Why Canadian Physicians are Concerned
about the Policies Regulating Pesticide Use
Presentation by Kelly Martin, M.D.,
to the Standing Committee on the Environment
Review of the Evidence
In 1997 the Ontario College of Family Physicians
requested a review of the evidence on pesticides and human
health effects, which I authored. The increasing concern by
the public created the demand for physician knowledge in
this area. The Cochrane approach, which uses a pre-stated
methodology to search the literature and assess the quality
of studies, was used to assess the evidence on the effects
of pesticides on the pediatric and adult population in
Canada.
Serious Problems with Pesticide Regulation
This review led us to conclude that there is a serious
problem with the amounts of pesticide that the population is
exposed to, particularly the pediatric population. As well,
there are great deficiencies in the way in which risk is
being assessed in Canada, underestimating the amounts and
the effects of pesticides on the human population. In the
research that has evaluated this risk, it is fair to
conclude that the number and quality of studies done on each
specific health outcome varies, particularly in the ability
to quantify exposure to pesticides. However, the combined
evidence from animal and human studies is sufficient to
create concern regarding the health effects of pesticides at
the levels that Canadians are presently exposed. We will
never have the opportunity to randomly and blindly assign
human subjects to pesticides and compare their health to
those that are unexposed. Thus, as in most areas of
medicine, we must rely on observational studies that can
provide very sound evidence in conjunction with animal
studies.
Producers must demonstrate that pesticides are safe. In
similar situations in the past, we have waited decades to
take action in situations while epidemiological evidence
mounts and those with financial interests argue for evidence
of cause and effect. This has led to the 20+ year delay in
taking action on cigarettes, lead and numerous other toxins.
The public pays high costs for these delays: in their
health, in the financing of cleanups, further research and
health care costs. More recently, the HPB has officially
adopted the "Precautionary Principle" and is now in the
position to apply it, to avoid the mistakes made in the
past. If the Health Protection Branch is truly in existence
to protect the health of Canadians, and is to live by its
agreement to implement the precautionary principle, then it
must now take some concrete action on the testing and use of
pesticides. It is no longer acceptable to expect the
scientific community to prove beyond a doubt that there are
serious health implications while the public pays for the
health care costs, clean ups and years of research. With
reasonable evidence of harm, producers of pesticides must
now be responsible to prove beyond a doubt that these
chemicals are safe.
The Effects of Pesticides on Human Health
The following findings are of particular interest in the
review of the importance of policy on pesticide regulation.
National Research Council (US) Report
Some of the most thorough review of the evidence comes
from the National Research Council (US) report on Pesticides
in the Diets of Infants and Children. This is an impressive
committee of researchers, physicians and risk assessors who
conclude that:
Infants and Children are at Greater Risk from the
Effects of Pesticides
Studies of fungicides, herbicides and insecticides
demonstrate that each of these compounds is more toxic to
the newborn than the adult. This has very practical
implications. For example, the presently acceptable levels
of aldicarb on watermelons is such that a 10 kg child
could easily consume enough of the pesticide to experience
acute toxicity, including vomiting, seizures and
respiratory failure1.
Pesticides are effective in killing pests through their
neurotoxic effects. Infants appear to be particularly
susceptible to the effects of these pesticides because
they have incompletely developed acetylcholinesterase
systems and their immature livers cannot detoxify these
compounds2.
We Cannot Predict the Risk of Infants and Children
on the Basis of Adult Evidence
A number of researchers have demonstrated that
age-related differences, particularly in the effects of
pesticides on neurologically mediated motor activity, could
not have been predicted on the basis of the studies that are
presently being used in risk assessment2. The research
demonstrates that more sensitive indices need to be used to
monitor potentially vulnerable systems in infants and
children, including the hormonal and reproductive systems,
the immune system, and the neurological and behavioural
systems.
The Use of Animal Evidence is Not Sufficient for
Predicting Human Risk
The evidence suggests that human infants and children are
much more susceptible to the effects of pesticides,
particularly organophosphates and carbamates, than animal
species2. The present assessment of the risk of pesticides
is almost exclusively based on animal studies and this may
greatly underestimate the risk to humans, particularly
infants and children.
