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PARAQUAT in developing countries
Submitted to the Int J Occup Environ Health on July 24, 2001
Catharina Wesseling M.D., Ph.D.
1
, Berna van Wendel de Joode M.Sc.
2,3
, Clemens Ruepert
M.Sc.
1
, Catalina León M.D., M.Sc.
1
, Patricia Monge M.D., M.Sc.
1
, Hernán Hermosillo
M.Sc.
4
, Timo Partanen Ph.D.
1
1. Central American Institute for Studies on Toxic Substances (IRET), Universidad
Nacional, Heredia, Costa Rica
2. Institute for Risk Assessment Sciences, University of Utrecht, The Netherlands
3. Department of Chemical Exposure Assessment, TNO Chemistry, Zeist, The Netherlands
(BvWdJ)
4. Foro Emaús, Limón, Costa Rica
Corresponding author
Catharina Wesseling
Central American Institute for Studies on Toxic Substances (IRET)
Universidad Nacional
Apdo 83
3000 Heredia, Costa Rica
Phone +506 277 3584; fax: +506 2773583
Email cwesseli@una.ac.cr
2
ABSTRACT
Paraquat, a controversial herbicide, is one of the most used pesticides globally, in most
countries without restrictions. It is considered safe by industry and the bulk of regulators
worldwide, especially in the context of stewardship programs. However, the few recent
studies on exposure assessment and health effects demonstrate that determinants of exposure
that were identified thirty years ago still prevail in developing countries. Little is known about
systemic absorption of paraquat from occupational exposures. The relations between exposure
determinants, levels of external exposure, biomarkers of exposure, and outcomes are far from
clear. For example, measured low inhalation levels are inconsistent with frequent episodes of
nosebleeds, and it remains uncertain at which inhalation levels nosebleeds occurs and whether
these levels may be relevant for systemic uptake. Non-worker populations are also at risk for
exposure and health effects, in particular children. High rates of severe acute poisonings, both
suicidal and unintentional, have been documented in many countries, also in recent years.
There are no strong data that total paraquat poisonings have substantially diminished, and
paraquat poisoning clearly remains a severe public health problem in many countries. In
addition, topical injuries, including skin problems ranging from mild dermatitis up to severe
chemical burns, eye injury, nail damage, and nosebleed, have been observed in proportions as
high as 50% of exposed workers in both early and recent surveys. Long-term and delayed
health effects may occur, including Parkinson’s Disease, lung effects, and skin cancer.
Regulatory agencies have not fully recognized either the inherent toxicity of paraquat for
human beings or the particular risks derived from exposures in developing countries.
Independent risk assessment in the developing country context and application of the
precautionary principle are necessary to prevent the occurrence of adverse affects from
dangerous pesticides such as paraquat in susceptible third World populations.
3
INTRODUCTION
The contact herbicide paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) disrupts
photosynthesis processes in plants. Paraquat is used in over 120 countries, commonly sold as
Gramoxone
, a 20% solution. It is currently the third best-selling pesticide globally, produced
by of the world’s largest agrochemical company currently by name SYNGENTA,
(www.syngenta.com/en/customer, July 2001)
. Paraquat is labor saving and cheap, and
therefore especially popular and accessible to farmers in developing countries.
The use of paraquat has been questioned and discussed for decades in international regulatory,
NGO, and scientific fora.
1-13
Reasons for alarm were frequent suicides, unintentional
poisonings in children and adults, and skin and eye injuries. In the late 1980s, manufacturers
added a blue pigment, a stenching compound, and an emetic substance to the formulation to
make severe unintentional poisonings due to oral intake virtually impossible.
14
Industry has
repeatedly claimed that paraquat has an excellent occupational safety record, when labeled
instructions are followed.
14-17
In response to a report on high frequency of suicidal paraquat
poisonings in Trinidad,
18
the manufacturer recently stated that paraquat suicides are
decreasing, and that safe use practices and training have decreased if not eliminated
unintentional poisonings. They claim that “banning paraquat could add to the social distress
associated with high suicide rates among subsistance farmers, by banning an essential tool to
feed their families and enhance their prosperities”.
17
Paraquat has been banned or restricted in a number of countries. The US Environmental
Protection Agency (EPA) allows its purchase and use solely by certified applicators.
19
Paraquat is prohibited in Sweden, Finland, and Austria based on acute toxicity and absence of
antidote. In Norway, the manufacturers canceled voluntarily its registration.
