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Carbamates: Human Exposure and Health Effects
Simone Morais, Elsa Dias and Maria de Lourdes Pereira
ABSTRACT
The extensive use of carbamate pesticides in modern agriculture has raised serious
public concern regarding the environment and food safety. Due to their broad
spectrum of biological activity, carbamates can be used as insecticides, fungicides,
nematocides, acaracides, molluscicides sprout inhibitors or herbicides.
Contamination of fruits and vegetables may result from treatment as well as from
conditions such as improper use of pesticides, residues from preceding treatments in
the soil and cross-contamination. Sources of residues in products of animal origin
include contaminated water or feed, pesticide-treated housing, and contaminated
milk. The presence of pesticide residues is a concern for consumers because
carbamates are known to have potential harmful effects to other non-targeted
organisms than pests and diseases. The major concerns are their toxic effects such as
interfering with the reproductive systems and foetal development. In this chapter,
the more relevant contributions, of the last ten years, to the current knowledge on
several aspects regarding carbamate pesticides, such as mode of action, effects on
human health, legislation, monitoring, human exposure to carbamate residues, risk
and exposure assessment will be discussed.
INTRODUCTION
Pesticides are of vital importance in the fight against diseases, for the production
and storage of food being widely used for pest control in agriculture, gardening,
homes and soil treatment (Crespo-Corral et al., 2008, Janssen, 1997). In spite of
their extensive use, an average of 35% of the produce is lost worldwide (Janssen,
1997). Carbamates represent one of the main category of synthetic organic
pesticides since their introduction into the agrochemical market in the 1950s
(Tomlin, 1997) and are used annually on a large scale worldwide (Paíga et al.
2009a). They constitute a versatile class of compounds used as insecticides,
fungicides, nematocides, acaracides, molluscicides, sprout inhibitors or herbicides.
Classification of pesticides to functionalities and chemical properties is available on
several informative website (www.epa.gov/pesticides/about/types.htm and
http://www.alanwood.net/pesticides). Although carbamates present low
bioaccumulation potentials and short-term toxicity (relatively short biological half-
lives and are fairly rapidly metabolized and excreted), they are considered
hazardous to the environment and human health being included in the priority list
released by the United States Environmental Protection Agency (US EPA, 1992).
Apart from their pesticide properties, the role of three carbamate insecticides
(carbaryl, baygon and carbofuran), as possible cancer chemotherapeutic agents was
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recently explored on preliminary studies in vitro using trypsinized squamous cell
carcinoma, since they inhibit cellular metabolism including energy, protein, and
nucleic acid metabolism, thereby, causing cell regression and death (Amanullah and
Hari, 2011).
Three classes of carbamate compounds are known: i) the ester derivatives; ii) those
with the general structure R1NHC(O)OR2, in which R1 and R2 are aromatic and/or
aliphatic moieties, and iii) those containing a benzimidazole group (IPCS, 1986).
In this chapter, the more relevant contributions, of the last ten years, to the current
knowledge on several aspects regarding carbamate pesticides, such as mode of
action, effects on human health, legislation, monitoring, human exposure to
carbamate residues, risk and exposure assessment will be discussed.
MODE OF ACTION AND TOXICOLOGY
The mechanism of carbamates poisoning, except herbicidal carbamates, involves
carbamylating of the active site of acetylcholinesterase leading to the inactivation of
this essential enzyme which has an important role in nervous system of humans, and
other animal species (Ecobichon, 2001). Carbamate compounds are often called
anticholinesterases. In the presence of inhibitors, acetylcholinesterase becomes
progressively inhibited and is not further capable of hydrolyzing acetylcholine to
choline and acetic acid (Jokanovic, 2009; Jokanovic and Maksimovic, 1997).
Consequently, acetylcholine accumulates at cholinergic receptor sites and produces
effects equivalent to excessive stimulation of cholinergic receptors throughout the
central and peripheral nervous system. Inhibited enzyme can be spontaneously
reactivated, with reversal of inhibition occurring typically with half-time of an hour
or less after exposure (Jokanovic, 2009). This fact may reduce the possible period of
intoxication in situations of accidental overexposure or suicide attempts. The
inhibition of other esterases may also occur (Thompson, 1999).
