Department of Environmental Medicine, University of Rochester School of
Medicine, Rochester, New York 14642, USA. tcw30@aol.com
The three modern "faces" of mercury are our perceptions of risk from the
exposure of billions of people to methyl mercury in fish, mercury vapor from
amalgam tooth fillings, and ethyl mercury in the form of thimerosal added as an
antiseptic to widely used vaccines. In this article I review human exposure to
and the toxicology of each of these three species of mercury. Mechanisms of
action are discussed where possible. Key gaps in our current knowledge are
identified from the points of view both of risk assessment and of mechanisms of
action.
Neurodevelopmental investigations among methylmercury-exposed
children in French Guiana.
Cordier S, Garel M, Mandereau L, Morcel H, Doineau P, Gosme-Seguret S, Josse
D, White R, Amiel-Tison C.
Unit 170-Epidemiological and Statistical Research on Environment and Health,
National Institute of Health and Medical Research (INSERM), 94807 Villejuif
Cedex, France.
French Guiana, like its neighbors, suffers from environmental pollution with
methylmercury from gold mining activities, and Amerindian communities are
particularly affected. A neurological and a neurospsychological evaluation were
carried out in children of three Amerindian communities with various levels of
pollution: 156 children from the Upper Maroni (high exposure), 69 from Camopi on
the Oyapock river (median exposure), and 153 from Awala on the Atlantic coast
(low exposure). Exposure to methylmercury was measured by determination of total
mercury in the hair of the children and their mothers (geometric mean, 12.7
microg/g in Upper Maroni). No major neurologic signs were observed in the
children examined. After adjustment for potential confounders, we found a
dose-dependent association between maternal hair mercury level and increased
deep tendon reflexes, poorer coordination of the legs, and decreased performance
in the Stanford-Binet Copying score, which measures visuospatial organization.
In this last test, the frequency of rotation errors was high in the 5-6 years
age group and increased with mercury exposure. These associations depended on
the sex of child and were stronger among boys. The interpretation of these
results is limited mainly by the cross-sectional design of the study.
It identifies specific neurological and
neuropsychological deficits, in some cases modulated by sex, which are
consistent with known targets of mercury neurotoxicity.
2002 Elsevier Science (USA)
Vaccines without thiomersal: why so necessary, why so long
coming?
van't Veen AJ.
Department of Dermatology and Venereology, Erasmus University Hospital
Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
The inorganic mercurial thiomersal (merthiolate) has been used as an effective
preservative in numerous medical and non-medical products since the early 1930s.
Both the potential toxicity of thiomersal and sensitisation to thiomersal in
relation to the application of thiomersal-containing vaccines and
immunoglobulins, especially in children, have been debated in the literature.
The very low thiomersal
concentrations in pharmacological and biological products are relatively
non-toxic, but probably not in
utero and during the first 6
months of life. The developing brain of the fetus is most susceptible to thiomersal
and, therefore, women of childbearing age, in particular, should not receive
thiomersal-containing
products. Definitive data of doses at which developmental effects occur are not
available. Moreover, revelation of subtle effects of toxicity needs long term
observation of children. The ethylmercury radical of the thiomersal
molecule appears to be the prominent sensitiser.
The prevalence of thiomersal
hypersensitivity in mostly selected populations varies up to 18%, but higher
figures have been reported. The overall exposure to thiomersal differs
considerably between countries. In many cases a positive routine patch test to
thiomersal should be considered an accidental finding without or, probably more
accurately, with low clinical relevance. In practice, some preventive measures
can be taken with respect to thiomersal hypersensitivity. However, with regard
to the debate on primary sensitisation during childhood and renewed attention
for a reduction of children's exposure to mercury from all sources, the use of
thiomersal should preferably be eliminated or at least be reduced. In 1999 the
manufacturers of vaccines and immunoglobulins in the US and Europe were
approached with this in mind. The
potential toxicity in children seems to be of much more concern to them than the
hidden sensitising
properties of thiomersal.
