal phase of clearance. Table 4 presents the
parameter
estimates derived from the two-compartment model analysis. A comparison of
the model
prediction and the observed blood concentration data are shown in Figure 5.
The model
predicted some accumulation in peak blood Hg concentrations, and minimal
accumulation in trough concentrations. Since blood concentration data were
not
available before day 2, the predicted peak concentrations are extrapolations
and should be
viewed with caution. The initial volume of distribution in the central
compartment was
1.7 L/kg, which is comparable to the overall distribution volume for oral
MeHg. The
initial and terminal blood half-life was 2.1 and 8.6 days, respectively.
Mercury derived
from thimerosal is eliminated much more rapidly than MeHg. The steady-state
volume
of distribution (i.e., Vss or the fully equilibrated volume) was estimated
to be 2.5 L/kg,
which is 50% larger than the initial distribution volume (i.e., Vc). Hence,
the effective
peripheral compartment volume at steady state is about 0.8 L/kg.
Alternately, this means
that, at steady state, partitioning of the body burden of Hg between the
tissue regions
associated with the central and peripheral compartments is about 2:1. The
blood
clearance of total Hg was estimated to be 248 ml/day/kg, which is 5.4-fold
higher than
the estimate for oral MeHg.
Figure 6 presents a scatter-plot of the blood and brain total Hg
concentration data
for infants sacrificed at various times during the washout. There was a
significant
decrease in total Hg concentration in the blood during the washout period
(p< 0.01). The
apparent T1/2 for total Hg in blood is 6.9�1.7 days. There was also a
significant decrease
in total Hg concentration in the brain over time (p< 0.01), with an apparent
T1/2 of
24.2�7.4 days. The T1/2 for total Hg in brain was significantly longer than
the T1/2 for
total Hg in blood (p< 0.01) for the thimerosal-exposed infants. In addition,
the T1/2 for
total Hg in blood and brain for these infants (6.9�1.7 days and 24.2�7.4
days) are
significantly shorter (p< 0.01) than the T1/2 for total Hg in blood and
brain for the MeHg
infants (19.1�5.1 days and 59.5�24.1 days). The concentration of total Hg in
the brain of
the thimerosal-exposed infants is 2.6 to 4.6-fold higher than in the blood
(mean�SE =
3.5�0.5) 2 days after the last injection. Again, this ratio increased as the
sacrifice was
performed at longer durations from the last dose, primarily due to the
difference in the
15
half-lives of total Hg in the blood and brain.
A plot of the organic and inorganic Hg concentrations in the brain of
thimerosalexposed
infants sacrificed at various times during the washout period is shown in
Figure
7. There was a significant decrease in organic Hg in the brain over the
washout period
(p< 0.01). The apparent T1/2 for the washout of organic Hg from the brain
was 14.2�5.2
days, which is significantly shorter than the T1/2 for total Hg in brain (p<
0.01). The
inorganic form of Hg was readily measurable in the brain of the
thimerosal-exposed
infants. The average concentration of inorganic Hg did not change across the
28 days of
washout and was approximately 16 ng/ml (see figure 9). This level of
inorganic Hg
represented 21 % to 86% of the total Hg in the brain (mean�SE = 70�4%),
depending on
the sacrifice time. These values are considerably higher than the inorganic
fraction
observed in the brain of MeHg infants (6% to10%).
Discussion
There are notable similarities and differences in the kinetics of Hg
following oral
administration of MeHg and i.m. injection of thimerosal in vaccines. The
absorption rate
and initial distribution volume of total Hg appear to be similar between
i.m. thimerosal
and oral MeHg. This means approximately equal peak total blood Hg levels
following a
single exposure to either MeHg or thimersoal or following episodic exposures
that are
apart by longer than four elimination half-life (i.e., >80 days for MeHg or
