25EPIDEMIOLOGICAL STUDIES OFANTICHOLINESTERASE PESTICIDE POISONINGIN CHILE

FLORIA PANCETTI

Laboratory of Environmental Neurotoxicology, Department of Biomedical Sciences, Faculty of Medicine, Universidad Catolica del Norte,Coquimbo, Chile

MURIEL RAMIREZ AND MAURICIO CASTILLO

Department of Public Health, Faculty of Medicine, Universidad Catolica del Norte, Coquimbo, Chile

25.1 Introduction 357

25.2 Regulatory Aspects on the Use of Organophosphatesand Carbamates in Chile 35725.2.1 Aspects of Occupational Health 35925.2.2 Handling of Residues 35925.2.3 Organophosphates and Carbamates Most

Frequently Sold and Used in Chile 359

25.2.4 Epidemiological Surveillance System forAcute Pesticide Intoxications in Chile 360

25.3 Epidemiology of Acute and Chronic Intoxications 361

25.4 Conclusions 363

References 363

25.1 INTRODUCTION

The human population is continuously exposed to environ-mental polluting agents that are harmful to health. Amongthese are organophosphate and carbamate pesticides, whichare widely used as insecticides for domestic use and in agri-culture. In recent years, despite the increasing level of regu-lation in the use and sale of such products in Chile, theircommercialization there has intensified. Consequently,many cases of accidental intoxication presenting to the emer-gency services are caused by insecticides sold for domesticuse. Chronic exposure is also reported as a result of the con-sumption of food containing residues of these products and,in rural areas, from breathing air polluted with organophos-phates from aerial fumigations.

This chapter mainly focuses on a description of the regu-latory aspects of pesticides, their commercialization profile,

systems of epidemiological surveillance, and the epidemiolo-gical profile of intoxication by pesticides in Chile.

25.2 REGULATORY ASPECTS ON THE USE OFORGANOPHOSPHATES AND CARBAMATES INCHILE

In Chile, the regulatory aspects on the use of pesticides arehandled by two governmental agencies: the Ministry ofHealth, through the Institute of Public Health (ISP), andthe Ministry of Agriculture, through the Agricultural andCattle Service (SAG). The first agency deals with aspectsof pesticide regulation for sanitary and domestic use asdescribed in Decree no. 157 from the Ministry of Healthfor 2005. This regulation contains directives on the regis-tration, authorization, manufacture, import, storage, packing,

Anticholinesterase Pesticides: Metabolism, Neurotoxicity, and Epidemiology. Edited by Tetsuo Satoh and Ramesh C. GuptaCopyright # 2010 John Wiley & Sons, Inc.

357

expenditure, possession, transportation, distribution, pro-motion, advertising, application, and elimination of thepesticides in this group. Briefly, it defines a pesticide of sani-tary and domestic use as one that is destined to attacksanitary vectors that infect both the inside and outside ofbuildings, industries and industrial processes, warehouses,containers, educational or commercial establishments,parks, gardens, cemeteries, and transportation services forland, sea, or air travel. It also includes repellents or substan-ces that are not directly applied onto human or animal skin,that is, those present in commercial products such as paints,glazes, and products for the bathroom. The conditions ofapplication are also controlled by this regulation, allowingthe application and selling of pesticides only to companiesauthorized by the Ministry of Health and only if the appli-cation is carried out by qualified personnel. In addition,precautions against risks of direct or indirect poisoning thatcould affect personnel, manipulators, and domestic animalsare required. It specifies that an employer is responsible forthe use of proper equipment for the safety of employees.The regulation also sets requirements for pesticide-applyingcompanies to initiate activities such as sanitary authorization,training of personnel, and appropriate conditions in theworkplace.

SAG, meanwhile, is in charge of controlling plaguesand diseases of economic importance in accordance withgovernmental policies related to agriculture and livestock.Specifically, the Sub-Department of Pesticides andFertilizers within SAG is responsible for national policy onthe use of agrochemicals. Its functions are the following:

1. To develop and apply policies orientated to improveefficiency in the evaluation and approval of chemicalentities for use in the farm and cattle industry, inorder to have effective products with minimal human,animal, and environmental risks, and avoiding negativeimpacts on national and international trade.

2. To assure the proper use of pesticides and fertilizersand to reduce the risks associated to their applicationin the country.

3. To develop a system of environmental alertness inorder to identify situations that affect agricultural pro-duction, animal and human health, and the environ-ment as a consequence of pesticide and fertilizer usage.