In The Netherlands, unlike many other countries, the exposure to
thiomersal from pharmaceutical sources has already been reduced.
Replacement of thiomersal
in all products should have a high priority in all countries.
Mercury pollution in the Tapajos River basin, Amazon:
mercury level of head hair and health effects.
Harada M, Nakanishi J, Yasoda E, Pinheiro MC, Oikawa T, de Assis Guimaraes
G, da Silva Cardoso B, Kizaki T, Ohno H.
Department of Social Welfare Studies, Kumamoto Gakuen University, Japan.
There is increasing concern about the potential neurotoxic effects of exposure
to methylmercury for the 6 million people living in the Amazon, even in
regions situated far away from the gold mines (garimpos), considered to be the
major source of mercury pollution. In November 1998, a spot investigation on
mercury contamination was conducted in three fishing villages (Barreiras,
Rainha, and Sao Luiz do Tapajos) on the Tapajos River, an effluent of the
Amazon, situated several hundred kilometers downstream from the gold-mining
areas. A total of 132 fishermen and their families volunteered for the current
study. As was anticipated, the total mercury levels in the head hair collected
from the fishing villages were relatively high (14.1-20.8 ppm on the average)
and the number of subjects with a high total mercury level over 10 ppm (the
least upper bound of a normal value) was 103 (78.0%) in total, along with
various symptoms, thereby suggesting wide mercury contamination in the Tapajos
River basin. Moreover, in view of the absence of other diseases (e.g.,
alcoholism or malaria), a high intake of fish containing a methylmercury
level, and high hair mercury levels in addition to the various symptoms such
as sensory disturbance (especially glove-and-stocking type, which is
characteristic of Minamata disease), tremor, failure in two-point
discrimination, and slight balancing failure, several subjects examined were
diagnosed with mild Minamata disease. The findings obtained suggest, thus,
that the mercury pollution in the Amazon should be crucially observed for head
hair mercury level and health in a much broader region.
Balancing risks and benefits: Primum non nocere is too
simplistic.
Halsey NA, Goldman L.
Institute for Vaccine Safety, Johns Hopkins University Bloomberg School of
PublicHealth, Baltimore, MD 21205, USA. nhalsey@jhsph.edu
PMID: 11483816 [PubMed - indexed for MEDLINE]
Balancing Risks and Benefits: Primum non nocere Is Too
Simplistic
COMMENTARY By:
Neal A. Halsey, MD
Institute for Vaccine Safety
Johns Hopkins University Bloomberg School of Public Health
Baltimore, MD 21205
Lynn Goldman, MD
Department of Environmental Health Sciences
Johns Hopkins University Bloomberg School of Public Health
Baltimore, MD 21205
[This material contains technical language. PEDIATRICS Vol. 108 No. 2
August 2001, pp. 466-467.]
The commentary by Seal and Daum entitled “What Happened to Primum non
nocere?”1 [“First, do no harm”] that appeared in the May 2001 issue of
Pediatrics criticized the July 1999 recommendation of the American Academy of
Pediatrics (AAP) and US Public Health Service (USPHS) to delay the birth dose
of hepatitis B vaccine for infants born to hepatitis B surface antigen (HBsAg)-negative
women to reduce infant exposure to thimerosal.2 The commentary contains
incorrect statements and oversimplifies the complex process of balancing
multiple risks and benefits when formulating vaccine policy as summarized in
the excellent article by Feudtner and Marcuse3 in the same issue.
Some professionals had difficulty
understanding the need for the July 1999 recommendations because they didn’t
fully understand the risks from organomercury
exposure and the amounts of
ethylmercury present in
vaccines. Several developments in the past 2 years have reinforced the wisdom
of the recommendations made in July 1999.
Seal and Daum stated that methylmercury
“might” be harmful to the developing fetal central nervous system.
Methylmercury is neurotoxic
at all ages, and the developing fetal brain is at least 10-fold more sensitive
than
the adult brain.4
They also
incorrectly stated that “no data existed that implicated ethylmercury”
as a cause of neurotoxicity.