Basing Acceptable Levels of Pesticide Residues on
the Risk of Death in an Acute Exposure is Not Appropriate
for Predicting Long-Term Human Risk
Present risk assessment uses lethality (death) and cancer
outcomes in animals as the primary end points. The use of
these endpoints does nothing to predict the risk of damage
to organ systems that would occur from low levels over
longer periods of time such as; reproductive effects on
fertility, genitalia abnormalities and other fetal effects,
neurological effects, behavioural and psychological effects
and immunological effects.
Quantification of Infant and Child Exposure is
Inadequate
The committee concluded that there is no good information
on the quantity of pesticides that infants and children are
exposed to. They consume much greater amounts of certain
foods that contain numerous pesticide residues, and this
becomes very pertinent when the pesticide exposure is
calculated on a residue per kilogram of body weight. For
these reasons, it is not acceptable to use the estimations
of pesticide exposure based on adult exposure2. In Canada,
we have even less information. There has not been a market
basket assessment of food consumption since that done prior
to 1992 (verbal report from Agriculture Canada). We have
never done any collection of information on the dietary
patterns of infants and children and thus have no
information from which to quantify their pesticide exposure
through water and food consumption. This, in conjunction
with their exposure from many play surfaces, lawn and garden
spraying, and exposure from indoor application of
pesticides, needs to be quantified to set reasonable maximum
allowable limits of pesticides in foods, water and post-lawn
and garden application2. This is stated as a priority of the
US EPA3 but is not being considered in Canada.
Conclusions
A group of acclaimed scientists from the National
Research Council have thoroughly reviewed the evidence and
conclude that the pediatric population is at considerable
risk given the current methods of setting allowable limits
of pesticides. The American government has taken steps to
attend to these issues (FQPA 1996). Seven years later the
Canadian government has done nothing, and talks of taking
some actions by 2005. This is well substantiated evidence
with clearly stated actions that need to be taken. The
solutions are being held up by Canadian policy makers'
inability to make the health of our infants and children a
priority.
Scientific Evidence - Pesticides and Human Health
Effects
This is a brief summary of a selected number of the
health effects.
Non-Hodgkin's Lymphoma
The most convincing evidence that herbicides (pesticides
used most commonly in agriculture) are human carcinogens
come from epidemiologic studies. A number of studies have
revealed elevated risks of non-Hodgkins's lymphoma with
chronic exposure to herbicides, with the relative risk of
developing non-Hodgkin's lymphoma being 5-6 times the normal
risk4-9. In those studies that have examined dose-response
relationships, they have found statistically significant
increases in the risk of developing non-Hodgkin's lymphoma
with increasing amounts of herbicides used4, 6, 8. These are
the findings reported by the National Cancer Institute of
Canada's Advisory Committee on Cancer Control10 and are well
accepted relationships between pesticides in populations
with common exposures, like farmers and golf course
caretakers.
Childhood non-Hodgkin's lymphoma has been shown to be
associated with household or garden insecticide use11 as
well as home extermination using pesticides12 and parental
occupational exposure to pesticides13.
Leukemia
Beginning in the late 1970s, there have been reports
linking pesticides to leukemia in children. Case-control
studies have linked pesticide exposure to childhood cancer,
in some instances with greater magnitude of risk than in
studies of occupationally exposed adults14. A number of
studies have demonstrated that maternal employment in
agriculture has been shown to be associated with
leukemia14-16. Use of pesticides on the lawn or garden
during pregnancy was associated with a 5.6 fold increase in
childhood leukemia in a Los Angeles study17. Pest strips,
typically made with organophospates, were associated with
childhood leukemia in another US study12. The
organochlorines have been associated with an increased risk
of leukemia14. Although the majority of these are no longer
used in Canada, there is continued use of organochlorines in
the medical sector as well as in agriculture. Their
continued use and the persistent presence of these chemicals
in water, meat, poultry and vegetable food sources make the
organochlorines a continued risk.
Neurological Effects
The acute neurological effects of pesticides are well
known as the mechanism of action of most pesticides is
neurological toxicity, which acts in the same way on humans.