20
In Germany and
in The Netherlands, paraquat was banned because of its persistence in soil. The ban was
subsequently lifted.
21
Paraquat is being reviewed in the European Union and is in use in 10 of
the 15 EU member states (http://europa.eu.int
, status of current authorizations in December
2000).
In developing countries, where health hazards of pesticides are pronounced, paraquat is
minimally restricted. In Indonesia, its use is restricted to large estates and certified
applicators.
22
In April 2001, the government of Chile prohibited aerial applications
(http://www.sag.gob.cl
). In September 2000, the Central American Ministers of Health signed
4
an agreement on restricting the most toxic pesticides, including paraquat.
23
The agreement has
not been implemented yet.
The recommendation for classification by acute hazard of the World Health Organization’s
International Program on Chemical Safety (IPCS), followed by most developing countries,
endorses a laissez-faire for paraquat by classifying it as a moderately toxic Class II pesticide,
based on oral toxicity data in rats.
24
Paraquat was initially considered by the Prior Informed
Consent (PIC) Expert Group for inclusion in the list of PIC pesticides of the FAO Code of
Conduct, as a pesticide with special problems in developing countries. Heavy industry
lobbying however has kept paraquat excluded from the PIC list. The PIC Expert Group
suggested during the 1992 FAO/UNEP joint meeting on PIC in Rome, that “FAO consult
with PAHO regarding the reported accidents, deaths and incidents in Latin America and
consider a consultancy involving visits to five or six countries to investigate the reports of
incidents and provide a report on the actual conditions of use”. This consultancy never took
place. In 1995, discussions on the PIC Convention stopped any further actions (Barbara
Dinham, personal communication). The World Bank agreed to consider not recommending
paraquat in World Bank projects,
9
but never implemented this policy.
Deficient working conditions, improper maintenance, climatic conditions, illiteracy, and
general poverty make controlled and safe use of paraquat extremely difficult in developing
countries. This paper reviews data on use, human exposure, toxicity and health effects of
paraquat, focusing on Costa Rica, Central America, and other developing countries, in order
to provide an overview of basic data for risk assessment and decision making in developing
countries.
USE OF PARAQUAT AND HUMAN EXPOSURE
Use in Central America
Paraquat has for decades stayed among the pesticides imported by highest volume in Central
American countries: Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and
Panama.
23,25
It is used in for weed control on banana, coffee, plantain, sugarcane, corn, palm
heart, ornamentals, trees, citrus fruits, oil palm, macadamia, mango, avocados, and other
crops; as a pre-emergent herbicide on crops or for the cleaning of land; as a defoliant on
5
cotton; for destruction of potato stems and tops; as a post-harvest desiccant on pineapple; in
roadside weed control; and around buildings and homes, especially in rural areas (Database
IRET-UNA). Paraquat became widespread in the late 1970s. By the end of the 1980s,
technical grade paraquat was processed in pesticide formulating factories in the seven Central
American countries.
25
Being a contact herbicide, spraying of paraquat occurs with high
frequency, especially under humid weather conditions with rapid plant growth, for example
up every six to eight weeks on banana plantations. Import data, available for Costa Rica from
1981 (Database IRET-UNA), peaked at 750 tons in 1989, followed by a steep decline to 187
tons in 1995. The decrease was related to a substitution for other less toxic herbicides, such as
glyphosate. This occurred in particular on the banana plantations, under consumer pressure
from abroad, since paraquat could not be used anymore for bananas with an eco-label. At
present, the use of paraquat is on the rise again, due to increased use in other crops such as
pineapple, with over 420 tons having been imported in 1999 in Costa Rica (Figure 1). No
Central American country restricts the agricultural use of paraquat in any manner, with the
exception that it is not registered for aerial applications.
INSERT FIGURE 1
Occupational exposure
Exposure to paraquat occurs by dermal and ocular contact, by inhalation or by oral intake.
Early occupational exposure studies in Sri Lanka, Malaysia and the United States assessed
exposure levels of knapsack and field tractor applicators
26-29
and occupational exposures for
aerial applications.
30
More recently also some exposure assessments studies on knapsack
applicators have been performed in Sri Lanka
31
and Costa Rica.
32,33
Table 1 gives an overview
of the studies performed. The studies measured dermal, inhalation and/or urinary paraquat
levels of applicators and/or plantation workers. In general, dermal exposure levels seemed
most important, whereas measured inhalation levels were relatively low. Four out of six
studies assessing uptake found paraquat in urine at the end of one or more working days.