As reviewed by Ball et al,5
ethylmercury from thimerosal
has caused significant
neurotoxicity in infants,
children, and adults. Such data were available at the time of the 1999
recommendations and several references were included in the more complete AAP
statement on this issue.6
On July 11, 2000, the Committee on the
Toxicological Effects of Methylmercury of the National Research Council (NRC)
proposed a resolution of the conflict regarding the appropriate reference dose
(RfD) for
methylmercury exposure.7 The Committee proposed an RfD of 0.1 µg/kg/d, the
same dose that had been used by the Environmental Protection Agency. The
Committee used recently generated data from the Faroe Islands study as the
basis for the RfD. The Committee estimated that 60 000 children are born each
year in the United States with unsafe levels of methylmercury in their bodies.
More recently, the Centers for Disease Control and Prevention found
that levels of mercury in women of childbearing age in the United States are
at least as high as, and perhaps higher than, the NRC estimates, which were
based on modeled exposures.8
The adverse effects from intrauterine low-dose
methylmercury exposure are not detected early in life and include alterations
in attention, fine motor, and cognitive function that fit in the overall
category of learning impairment. The NRC noted that all sources of mercury
must be considered when determining the need for interventions.
For infants born to women who have
high levels of methylmercury, the possible additive effects from subsequent
exposure to ethylmercury
(from thimerosal) are not known but are of potential concern, especially given
that so many children start out life with mercury levels that exceed
recommended guidelines. Moreover, the potential exposures to ethylmercury
from thimerosal alone were in excess of 0.1 µg/kg/d at the time that doses
were administered, and such bolus administration would likely result in higher
blood levels and subsequent transmission to the brain.9
Based on the NRC report, on January 12, 2001, the
Food and Drug Administration (FDA) recommended that pregnant women, women of
childbearing age, infants, and very young children not consume swordfish,
shark,
tilefish, and mackerel because of unacceptably high levels of methylmercury.10
Swordfish contains an average of 1 part per million of methylmercury, or 28
µg/oz. If a meal is 3 oz, a 55- to 70-kg woman should not consume 84 µg of
methylmercury at any point during pregnancy. How would vaccine advisory groups
be perceived today if recommendations had not been made to reduce the
potential for administration of up to 75 µg of ethylmercury to infants in the
first 6 to 8 weeks of age? Most of the exposures to ethylmercury in vaccines
were avoidable. The AAP and the USPHS had a responsibility to inform
physicians and the public of new information about risks of exposure to
mercury from all sources at levels once thought to be safe, and to provide
guidance regarding the reduction of exposures from thimerosal.
Seal and Daum implied that exposures to
thimerosal were known to be safe in July 1999; however, ethylmercury had not
been studied in animals or humans from the standpoint of toxicity to the
developing brain. In particular, there were no epidemiologic studies of
intellectual development, learning disabilities, or other adverse effects that
might be associated with ethylmercury exposure in utero or early in life.
Preliminary studies from West Coast health maintenance organizations revealed
dose-related evidence of increased risk of learning disabilities, delayed
speech, and other abnormalities, but no such relationship was found in an East
Coast population.11 Additional studies are being planned by the National
Institutes of Health and the Centers for Disease Control and Prevention to
determine if there were any toxic effects from thimerosal exposure.
Another misundertanding by Seal and Daum was that
manufacturers and the FDA were well on their way to removing thimerosal from
vaccines for infants in July 1999. Without strong advocacy from the AAP and
USPHS, there would not have been the remarkably rapid removal of thimerosal
from vaccines administered to children. As of February 2001, manufacturers
were no longer producing vaccines that contain thimerosal as a preservative
for diphtheria, tetanus, and acellular pertussis vaccines combined (DTaP),
Haemophilus influenzae, or hepatitis B vaccines that are used in infants.