There are numerous reports of pediatric cases of neurotoxic
effects (seizures, confusion) after skin exposure to insect
repellents and medical treatment of head lice with
pediculocides. The evidence on the long term effect of
pesticides on the neurological system is less well
established but the existing studies strongly suggest that
there are chronic effects, especially with organophosphates
and carbamates, presently some of the most widely used
pesticides2. Studies of the long term effects strongly
suggest developmental effects from low level exposures
similar to the effects found for lead. Neuropsychological
and developmental data collected on children exposed to
certain pesticides in utero and infancy, particularly
polybrominated biphenyls (PBBs), shows that significant
differences exist in neuropsychological and development
outcomes related to the dose of exposure. There is a clear
mechanism for neurological toxicity with some human evidence
to support long term effects. These studies are more costly
and extensive because of the duration of follow-up required
but is an area that has been targeted by the American NRC as
needing immediate regulatory body support for action and
further study.
Immunotoxicity
Numerous animal studies show a variety of effects of
pesticides on the immune system, including decreased
antibody formation by 70% after exposure to common
pesticides such as captan, lindane,malathion as well as
decreased cell mediated immunity2. In human exposures to
pesticides, decreased functioning of the immune system has
been documented (T-cells react abnormally, decreased T4 and
T8 counts, increased energy) that is associated with an
increased report in clinical illness2. The amount of
research in this area has been limited, particularly in
human studies and in the long term effects of pesticides on
the immune system.
Other cancers
A number of studies have found associations between brain
cancers and pesticides as well as soft tissue sarcomas.
Conclusions
There is considerable debate between regulatory bodies
and industry regarding the quality of the evidence
associating pesticides with cancer outcomes. It is clear
that obtaining good exposure data in observational studies
is difficult. However, we have to accept that we will never
have the opportunity to conduct drug like trials with
pesticides where we expose children or adults to placebo vs
pesticides. Our knowledge of the toxicity of pesticides
makes this ethically unthinkable. We can work towards better
studies with greater numbers of subjects but our regulatory
system does not encourage this. Industry is presently
responsible for providing the "evidence" that the pesticide
is safe and this consists of acute exposures to rats or
laboratory animals where we look at lethality and some
cancer endpoints only. As has been outlined, this does not
reflect the real risk to humans.
Using the evidence that we have, animal and human, we can
conclude that a number of pesticides that we readily use
pose significant risks to human health. It is appropriate
that we take policy and public health measures to ensure
that the population is aware of the risks and that those
with reasonable evidence of harm be withdrawn until further
evidence demonstrates no harm.
Pesticide Policy and Recommendations For Improvements
Involvement with the regulation of pesticides in Canada
as a physician and epidemiologist is a disturbing
experience. It is hard to imagine that the disarray that
appears to exist from the outside in fact exists at a
greater level when one is actually involved in the process.
Canadians increasingly question the will and the ability of
this federal government to protect them from the risks of
pesticides. As a member of the Pesticide Management Advisory
Council (PMAC) and as a researcher evaluating the existing
evidence on the effects of pesticides on human health, I
think their concern is well founded. In fact, I think that
it would be much greater if they were fully aware of the
inadequate assessment of health risks that the Canadian
government requires prior to release of pesticides, the
inability to re-assess pesticides, some of which have not
been evaluated for risk for over 20 years and the close
relationship that the regulatory body, the PMRA, has
developed with industry, often putting economic concerns of
the private sector ahead of the need for public health
protection. We now have a thorough and damning report of the
process from the Commissioner of the Environment and
Sustainable Development. We are being pressured by the
American policy makers to at least meet some of their
minimal standards on risk assessment and re-evaluation. And,
the scientific and public community has lost all confidence
that the federal regulatory system is adequate. We have
talked about changes for over 20 years. More discussion is
not what is required. We need to set down clear objectives,
with time lines and accountability and force the regulatory
bodies to move on these issues.
Recommendations
Risk Assessment
Re-evaluation programs
Post-regulation monitoring
Understanding and Implementing the Precautionary
Principle
Pesticide Alternatives
Risk Assessment
Risk management decisions must be legislated policy and
not Ministerial decisions.
