American Journal Of Industrial Medicine  [Printer-friendly version]
November 14, 2006


[Rachel's introduction: A group of eminent scientists has called for
worldwide reductions in exposure to toxic lead, mercury and
manganese. They recommend that the U.S. cut its lead standard for
children by half.]

By Philip Landrigan and others**

On 17-18 June, 2006, the Scientific Committee on Neurotoxicology and
Psychophysiology and the Scientific Committee on the Toxicology of
Metals of the International Commission on Occupational Health (ICOH)
convened an International Workshop on "Neurotoxic Metals: Lead,
Mercury, and Manganese -- From Research to Prevention (NTOXMET)" at
the University of Brescia [Brescia, Italy]. Scientists and physicians
from 27 nations participated.

Data were presented for each of the three metals on environmental
sources, fate and distribution; human exposure; clinical, subclinical,
and developmental neurotoxicity; epidemiology; risk assessment; and
prospects for prevention. Ongoing and future studies were described
and discussed.

For each of the metals, initial recognition of neurotoxicity occurred
in the context of high-dose exposure. For example, lead poisoning was
first recognized in miners, smelters, and type setters, methylmercury
poisoning in inhabitants of the fishing community of Minamata, and
manganese poisoning in miners and ferroalloy workers. Subsequent
development of more sensitive and sophisticated analytical instruments
led to the recognition of subclinical toxicity [toxicity without overt
symptoms] and developmental neurotoxicity at progressively lower
levels of exposure. In each case, the extent of toxicity was much
greater than initially appreciated and the size of the affected
population much larger. Many decades typically elapsed between the
initial recognition of neurotoxicity and the initiation of programs
for prevention. Early warnings were frequently ignored and even
actively resisted.

The historical observation that long delays had typically elapsed
before the initiation of prevention prompted extensive discussion at
the Workshop about the need to develop more effective strategies. From
this discussion, a series of recommendations emerged on future
directions for research and prevention of the neurotoxicity of metals.

At the closing session of the International Workshop at Brescia, the
following recommendations on the prevention of the Neurotoxicity of
Metals were adopted by consensus:

Intensified attention must be paid to early warnings of neurotoxicity.
Clinical observations or toxicological data suggesting the existence
of neurotoxicity including subclinical and developmental toxicity must
be taken very seriously. Such observations should prompt consideration
of prudent preventive action.

All uses of lead including recycling should be reviewed in all nations
and uses contributing to environmental and human exposures, such as
uses in toys, paint, water pipes, building materials, solder,
electronics, medications, and cosmetics ended. The transfer of these
products from one country to another should also be avoided. This
approach has been adopted successfully in the EU and needs to be
extended worldwide.

In particular, tetraalkyllead must be eliminated without delay from
the gasoline supplies of all nations. The removal of organic lead from
gasoline has produced declines of greater than 90% in population mean
[average] blood lead levels in industrially developed nations, and
this success is now being repeated in some of the developing nations.
This action represents one of the great public health triumphs of the
late 20th century and needs urgently to be extended to all nations.

Current exposure standards for lead need urgently to be reduced.
Current standards were established many years ago and do not reflect
recent advances in scientific knowledge about toxic effects at levels
of exposure below these standards. The Brescia Workshop recommends

* For children, the action level, which triggers community prevention
efforts to reduce exposure sources, should be immediately reduced to a
blood lead concentration of 50 ug/L [50 micrograms/Liter = 5
micrograms per deciLiter] in nations worldwide. This level is proposed
as a temporary level that may need to be revised further downward in
future years as new evidence accumulates on toxicity at still lower
blood lead levels. This reduction of the blood lead action level will
reduce the incidence of subclinical neurotoxicity in children as well
as the delayed consequences of developmental toxicity.

* For industrial workers, the standard for lead in blood should be
reduced immediately to 300 micrograms/Liter in nations worldwide.
Additional consideration should be given to further reducing this
standard to 200 micrograms/Liter and below in the years ahead. This
reduction in exposure standard will reduce the incidence of
subclinical neurotoxicity and other toxic effects during the working
life and responds to new documentation presented at the Workshop that
long-term lead exposure increases the risk of dementia in later life.

* For female industrial workers of reproductive age, the standard for
lead in blood should be reduced immediately in nations worldwide to
the lowest obtainable, preferably to 50 micrograms/Liter [= 5
micrograms/deciLiter], a level consistent with the recommended blood
lead standard for children. Lead passes freely across the placenta
from the maternal to the fetal circulation to enter the developing
brain where it causes prenatal brain injury. This recommended
reduction in maternal lead exposure will reduce the incidence of fetal
neurotoxicity in the offspring of women workers.

Exposures of pregnant women and women of reproductive age to
methylmercury need to be reduced to prevent subclinical fetal
neurotoxicity. Evidence is strong that prenatal exposure to
methylmercury causes fetal neurotoxicity. Consumption of fish with
high mercury concentration by pregnant women is the primary route of
exposure. More than 50% of the mercury in fish may be of industrial

Strategies for reducing mercury exposure recommended by the Brescia
Workshop are the following:

* All industrial uses, recycling processes, and other industrial input
of mercury into the environment should be reviewed in all nations, and
non-essential uses should be eliminated and releases controlled. This
approach has been successfully introduced in the EU and is actively
promoted by the United Nations Environmental Programme.

* Mercury emissions from coal-fired power plants need to be curtailed.