>28 days for
thimerosal). Studies in preterm and term human infants have reported similar
results
(Stajich et al. 2000). Infants receiving 12.5 ug of mercury from a single
hepatitis b
vaccine had blood mercury levels at 48 to 72 hours consistent with what
would be
anticipated after an equal dose of MeHg.
While the initial distribution volume of total Hg is similar for the 2
groups, a
biphasic exponential decline in total blood Hg is observed only following
i.m. injections
of thimerosal. This suggests continual distribution into and localization in
tissue sites
over time. It is relevant to note that the kidney-to-blood concentration
gradient of total
Hg is much higher in the thimerosal infants than in the MeHg infants
(mean�SE 95.1�10
vs 5.8�0.6). The second slower phase of washout could also represent the
gradual
biotransformation of ethylmercury (the presumed principal organic form of Hg
after
thimerosal administration) to Hg-containing metabolites that have a
different tissue
16
distribution or are more slowly eliminated. Further investigations of the
disposition fate
of thimerosal-derived mercury should address these issues.
Total Hg derived from i.m. thimerosal is cleared from the infant M.
fascicularis
much more quickly than MeHg. The washout T1/2 of total blood Hg following
i.m.
injections of thimerosal in vaccines is much shorter than the T1/2 of MeHg
(6.9 vs. 19.1
days). These results support the earlier conclusion of Magos (2003) that
mercury is
cleared from the body faster after the administration of ethylmercury than
after the
administration of MeHg. More interestingly, the washout blood Hg T1/2 in the
thimerosal-exposed infant macaques is remarkably similar to the blood
mercury T1/2 of
approximately 7 days in human infants injected with thimerosal-containing
vaccines
reported by Pichichero et al. (2002).
An important consequence of the difference in blood half-lives is the
remarkable
accumulation of blood Hg during repeated exposure to MeHg. While the initial
blood Hg
concentration (at 2 days after the first dose) did not differ between the
MeHg and
thimerosal groups, the peak blood Hg concentration in the MeHg-exposed
infants rose to
a level nearly 3 times higher than in the thimerosal infants after the 4th
dose.
Furthermore, the blood clearance of total Hg is 5.4-fold higher after i.m.
thimerosal than
after oral MeHg exposure. This means that for an equivalent level of chronic
exposure,
the area under the curve (AUC) of total blood mercury concentrations in
infants receiving
repeated i.m. injections of thimerosal-containing vaccines will be
significantly lower than
infants exposed chronically to MeHg via the oral route.
A much lower brain concentration of total Hg was observed in the thimerosal
infants compared to the MeHg infants, i.e., a 3- to 4-fold difference for an
equivalent
exposure of Hg. Moreover, total Hg is cleared much more rapidly from the
brain after
thimerosal than after methymercury exposure (24 vs 60 days). It appears that
the
difference in brain Hg exposure between thimerosal and MeHg is largely
driven by their
differences in systemic disposition kinetics (i.e., the blood level). The
average brain-toblood
partitioning ratio of total Hg in the thimerosal group was slightly higher
than that
in the MeHg group (3.5�0.5 vs 2.5�0.6, t-test, p=0.11). Thus, the
brain-to-blood mercury
concentration ratio established for MeHg will underestimate the amount of
mercury in the
brain after exposure to thimerosal.
17
The large difference in the blood Hg half-life compared to the brain
half-life for
the thimerosal-exposed infants (6.9 days vs 24 days) indicates that blood Hg
may not be a
good indicator of risk of adverse effects on the brain, particularly under
conditions of
rapidly changing blood levels such as those observed following vaccinations.
The blood
concentrations of the thimerosal-exposed infants in the current study are
within the range