Presently, and in the revised risk assessment that the
PMRA is proposing, the risk and value decisions are made by
the Minister. They argue that our legislative system does
not allow the inclusion of this in policy as is done, for
example, in the US. Clearly, the Minister is not in the
position to make risk assessment decisions and it is not
appropriate to have a moving target in terms of what risk is
acceptable in each pesticide that is evaluated or
re-evaluated. This leaves scientific decisions open to
political influences and risks inappropriate or very delayed
decisions being made. The level of risk that we, as
Canadians, are willing to accept needs to be clearly defined
and included in detailed policy, as it is done in other
countries.
The risk assessment process has to be clearly defined and
available so that discussion of the adequacy of this process
can occur. One can easily obtain very complete information
on the risk assessment process in other countries - but it
is unobtainable in Canada. For example, the PMAC has been
requesting this information for the last 18 months from the
PMRA. One assumes that if risk assessment is ongoing and
that, when the PMRA is projecting 2005/6 as the earliest
possible date for revision of this process, that we do in
fact have a process. The PMRA continues to assure the
advisory committees, as well as yourselves, that issues of
pediatric risk, multiple exposures etc are presently being
attended to in risk assessment. Many of those involved in
the process argue is not the case and from the material
presented to the PMAC by the HPB, it is simply not true that
we are incorporating the elements that result in increased
risk to infants and children nor are we assessing the effect
of real life (multiple simultaneous) exposure. Clearly, if
this regulatory body cannot come up with any outline of what
is being done we cannot pretend that we have a standardized
risk assessment process. This is an issue of the regulatory
body being in disarray, with no mandate or will to make the
basis of the assessment of pesticides transparent. We need a
clearly defined risk assessment process that is available
for critique and discussion now &endash; not in 2005 as
presently proposed.
The PMRA has outlined the two elements of risk assessment
as they see them - Risk and Value (see letter from the PMRA
of 09/03/99). Human risk assessment, under the auspices of
the HPB, can be concerned only with the acceptable human
risk. If a product does not meet this, regardless of it's
cost effectiveness, it is not acceptable for use. The HPB
needs to clearly define cutoffs for acceptable risk - in a
way that it is clear when it is exceeded. Further to this,
we need to have specific actions to be taken when a
pesticide, either alone or in the combinations in which
Canadians are exposed, exceeds this risk.
Risk Assessment must be based on Human Risk
The present practice of using animal (mice and rat) data
for estimating human risk is not adequate. Numerous studies,
outlined by the NRC, have demonstrated that the organ
systems affected varies amongst species. They also clearly
identify that the 16+ years of ongoing organ development in
the human child makes the chronic impact of pesticides very
different than that seen in the rat or mouse that reaches
maturity in weeks2. Because of these differences human
epidemiological studies must be used in conjunction with
animal studies. Both approaches have limitations however the
PMRA must require human epidemiological studies and be
prepared to collaborate with other departments to support
the required research.
Maximum Residue Limits (MRLs)
The risk of pesticides must be based on the true
experience of exposure. Canadians are exposed to pesticides
through food, water, contact with sprayed surfaces (both
lawns and in their homes), inhalation and through
occupational exposure. As well, many pesticides of the same
family will be found on any food product or water source.
When safety of a pesticide is assessed, we must consider the
average and maximum dose that Canadians of all ages are
consuming. For example, in our present system one
organophosphate is decided to be safe at level x.
Agriculture Canada reports that the average Canadian grown
peach contains the residues of, on average, 40 of these
organophosphates. They all work at the level of the
neurotransmitter, thus their effect is at least additive if
not multiplicative. It is unacceptable to regulate in a
manner that we ensure that each organophosphate on that
peach should be less than the maximum allowable level.
Instead, the combined effect of the 40 residues plus the
exposure from other food, water, etc., sources must be less
than the maximum allowable level for all populations.
The PMRA has to ensure that the risk assessment process
reflects Canadian risk. They must mandate that risk
assessment includes human studies and multiple exposures.
This must be implemented now, not in 2005 or some moving
time target.
Thorough Evaluation of Developmental Neurotoxicity and
Endocrine Disruption should be a mandatory requirement. This
information should be provided before a product is
considered for evaluation or re-evaluation. The evidence of
the effect of pesticides on these endpoints if substantial
enough to warrant their evaluation on all pesticides that
are used in the Canadian market.