4. To help to improve the quality and safety of fruits andvegetables.

5. To know and evaluate the impact of pesticide and fer-tilizer application on the environment and to developa procedure of inspection for agrochemical usage inthe country.

6. To inform the community about the policies ofregulation and surveillance applied by SAG related toagrochemicals usage.

According to the procedures for authorization of the use ofnational or imported agrochemicals commercialized in thecountry, evaluation of a product is carried out by a multidis-ciplinary group including a medical toxicologist, pro-fessionals of the Laboratory of Environmental Toxicology,and professionals of the Sub-Department of Pesticides andFertilizers, all from SAG. The request for authorizationmust be presented with all the documents indicated inResolution no. 3670 (1999) of SAG. At present, there are208 commercially authorized pesticides containing organo-phosphate, carbamate, or other derived molecules in their for-mulation as active ingredient. Ethyl and methyl parathion, aswell as mevinphos, are banned.

In the process of inspection, samples of importedpesticides are taken in order to verify by chemical analysisthat the percentage of active ingredient is in agreement withthe information recorded on the authorized documentation.In addition, analysis of the composition of all pesticidesformulated in Chile is carried out before they can be com-mercialized. SAG also has a training program for applicatorson the proper use and management of pesticides inagriculture. This training is carried out as a whole by theNational Service of Training and Employment, and isalso directed at agricultural professional and technical per-sonnel, full- and part-time workers, and farmers havingvaried degrees of education and instruction. These courseshave a minimum duration of 30 hours, are of theoreticaland practical character, and deal with topics such as thelegislation and regulations related to agricultural pesticideuse and their application, classification and managing ofthese agrochemicals, their impact on the environment, andthe emergencies and poisonings resulting from pesticides.Approval from such training courses is a requirementbefore obtaining a job that allows the application of pesticideas recognized by the SAG.

Finally, SAG is also responsible for the toxicologicalclassification and proper labeling of agricultural pesticides.The toxicological classification was established in 2000according to the Resolution no. 2196 of SAG. It is basedon the classification recommended by the World HealthOrganization (WHO) according to the toxicity of the activeingredients, as shown in Table 25.1.

The proper labeling of pesticides is carried out accordingto Resolution no. 2195 of SAG. This resolution establishesthe guidelines for proper labeling, which must include thefollowing: identification of the product, recommendationsfor its usage, precautions and warnings, and symbols,colors, toxicity classification, and pictograms according tothe toxicological classification of the WHO.

The Ministry of Health also applies other regulationsrelated directly or indirectly to the usage of pesticides.These include Chilean Norm no. 409, which regulatesthe maximum level of pesticides in drinkable water, theSanitary Regulation of Food no. 977 (1996) and the

358 EPIDEMIOLOGICAL STUDIES OF ANTICHOLINESTERASE PESTICIDE POISONING IN CHILE

Regulation on Basic Sanitary and Environmental Conditionsin the Work Place no. 594 (1999).

25.2.1 Aspects of Occupational Health

The Regulation on Basic Sanitary and EnvironmentalConditions in the Work Place establishes the permissiblelimits of environmental exposure to chemical and physicalagents, and the limits of biological tolerance for workersexposed to occupational risks. Responsibility for inspectionand enforcement for this regulatory body lies with theRegional Sanitary Authorities (SEREMI) of the Ministry ofHealth. The regulation sets the permissible limits for environ-mental concentrations of organophosphates and carbamates(Table 25.2).

Furthermore, the Regulation on Basic Sanitary andEnvironmental Conditions in the Work Place determinesthe limits of biological tolerance of pesticides or their metab-olites in the worker. Specifically, for exposure to organopho-sphates and carbamates, the biological indicator is the activityof plasma cholinesterase (also known as pseudocholinester-ase or butyrylcholinesterase). The limit of biological toler-ance is considered 70% of the basal level of enzymaticactivity for a given worker. Samples must be taken beforeand after pesticide application. Where biological evaluationshows that the limits of biological tolerance have beenexceeded, the employer would have to immediately initiatethe necessary actions to avoid health complications to the

worker as a consequence of poor working conditions.Furthermore, the regulation prohibits the presence of person-nel without adequate personal protection during and follow-ing the period of application until it is deemed safe to bewithout protection in open or closed zones where pesticidesare applied.