Herbicidal carbamates (such as carbetamide) which are a limited number of
compounds are not inhibitors of cholinesterase and are cell division inhibitors
(Tomlin, 1997). Plants can metabolize carbamates in which arylhydroxylation and
conjugation, or hydrolytic breakdown are the main routes of detoxification. The
results of a number of studies suggest that carbamates are exclusively distributed via
the apoplastic system in plants (IPCS, 1986).
The acute toxicity of the different carbamates ranges from highly toxic to only
slightly toxic or practically non-toxic (IPCS, 1986). Concerning the main carbamate
insecticides in use, their relative toxic potency estimated human values, (Erdman,
2003) vary from high toxicity (LD50 <50 mg/kg; for aldicarb, aldoxycarb,
aminocarb, bendiocarb, carbofuran, dimetan, dimetilan, dioxacarb formetanate,
methiocarb, methomyl, oxamyl and propoxur) to moderate toxicity (LD50 = 50-200
mg/kg; bufencarb, carbosulfan, pirimicarb, promecarb, thiodicarb, trimethacarb) and
to low toxicity (LD50 > 200 mg/kg; fenocarb, carbaryl, isoprocarb, MPMC
(Meobal), MTMC (Metacrate, Tsumacide), XMC (Cosban)).
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The acute dermal toxicity of carbamates is generally low to moderate; an exception
is aldicarb, which is highly toxic. Data are available for only a limited number of
substances (IPCS, 1986).
Short- and long-term toxicity studies have been carried out. Some carbamates are
very toxic and others are less toxic in long-term studies. For many years, long-term
toxicity data on carbamates have been evaluated by the FAO/WHO Joint Meeting
on Pesticide Residues (JMPR), and a number of ADI (the estimate of the amount of
a substance in food, mg/kg body weight/day, that can be ingested daily over a
lifetime without appreciable health risk to the consumer (WHO 1997)) for
carbamates have been established (IPCS, 1986).
Among other pesticides, carbamates have been included in the list of known
endocrine disruptor compounds (Schulte-Oehlmann et al., 2011). In this well-
designed review authors provide a databanks of a wide range of pesticides with
potentially endocrine-disrupting properties, discussion on some key questions
regarding the multiplicity of variables involved.
The onset of clinical effects subsequent to carbamate exposure depends on the dose,
route of exposure, type of carbamate involved, use of protective gear, and the
premorbid state of the victim (Rosman et al., 2009). Ingestion or inhalation of
carbamates results in a more rapid onset of clinical effects as compared with dermal
exposure. Acute carbamate poisoning episodes were recently described among
pesticide sprayers due to inadequate personal protection (Jensen et al., 2010). There
is an increase of pesticide exposure and poisoning in children around the world with
consequent morbidity and mortality (El-Naggar 2009; Balme et al., 2010; Jayashree
et al., 2011) Clinical manifestations for carbamates (excluding herbicides) result
from accumulation of ACh in the synapses and overstimulation of muscarinic and
nicotinic receptors throughout target organs. The main clinical manifestations of the
carbamate intoxication are muscarinic signs (miosis, salivation, sweating,
lacrimation, rhinorrhea, abdominal cramping, vomiting, diarrhea, urinary
incontinence, bronchospasm, dyspnea, hypoxemia, bradycardia, bronchial
secretions, pulmonary edema and respiratory failure), nicotinic signs (less frequent;
muscular twitching, fasciculations, muscle weakens including the respiratory
muscles, paralysis, tachycardia, hypertension) and central nervous system signs
(rare) (Rosman et al., 2009). The large demand for educational materials that
summarize the acute toxicity of pesticides is illustrated by the publication of five
editions of the Environmental Protection Agency’s Recognition and Management of
Pesticide Poisonings (US EPA, 1999; Frazier, 2007).
The medical management of carbamate poisoning consists of supportive measures
and specific antidotal treatment, that is, the anticholinergic compound atropine
(Rosman et al., 2009). Recovery without medical treatment of cases of accidental
overexposure with various carbamate pesticides spontaneously occurred, generally,
within 4 h of exposure that caused symptoms of headache, dizziness, weakness,
excessive salivation, nausea, or vomiting. For accidental or intentional poisoning
that produced symptoms such as visual disturbances, profuse sweating, abdominal
pain, incoordination, fasciculations, breathing difficulties, or changes in pulse rate,
treatment with atropine combined with general supportive treatment, such as
artificial respiration and administration of fluids, has resulted in recovery of
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individuals within 1 day (Jokanovic, 2009). Deaths occurred only in severe cases
where treatment was delayed and/or insufficient atropine was administered.