One of us (N.A.H.) is the principal author of the
1992 AAP statement establishing the recommendation for universal hepatitis B
immunization of infants, and I am well aware of the important benefits of
administering
hepatitis B vaccine beginning at birth.12 The recommendation to delay the
birth dose for low-risk infants in July 1999 was not taken lightly by the AAP
or the USPHS. Although initiating vaccination at birth provides a safety
shield against errors in communication about maternal HBsAg status, we cannot
depend on this backup because some providers will continue to administer the
first dose of hepatitis B vaccine in combination with other vaccines beginning
at 6 to 8 weeks of age for infants born to HBsAg-negative mothers. Extra
efforts must be made to ensure screening of all women during pregnancy and to
minimize errors in communication from obstetric providers to providers of care
for newborns.
The process of making sound immunization policy
requires careful balancing of many factors as eloquently summarized by
Feudtner and Marcuse.3 To maintain public confidence in vaccines, we must
ensure the public that
safety is taken very seriously, and, when indicated, timely actions are taken
to reduce potential risks. Vaccine manufacturers and the FDA should be
applauded for the rapid changes in manufacturing and marketing practices
that led to an elimination of the use of thimerosal as a preservative in
routine vaccines for infants.
FOOTNOTES
Received for publication May 17, 2001; accepted Jun 15, 2001.
Address correspondence to Neal A. Halsey, MD, Johns Hopkins University
Bloomberg School of Public Health, Institute for Vaccine Safety, 615 N Wolfe
St, Rm 5515, Baltimore, MD 21205. E-mail:
nhalsey@jhsph.edu
ABBREVIATIONS
AAP, American Academy of Pediatrics; USPHS, US Public Health Service; HBsAg,
hepatitis B surface antigen; NRC, National Research Council; RfD, reference
dose; FDA, Food and Drug Administration.
Identification and characterization of uptake systems for
cystine and cysteine in cultured astrocytes and neurons: evidence for
methylmercury-targeted disruption of astrocyte transport.
Shanker G, Aschner M.
Department of Physiology and Pharmacology, Wake Forest University School of
Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA.
Maintenance of appropriate
intracellular glutathione (GSH)
levels is crucial for cellular defense against oxidative damage. A suggested
mechanism of methylmercury (MeHg)
neurotoxicity
implicates the involvement of oxygen radical formation and a decrease in
cellular levels of GSH.
Astrocytes play an important role in providing GSH precursors to neurons,
and as will be discussed in this review, altered GSH homeostasis likely
leads to impairment of astrocytic handling of glutamate, and neuronal energy
metabolism. The review summarizes recent observations on transport systems
for cysteine and cystine, precursors of GSH, in primary cultures of
astrocytes and neurons, and their sensitivity to MeHg treatment. Copyright
2001 Wiley-Liss, Inc.
Neurotoxicity and molecular effects of methylmercury.
Castoldi AF, Coccini T, Ceccatelli S, Manzo L.
University of Pavia and "Salvatore Maugeri" Foundation, Pavia, Italy.
acastoldi@fsm.it
The neurotoxicity
of high levels of methylmercury (MeHg)
and the high susceptibility of the developing brain are well established
both in humans and experimental animals. Prenatally
poisoned children display a range of effects varying from severe cerebral
palsy to subtle developmental delays. Still unknown is the lowest dose that
impairs neurodevelopment. The primary source of human exposure is the
fish. The data obtained so far from epidemiological studies on fish-eating
populations are not consistent. A reference dose of 0.1 microg MeHg/kg per
day has been established by the U.S. Environmental Protection Agency based
on a study on Iraqi children exposed to MeHg in utero. However, these
exposures occurred at high level for a limited period of time, and
consequently were not typical of lower chronic exposure levels associated
with fish consumption. Major
obstacles for estimation of a threshold dose for MeHg
include the delayed appearance of the neurodevelopmental
effects following prenatal exposure and limited knowledge of cellular and
molecular processes underlying these neurological changes. In this
respect, a strategy which aims at identifying sensitive molecular targets of
MeHg at environmentally relevant levels may prove particularly useful to
risk assessment. Here some examples of MeHg molecular effects occurring at
low doses/concentrations are presented.