of those reported for human infants following vaccination (Stajich et al
2000). Data from
the current study predicts that while little accumulation of Hg in the blood
occurs over
time with repeated vaccinations, accumulation of Hg in the brain of infants
will occur.
Thus, conclusion regarding the safety of thimerosl drawn from blood Hg
clearance data
in human infants receiving vaccines may not be valid, given the
significantly slower halflife
of Hg in the brain as observed in the infant macaques.
There was a much higher proportion of inorganic Hg in the brain of
thimerosal
infants than MeHg infants (up to 71% vs. 10%). Absolute inorganic Hg
concentrations in
the brains of the thimerosal-exposed infants were approximately twice that
of the MeHg
infants. Interestingly, the inorganic fraction in the kidneys of the same
cohort of infants
was also significantly higher following i.m. thimerosal than oral MeHg
exposure
(0.71�0.04 vs. 0.40�0.03). This suggest that the dealkylation of
ethylmercury is much
more extensive than that of MeHg.
Previous reports have indicated that the dealkylation of mercury is a
detoxification process that helps to protect the CNS (Magos et al. 1985;
Magos 2003).
These reports are largely based on histology and histochemistry studies of
adult rodents
exposed to mercury for a short period of time. The results of these studies
indicated that
damage to the cerebellum was only observed in MeHg treated animals who had
much
lower levels of inorganic mercury in the brain than animals comparably
treated with
ethylmercury. Moreover, the results did not indicate the presence of
inorganic mercury
deposits in the area where the cerebellar damage was localized (granular
layer).
In contrast, previous studies of adult M. fascicularis monkeys exposed
chronically to
MeHg have indicated that demethylation of mercury occurs in the brain over a
long
period of time following MeHg exposure and that this is not a detoxification
process
(Vahter et al. 1994, 1995; Charleston et al. 1994, 1995, 1996). Results from
these studies
indicated higher inorganic Hg concentrations in the brain 6 months after
MeHg exposure
18
had ended while organic Hg had cleared from the brain. The estimated
half-life of
organic Hg in the brain of these adult monkeys was consistent across various
brain
regions at approximately 37days (similar to the brain half-life in the
present infant
monkeys). The estimated half-life of inorganic Hg in the brain in the same
adult cohort
varied greatly across some regions of the brain, from 227 days to 540 days.
In other
regions, the concentrations of inorganic Hg remained the same (thalamus) or
doubled
(pituitary) 6 months after exposure to MeHg had ended (Vahter et al. 1994,
1995).
Stereologic and autometallographic studies on the brains of these adult
monkeys
indicated that the persistence of inorganic Hg in the brain was associated
with a
significant increase in the number of microglia in the brain, while the
number of
astrocytes declined. Notably, these effects were observed 6 months after
exposure to
methymercury ended, when inorganic Hg concentrations were at their highest
levels, or
in animals solely exposed to inorganic Hg (Charleston et al. 1994, 1995,
1996). The
effects in the adult macaques were associated with brain inorganic Hg levels
approximately 5 times higher than those observed in the present group of
infant
macaques. The longer-term effects (greater than 6 months) of inorganic Hg in
the brain
have not been examined. In addition, whether similar effects are observed at
lower levels
in the developing brain is not known. It is important to note that a recent
publication has
demonstrated �an active neuroinflammatory process� in brains of autistic
patients,
including a marked activation of microglia (Vargas et al. 2005).
In 1999, the American Academy of Pediatrics and the Public Health Service
published a joint statement that urged �all government agencies to work