Furthermore, oximes have been tested in experimental studies and have been shown
to be beneficial, alone and/or with atropine, in countering the toxicity of the
carbamates isolan, thimetilan, pyramat, dimetilan, aldicarb, neostigmine,
physostigmine, pyridostigmine and others (Dawson, 1995). Only carbaryl toxicity
reacted inversely and was increased by oxime (Dawson, 1995; Jokanovic, 2009).
Rosman et al. (2009) developed a simple decision-making algorithm for the medical
first responders in a mass casualties event (such as the use of carbamates
compounds by terrorists as a weapon), suspected to be caused by a cholinergic
substance (organophosphate or carbamate). According to the proposed algorithm,
treatment should consist of atropine and oxime regardless of the exact toxic
compound involved. They speculated that in a mass casualties event, the benefits of
using oximes outweigh the low level of potential risks (Rosman et al., 2009).
Health problems from pesticides in the absence of acute poisoning are also clinically
important. Several carbamates are rated as probable or possible carcinogens in
humans, according to the classification of USEPA (2004) and the IARC (IARC,
1991). Epidemiologic studies of pesticide exposure and cancer incidence was
recently reviewed by Weichenthal and colleagues (2010). This survey illustrates that
carbamates may induce different types of cancer at occupational levels. For
example, applicators with the highest LDs of exposure to aldicarb demonstrated
high incidence of colon cancer, when compared to nonexposed workers. However,
melanoma was associated to carbaryl exposed applicators.
The evidence available today shows that both men and women can experience
adverse reproductive effects from carbamate pesticides. When women are
sufficiently exposed to certain pesticides, several types of adverse reproductive
outcomes may occur, and developmental problems in their children may result.
According to Frazier (2007), the main adverse reproductive effects associated to
female exposures are neurodevelopmental or childhood behavioral problems
(carbaryl), and possible childhood leukemia (propoxur). However, no significant
effect on gestation, fertility and parturition indices, and average birth weight was
demonstrated on experimental studies with rats exposed to propoxur (Ngoula et al.,
2007). Regarding, male exposures associated with adverse reproductive effects, they
are related with carbaryl, carbosulfan and carbofuran and consist in sperm
aneuploidy and abnormal morphology in manufacturing workers (carbaryl); DNA
fragmentation in men treated for infertility (carbaryl); chromosome aberrations and
abnormal head morphology in mice spermatozoa (carbosulfan, carbofuran) (Giri et
al., 2002; Meeker et al., 2004; Xia et al., 2005).
LEGISLATION
In recent decades, significant analytical developments have been achieved in
pesticide residue analysis and, in many cases, focus has been put towards sample
preparation and analytical detection (Soler et al., 2004). This has allowed maximum
residue limits (MRLs) to become more and more stringent in food commodities and
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in water (Codex alimentarius. 2009; Hamilton et al., 2003). Hamilton et al. (2003),
in a IUPAC Technical Report, presented an interesting overview of regulatory limits
for pesticides in water issued by WHO, Australia, the US, New Zealand, Japan,
Canada, the European Union and Taiwan. The European Union has set new
Directives for pesticides in fruits and vegetables in order to meet health concerns
(Regulation EC no. 396/2005 that introduces changes to the European Directive
91/414/EEC) (European Comission, 2005). Typically, MRLs for carbamates range
from 0.01– 0.05 mg/kg depending on the commodity and the pesticide (European
Union, 2008). If a pesticide is not included in any of the above mentioned lists, the
default MRL of 0.01 mg/kg applies (Art 18(1b) of Reg. (EC) No 396/2005).