Re-evaluation Programs
The present intent of the PMRA is to re-evaluate all
products registered up to 1994 by 2005-6. Of 500 active
ingredients in registered pesticides &endash; over 300 were
approved before 1981 and over 150 before 1960. Priorities
for re-evaluation were outlined in 1986 by Agriculture
Canada. In 1988 the Auditor-General again identified the
shortcomings of the re-evaluations that still had not taken
place. In 1995 the PMRA was directed to develop and
implement a re-evaluation program. No funds have been
allocated specifically to the re-evaluation and the PMRA now
proposes to attempt completion sometime in the new
millennium. The present plan for financing the re-evaluation
is to use money "shifted from submission backlog review that
should increase as improvements to the efficiency of
submission review allow more resources." Industry is
strongly opposing this method of financing and such an
approach will almost definitely ensure that the
re-evaluation will not take place. Absence of an effective
re-evaluation means that we are living with the risks that
we thought were acceptable 20 or 30 years ago. Twenty years
of accumulated scientific evidence will clearly make great
differences in our assessment of the risk of these
pesticides. The PMRA needs to have an imposed list of
priority substances for re-evaluation with firm dates for
completion of the re-evaluation. The source of funding needs
to be clear and not the continuing obstacle to carrying out
this process. Twenty years of delay, now continued by the
PMRA, necessitates this forceful intervention.
Post-regulation Monitoring
There is presently no systematic monitoring of either
human or ecosystem health effects of pesticides. The
Commissioner of the Environment and Sustainable Development
concludes that the federal government's approach to
monitoring is disorganized and lacks focus. The Commissioner
reports that even for the most toxic pesticides, that have
been identified as "priority toxic residues," there is no
monitoring even in areas of heavy use. This results in the
government's inability to detect the presence of toxic
substances in our environment and inability to determine
what risks they pose.
As physicians, we are acutely aware of this lack of
monitoring. In situations where we have apparent pesticide
toxicities, particularly in infants and children following
dermal or inhalation exposure, our Poison Control Centres
can offer us no information on the incidence of these
occurrences, on the appropriate diagnostic or treatment
interventions and have no mechanism in place to record these
toxic exposures that we are seeing in the clinical setting.
We require a system where quantities and types of
pesticides being used in Canada are routinely documented. As
well, we are in need of an easily accessible system where
apparent human pesticide toxicities can be recorded.
Precautionary Principle and the PMRA - Understanding
and Implementing It
The PMRA states that "the required pre-market review of
pesticides is in itself implementation of the precautionary
principle." This clearly outlines the PMRA's lack of
understanding of one of the key principles that they are
obliged to implement. Reviewing a drug or food or pesticide
before allowing public exposure is a necessary part of
controlling public exposure to toxins. It has nothing to do
with the precautionary principle which states that "[w]here
there are reasonable grounds to believe that exposure to an
agent may cause serious or irreversible damage to human
health, the appropriate body will take cost-effective
precautionary measures, even if some cause and effect
relationships are not fully established scientifically.
Where possible, the body will strive to anticipate and
prevent health risks rather than merely to control those
that already exist." The PMRA needs to understand and
implement the precautionary principle. This applies to the
risk assessment process, to decisions regarding the amount
of acceptable risk and finally the decision to register or
re-register a pesticide. This is an obligation of the PMRA
and needs to be treated as such.
Alternatives to Pesticides
This needs to be a serious undertaking of the PMRA. It is
the mechanism by which we can rid ourselves of the serious
health effects of pesticides in the future. There is no
evidence that the PMRA is seriously committed to this aspect
of pesticide management. We need to see adequate resources
allocated with clear plans and time lines from this division
of the PMRA.