25.2.2 Handling of Residues

The Ministry of Health has a regulation [Decree no. 148(2003)] on the management of dangerous residues that estab-lishes a system for their classification. It also regulates theirgeneration, storage, transportation, elimination, recycling,safe landfills, and incineration. In addition, it includes aprocedure for declaration and follow-up of the residues.Dangerous residues are identified as those resulting fromthe production, preparation, and utilization of biocidalproducts, phytopharmaceutical products, and pesticides.Regarding pesticides, containers contaminated with organo-phosphates are considered to have potential toxicity,especially when their elimination could give rise to one ormore toxic substances in concentrations that could be danger-ous for the population. The regulation indicates that packagescontaining pesticide residues must undergo a triple wash thatconsists of washing down with water at least three successivetimes using no less than 10% of the volume of the containerfor every wash, or utilizing water applied at high pressure for1 minute. Subsequently, the package must be destroyed orrendered useless. In addition, the water resulting from thewash must be incorporated into the reservoir for pesticideapplication as part of the water for preparation or alternativelywill have to be handled as a dangerous residue.

25.2.3 Organophosphates and Carbamates MostFrequently Sold and Used in Chile

SAG dictates that sales of pesticides and fertilizers must bedeclared twice a year in accordance with Resolution no.2410 (1997). This information is obtained from data givenby distributors to regional offices of SAG throughout thecountry. The information is then passed on to theSub-Department of Pesticides and Fertilizers, where it is

TABLE 25.1 Toxicological Classification of Agrochemicals

Classification Acute LD50 (rats) (mg/kg)

Oral Cutaneous

Solid Liquid Solid LiquidExtremely hazardous (Class IA) ,5 ,20 ,10 ,40Highly hazardous (Class IB) 5–50 20–200 10–100 40–400Moderately hazardous (Class II) 50–500 200–2000 100–1000 400–4000Slightly hazardous (Class III) 500–2000 2000–3000 .1000 .4000Pesticides unlikely to present acute hazard .2000 .3000

TABLE 25.2 Permissible Limits for EnvironmentalConcentrations of Some Organophosphates and Carbamates

SubstancePermissible Limits

(mg/m3)

Carbaryl 4Carbofurane 0.08Chlorpyrifos 0.16Diazinon 0.08Dichlorvos 0.072Ferbam 8Malathion 8Monocrotophos 0.2

25.2 REGULATORY ASPECTS ON THE USE OF ORGANOPHOSPHATES AND CARBAMATES IN CHILE 359

processed and validated. However, in the case of pesticidesfor domestic use, this type of information does not exist.Pesticides are classified according to their serial registrationnumber (Table 25.3).

The units of measurement in which these products are soldcan be kilograms, liters, tablets, plates, and sprays, the mostcommon being kilograms and liters. Table 25.4 summarizesthe sales of organophosphate and carbamate pesticides foragricultural use for 2004. As can be seen, the majority ofsales according to volume correspond to chlorpyrifos, metha-midophos, azinphos metyl, and diazinon (SAG, 2006).

25.2.4 Epidemiological Surveillance System for AcutePesticide Intoxications in Chile

The surveillance of acute intoxications in Chile is based onDecree no. 88 of the Ministry of Health, published inOctober 2004, which makes it mandatory to notify acuteintoxications due to pesticides. The main purpose of the sur-veillance system is to contribute to reducing health problemsarising from the use of pesticides, including acute intoxi-cations and death. The general objective is to detect thecases and outbreaks of acute intoxications as early as possibleand to promptly apply preventative measures and controls.

The specific objectives of the surveillance system are asfollows:

1. To detect individual cases and outbreaks of acuteintoxications due to the use of pesticides at an earlystage;

2. To plan, evaluate, and apply control measures andintervention;

3. To determine the incidence of pesticide intoxications;

4. To describe the characteristics of the different types ofintoxication;

5. To identify the epidemiological profile of the cases, aprofile of the intoxicated people, populations and geo-graphical areas at risk, causes of intoxications, risk fac-tors, and circumstances associated with intoxications;

6. To contribute to the investigation and risk evaluation ofthe use of pesticides;

7. To supply information about the chronic effects ofpesticides;

8. To inform the results of the system.

Surveillance is carried out by means of a universal systemthat requires mandatory notification of suspected cases to thesanitary authority located in each province (SEREMI), there-fore covering the entire population. The first stage is detectionof cases by a medical doctor, who then notifies the sanitaryauthority. This notification triggers an investigation of thecases in order to confirm or discount the suspected case.Control measures are also taken at the same time.