However, the relations between exposure determinants, levels of external exposure, and levels
in urine were far from clear and not investigated with much detail.
Measured exposure levels and exposure circumstances among backpack sprayers seemed
quite comparable in the different studies, with the exception of the remarkably lower levels
observed in a study in the US.
27
Nevertheless, the interpretation of similar findings of studies
6
performed in several tropical countries differed considerably. The studies carried out by or in
collaboration with Imperial Chemical Industries (currently SYNGENTA) concluded that
paraquat is most unlikely to cause serious health problems under correct conditions of
use,
15,26,28,31
despite the fact that in several of these studies between 40 and 50% workers
experienced topical injuries.
26,34
Other researchers concluded that, even when measured levels
were unlikely to result in acute or chronic health effects, spray operators were continuously at
risk for high exposures that may lead to severe intoxication and injuries. Even on plantations
where serious efforts had been made to reduce risks, dangerous situations and events of
inadequate handling were registered.
32,33
INSERT TABLE 1
Dermal exposure
Dermal exposure was the most likely route of uptake in studies that reported paraquat in urine
(see Table 1). Paraquat is poorly absorbed through intact skin, but penetration is considerably
increased by damaged skin, which is of particular concern because paraquat itself is a skin
irritant.
35
Total dermal exposure levels in studies presented in table 1 were assessed by residue
analysis on pads and coveralls or from hand washing, with calculations of mg/h or mg/kg of
applied paraquat of actual or potential dermal exposure. It is noteworthy that the existing
exposure data have only limited value for risk assessment, however they give insight in
possible exposure routes and mechanisms. Conceptual models of dermal exposures and new
methods for dermal exposure assessment are only recently being developed and underlying
mechanisms of exposure scrutinized scientifically.
36
On banana plantations, dermal exposures varied rather due to differences between plantations,
than differences between applicators or between days.
32,33
The body parts identified with
highest exposure were hands, wrists, back, and scrotum. They included splashing during
preparation of the spray solution and open transportation, deposition of spraying mist, contact
with spray solution when filling knapsack, leaking of knapsack on back and groin, adjustment
of spray equipment, and walking through the sprayed vegetation.
Use of protective clothing is supposed to considerably reduce dermal exposure. However, few
studies have evaluated the effectiveness of personal protection or other safety measures.
33,37
Swan (1969) compared exposure of applicators using normal clothing with workers using
7
gloves, boots and respiratory protectors.
26
Less positive urine samples were identified in
workers using protective equipment (7-14% versus 18-50%) and less skin complaints were
reported. Spruit and van Puijvelde (1998) performed a small study to evaluate the use of
protective equipment at four banana plantations by means of fluorescent tracer and cotton
gauze.
33
All workers (n=8) had received training in safe use of protective equipment. Wearing
jeans and an apron on the back seemed to reduce exposure considerably. Dermal exposure
levels were lower than those measured by van Wendel de Joode et al. (1996) (see Table 1).
32
Exposure occurred especially in body areas with movements (knees, elbow, wrists) and those
becoming wet by transpiration or pressure from belts of the knapsack (armpits and shoulder
region). Despite the use of gloves, hands remained exposed due to cross contamination by
taking gloves off and on. Occlusion of pesticides by protective devices may result in increased
absorption.
38,39
Inhalation
In general, inhalation exposure is not considered a relevant exposure route, due to the low
volatility of paraquat and droplets being too large to enter the small airways during
application.
19
Ambient air concentrations are generally well below NIOSH and OSHA limits
(0.1 mg/m
3
and 0.5 mg/m
3
TWA, respectively) (see Table 1). However, van Wendel de Joode
et al. (1996) could not exclude that inhalation exposure was relevant for internal exposure.
32
Inhalation exposures measured in this study appeared to be strongly influenced by differences
between days, which could be due to variable wind speeds and other weather related
conditions. In Costa Rica, the use of motor driven backpacks to spray paraquat is not
uncommon. These may produce increase of the fraction of respirable particles.
26
It has also
been put forward that the respirable fraction of paraquat may become larger under certain
climatic conditions.
40
Several studies suggest that inhalation may play a role in systemic
paraquat absorption.
12,40,41
The low inhalation levels measured in the different studies seem inconsistent with the
frequent episodes of epistaxis or nose bleeds reported among exposed workers,
3,15,26,32,42,43
which are due to local irritation of the upper respiratory tract by paraquat particles.