Methylmercury inhibits cysteine uptake in cultured
primary astrocytes, but not in neurons.
Shanker G, Allen JW, Mutkus LA, Aschner M.
Department of Physiology and Pharmacology, Wake Forest University School of
Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1083, USA.
The maintenance of adequate intracellular glutathione (GSH) concentrations
is dependent on the availability and transport of the rate-limiting
substrate, cysteine. A suggested mechanism of methylmercury (MeHg)
neurotoxicity in brain involves the formation of oxygen radicals, and a
decrease in intracellular levels of GSH. Recently, we have characterized
various cysteine transport systems (both Na(+)-dependent and -independent)
in cerebrocortical astrocytes and hippocampal neurons. The present study was
carried out to investigate the effect of MeHg on cysteine uptake in both
astrocytes and neurons, and to determine whether cysteine transport is
differentially affected in the two cell types by MeHg treatment.
Sixty-minute pretreatment with
MeHg
caused significant concentration-dependent inhibition in cysteine
uptake in astrocytes,
but not in neurons. As most of the cysteine transport is
Na(+)-dependent (80-90% of total), additional studies focused on MeHg's
effect on the Na(+)-dependent cysteine transporters X(AG(-)) and ASC. An
additive inhibitory effect on cysteine uptake was observed in astrocytes
treated with MeHg (5 microM) plus sub-maximal inhibitory concentrations (0.1
and 0.5 mM) of threo-beta-hydroxy-aspartate (THA), a specific inhibitor of
the Na(+)-dependent transporter, X(AG(-)), compared to astrocytes treated
with MeHg (P<0.001) or THA alone (P<0.05). There was no additive effect of
MeHg and maximal inhibitory concentrations of THA (1.0 and 5.0 mM) on
astrocytic cysteine uptake inhibition. Additional studies examined the
sensitivity of the Na(+)-dependent ASC transport system to MeHg treatment.
Maximal inhibitory concentration of L-serine (10 mM) alone had a rather
modest inhibitory effect on cysteine uptake, and when applied in the
presence of MeHg there was no additive effect.
These results suggest that the
inhibition of cysteine
uptake by MeHg
in astrocytes
occurs through specific inhibition of both the X(AG(-))
as well as the ASC
transport system.
It is well known that Abraham Lincoln took a medicine called "blue mass" or
"blue pill," commonly prescribed in the 19th century. What is now hardly
known is that the main ingredient of blue mass was finely dispersed
elemental mercury. As his friends understood, mercury was often prescribed
for melancholy or "hypochondriasis," a condition Lincoln famously endured.
Mercury in the form of the blue pill
is a potential neurotoxin, which we have demonstrated by recreating and
testing the recipe. We present the testimony of many of Lincoln's
contemporaries to suggest that Lincoln suffered the neurobehavioural
consequences of mercury intoxication but, perhaps crucial to history, before
the main years of his presidency; he was astute enough to recognize the
effects and stop the medication soon after his inauguration.
Bernard S, Enayati A, Redwood L, Roger H, Binstock T.
ARC Research, Cranford, New Jersey 07901, USA.
Autism is a syndrome characterized by
impairments in social relatedness and communication, repetitive behaviors,
abnormal movements, and sensory dysfunction. Recent epidemiological studies
suggest that autism may affect 1 in 150 US children. Exposure to mercury can
cause immune, sensory, neurological, motor, and behavioral dysfunctions similar
to traits defining or associated with autism, and the similarities extend to
neuroanatomy,
neurotransmitters, and biochemistry. Thimerosal, a preservative added to many
vaccines, has become a major source of mercury in children who, within their
first two years, may have received a quantity of mercury that exceeds safety
guidelines. A review of medical literature and US government data suggests that:
(i)
many cases of idiopathic autism are induced by early mercury exposure from
thimerosal; (ii) this type of autism represents an unrecognized mercurial
syndrome; and (iii) genetic and non-genetic factors establish a predisposition
whereby thimerosal's
adverse effects occur only in some children. Copyright 2001 Harcourt
Publishers Ltd.