The system is also capable of detecting non-notified casesthrough laboratories that perform specific tests related topesticide intoxications. The national regulation gives differ-ent definitions of cases, including suspected cases, confirmedcases, possible cases, discarded cases, outbreaks of acuteintoxication, types of exposure (occupational, accidentalnon-occupational, voluntary, and intentional).

Different institutions within the system have specific func-tions and degrees of responsibilities: health centers (clinic orhospital); health authority (SEREMI); Ministry of Health(Epidemiology Department); Ministry of Health (Statisticsand Health Information Department); and Public Health

TABLE 25.3 Classification of Pesticides According to theirSerial Registration Number

Serial Type

1000 Insecticides, acaricides,rodenticides, others

2000 Fungicides, bactericides3000 Herbicides4000 Miscellaneous

TABLE 25.4 Organophosphates and Carbamates Sold inChile During 2004

Active ingredient Quantity kg or L Type

Chlorpyrifos 1,283,729.1 OrganophosphateMethamidophos 425,941 OrganophosphateAzinphosmethyl 396,699.8 OrganophosphateDiazinon 274,367.3 OrganophosphateCarbaryl 169,561.7 CarbamateCarbofuran 147,616.9 CarbamateDimethoate 112,393.3 OrganophosphateMethomyl 91,718.9 CarbamateMethidathion 69,700.5 OrganophosphateFenamiphos 48,824 OrganophosphateEthoprophos 27,680.4 OrganophosphateAldicarb 25,118 CarbamateProfenofos 18,909 OrganophosphateMalalhion 17,905 OrganophosphateCadusafos 16,740 OrganophosphatePhosmet 14,703 OrganophosphateOxamyl 8936.2 CarbamatePirimicarb 8571 CarbamateMethiocarb 7771.6 CarbamateDichlorvos 5902 OrganophosphateFormetanate

hydrochloride5089 Carbamate

Pirimiphos methyl 3540.8 OrganophosphateMetam sodium 2522 CarbamateAcephato 1358.9 OrganophosphateVamidothion 813 OrganophosphateFenoxycarb 191.6 CarbamateChlorfenvinphos 36 Organophosphate

360 EPIDEMIOLOGICAL STUDIES OF ANTICHOLINESTERASE PESTICIDE POISONING IN CHILE

Institute (ISP). The flow of information occurs in thefollowing order. Initially the case (or outbreak) is notifiedby the health center (hospital or clinic) to the healthauthority. The sanitary authority conducts the investigation,confirms (or discards the situation), and takes controlmeasures according to the information collected and ana-lyzed. They also receive information from laboratories andthen notify the Ministry of Health. The ISP shouldsupport, monitor, and evaluate the laboratories that performspecific biological tests related to pesticide intoxication.The Ministry of Health circulates the information to allthe parties involved on a monthly basis. Finally, it is possibleto notify on line using the Ministry of Health web page. Thepaperwork includes forms for case notification, formsfor outbreak notification, forms for individual case investi-gation, forms for outbreak investigation, and monthly datacollection sheets.

The information obtained through the surveillance systemis used to calculate the following indicators:

1. Incidence rate of acute intoxications;

2. Mortality rate due to pesticide intoxication;

3. Percentage of deaths for all notified cases;

4. Percentage of people hospitalized for the total numberof cases;

5. Percentage of monthly cases;

6. Percentage of cases for region and county;

7. Percentage of cases for sex;

8. Percentage of cases for age group;

9. Percentage of cases for chemical group, activemolecule, use, and toxicological classification;

10. Percentage of cases for cause of intoxication: inten-tional, accidental, occupational or non-occupational,suicide, homicide, and so on;

11. Percentage of cases for type of exposure;

12. Profile of cases in outbreak;

13. Occupational cases: incidence by occupational group,mortality by occupational group, and percentage ofcases according to occupational factors;

14. Percentage of sanitary measures taken;

15. Indirect indicators of the pesticide exposure: amountsof pesticides that have been imported and used.

25.3 EPIDEMIOLOGY OF ACUTE ANDCHRONIC INTOXICATIONS

The National Institute of Statistics (INE) reported thatbetween the years 1997 and 2007, the total area cultivatedin the country increased by 70%. Agricultural exports alsoincreased from $1156 million in 1990 to $3874 million in

2004 and make up �4.4% of the gross national product(ODEPA, 2005). Obviously, this increase in agriculturalactivity has been accompanied by an increase in the use ofpesticides. For example, insecticide import for agriculturaluse increased �20% between 2001 and 2005 according todata from INE (INE, 2006). The last agricultural censusrevealed that there are 188,184 permanent agriculturalworkers in Chile, and this number increased to 1,326,712when seasonal workers were included, 48% of these beingwomen, therefore representing an important labor force(INE, 2007).