* All chloralkali plants worldwide should be urgently converted to
alternative technologies that are not based on mercury, and mercury
stores and wastes must be safely deposited.

* Gold mining with mercury must be controlled and enforced with safety
guidelines, and alternative technology should be promoted.

* Dietary advisories should be developed as effective, culturally
appropriate means to limit childbearing women's consumption of fish
contaminated with methylmercury. Taking into account nutrient contents
and availability, healthy diets should be recommended with fish and
seafood containing minimal levels of contamination.

Exposures of pregnant women and young children to manganese need to be
reduced to prevent subclinical neurotoxicity. Important new data on
the neurotoxicity of manganese were presented at Brescia. In adult
workers, these data suggest that manganese produces subclinical
neurotoxicity at levels of exposure below those that produce
parkinsonism. In children, evidence from two recent epidemiological
studies suggests that exposure to manganese in early life causes
subclinical developmental neurotoxicity.

The addition of organic manganese compounds to gasoline should be
halted immediately in all nations. The data presented at the Brescia
Workshop raise grave concerns about the likelihood that addition of
manganese to gasoline could cause widespread developmental toxicity
similar to that caused by the worldwide addition of tetraalkyllead to
gasoline. In light of this information, it would be extremely unwise
to add manganese to gasoline.

Exposure standards for manganese need to be reconsidered. The drinking
water standards for manganese in many countries are not based on
health concerns, and those that are, do not protect against
developmental neurotoxicity resulting from exposures in utero and in
early postnatal life. The current occupational exposure standard may
not protect workers against subclinical neurotoxicity. The value for
air manganese concentration in inhalable/total dust of 100 mg/m3
should be adopted to protect the workers from prolonged exposure and
consequent long-term effects.

Economic impacts of the neurotoxicity caused by metals must be
considered. The costs of toxicity may be far greater than the costs of
pollution control. The major contributor to these costs is damage to
the developing central nervous system. Such injury can result in
lifelong loss of intelligence and motor capacities, permanent
psychological disturbances, and disruption of behavior. These effects
can produce reduction of economic productivity, and when this
reduction occurs widely across a society, the resulting economic
impacts are great. The costs of pollution recur annually in each
exposed birth cohort, adults, and elderly while the costs of control
are one-time costs. Need is great for continuing research into the
neurotoxicity of metals. Recent studies of neurotoxicology of each of
the metals discussed at the Brescia Workshop inform us that we can
anticipate harmful effects of increasingly lower levels of exposure to
metals, previously f. considered safe as larger studies using
sensitive measures of exposure and outcome, and better statistical
techniques are conducted.

a. For lead, mercury, and manganese, much remains to be learned about
the delayed consequences of developmental toxicity and the prolonged
exposure to low levels in the adults, as possible causes of
neurodegeneration. This research is critical to guide both future
research in metals as paradigms of neurotoxic pollutants and targeted
programs of prevention.

b. Prospective cohort studies from birth are needed, parallel to study
on adults and elderly with a retrospective assessment of exposure.

c. Neurotoxicological research, including research on developmental
neurotoxicology, is needed on metals not considered at the Brescia
Workshop -- arsenic and aluminum, in particular, and on interactions
with essential elements, pesticides, and persistent organic

d. Research is needed into genetic and other factors that contribute
to susceptibility to metal toxicity.

e. Research is needed into various determinants of the rearing
environment, including the social setting, that can modify the
exposure indicators to neurotoxic metals


Philip Landrigan is a member of the ICOH Scientific Committees on
Toxicology of Metals and Neurotoxicology and Psychophysiology.

Monica Nordberg is the Chair of the ICOH Scientific Committee on
Toxicology of Metals.

Roberto Lucchini is the Chair of the ICOH Scientific Committee on
Neurotoxicology and Psychophysiology and member of the Scientific
Committee on Toxicology of Metals.

Gunnar Nordberg was the past Chair of the ICOH Scientific Committee on
Toxicology of Metals.

Philippe Grandjean is a member of the ICOH Scientific Committees on
Toxicology of Metals and Neurotoxicology and Psychophysiology.

Anders Iregren was the past Chair of the ICOH Scientific Committee on
Neurotoxicology and Psychophysiology.

Lorenzo Alessio is a member of the ICOH Scientific Committee on
Toxicology of Metals.


** Statement authored by Philip Landrigam,[1] Monica Nordberg,[2]
Roberto Lucchini,[3] Gunnar Nordberg,[4] Philippe Grandjean,[5] Anders
Iregren,[6] and Lorenzo Alessio[1]

[1] Department of Community and Preventive Medicine, Mount Sinai
School of Medicine, One Gustave L. Levy Place, New York

[2] Institute of Environmental Medicine, Karolinska Institutet,
Stockholm, Sweden

[3] University of Brescia, Institute of Occupational Health, Ple
Spedali Civili, Brescia BS, Italy

[4] Department of Public Health and Clinical Medicine, Umea
University,Environmental Med- icine, Umea, Sweden

[5] Institute of Public Health, University of Southern Denmark,
Winslowparken, Odense, Denmark

[6] National Institute for Working Life, Chemical Risk Assessment,
Stockholm, Sweden

* Correspondence to: Philip Landrigan, Department of Community and
Preventive Medicine, Mount Sinai School of Medicine, One Gustave L.
Levy Place, Box 1057, NewYork 10029-6574. E-mail:

The views presented in the Declaration are the consensus reached by
the participants in the workshop and do not necessarily reflect the
decisions or stated policies of the affiliation organizations.