Recently, regulation (EC) No 901/2009 has been produced concerning a coordinated
multiannual Community control programme for 2010 to 2012 to ensure compliance
with MRLs and to assess the consumer exposure to pesticide residues in and on food
of plant and animal origin (Morais et al., 2011). The Member States shall, during
2010 - 2012 analyze samples for the product/pesticide residue combinations. When
pesticides are applied according to good agricultural practices, MRLs are not
exceeded, but their incorrect application may leave harmful residues, which involve
possible health risk and environmental pollution (Hassanzadeh et al., 2010)
ANALYTICAL METHODS
Pesticides comprise a large group of substances with the only common characteristic
of being effective against a pest and constituting a challenge to the analyst (Soler et
al., 2004; Paíga et al., 2009a, 2009b). Carbamates have been analyzed for various
application areas such as environmental analysis, food safety, toxicology, and
occupational health. Currently, most interest in the analysis of pesticides is in the
field of food safety, thus especially in various types of vegetables and fruits. In
addition, pesticides are analyzed in environmental samples, such as different water
compartments, soil, sediments, sludge, and animal tissue like fish, and in human
body fluids and tissues (Niessen, 2010). The presence of pesticide residues and/or
their degradation products, which sometimes are more toxic than their precursors in
the environment and in foodstuffs, calls for the use of very sensitive analytical
methods, capable of determining these compounds at concentration levels equal or
lower than the MRLs established by international organizations (Crespo-Corral et
al., 2008). Different techniques have been employed for carbamates determination
(Caetano et al., 2008; Wu et al., 2009; Somerset et al., 2011; Van Dyk and
Pletschke, 2011; Llorent-Martínez et al., 2011) but the most efficient approaches
involve the use of chromatographic methods. Liquid chromatography (LC) coupled
with mass spectrometry (LC/MS) is one of the most powerful techniques for
monitoring carbamates that are thermally unstable and hence do not perform well
easily in a gas chromatography MS multimethod (Sagratini et al., 2007; Chung and
Chan, 2010; Park et al., 2010). In particular, it has been shown that, in combination
with tandem mass spectrometry (ion trap or triple quadrupole), LC is a very
sensitive technique to reveal carbamates and other pesticides residues in fruits
(Granby et al., 2004; Soler et al., 2005; Niessen, 2010). Instruments with either
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atmospheric pressure chemical ionisation (APCI) or electrospray ionisation (ESI)
are the most commonly used (Granby et al., 2004; Kruve et al., 2011).
Regarding sample preparation (Chen et al., 2008; Paíga et al., 2009a, 2009b), it
traditionally involves an extraction with an organic solvent such as include matrix
solid-phase dispersion, solid-phase extraction, supercritical fluid extraction, solid-
phase microextraction, stir bar sorptive extraction and more recently the ‘quick,
easy, cheap, effective, rugged, and safe’ (QuECheRS) method (Anastassiades et al.,
2003; Wilkowska et al., 2011).
Nowadays, several rapid, relatively inexpensive, sensitive screening analytical
biosensors that need little sample pre-treatment are constantly being developed for
the identification and quantification of carbamate compounds (Caetano et al., 2008;
Wu et al., 2009; Somerset et al., 2011; Van Dyk and Pletschke, 2011). Biosensors
are based on the intimate contact between a bio-recognition element that interacts
with the analyte of interest and a transducer element that converts the bio-
recognition event into a measurable signal. Among the different types of biosensors,
the electrochemical sensors are of special interest due to the high sensitivity inherent
to the electrochemical detection and the possibility to miniaturize the required
instrumentation, thereby making the construction of compact and portable analysis
devices possible (Campàs et al., 2009; Somerset et al., 2011). Somerset et al. (2011)
reported detection limit of 0.880 nmol/L for carbaryl, 0.249 nmol/L for carbofuran
and 0.111 nmol/L for methomyl using a mercaptobenzothiazole-on-gold biosensor
system. From the literature reviewed by Van Dyk and Pletschke (2011), the lower
detection limits are also in the range of 0.1 nmol/L (for carbofuran, Ciucu et al.,
2003) being clear that enzymatic methods, and biosensors, usually are not able to
achieve the sensitivity of chromatographic methods. However, authors claimed that
they can serve as a tool for screening of hundreds of samples in a short period of
time complementing the existing methods and allowing for a more rapid assessment
of problematic environments. Each method has unique advantages which can
complement each other (Rodriguez-Mozaz et al., 2007; Van Dyk and Pletschke,
2011).
CARBAMATE BIOMARKERS
Biomonitoring is defined as the repeated, controlled measurement of chemical or
biological markers in fluids, tissues or other accessible samples from subjects
exposed or exposed in the past or to be exposed to chemical, physical or biological
risk factors in the workplace and/or the general environment (Manno et al., 2010).
Some bioindicators are commonly used since they can reflect the effect of
contaminants on cellular metabolism and global homeostasis (Tan et al., 2011).