rapidly toward
reducing children�s exposure to mercury from all sources.� The statement
recommended
that thimerosal be removed from vaccines as soon as possible as part of this
overall
process (American Academy of Pediatrics 1999). Between 1999 and 2001,
vaccines
currently recommended for children 6 years of age and under were made
available in
thimerosal-free formulations in the United States (CDC 2001). Exposures to
thimerosal
through pediatric vaccines, however, still occur in other countries where
multiple-dose
vials are used to maintain childhood immunization programs and the control
of
preventable disease (Knezdvic et al. 2004).
Recent publications have proposed a direct link between the use of
thimerosal
19
containing vaccines and the significant rise in the number of children being
diagnosed
with autism, a serious and prevalent developmental disorder (for review, see
IOM 2001).
Results from an initial Institute of Medicine (IOM) review of the safety of
vaccines found
that there was not sufficient evidence to render an opinion on the
relationship between
ethylmercury exposure and developmental disorders in children (IOM 2001).
The IOM
review did, however, note the possibility of such a relationship and
recommended further
studies be conducted. A recently published second IOM review (IOM 2004)
appears to
have abandoned the earlier recommendation as well as back away from the
American
Academy of Pediatrics goal. This approach is difficult to understand, given
our current
limited knowledge of the toxicokinetics and developmental neurotoxicity of
thimerosal, a
compound that has been (and will continue to be) injected in millions of
newborns and
infants.
The key findings of the current study are the differences in the disposition
kinetics
and demethylation rates of thimerosal and MeHg. Consequently, MeHg is not a
suitable
reference for risk assessment from exposure to thimerosal derived Hg.
Knowledge of the
biotransformation of thimerosal, the chemical identity of the Hg-containing
species in the
blood and brain, and the neurotoxic potential of intact thimerosal and its
various
biotransformation products, including ethylmercury are urgently needed to
afford a
meaningful interpretation of the potential developmental effects of
immunization with
thimerosal-containing vaccines in newborns and infants. This information is
critical if
we are to respond to public concerns regarding the safety of childhood
immunizations.
20
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23
Table 1. Study Design and Schedule
Age (Days)
Birth
Age (
0) 2 4 7 9 11 14 16 18 21 23 25 28 31 35 38 42 45 49
Mercury Dose1
(Oral MeHg) 20 20 20 20
Mercury Dose2
(I.M. Thimerosal in Vaccine)
OPV-0
HB-20
OPV-0
HB-4
DTP-8
Hib-8
OPV-0
DTP-10
Hib-10
OPV-0
HB-4
DTP-8
Hib-8
Blood Draws3 0 2 4 7 2 4 7 2 4 7 2 4 7 10 14 17 21 24 28
Sacrifice Day4 2 4 7 28
1Dose of MeHg in �g/kg
2Dose of ethylmercury in �g/kg
3Days after most recent dose
4Days after last (4th) dose
24
Table 2. Mean (SE) body and brain weight (grams) and brain to body ratio at
sacrifice for
controls, MeHg exposed and thimerosal exposed animals.
Exposure Group Body Weight Brain Weight Brain to Body Ratio
Controls (n=9) 509.3 (52.0) 52.1 (2.5) 0.107 (0.009)
MeHg Exposed (n=17) 499.1 (17.5) 51.1 (1.1) 0.103 (0.003)
Thimerosal Exposed (n=17) 529.1 (25.4) 52.7 (1.2) 0.102 (0.003)
25
Table 3. Parameter estimates derived from a one-compartment analysis of the
mean
blood total Hg concentration for the oral methylmercury group (N=17).
Model Parameters Mean � SD
V/F (L/kg) 1.67 � 0.07
ka (day-1) 2.07 � 1.04
K (day-1) 0.0276 � 0.0024
T1/2 (days) 21.5
Cl/F (ml/day/kg) 46.1
26
Table 4. Parameter estimates derived from a two-compartment analysis of the
mean
blood total Hg concentration for the i.m. thimerosal group (N=17).
Model Parameters Mean � SD
ka (day-1) 3.24 � 3.00
k12 (day-1) 0.081 � 0.076
k21 (day-1) 0.177 � 0.138
k10 (day-1) 0.148 � 0.024
T1/2, a (day) 2.13