Despite the above information, there is little research deal-ing with the epidemiology of acute or chronic intoxicationsby pesticides. The few studies that have been published andthat appear in Pubmed are summarized in Table 25.5, orderedby year of publication. The publication by Mena et al. (2004)reviews data obtained from the Center of ToxicologicalInformation of the Pontificia Universidad Catolica de Chile(CITUC), which was derived from telephone calls requestinginformation and help regarding domestic intoxicationsbetween 1992 and 2002 (Mena et al., 2004). This is a privatetoxicological center, which has a system for reporting casesthat is based on that stipulated in the International Programfor Chemical Security from the WHO (Paris and Rıos,

TABLE 25.5 Published Articles about Epidemiology ofPesticide Intoxication in Chile

Year Authors Title Journal

1989 Gonzalez-Vegaet al.

Parathionpoisoningtreated in a ruralhospital

Revista Medica deChile 117:1052–1053

1998 Venegaset al.

Micronucleianalysis inlymphocytes ofpesticidesprayers fromConcepcionChile

Teratogenesis,Carcinogenesis,and Mutagenesis18:123–129

2000 Rojas et al. Congenitalmalformationsand pesticideexposure

Revista Medica deChile 128: 399–404

2004 Mena et al. Epidemiology ofintoxications inChile: ten yearsof registry

Revista Medica deChile 132: 493–499

2005 Marquezet al.

Cytogeneticdamage infemale Chileanagriculturalworkers tomixtures ofpesticides

Environmental andMolecularMutagenesis45:1–7

25.3 EPIDEMIOLOGY OF ACUTE AND CHRONIC INTOXICATIONS 361

2001). Intoxication by pesticides occupies third place in thenumber of reported cases (11.3%). Medications are in firstplace (49.2%) followed by cleaning products (12.1%), andin fourth and fifth positions are industrial and chemical pro-ducts (10.5%) and cosmetics (2.7%) (Fig. 25.1). It is impor-tant to note that this study also revealed that the majority ofreported intoxications were accidental (78.6%), and thatintoxication in children less than five years of age was thereason for 50% of the calls.

The epidemiology of pesticide intoxications from theMinistry of Health referred to in this chapter provides moreprecise information on properly notified pesticide intoxi-cations. Figure 25.2 clearly demonstrates the increasingnumber of pesticide intoxications during the months betweenOctober and March, a period that corresponds to the springand summer seasons, when fumigation takes place in agricul-tural and forestry plantations. In 2007, during the months ofJanuary, March, April, June, July, and October, the numberof cases was above the median (expected cases). Most

intoxications occurred in the workplace (54%), followed byaccidental intoxications not related to the workplace(27%), and finally those that were intentional (17%). Thealert system operating within the Ministry of Health alsoreports the type of pesticide causing the intoxication, andorganophosphates lead the list as responsible for 39% ofcases (Vallebuona, 2008).

In relation to chronic intoxications, the epidemiologicalalert system from the Ministry of Health does not have anyrecords. In Chile, chronic intoxications are under-diagnosedand have become a serious public health problem in recentyears. However, Table 25.5 mentions three research articleson epidemiology dealing with the problem of chronic pesti-cide exposure. With the objective of finding a relationshipbetween chronic exposure to pesticides and cytogeneticdamage, Venegas and colleagues (1998) analyzed the pres-ence of micronuclei in lymphocytes from 22 pesticideworkers living in the city of Concepcion and found no signifi-cant difference from the control group. However, a study car-ried out in 2005 examined possible cytogenetic damage in agroup of 64 seasonally working women who were exposed toa mixture of different pesticides (insecticides, fungicides, andherbicides) in the same city, and found an increase in the fre-quency of binucleated lymphocytes with micronuclei in theexposed group when compared with the control group, indi-cating that occupational exposure to a mixture of pesticidesproduces cytogenetic damage (Marquez et al., 2005). It isimportant to mention that, among other organophosphates,these women were exposed to azinphos methyl, diazinon,and methamidophos. Finally, Rojas and colleagues (2000)demonstrated a correlation between chronic exposure to pes-ticides of parents with the appearance of congenital malfor-mations in newborns in the Hospital of Rancagua, which isin a highly agricultural zone of the country. The incidenceof congenital malformations was 41.2% between 1996 and

Figure 25.1 Type of substances involved in toxicological acci-dents reported to CITUC during the period 1995–2002. FromMena et al., 2004.