19
It is
possible that inhalation exposure levels are incidentally higher than those reported in the
studies of Table 1, since none of the studies with assessment of inhalation exposures
mentioned the occurrence of epistaxis during the measurements. However, it remains unclear
8
at which inhalation exposure levels epistaxis occurs and whether these levels may be relevant
for systemic uptake.
Oral exposure
Oral exposure may occur during work when ingesting paraquat solution by mistake, through
splashes in the mouth during mixing and transporting, by eating with contaminated hands, by
blowing or sucking spray nozzles, or when eating contaminated food.
12,15,28,32,44
In addition,
oral ingestion may also occur as a result of swallowing the ‘run off’ on the face caused by
droplets when the operator is working in the spray mist.
15
Retention of paraquat particles in
the nose and mouth, as evidenced by soar throat and nosebleed, may contribute to the internal
dose by swallowing.
12
Nonoccupational exposure: risk for children
The border between occupational and nonoccupational accidental exposure is not always easy
to distinguish. Accidental oral exposure may occur under a variety of circumstances.
Confusion of paraquat concentrate or solution due to inappropriate storage in refreshment or
liquor bottles has apparently diminished but still occurs. Accidental intake at home is in Costa
Rica often in association with alcohol intake.
45
Children’s exposures are of special concern. To determine oral exposure of children from
containers for garden use, a US EPA study analyzed paraquat residues of diluted spray on
nozzles and nozzle discharge. Based on a LD
50
for rats of 100 mg/kg, the maximum observed
value for oral exposure would represent 0.14% of the toxic dose for a child of 12.3 kg. The
authors concluded that despite the ample safety margin there is a potential hazard, in
particular because of higher toxicity in humans than in rats.
27
In Costa Rica, between 1991
and 1995, the exposure circumstances of severe and fatal poisoning in children age 1-6
included the cases of two toddlers placing respectively a rinsed spray jet and a bottle top into
their mouths, two cases of confusion of bottles stored in the kitchen, two cases of children
playing with empty bottles, and a 7-year old sister giving “cough medicine” to a younger
brother.
45
9
TOXICITY DATA AND HEALTH EFFECTS
Acute systemic toxicity
Systemic paraquat poisoning is characterized by burns of the upper digestive tract when
ingested, and by multi-organ failure, including the lungs as the main target organ, and liver,
kidneys and, less frequently, the central nervous system, heart, suprarenal glands, and
muscles. In fatal cases, depending on the dose, death is due to respiratory failure from lung
edema within a few days or from lung fibrosis up to over a month after the poisoning event.
No antidote or effective treatment is known.
11,43
Toxicity data from animal bioassays used by regulatory agencies are not fully consistent. US
EPA classifies the acute toxicity of paraquat due to oral intake as Category II, moderately
toxic, based on the LD
50
of 283 and 344 mg/kg in female and male rats,
19
while WHO-IPCS
uses a LD
50
of 150 in rats as the basis for its classification.
24
Acute oral toxicity is much
higher in other mammals, for example guinea pigs (22-30 mg/kg), monkeys (50 mg/kg), cats
(40-50 mg/kg) and dogs (25–50 mg/kg).
43,46
For humans, the lowest fatal dose recorded is 17
mg/kg.
43
Still lower doses may be fatal, especially in children.
12,47
EPA classifies systemic toxicity of paraquat from dermal absorption as slightly toxic,
category III, based on LD
50
> 2000 mg/kg (no observed mortality dosing rats during 24 hours
with 2000 mg/kg).
19
In other animal bioassays, the dermal toxicity of paraquat has been
reported to be much higher with LD
50
of 80 and 90 mg/kg in male and female rats,
43
and 236-
500 mg/kg in the rabbit.
43,46
In addition, paraquat is caustic and may, by increased dermal
absorption, originate systemic poisonings.
7,35,48
US EPA classifies the acute toxicity by inhalation as Category I, highly toxic based on an
inhalation LC
50
of the respirable fraction of paraquat of 1 µg/L. However, since agricultural
formulations of paraquat contain few respirable particles and paraquat’s volatility is low as
discussed above, EPA does not consider the respiratory toxicity a toxicological endpoint of
concern for systemic paraquat absorption and does not consider it in its risk assessment.
19
Systemic toxicity after respiratory exposures has however been reported.