T1/2, � (day) 8.62
Vc/F (L/kg) 1.68 � 0.30
Vss/F (L/kg) 2.45
Vp (L/kg) 0.77
Cl/F (ml/day/kg) 248
27
Figure 1. Weight gain of infants during study
28
Figure 2. Comparison of model predicted and observed mean blood total Hg
concentration during and after four weekly oral doses (20 �g/kg) of
methylmercury.
29
Figure 3. A semi-logarithmic plot of washout of total Hg in blood (??) and
the brain (??)
after 4 weekly oral doses (20 �g/kg) of methylmercury. The data were
collected from
groups of infants sacrificed at 2, 4, 7 and 28 days following the last dose.
The lines
represent nonlinear regression fit of the data to a monoexpoential model.
The regression
estimate (� standard error) of T1/2 is shown along with the correlation
coefficient (r).
30
Figure 4. A semi-logarithmic plot of the washout of organic (?) and
inorganic (?) Hg in
the brain after 4 weekly oral doses (20 �g/kg) of methylmercury. The data
were
collected from groups of infants sacrificed at 2, 4, 7 and 28 days following
the last dose.
The lines represent nonlinear regression fit of the data to a monoexpoential
model. The
regression estimate (� standard error) of T1/2 for organic Hg is shown along
with the
correlation coefficient (r). The half-life of inorganic Hg is too long (>120
days) to be
accurately estimated from the present data (i.e., r is not significantly
different from 0).
31
Figure 5. Comparison of model predicted and observed mean blood total Hg
concentration during and after four weekly i.m. injection of vaccine
containing
thimerosal at 20 �g/kg of Hg.
32
Figure 6. A semi-logarithmic plot of washout of total Hg in blood (??) and
the brain (??)
after four weekly i.m. injections of vaccine thimerosal at 20 �g/kg of Hg.
The data were
collected from groups of infants sacrificed at 2, 4, 7, 10, 17 and 21 days
following the last
dose. The lines represent nonlinear regression fit of the data to a
monoexpoential model.
The regression estimate (� standard error) of T1/2 is shown along with the
correlation
coefficient (r).
33
Figure 7. A semi-logarithmic plot of washout of organic (?) and inorganic
(?) Hg in the
brain after 4 weekly i.m.injection of vaccines containing thiomerosal at 20
�g/kg of Hg.
The data were collected from groups of infants sacrificed at 2, 4, 7 and 28
days following
the last dose. The lines represent nonlinear regression fit of the data to a
monoexpoential
model. The regression estimate (� standard error) of T1/2 for organic Hg is
shown along
with the correlation coefficient (r). The half-life of inorganic Hg is too
long (>120 days)
to be accurately estimated from the present data (i.e., r is not
significantly different from
0).
34
List of abbreviations
MeHg- methylmercury
EPA- Environmental Protection Agency
Hg- mercury
Hg2+- mercuric mercury
Hg0- elemental mercury
i.m.- intramuscular
�g/kg/day- micrograms per kilogram per day
�g/ml- micrograms per milliliter
�g/L- micrograms per liter
L/kg- liters per kilogram
ml/day/kg- milliliters per day per kilogram
mg/kg- micrograms per kilogram
NaCl- sodium chloride
NaOH- sodium hydroxide
SnCl2-stannous chloride
ng Hg/ml- nanograms mercury per milliliter
ng/ml- nanograms per milliliter
ng/g- nanograms per gram
ppm- parts per million
K- elimination rate constant
V/F-volume of distribution (F is the implicit bioavailability term)
ka- absorption rate constant
T1/2- half-lives
Cl/F- blood clearance
AIC- Akaike Information Criterion
k12- rate constants for Hg transfer from the central to the peripheral
compartment
k21- return from the peripheral to the central compartment
k10- elimination rate constant from the central compartment
Vc- initial distribution volume
Vc/F- apparent volume of the central compartment
35
Vss- fully equilibrated volume
Vss/F- apparent distribution volume at steady-state
Vp=Vss � Vc- peripheral volume referenced to blood concentration
SE- standard error
AUC- area under the curve
CNS- central nervous system
IOM- Institute of Medicine