Figure 25.2 Number of reported cases of acute intoxications by plaguicides during January–December 2007. From Vallebuona, 2008.

362 EPIDEMIOLOGICAL STUDIES OF ANTICHOLINESTERASE PESTICIDE POISONING IN CHILE

1998. A newborn was considered exposed if its motherworked in agricultural activities or if its father had a jobrelated to the use of pesticides, or if they lived close to fumi-gated fields. A higher prevalence of Down syndrome, spinabifida, and hydrocephalia was found in the city ofRancagua, and a comparison of the cases with a controlgroup showed an association between congenital malfor-mations and a history of maternal exposure with a percentageof 54.4% (Rojas et al., 2000).

25.4 CONCLUSIONS

In Chile, management of pesticide data bases is carried out bydifferent governmental agencies depending on whether thepesticide is for agricultural or domestic use. In the firstcase, the agency responsible for regulating the import, use,and sale of pesticides for agricultural and livestock purposesis the SAG, which is part of the Ministry of Agriculture. In thelatter case, the responsible agency is the ISP, which is part ofthe Ministry of Health. At present, there are 208 authorizedcommercial pesticides containing organophosphate, carba-mate, or other derived molecules as the active ingredient intheir formulation. Ethyl and methyl parathion, as well asmevinphos, are banned. Information concerning the amountof pesticide sales is registered by the SAG, and only corre-sponds to pesticides sold for agricultural and livestockpurposes. The organophosphate pesticides sold most widelyin Chile in 2004 were chlorpyrifos, then methamidophos,azinphos methyl, and diazinon. The epidemiological alertsystem of the Ministry of Health deals with the report andfollow-up of acute intoxications, but chronic exposure isunder-diagnosed and this is reflected in the small number ofepidemiological studies published on populations chronicallyexposed to these substances.

REFERENCES

Gonzalez-Vega, W., Munoz, M., and Buchel, V. (1989). Parathionpoisoning treated in a rural hospital. Rev. Med. Chile 117:1052–1053.

INE (Instituto Nacional de Estadısticas) (2006). Medio Ambiente:Informe Anual 2001–2005. Instituto Nacional de EstadısticasIn: Rojas, D., (Ed.), Instituto Nacional de Estadısticas,Santiago de Chile, p. 215.

INE (Instituto Nacional de Estadısticas) (2007). VII CensoAgropecuario y Forestal (http://www.censoagropecuario.cl/).

Marquez, C., Villalobos, C., Poblete, S., Villalobos, E., Garcıa,M.A., and Duk, S. (2005). Cytogenetic damage in femaleChilean agricultural workers exposed to mixtures of pesticides.Environ. Mol. Mutagen. 45: 1–7.

Mena, C., Bettini, M., Cerda, P., Concha, F., and Paris, E. (2004).Epidemiology of intoxications in Chile: ten years of registry.Rev. Med. Chile 132: 493–499.

ODEPA (Oficina de Estudios y Polıticas Agrarias). (2005).Compendio estadıstico silvo-agropecuario 1990–2004 (www.odepa.gob.cl), Ministry of Agriculture, Chile, p. 14.

Paris, E., and Rıos, J.C. (2001). Intoxicaciones: epidemiologıa,clınica y tratamiento. Ediciones Universidad Catolica de Chile,Santiago, Chile, p. 13–27.

Rojas, A., Ojeda, M.E., and Barraza, X. (2000). Congenital malfor-mations and pesticide exposure. Rev. Med. Chile 128: 399–404.

SAG (Servicio Agrıcola y Ganadero) (2006). Declaracion de ventasde plaguicidas 2004. Sub-Departamento de Plaguicidas yFertilizantes (www.sag.gob.cl), Ministry of Agriculture, Chile,pp. 22–24.

Vallebuona, C. (2008). Red Nacional de Vigilancia Epidemiologicade Intoxicaciones Agudas por Plaguicidas REVEP, in BoletınElectronico Mensual de Vigilancia Epidemiologica, Ministryof Health, Chile, Issue 60, p. 11.

Venegas, W., Zapata, I., Carbonell, E., and Marcos, R. (1998).Micronuclei analysis in lymphocytes of pesticide sprayers fromConcepcion, Chile. Teratog. Carcinog. Mutagen. 18: 123–129.

REFERENCES 363