12,40,41
10
Epidemiology of severe and fatal paraquat poisonings
Thousands of paraquat poisonings and fatalities have been reported in case reports, case
series, surveys and through surveillance systems, in particular in developing countries. Table
2 illustrates incidence and mortality for paraquat poisoning in selected countries, including
epidemics with a very high fatality rate in Asia and Latin America, including Malaysia, Fiji,
Japan, Sri Lanka, Surinam, Mexico, Costa Rica, Trinidad y Tobago, and Samoa.
49-59
Incidence and mortality rates vary enormously according to patterns of paraquat use,
prevention and control programs, type of register, and reporting practices.
Despite likely underreporting, in some developing countries
45,52,58,59
rates were between 10
and 300 fold those reported in the USA, UK, Ireland or Finland.
5,59-62
Recent figures available
for Central America and the Pacific Islands are of similar magnitude as in many countries in
the 1980s. Despite precautionary measures, the incidence of fatal paraquat poisonings,
particularly suicides, increased in Costa Rica during 1992-1998 as compared to the period
1980-1986.
45
Reports of severe unintentional poisonings and suicides have continued to
appear also from many other countries.
63-71
INSERT TABLE 2
The surveys in Table 2 refer mainly to suicidal poisonings, but many include also cases of
unintentional paraquat poisoning. The annual incidence rate of severe hospitalized paraquat
poisonings in Costa Rica is estimated at 44 per million inhabitants, and the incidence of fatal
paraquat poisonings at 15 per million during 1980-1986. Seventy five percent were accidental
and occupational poisonings. Forty-eight percent of the paraquat fatalities with an identified
cause were unintentional, mostly after accidental ingestion but also after occupational
exposure.
12,56,72
Severe paraquat poisonings and fatalities in children have been
reported,
5,12,47,56,72-77
ranging from accidents with extremely low doses
12,47,72
up to
homicides.
76,77
Although by far the majority of paraquat poisonings occur by oral intake, a number of severe
and fatal occupational and accidental poisoning reports after skin absorption are available.
78-89
One report concerned an unintended death following vaginal absorption.
90
It has been alleged
that systemic effects do not occur at recommended dilution rates.
15,16
However, in 1983 a fatal
case was reported of a farmer having applied a paraquat solution diluted according label
instructions (0.5% solution of paraquat) during 3.5 hours that resulted in skin exposure due to
11
a leaking knapsack.
80
The farmer died within a week after application due to paraquat induced
systemic intoxication. Wesseling et al (1997) described fifteen unintentional fatal paraquat
poisonings, of which five were due to contact with diluted spray solution.
12
Irritation of skin and eyes
US EPA concluded that paraquat causes moderate to severe eye irritation (Toxicity Category
II) and minimal dermal irritation (Category IV), based on toxicity experiments in rabbits.
19
In
fact, dermal lesions observed in workers range from mild irritation to blistering and ulceration
(second and third degree chemical burns), often in the genital area.
3,43
Eye injuries may range
from blepharitis and conjunctivitis to ulcerations or keratosis of the cornea; and nail damage
due to prolonged hand contact with paraquat ranges from localized discoloration to temporary
nail loss.
3,43
Skin, nail, and eye lesions have been reported,
42,74, 91-94
including in children.
72,74,84
Workers
in formulating factories were at high risk. A survey among 18 paraquat formulation workers
in the UK found that 14 (78%) had experienced nail damage, nosebleed, blepharitis, or skin
lesions with delayed healing. In Malaysia, 15 out of 18 formulators presented topical lesions,
such as dermatitis or chemical burns (50%), and eye injury or blepharitis (39%).
42
Few data
from epidemiological studies or surveillance systems are available on topical injuries among
agricultural workers. In California between 1971 and 1985, 231 paraquat-related cases of
illness were reported, 38% being systemic poisonings and 62% topical injuries,
85
less than 10
topical cases per year. However, skin burns and eye lesions from paraquat exposure are
common among herbicide sprayers in developing countries, where no accurate statistics are
available. In a number of the previously mentioned exposure assessment studies paraquat-
related topical injuries were mentioned. In Malaysia, in one study approximately 50% and in
another study 44% (12/27) of paraquat sprayers experienced skin or eye injuries during
fourteen and twelve week spraying programs, respectively.
26,34
In Costa Rica, out of 11
paraquat sprayers on banana plantations three mentioned blistering of skin on hands, thighs,
legs, back, and scrotum; two experienced eye irritation, three nail damage, three epistaxis, and
one a burning sensation in the nose, during the preceding year.