http://www.drhyman.com/pdf/hyman_at.pdf.

http://www.nomercury.org/science.htm
http://www.upi.com/ConsumerHealthDaily/view.php?StoryID=20061024-015555-8479r

"The (National Institutes of Health)-funded study ... found that thimerosal,
best known for its use as an ethylmercury-based preservative in infant
vaccines and pregnancy shots, is actually more toxic to the brain than
methylmercury."

1: Pediatrics. 2001 May;107(5):1147-54.Related Articles, Links


Comment in:
Pediatrics. 2001 May;107(5):1177-8.

An assessment of thimerosal use in childhood vaccines.

Ball LK, Ball R, Pratt RD.

Division of Vaccines and Related Products Applications, Office of Vaccines
Research and Review, Center for Biologics Evaluation and Research, Foodand
Drug Administration, Rockville, Maryland 20852, USA. balll(a)cber.fda.gov

BACKGROUND: On July 7, 1999, the American Academy of Pediatrics and the US
Public Health Service issued a joint statement calling for removal of
thimerosal, a mercury-containing preservative, from vaccines. This action
was prompted in part by a risk assessment from the Food and Drug
Administration that is presented here. METHODS: The risk assessment
consisted of hazard identification, dose-response assessment, exposure
assessment, and risk characterization. The literature was reviewed to
identify known toxicity of thimerosal, ethylmercury (a metabolite of
thimerosal) and methylmercury (a similar organic mercury compound) and to
determine the doses at which toxicity occurs. Maximal potential exposure to
mercury from vaccines was calculated for children at 6 months old and 2
years, under the US childhood immunization schedule, and compared with the
limits for mercury exposure developed by the Environmental Protection Agency
(EPA), the Agency for Toxic Substance and Disease Registry, the Food and
Drug Administration, and the World Health Organization. RESULTS:
Delayed-type hypersensitivity reactions from thimerosal exposure are
well-recognized. Identified acute toxicity from inadvertent high-dose
exposure to thimerosal includes neurotoxicity and nephrotoxicity. Limited
data on toxicity from low-dose exposures to ethylmercury are available, but
toxicity may be similar to that of methylmercury. Chronic, low-dose
methylmercury exposure may cause subtle neurologic abnormalities. Depending
on the immunization schedule, vaccine formulation, and infant weight,
cumulative exposure of infants to mercury from thimerosal during the first 6
months of life may exceed EPA guidelines. CONCLUSION: Our review revealed no
evidence of harm caused by doses of thimerosal in vaccines, except for local
hypersensitivity reactions. However, some infants may be exposed to
cumulative levels of mercury during the first 6 months of life that exceed
EPA recommendations. Exposure of infants to mercury in vaccines can be
reduced or eliminated by using products formulated without thimerosal as a
preservative.

Publication Types:
Review
Review, Tutorial

PMID: 11331700 [PubMed - indexed for MEDLINE]

Blood work from kids SHOULD have been taken within two to four hours, NOT
days
after vaccines, thimerosal crosses the blood brain barrier and is stored in
the
brain.


Kids were given as much as seven to nine shots a day and thimerosal level
reaching 100% OVER the acceptable limit.


Rogam (sp?) was given to pregnant women, doctors not knowing it contained
thimerosal.


At a conservative rate of 10% of kids affected, that's 50,000 kids in the
US.
Rate likely to be higher.


The CDC says records of adverse effects can be found, however it was told
the
hoops people must jump through to get these records. One doctor even
submitted
150 pages to get through this red tape, but that was not good enough.


Invalid data in reaching the statistics of affected kids.

1: Pediatrics. 2001 May;107(5):1147-54.Related Articles, Links


Comment in:
Pediatrics. 2001 May;107(5):1177-8.

An assessment of thimerosal use in childhood vaccines.

Ball LK, Ball R, Pratt RD.