Predicted mercury concentrations in hair from infant
immunizations: cause for concern.
Redwood L, Bernard S, Brown D.
Coalition for Safe Minds, Cranford, NJ 07016, USA. tlredwood@mindspring.com
Mercury (Hg) is considered one of the
worlds most toxic metals. Current thinking suggests that exposure to mercury
occurs primarily from seafood contamination and rare catastrophic events.
Recently, another common source of exposure has been identified. Thimerosal
(TMS), a preservative found in many infant vaccines, contains 49.6% ethyl
mercury (EtHg)
by weight and typically contributes 25 microg
of EtHg
per dose of infant vaccine. As part of an ongoing review, the Food and Drug
Administration (FDA) announced in 1999 that infants who received multiple
TMS-preserved vaccines may have been exposed to cumulative Hg in excess of
Federal safety guidelines. According to the centers for disease control (CDC)
recommended immunization schedule, infants may have been exposed to 12.5 microg
Hg at birth, 62.5 microgEtHg
at 2 months, 50 microgEtHg
at 4 months, 62.5 microgEtHg
at 6 months, and 50 microgEtHg
at approximately 18 months, for a total of 237.5 microgEtHg
during the first 18 months of life, if all TMS-containing vaccines were
administered. Neurobehavioral alterations, especially to the more susceptible
fetus and infant, are known to occur after relatively low dose exposures to
organic mercury compounds. In effort, to further elucidate the levels of
ethyl mercury resulting from exposure to vaccinal TMS, we estimated hair Hg
concentrations expected to result from the recommended CDC schedule utilizing a
one compartment pharmacokinetic model. This model was developed to predict hair
concentrations from acute exposure to methymercury (MeHg) in fish.
Modeled hair Hg concentrations in
infants exposed to vaccinal
TMS are in excess of the Environmental Protection Agency (EPA) safety guidelines
of 1 ppm
for up to 365 days, with several peak concentrations within this period. More
sensitive individuals and those with additional sources of exposure would have
higher Hg concentrations. Given that exposure to low levels of mercury during
critical stages of development has been associated with neurological disorders
in children, including ADD, learning difficulties, and speech delays, the
predicted hair Hg concentration resulting from childhood immunizations is cause
for concern. Based on these findings, the impact which vaccinal
mercury has had on the health of American children warrants further
investigation.
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@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.
Department of Vaccines and Biologicals, World Health Organization, Geneva,
Switzerland. clementscj@who.ch
The mercury-based vaccine preservative thiomersal has come under scrutiny in
recent months because of its presence in certain vaccines that provide the
foundation of childhood immunisation schedules. Over the past decade new
vaccines have been added to the recommended childhood schedule, and the
relatively smaller bodyweight of infants has led to concern that the cumulative
exposure of mercury from infant vaccines may exceed certain guidelines for the
human consumption of mercury. In the US, government agencies and professional
societies have recently recommended that thiomersal be removed altogether from
vaccines. Some involved in developing vaccine policy feel that the evidence to
support these safety concerns has not risen to the level required for such a
response. This apparent divergence of opinion has left healthcare professionals
and the public with uncertainty about the potential health effects from low
level exposure to thiomersal as well as the necessity of removing thiomersal
from vaccines. At present, scientific investigation has not found conclusive
evidence of harm from thiomersal in vaccines. As a precautionary measure,
efforts are under way to remove or replace thiomersal from vaccines and
providers should anticipate the availability of more vaccine products that are
thiomersal-free over the coming years.
From the article: "While
much remains to be understood about the implications of various concentrations,
it seems that some infants may receive doses of mercury from vaccines that,
while not obviously toxic, may be of concern and are in breach of various agency
recommendations."
Iatrogenic exposure to mercury after hepatitis B vaccination
in preterm infants.
Stajich GV, Lopez GP, Harry SW, Sexson WR.