32
In Costa Rica, a number of surveys on occupational injuries among wage-earning workers
have been carried out by the Central American Institute for Studies on Toxic Substances
between 1982 and 1996.
56,95-97
A summary of the results is presented in Table 3. In absolute
12
numbers, hundreds of paraquat injuries occur each year in Costa Rica, most of them in the
banana producing Atlantic Region. The majority (60%) of victims presented skin burns or
dermatitis and 26% chemical eye injuries. The remaining 14% represented systemic
poisonings, nosebleeds and nail damage.
97
Incidence rates decreased over time, 1996 being
the lowest (0.5 per 1000 banana workers during a one-month period). Most injuries
concentrated on herbicide applicators, with a monthly rate of 26.7 and 13.3 per 1000 for 1993
and 1996, respectively.
INSERT TABLE 3
Long-term and delayed health effects
EPA California acknowledges evidence of chronic effects from long-term exposures in lung,
liver, kidneys and eyes in rats, dogs and mice.
98
US EPA recognizes lung effects and dermal
lesions.
19
Paraquat does not appear to be mutagenic, but is weakly genotoxic.
19,98
Developmental and reproductive effects occur at doses higher than the maternal toxicity
dose.
19,98
However, paraquat crosses the placenta. Fetal death in pregnant women poisoned by
paraquat and neonatal death after induced delivery have been reported.
72,99,100
Neurotoxicity
has not been evaluated by regulatory agencies. Animal bioassays
101,102
and clinical and
pathological scrutiny of human poisonings
103,104
revealed behavioral dysfunction and
histologic changes in the brain. Paraquat has been linked with Parkinson’s disease.
105,106
A
synergistic mechanism with ethylene bisdithiocarbamate fungicides has been proposed.
107
A number of studies failed to find lung damage in workers with prolonged exposure to
paraquat in the United Kingdom,
42
Malaysia,
26,42,34
and Sri Lanka.
108
However, in several
studies diagnostic tools, such as review of clinical records
42
and X-ray and clinical
examinations,
26
were insensitive, or the exposures were much lower than in other
occupational settings in developing countries.
108
Thus, a study in Nicaragua reported a dose-
response gradient between intensity of exposure, as measured by history of skin lesions and
the prevalence of respiratory symptoms.
109
In South Africa, clinical and histological lung
lesions were observed among exposed workers who had skin injuries.
2
Arterial oxygen
desaturation during exercise has been associated with long-term paraquat exposure.
110
This
test was not used in the earlier nonpositive studies.
34,108
SYNGENTA is now funding a US$
677,000 project to evaluate long-term lung effects among paraquat exposed workers in Costa
Rica (http//obgyn.net.ads. Health & Medicine Week, May 14, 2001).
13
Carcinogenicity
The International Agency for Research on Cancer (IARC) has not evaluated paraquat for
carcinogenicity. In the 1980s, US EPA concluded that there was some evidence for
carcinogenic effects from paraquat based on a study in rats with excesses of adenomas and
carcinomas in the lung, and squamous cell carcinomas in the forehead. Pathologists disagreed
on how many of the proliferative lung lesions were neoplasias and, in the end, the lesions
were considered secondary to chronic inflammation processes.
98
Following a claim of
industry that the tumors of the forehead appeared locations and could therefore not be
considered as a single entity, the statistically significant excesses disappeared after
stratification, and the results were reinterpreted as negative.
19
EPA California concluded that
the tumors were not the result of oral intake of the powdered feed containing paraquat, but
several members of the review committee felt that the tumors could have been the result of
topical contact with the feed.
98
On various arguments, paraquat’s Class C (limited evidence in
animals and lack of data in humans) was downgraded to Class E (evidence of non-
carcinogenicity in humans)
19
with no consideration of human evidence.
In Taiwan, squamous cell carcinoma of the skin has been associated with combined exposure
to sunlight, paraquat, actinic keratosis, and solar lentigo among workers in 28 paraquat
factories.
111
In Costa Rica, a geographic study on geographical study found excesses of
different skin cancers (lip, penile cancer, non-melanomous skin cancer and skin melanoma) in
coffee growing regions, as well as an excess of skin melanoma in men in the banana
producing Atlantic region,
112
both crops with extensive paraquat use. A cohort study among
Costa Rican banana workers also found an increased risk for skin melanoma.