Division of Vaccines and Related Products Applications, Office of Vaccines
Research and Review, Center for Biologics Evaluation and Research, Foodand
Drug Administration, Rockville, Maryland 20852, USA. balll(a)cber.fda.gov

BACKGROUND: On July 7, 1999, the American Academy of Pediatrics and the US
Public Health Service issued a joint statement calling for removal of
thimerosal, a mercury-containing preservative, from vaccines. This action
was prompted in part by a risk assessment from the Food and Drug
Administration that is presented here. METHODS: The risk assessment
consisted of hazard identification, dose-response assessment, exposure
assessment, and risk characterization. The literature was reviewed to
identify known toxicity of thimerosal, ethylmercury (a metabolite of
thimerosal) and methylmercury (a similar organic mercury compound) and to
determine the doses at which toxicity occurs. Maximal potential exposure to
mercury from vaccines was calculated for children at 6 months old and 2
years, under the US childhood immunization schedule, and compared with the
limits for mercury exposure developed by the Environmental Protection Agency
(EPA), the Agency for Toxic Substance and Disease Registry, the Food and
Drug Administration, and the World Health Organization. RESULTS:
Delayed-type hypersensitivity reactions from thimerosal exposure are
well-recognized. Identified acute toxicity from inadvertent high-dose
exposure to thimerosal includes neurotoxicity and nephrotoxicity. Limited
data on toxicity from low-dose exposures to ethylmercury are available, but
toxicity may be similar to that of methylmercury. Chronic, low-dose
methylmercury exposure may cause subtle neurologic abnormalities. Depending
on the immunization schedule, vaccine formulation, and infant weight,
cumulative exposure of infants to mercury from thimerosal during the first 6
months of life may exceed EPA guidelines. CONCLUSION: Our review revealed no
evidence of harm caused by doses of thimerosal in vaccines, except for local
hypersensitivity reactions. However, some infants may be exposed to
cumulative levels of mercury during the first 6 months of life that exceed
EPA recommendations. Exposure of infants to mercury in vaccines can be
reduced or eliminated by using products formulated without thimerosal as a
preservative.

Publication Types:
Review
Review, Tutorial

PMID: 11331700 [PubMed - indexed for MEDLINE]

http://poisonevercure.150m.com/autism.htm

Autistic children are shown to retain abnormally high concentrations of
mercury from environmental sources such as vaccines.

********* (Until recently, the FDA administration concealed their knowledge
that thimerosal has been known to cross through the blood-brain barrier and
concentrate in the brain).***********

In a recent communication with Congressman Dr. Weldon, CDC conceded that
some of the routinely recommended vaccines contained the full amount of
thimerosal (25 mcg) as late as 2003. Those are not to expire until towards
the end of 2005. There is no existing reason to believe that manufactures
have it in mind to completely remove thimerosal from childhood vaccines in
the near future. Much to my alarm, documents recently obtained from the
World Health Organization (WHO)state that their policy is to lobby strongly
for maintaining thimerosal in vaccines as they see it necessary to use
childhood vaccines in third world countries. The mentality is that if
thimerosal is taken out of American childhood vaccines, the third world
countries will not accept thimerosal-containing childhood vaccines. This
seems to be a clear disturbing indication that, for whatever reason, WHO
desires to inoculate third world country populations with thimerosal
containing vaccines. This is an agency that claims to have an interest in
making sure that children in developing countries have the best
opportunities at life. How is that possible when they are being
deliberately poisoned with high concentrations of a neurotoxins?
There exists many decades worth of peer-reviewed literature (literally
hundreds) on the dangers of thimerosal which include case-reports, animal
studies, tissues culture studies, genetic studies, toxicology studies, and
biochemical studies. According to the above article, CDC, HHS and AAP warns
that 1/166 children have autistic spectrum disorders and even more alarming,
1/6 children have developmental and or behavioral disorders.
The World Health Organization's (WHO) Expert Committee on Biological
Standardization acknowledges that thimerosal is essential during vaccine
production to inactivate certain pathogenic organisms and toxins and prevent
microbial growth during vaccine storage and use. (click here to view
document). Read the Eli Lilly's, manufacturer of thimerosal, safety data
sheet on thimerosal. According to this document, thimerosal will react with
strong oxidizing agents and one listed is peroxides. Another vaccine
component. Also listed are the effects, including signs and symptoms of
exposure such as topical allergic dermatitis, topical hypersensitivity
reactions. Early signs of mercury poisoning are noted as nervous system
effects which include narrowing of the visual field and numbness in the
extremities. "Exposure to mercury in utero and in children can cause mild
to severe mental retardation and mild to severe motor coordination's
impairment". Primary routes of entry are listed as inhalation and skin
contact. For shipping information, there's no question of the label:
POISONS accompanied by the skull and bones picture label.
Mercury over stimulates the brain's immune system. Over stimulation of the
brain results in activation of the microglia widely dispersed in the brain.
When the microglia are activated, they release toxins killing surrounding
brains
From: Jan Drew on