González-Fernández et al. (2008) focused on a wide range of conventional
biomarkers and explored a preliminary working scheme for the integration of the
triple -omic approach (transcriptomics, proteomics, and metallomics) in
environmental monitoring. These authors found them useful and a comprehensive
alternative in the study of environmental issues and the diagnosis of contamination
threats. The expansion of omic technologies in recent years have contributed to
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occupational environmental health research through the look at the complete
complement of genes its expression and regulation, proteins and metabolites
(Vlaanderen et al., 2010). These authors explored in a well design review the
currently fields (genotyping, transcriptomics, epigenomics, proteomics and
metabolomics) pointing for new insights in the near future. George and Shukla
(2011) provided also a complete review of the research activities in the area of
toxicoproteomics focusing on the effects of carcinogenic pesticides, namely
carbamates. Although these authors considered proteomic technologies as relevant
tools in this domain, other issues were also important to elucidate the sequential
steps of pesticide-induced carcinogenesis (e.g. the analysis of metabolic activation
of chemicals, genome analysis, mRNA measurements, and classical biochemical
analysis). In their point of view a better dialogue among those areas and a
transdiciplinary approach is needed to better understand the impact of these
chemicals on oncology research.
The measurement of current perception threshold (CPT) using Neurometer
CPT/Eagle, on the index finger and the great toe can be used as a biomarker to
monitor the effects of carbamate exposure among exposed workers (Lubis et al.,
2008). By using three neuroselective frequencies range (2000, 250, and 5 Hz) the
CPT values were prominent among farmers on both the medial and peroneal nerves.
Sams and co-workers (2010) proposed the quantification of 5,6-dimethyl-2-
(methylamino)pyrimidin-4-ol (MDHP) in urine, as a sensitive and specific
biomarker of exposure to pirimicarb. Using liquid chromatography with mass
spectrometry detection (LC–MS), these authors quantified this secondary metabolite
in urine of exposed volunteers.
The osmotic fragility of erythrocytes as a potential biomarker of oxidative
membrane damage in carbamate pesticide-induced damage to erythrocytes was
recently described (Sharma et al., 2010).
As reported previously, several carbamates may reduce male fertility inducing
alterations on testicular morphology. For this reason, the selection of
histopathological markers is highly dependent upon the toxicant mechanism of
action, dose, and duration of exposure (Moffit et al., 2007). These authors discussed
the example of carbendanzim, a well known Sertoli cell toxicant, which was used to
underline the role of cytoskeleton alterations as markers of testicular injury. These
authors pointed also to multiple histopathological endpoints (e.g. seminiferous
tubule diameter, sloughing and vacuolization of seminiferous epithelium, spermatid
head retention, and germ cell apoptosis) for a better understanding of the the loss of
testicular function.
HUMAN EXPOSURE TO CARBAMATE RESIDUES
The presence of pesticide residues is a concern for consumers because carbamates
are known to have potential harmful effects to other non-targeted organisms than
pests and diseases (Gilden et al., 2010). People have environmental exposures to
pesticides mainly through diet. Human intake due to pesticide residues in food
commodities is usually much higher than those related to water consumption and air
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inhalation (except for occupational exposure or at home application, e.g. home
gardens or the handling with domestic animals). The evaluation of pesticide residues
in food is nowadays a priority objective to ensure food quality and to protect
consumers against possible health risks (Sagratini et al., 2007).
Fruits and vegetables are important components of the human diet since they
provide essential nutrients that are required for most of the reactions occurring in the
body. A high intake of fruits and vegetables (five or more servings per day) has
been encouraged not only to prevent consequences due to vitamin deficiency but
also to reduce the incidence of major diseases such as cancer, cardiovascular
diseases and obesity (Keikotlhaile et al., 2011). Contamination of fruits and
vegetables may result from treatment as well as from conditions such as improper
use of pesticides, residues from preceding treatments in the soil and cross-
contamination (particularly during harvesting) (Janssen, 1997; Shi et al., 2011). Due
to their high solubility in water, carbamates are distributed in aqueous food such as
fruit and related derivatives. Sources of residues in products of animal origin include
contaminated water or feed, pesticide-treated housing, and contaminated milk.