113
RISK ASSESSMENT AND REGULATORY RECOMMENDATIONS
Decision-making processes in developing countries tend to be less transparent than in
industrialized countries. In Latin American countries, national regulatory authorities
habitually assign a compound into acute toxicity categories according to the WHO-IPCS
recommendations for hazard classification.
24
Other international bodies and agreements, such
as FAO food tolerances and the Prior Informed Consent (PIC) of the FAO Code of Conduct
are considered in registration.
114,115
Latin American countries are strongly influenced also by
US EPA, although as a rule only in broad terms, “to ban or not to ban”. Any pesticide
14
forbidden, never registered, or with a voluntary cancellation by the manufacturer may still
have food tolerances. The main driving regulatory restrictions for developing countries today
are the food tolerances related to the agricultural exports.
The EPA toxicity classifications and risk management decisions are of limited use in Latin
America. First, the toxicity classifications by EPA as well as other major regulatory bodies
are based on standard experimental testing protocols in strict laboratory conditions. Second,
when assessing the risks, toxicity data are integrated with exposure data, collected under
conditions of good agricultural practices that have little resemblance with the circumstances
prevailing in developing countries. Available epidemiological evidence of human health
effects from outside the USA has been considered only marginally at best. Third, EPA
restrictions are adopted south of the US border only in cases of a total ban including food
tolerances. This is not the case with paraquat. More subtle risk assessment details, including a
robust RUP (Restricted Use Pesticide) status of paraquat in the US, are not incorporated into
national legislations in the South. A considerable proportion of paraquat in Central America is
imported from the US, without major warning about the restricted regulatory status.
Risk management of paraquat in the US and elsewhere relies largely on safety instructions on
the label. Adversities that are consequence of not complying with label instructions are not
considered the manufacturers responsibility. In developing countries, the application of
paraquat in accordance with correct procedures as indicated on the label seem unrealistic,
even in the presence of industry efforts to promote safe and effective use of paraquat by
education and training.
22,116
A label may indicate many good agricultural practices, but the
possibility to follow these instructions in the field may be very low. In addition, the
effectiveness of training programs performed by industry is not evaluated in proper terms of
exposure, health effects, or risk reduction.
117
The key issue is that in Central America, and in
most other developing regions as well, insight in the risks from exposure in the local context
and the know how are lacking. Risk assessment concepts or strategies as the precautionary
principle are not applied when it comes to registering the use of a pesticide such as paraquat.
CONCLUSIONS AND FINAL REFLECTIONS
• Paraquat is one of the most used pesticides globally and in most countries without
restrictions.
• Relatively few exposure and hardly any intervention studies have been performed.
15
• The understanding of exposure determinants such as climatic circumstances, types of
crops, or application methods is limited. It is clear, nonetheless, that paraquat often is
applied under hazardous conditions and that in developing countries application
techniques have not considerably improved during the last thirty years. Transport systems
are still open systems, application equipment easily fails resulting in high exposures
• Possibilities to reduce exposure by wearing protective clothing seem limited. The
effectiveness of control measures under tropical conditions remains largely unevaluated.
! Relatively few recent surveys on paraquat poisonings are available. It is uncertain whether
this reflects a decline in severe poisoning or partially loss of interest in the problem.
! Suicides increased in Costa Rica in the 1990s compared to the 1980s. Recent reports on
suicides come also from other developing countries.
! Despite incompleteness of data and consequent difficulties of interpretation and
comparison, paraquat still represents a severe public health problem.
! Occupational and nonoccupational hazards may materialize at any time in a developing
country.
! The responsibility for suicidal use of paraquat rests also on the manufacturer. Unrestricted
access to a liquid, of which a very small amount may be fatal, makes a suicidal or
parasuicidal decision easy.
! Regulatory agencies have not fully recognized either the inherent toxicity of paraquat for
human beings or the particular risks derived from exposures in developing countries.
! Independent studies of occupational exposure assessment and health effects are needed.
! The impact of interventions, such as industry stewardship programs, should be properly
evaluated.
! If the precautionary principle would be applied in developing countries for the regulation
of pesticides, many of the prevailing problems would be prevented.
! The Central American Institute for Studies on Toxic Substances (IRET) will initiate an
independent health risk assessment for paraquat in the Central American context.
16
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Figure 1: Tons of paraquat imported in Costa Rica: formulated and technical grade solution
between 1981 and 1999; active ingredient between 1992 and 1999.