"Peter Bowditch" <myfirstname(a)ratbags.com> wrote in message
news:c13es2hehs3ht63ih4qouopi5bdbt6efhv(a)4ax.com...
> "Jan" <jdrew63929(a)aol.com> wrote:
>
>>On Feb 4, 3:35?pm, Peter Bowditch <myfirstn...(a)ratbags.com> wrote:
>>> "Jan" <jdrew63...(a)aol.com> wrote:
>>> >On Feb 4, 1:16?am, Peter Bowditch <myfirstn...(a)ratbags.com> wrote:
>>> >> Mike <m...(a)xyz.com> wrote:
>>> >> >Mark Probert wrote:
>>> >> >> Mike wrote:
>>> >> >>> David Wright wrote:
>>> >> >>>> In article <DUPwh.78$yH3.42(a)trndny07>, Mike <m...(a)xyz.com>
>>> >> >>>> wrote:
>>> >> >>>>> David Wright wrote:
>>> >> >>>>>> Children are almost never given TT or Td. (e amount of
>>> >> >>>>>> thimerosal in
>>> >> >>>>>> even the heaviest pediatric HepB dose is less than you'd get
>>> >> >>>>>> from a
>>> >> >>>>>> tuna sandwich.
>>> >> >>>>> It is not so innocuous when you take body weight into account.
>>> >> >>>>> One
>>> >> >>>>> tuna sandwich for a 9 lb infant is like 20 sandwiches for a 180
>>> >> >>>>> lb
>>> >> >>>>> adult. Actually it is even worse than that because an infant
>>> >> >>>>> body is
>>> >> >>>>> much weaker, especially for very young children who do not have
>>> >> >>>>> blood brain barrier yet.
>>>
>>> >> >>>> Except that the amount of mercury is even smaller than the doses
>>> >> >>>> you
>>> >> >>>> seem to be worried about.
>>>
>>> >> >>> Smaller than what? Pregnant women are advised to avoid tuna
>>> >> >>> sandwiches
>>> >> >>> to protect their future children, why should the children be
>>> >> >>> getting
>>> >> >>> an equivalent of 20 tuna sandwiches?
>>>
>>> >> >> Do you know the difference between ethyl and methyl mercury? I'll
>>> >> >> give
>>> >> >> you a hint, it is not just the 'm'.
>>>
>>> >> >Yes, I do. According to a research on monkeys ethylmercury is MORE
>>> >> >toxic
>>> >> >for the brain than methylmercury.
>>> >> >http://www.safeminds.org/research/library/Burbacher-EHP-Primates-Apri...
>>>
>>> >> Why am I not surprised to find to find that SafeMinds are telling
>>> >> lies?
>>>
>>> >What lies?
>>>
>>> How about "ethylmercury is MORE toxic for the brain than
>>> methylmercury"? That will do for a start.
>>>
>>>
>>>
>>> >You are the master along with the *gang* who lies.
>>>
>>> I will have to bring back KACHING!! You are falling back into bad
>>> habits.
>>
>>Bad habits like posting the truth.
>
> Start that any time you like.

I started back in 1999 and continued. Unlike you.
>
>>>
>>>
>>>
>>> >> <snip more of the same> truth.
>>> >> --
>>> >> Peter Bowditch
>>>
>>> > Hide quoted text -
>>>
>>> >> - Show quoted text -
>>>
>>> --
>>> Peter Bowditch
>>>
>>> - Show quoted text -
>>


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