Mercer University, Southern School of Pharmacy, Atlanta, Georgia 30341, USA.
Thimerosal, a derivative of mercury, is
used as a preservative in hepatitis B vaccines. We measured total mercury levels
before and after the administration of this vaccine in 15 preterm and 5 term
infants. Comparison of pre- and post-vaccination mercury levels showed a
significant increase in both preterm and term infants after vaccination.
Additionally, post-vaccination mercury levels were significantly higher in
preterm infants as compared with term infants. Because mercury is known to be a
potential neurotoxin to infants, further study of its pharmacodynamics
is warranted.
OBJECTIVE: To determine whether neonatal neurologic function is adversely
affected by seafood contaminants from maternal diet during pregnancy. STUDY
DESIGN: One hundred eighty-two singleton term births were evaluated in the
Faeroe Islands, where marine food includes pilot whale. Maternal serum, hair,
and milk and umbilical cord blood were analyzed for contaminants. Levels of
essential fatty acids, selenium, and thyroid hormones were determined in cord
blood. Each infant's neurologic optimality score was determined at 2 weeks of
age adjusted for gestational age, and predictors were assessed by regression
analysis. RESULTS: Exposures to methylmercury and polychlorinated biphenyls
were increased in relation to maternal seafood intake, as were omega3 fatty
acid concentrations in cord serum. Thyroid function was normal. After
adjustment for confounders, a 10-fold increase of the cord-blood mercury
concentration was associated with a decreased neurologic optimality score of
2.0 (P =. 03). This effect corresponds to a decrease in gestational age of
about 3 weeks. Other indicators of the seafood diet had no effect on this
outcome. CONCLUSIONS: Prenatal
exposure to methylmercury from contaminated seafood was associated with an
increased risk of
neurodevelopmental deficit.
Thus in this North Atlantic population, methylmercury constituted an important
neurologic
risk factor, although effects of other seafood components were not detectable.
Department of Paediatrics, The Chinese University of Hong Kong, 6th Floor,
Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong SAR,
China. Albertm68mcli@yahoo.com
A 5 year old Chinese boy presented with recurrent oral ulceration followed by
motor and vocal tics. The Chinese herbal spray he used for his mouth ulcers was
found to have a high mercury content. His blood mercury concentration was
raised. Isolated tics as the sole presentation of mercury intoxication has not
previously been reported.
Neuron loss in cerebellar cortex of rats exposed to mercury
vapor: a stereological study.
Sorensen FW, Larsen JO, Eide R, Schionning JD.
Department of Neurobiology, Institute of Anatomy, University of Aarhus,
Denmark. u920932@svfedb.aau.dk
Mercury vapor produces tremor in humans and experimental animals. We have
previously reported that mercury vapor intoxication over an 8-week period
induces only subtle changes in dorsal root ganglia and nerve roots in rats. In
the present study we have carried out stereological analyses of the cerebellum
of the same rats, and demonstrated significant losses of Purkinje cells
(12.7%, 2P = 0.005) and granule cells (15.6%, 2P = 0.016). All sizes of
Purkinje cells were lost with an equal probability, i.e. there were no
indication of any preferential loss of any subpopulation of the neurons. The
volume of the granular cell layer was significantly reduced (18.9%, 2P = 0.0
15), whereas the volumes of the molecular layer and the white matter were
unchanged. Previous stereological studies have demonstrated that methyl
mercury intoxication primarily induces degeneration in the peripheral nervous
system, while sparing the cerebellum.
We therefore suggest that metallic mercury vapor and methyl mercury have
different toxicological profiles in rats, where metallic mercury vapor mainly
affects the central nervous system and methyl mercury mainly affects the
peripheral nervous system.
Department of Behavioral Science and Health Education, Rollins School of
Public Health, Emory University, Atlanta, GA 30322, USA. rletz@sph.emory.edu
A battery of tests of peripheral and central nervous system function was
administered to 205 former workers of a large heavy industrial plant, 104 of
whom were previously exposed to inorganic mercury. The mean age of those
examined was 71 years. Exposed subjects had participated in a urine-mercury
exposure monitoring program during the time of operation of a process that
required the use of mercury and its subsequent clean-up. Mercury exposure had
been high (mean peak urine mercury concentration was >600 microg/l) and had
ended 30 years or more prior to the investigation.