Carbaryl is one of the residues most frequently reported in previous studies (Rawn
et al., 2006; Paíga et al., 2009a, 2009b; Jensen et al., 2009; Hassanzadeh et al.,
2010). Carbaryl controls a great number of species of insects on fruits, and other
crops, forests, as well as on poultry, farm animals, and pets (US EPA, 2003).
Hassanzadeh et al. (2010) studied the residue content of carbaryl applied on
greenhouse cucumbers from Iran and its reduction by duration of a pre-harvest
interval and post-harvest household processing. Carbaryl residues were detected in
concentration ranges of 0.22–4.91 mg/kg indicating that residues in cucumber were
higher than its European Union MRL (0.05 mg/kg) value 14 days after application.
They suggested that a waiting period of more than 14 days should be observed
before harvesting or consumption of cucumbers, in order to protect consumer health.
They concluded that household processing, such as washing and peeling and
refrigeration storage, was effective in reducing the carbaryl residue levels being
peeling the most effective way to reduce the carbaryl residues of the cucumber
samples.
Paíga et al. (2009a) analyzed a total number of 28 different fresh tomato samples
and 6 processed tomato products from different locations in Northern Portugal.
Although S-ethyl-N,N-dipropylthiocarbamate (EPTC) was not authorized for use in
tomato cultures, it was detected in all fresh samples at the estimated level of about 4
g/kg. Butylate was detected in tomato pulp and tinned tomato, at estimated levels
of 4 g/kg.
Caldas et al. (2011) characterized the dietary risks of organophosphorus and
dithiocarbamate pesticides in a total diet study at a Brazilian university restaurant.
They observed that dithiocarbamat reach a value of 0.08 mg/kg corresponding to an
intake by fruit consumption of 0.112 µg/kg body weight per day.
Kobayashi et al. (2011) performed a survey of pesticide residues in 595 imported
frozen products on the Tokyo market from April 1989 to March 2008. Carbaryl was
detected in berries (blueberry, raspberry and strawberry) and methomyl in okra and
spinach at the level of 0.005-0.01 mg/kg.
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Jensen et al. (2009) assessed the cumulative acute exposure of the population of
Denmark to 25 organophosphorus and carbamate pesticide residues from the
consumption of fruit, vegetables and cereals. Residue data obtained from the Danish
monitoring programme carried out in the period 2004–2007, which included 6704
samples of fruit, vegetables and cereals were used in the calculations. Exotic fruits,
including passion fruit, mango, guava, carambola, kaki, rambutan and kumquat had
the highest detection frequency (13.9%), followed by cherry (12.5%), mandarin
(9.9%), lemon (8.6%), asparagus (7.7%), peach/nectarines (7.6%), rice (7.3%),
grapefruit (6.9%), and pineapple (6.9%). Commodities with the highest mean
concentrations were basil followed by lemon, grapefruit, dates, oranges and
mandarin. Carbaryl was detected at concentrations ranging from 0.0018 mg/kg (in
mushrooms) to 0.1369 mg/kg (in grape table) Jensen et al. (2009).
Rawn et al. (2006) determined seven parent N-methyl carbamate insecticides, in
addition to two transformation products of aldicarb (aldicarb sulfoxide and aldicarb
sulfone), and a single transformation product of carbofuran (3-hydroxycarbofuran)
in infant and junior foods available on the Canadian retail market between 2001 and
2003. Carbaryl was the most frequently (7.6%) detected compound and
concentrations ranged from 0.6 to 18 ng/g. Detectable levels of carbaryl were most
frequently found in foods prepared with fruit. Methomyl was detected (0.8 ng/g) in
one chicken with broth sample analyzed in the present study. In all cases, the
concentrations observed were orders of magnitude below the maximum residue
limits established for these compounds in the corresponding raw food commodities
in Canada (Rawn et al., 2006). Dietary intakes of carbaryl and methomyl based on
the consumption of infant foods tested ranged between 0.2–343 and 0.4–2.0 ng/kg
body weight per day, respectively (Rawn et al., 2006). These authors (Rawn et al.
2004) also quantified the N-methyl carbamate concentrations for apple and grape
juices available on the retail market in Canada. Carbaryl was the most frequently
(58.6%) detected carbamate in juice samples studied. It was observed more
frequently in grape juices than in apple or mixed juices. Oxamyl and methomyl
were detected in apple juice samples, although they were below detection limits in
all grape and mixed juice samples analysed. Maximum levels of carbaryl, methomyl
and oxamyl were 93, 6.7 and 4.6 ng/L, respectively.