Conclusions
The PMRA must recognize that it is a part of the Health
Protection Branch and as such its primary responsibility is
to protect the health of Canadians. Other aspects of
pesticide regulation, including economic considerations are
secondary to this objective. As such, the PMRA and
associated departments must recognize that their primary
role is in the assessment of evidence on the effects of
pesticides and the implementation of policy that ensures
that there are clear guidelines to removing pesticides that
pose an unacceptable risk to human health. The Environmental
Commissioner's Report outlines troubling criticisms of the
current federal regulation of pesticides &endash; concluding
that these deficits make the federal government's ability to
assess and prevent harmful effects of toxic substances
uncertain. These include lack of cooperation or
collaboration between government agencies, lack of public
access to pesticide related information, lack of effective
monitoring of the environmental fate and the health effects
of pesticides, inconsistent procedures for applying risk
assessment and risk management. These problems must be
responded to with solutions that incorporate clear
timelines. The Environmental Commissioner also notes that
the Toxic Substance Management Policy is an over arching
tool which provides the federal government's most important
basis for implementing a preventative and precautionary
approach. They conclude that neither the PMRA nor the
Federal Government Departments have adequately implemented
this policy. This should be an immediate priority imposed
upon the PMRA and the departments involved in the regulation
of pesticides.
Reference List
1. Goldman LR, Beller M, and Jackson RJ. Aldicarb food
poisonings in California, 1985-1988: Toxicity estimates for
humans. Archives of Environmental Health 1990; 45:141-147.
2. National Research Council. Pesticides in the Diets of
Infants and Children. Washington, USA: National Academy of
Science, 1993.
3. Fenner-Crisp PA. Pesticides - The NAS Report: How Can
the Recommendations Be Implemented? Environmental Health
Perspectives 1995; 103:159-162.
4. Hoar SK, Blair Aeal. Agricultural herbicide use and
risk of lymphoma and soft-tissue sarcoma. Journal of the
American Medical Association 1986; 256:1141-1147.
5. Hoar ZS, Blair A, Holmes FF, Boysen CD, Robel RJ. A
case referent study of soft-tissue sarcoma and Hodgkin's
disease: farming and insecticide use. Scand J Work Environ
Health 1988; 14:224-230.
6. Hoar ZS, Weisenburger DD, Babbitt PA, Saal RC, Vaught
JB, Cantor KPea. A case-control study of non-Hodgkin's
lymphoma and the herbicide 2,4 - dichlorophenoxyacetic acid
(2,4-D) in eastern Nebraska. Epidemiology 1990; 1:349-356.
7. Persson B, Dahlander AM, Fredriksson M, Brage HN,
Ohlson CG, Aselson O. Malignant lymphomas and occupational
exposure. Br J Ind Med 1989; 46:515-520.
8. Wigle DT, Semenciw RM, et al.. Mortality study of
Canadian male farm operators: non-Hodgkins's lymphoma and
mortality and agricultural practices in Saskatchewan.
Journal of the National Cancer Institute 1990; 82:575-582.
9. Woods JS, Polissar L, Severson RK, Heuser LS, Kulander
BG. Soft tissue sarcoma and non-hodgkin's lymphoma in
relation to phenoxyherbicide and chlorinated phenol exposure
in western Washington. Journal of the National Cancer
Institute 1987; 78:899-910.
10. Ritter L, For the Ad Hoc Panel on Pesticides and
Cancer. Report of a Panel on the Relationship between Public
Exposure to Pesticides and Cancer. Cancer 1997;
80:2019-2033.
11. Anonymous editor. Childhood non-Hodgkin's lymphoma.
1991;
12. Leiss JK, Savitz DA. Home pesticide use and childhood
cancer A case-control study. American Journal of Public
Health 1995; 85:249-252.
13. Kristensen P, Andersen A, Irgens LMea. Cancer in
offspring of parents engaged in agricultural activities in
Norway: Incidence and risk factors in the farm environment.
Int J Cancer 1996; 65:39-50.
14. Hoar Zahm S, Ward MH, Blair A. Pesticides and Cancer.
Occupational Medicine: Sate of the Art Reviews. 1997;
12:269-289.
15. Shu SO, Gao YT, Brinton LAea. A population-based case
control study of childhood leukemia in Shanghai. Cancer
1988; 62:635-644.
16. Buckley JD. Occupational exposures of parents of
children with acute nonlymphocytic leukemia: A report from
the Children's Cancer Study Group. Cancer Res 1989;
49:4030-4037.
17. Lowengart RA, Peters JM, Cicioni C. Childhhood
leukemia and parents' occupation and home exposures. Journal
of the National Cancer Institute 1987; 79:39-46.
CAPE Home page
http://www.cape.ca/toxics/pesticideskelly.html