Peripheral nerve function outcomes that were statistically significantly
associated with cumulative mercury exposure after controlling for covariates
included classification as having peripheral neuropathy, peroneal
motor nerve conduction velocity, ulnar
motor nerve conduction velocity, and peroneal
motor nerve F-wave latency. Quantitative assessment of resting tremor
was nearly significantly associated with cumulative mercury exposure (p=0.07).
Among tests of central nervous system
function, results of the
Handeye Coordination test were
significantly associated with cumulative mercury exposure after controlling
for covariates. Cumulative mercury exposure was not observed to be
associated with a quantitative measure of dementia or with a number of
cognitive neurobehavioral test outcomes.
The statistically significant
associations with mercury exposure were observed in spite of greater mortality
among the exposed group than the unexposed group. These results suggest that
substantial occupational mercury exposure can have long-term adverse effects
on the peripheral nervous system detectable decades after cessation of
exposure. Such long-term adverse effects were not observed for a
measure of dementia or other measures of cognitive function.
Distinct pattern of neuronal degeneration in the fetal rat
brain induced by consecutive transplacental administration of methylmercury.
Kakita A, Wakabayashi K, Su M, Sakamoto M, Ikuta F, Takahashi H.
Department of Pathology, Brain Research Institute, Niigata University, 1
Asahimachi, Niigata, Japan. kakita@bri.niigata-u.ac.jp
The transplacental neurotoxicity of methylmercury (MeHg) on the fetal rat
brain was studied. Adult female rats were administered 1, 2 or 3 mg/kg/day
methylmercury chloride (MMC) orally for either 5 or 12 days, and were then
mated. They were subsequently administered MMC in the same manner until the
end of gestation. On embryonic day 22, a proportion of the fetal brains were
histologically examined. Neuronal
degeneration of varying degree was detected consistently in the brain stem,
cingulate
cortex, thalamus and cerebral basal area, including the hypothalamus. The
distribution pattern of neuronal damage was different from those in rats
treated with MeHg
in the postnatal or adult stages. This finding suggests that pathomechanisms
in MeHg
intoxication operate distinctively in the fetal brain. The offspring derived
from dams treated with 1 mg/kg/day MMC
for 5 pregestational
days and throughout pregnancy survived with inherent brain lesions. This
experimental model could be a useful tool for research on the neurotoxicity
of MeHg
in the human fetal brain.
Limiting infant exposure to thimerosal in vaccines and other
sources of mercury.
Halsey NA.
Publication Types:
Comment
Editorial
From the article:
"Exposure to ethylmercury
from vaccines containing thimerosal in the first 6 monts
of life ranges from 0 to 187 micrograms based on which vaccines are
administered. Since many vaccines do not contain thimerosal, most children
receive less than the total amount of mercury indicated in the guidelines during
the first 6 months of life. If all thimerosal-containing vaccines are
given, the total exposures exceed the EPA guidelines, and possibly other
guidelines, for the smallest infants. There are safety or uncertainty
factors (10-fold for the EPA) built into the guidelines, and experts believe
there is no evidence of harm from exposure to thimerosal in vaccines.
However, clinicians are uncertain as to how much mercury can be safely given at
1 time when multiple thimerosal-containing vaccines are administered
simultaneously.
Data from 2 recent studies examining
the relationship between methylmercury exposure and neuropsychological
outcome in children suggest that intermittent large exposures may pose more risk
than small daily doses."
ALL INFORMATION, DATA, AND
MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
PURPOSES ONLY AND IS NOT TO BE CONSTRUED AS REFLECTING THE KNOWLEDGE OR OPINIONS
OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR
LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND
COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH
YOUR HEALTH CARE PROVIDER.