Kumari et al. (2004) reported the monitoring of pesticidal contamination of
farmgate vegetables from Hisar, India. A total of 84 farm gate samples of seasonal
vegetables was analyzed for organophosphates, synthetic pyrethroids,
organochlorines and carbamates. Only aldicarb among the carbamates was detected
in potato (at the range of 0.003-0.082 µg/g).
RISK ASSESSMENT
Common exposed professionals include pesticide applicators, and harvesting crops,
and farmers. However, humans may be also exposed to carbamates through over-
exposure at home application (e.g. home gardens, the handling with domestic
animals). Biological and environmental monitoring are the main tools presently
available for the “in-the-field” pesticide risk assessment, although some limitations
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must be considered, since effective activities occurs in an open air (Colosio et al.,
2011). For this reason, Colosio et al. (2011) developed an integrated user-friendly
tool for risk assessment and management in agriculture, in which the computational
modelling was added to biological, and environmental monitoring.
Most of the population may be exposed to carbamates through dietary (e.g.
consumption of treated fruits, vegetables and contaminated water) (Lu et al., 2010).
Hazard characterization involves comparing the pesticide exposure concentration
with the ADI or the ARfD (the estimate of the amount of a substance in food that
can be ingested over a short period of time, usually during one meal or one day,
without appreciable health risk to the consumer) (WHO 1997; Keikotlhaile et al.,
2011). In exposure assessment, the potential intake or consumption of pesticide
residues is divided by the body weight and compared to ADI or ARfD (Exposure =
(Concentration of pesticide residue x Food consumed)/ body weight) (Keikotlhaile
et al., 2011).
Long-term averaged daily intake of contaminants such as pesticide residues in food
may be estimated using NORMTOX (Ragas and Huijbregts, 1998; Ragas et al.,
2009). Schulte-Oehlmann et al. (2011) reviewed the monitoring data over a 10-year
period and revealed that although the percentage of foodstuff without detectable
pesticide residues in Germany has continuously decreased from 64 to 51.5%, for
carbaryl ARfDs were exceeded substantially. Among other pesticides, carbamates
were also rated as endocrine-active factors (Schulte-Oehlmann et al., 2011). In view
of the probable health risk of a wide range of pesticides, a new EU regulation is
being prepared, including the test criteria for these chemicals to be finalized by
2013.
Humans are sequentially or simultaneously exposed to a wide range of pollutants,
instead to only one. Due to the main limitations and complex approach to certainly
evaluate the health effects of complex mixtures few studies were undertaken to
explore this complexity. Recently, Ragas and co-workers (2011) have investigated
the cumulative health risk effects of a wide range of stressors, including pesticides,
on different target groups (young children, working adults and elderly). This survey
was based on the time spent in different microenvironments, the outdoor movement,
and food consumption patterns. Different scenarios for assessing mixture effects for
a better understanding of mechanism of action, and interactions (antagonistic or
synergistic) were considered. In conclusion, this review underlines the need for
person-oriented exposure models that can simulate the cumulative exposure history
of individuals based on realistic activity and consumption patterns; in addition, a
better mechanistic understanding of the effects of cumulative stressors is relevant.
CONCLUSIONS
The increase of carbamate applications makes the implications for the
environmental and biomedical research communities a significant endeavor. Diet,
and principally fruit and fruit juices, is the major carbamates source for non-
occupationally exposed population. The dietary acute intake of some carbamates
(AChE inhibitors) as previously evaluated by the FAO/WHO Joint Meeting on
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Pesticide Residues indicated a possible risk to health, which has restrained the
Codex Alimentarius Committee from setting a maximum residue level for many of
these compounds. As already stated by other authors (Van Dyk and Pletschke,
2011), an effective strategy for dealing with pesticide contamination in the
environment has to commence with an assessment of the extent of the problem.
However, monitoring programs for pesticides are scarce, particularly in developing
countries. Furthermore, more research is needed in order to characterize the
cumulative and synergistic effects of these pesticides, as well as, the interaction
among those contaminants and other pollutants.
ACKNOWLEDGEMENTS
Authors wish to the Research Centre on Ceramic and Composite Materials
(CICECO) from Aveiro University. This work was also supported by the Fundação
para a Ciência e a Tecnologia through the grant no. PEst-C/EQB/LA0006/2011.
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