anticholinesterase pesticides (metabolism, neurotoxicity, and epidemiology) || epidemiological...

37EPIDEMIOLOGICAL STUDIES OFANTICHOLINESTERASE PESTICIDEPOISONING IN TAIWAN

TZENG JIH LIN

Department of Emergency, Kaohsiung Medical University Hospital and Department of Emergency Medicine, Faculty of Medicine,College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

DONG ZONG HUNG

Toxicology Center, China Medical University Hospital, Institute of Drug Safety, China Medical University, Taichung, Taiwan

JIN LIAN TSAI

Graduate Institute of Occupational Safety and Health, Kaohsiung Medical University, Kaohsiung, Taiwan

SHENG CHUAN HU

Department of Emergency Medicine, Buddhist Tzu Chi University and Buddhist Tzu Chi General Hospital, Hualien, Taiwan

JOU-FANG DENG

Division of Clinical Toxicology, Department of Internal Medicine, Taipei Veterans General Hospital and Faculty of Medicine,National Yang-Ming University, Taipei, Taiwan

37.1 Introduction 510

37.2 OP Poisoning 51037.2.1 Yearly Incidences of OP Exposures 51037.2.2 Demographic Data 51037.2.3 Types of OP Exposures 51137.2.4 Locations of Callers to PCCs 51137.2.5 Reasons for Exposures 51237.2.6 Routes of OP Exposures 51237.2.7 Coingestants of OP Exposures 51237.2.8 Characteristics of Single OP Exposures 51237.2.9 Clinical Outcomes of OP Exposures 51637.2.10 Antidote Use in OP Exposures 516

37.3 CM Poisoning 51637.3.1 Incidence of CM Exposures Each Year 516

37.3.2 Demographic Data 51637.3.3 Types of CM Exposures 51637.3.4 Locations of Callers to PCCs 51637.3.5 Reasons for Exposures 51737.3.6 Routes of Exposures 51737.3.7 Coingestants of CM Exposures 51837.3.8 Characteristics of Single CM Exposures 51837.3.9 Clinical Outcomes of CM Exposures 51837.3.10 Antidote Use in CM Exposures 520

37.4 Conclusions 520

Acknowledgments 520

References 520

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

509

37.1 INTRODUCTION

Pesticide poisoning is a worldwide concern and with similaroccurrences in many developing countries, although nolarge-scale international epidemiological data are availablefor comparison. This issue is now of even greater concernsince the use of some pesticides for financial gain or politicalpurpose with the threat of terrorism. Organophosphates (OPs)and carbamates (CMs), the two groups of pesticides with amechanism affecting anticholinesterase activity, are the twomost well known and commonly used pesticides used in agri-cultural food production and sanitation of household environ-ments. Based on data collected by the Taiwan NationalPoison Control Center during the period 1985–1993, pesti-cide exposures were the leading single cause of human poi-soning incidents (29.3%). Among all pesticide poisoningexposures, OPs and CMs were the leading and fourth mostcommon offending agents in Taiwan (Lin et al., 2008;Yang et al., 1996). Comparing the limited data collected inan international survey performed using several poison con-trol centers (PCCs), although OP poisoning is the main pro-blem in Taiwan, it occurs less often in other countries ofthe world (Good et al., 2007). The results also indicate that,among the PCCs surveyed, of 11 countries, only Sri Lankaspecifically listed OPs within their top 20 most common poi-soning exposures (Good et al., 2007). PCCs from Australia,Germany, Iceland, Ireland, the Netherlands, New Zealand,Norway, Philippines, Scotland, and the United States didnot list OPs in the top 20 poison exposures. At the inter-national level, it is widely understood that the occurrence ofOP poisoning is rather underestimated. The clinical manifes-tations of acute OP poisoning are usually quite clear;however, in Taiwan, some cases of OP poisonings havebeen reported with main manifestations of respiratory failure,mimicking food poisonings, prolonged QTc, acute pancreati-tis, cortical visual loss, intermediate syndrome, coital-likeinvoluntary movements, and acidosis other than cholinergicsyndromes (Chuang et al., 1996; Fang et al., 1995; Hsiaoet al., 1996; Lee et al., 2006; Liu et al., 2008; Tsai et al.,2006; Tsao et al., 1990; Wang et al., 1999). Clinically, thetoxicity of CM poisoning is not as severe as OP poisoning,and pharmacologically it is rather reversible; however, itmay lead to significant morbidity and mortality if appropriateclinical treatment is not provided. Whether intentional oraccidental, a few significant poisoning outbreaks involvingCMs have been documented in the literature. A food-relatedmethomyl exposure resulted in the rapid onset of a poisoningoutbreak, with 124 individuals involved (Tsai et al., 2003). Inthat outbreak, of the 55 adult patients surveyed, the mostcommon clinical effects were gait ataxia, dizziness, general-ized weakness, and vomiting. Carbofuran has been reportedto induce delayed neuropathy as another example of clinicaldiversity (Yang et al., 2000). We describe the characters ofOP and CM poisoning exposures using the data collected

by the poison center network of Taiwan from 1985 through2007 by descriptive statistic analysis.

37.2 OP POISONING

37.2.1 Yearly Incidences of OP Exposures

There were 5137 human OP poisoning exposures reported toTaiwan’s network of PCCs from July 1985 throughDecember 2007. The yearly case numbers of OP exposuresare presented in Table 37.1 (Lin et al., 2008).

37.2.2 Demographic Data

From Table 37.2 it can be seen that, of 5137 cases, the overallratio of males to females was 1.94 (65.70% versus 33.79%),with 26 cases having no identification of gender (0.51%). Themean patient age (+ standard deviation, s.d.) were 46.48+18.32 years. The minimum patient age was 0.1 years oldand the maximum patient age was 96 years old. Cases over19 years old (93.32%) were the most popular group ofexposure (Tables 37.2 and 37.3).

TABLE 37.1 Yearly Incidences of OP ExposuresRelated to Age

Age (years)

Year ,6 6–19 .19 Unknown Total

1985 3 31986 1 5 35 411987 4 13 94 1 1121988 5 12 160 2 1791989 3 4 156 2 1651990 3 11 197 5 2161991 9 12 253 6 2801992 13 7 193 1 2141993 6 7 195 1 2091994 2 8 157 3 1701995 8 18 261 5 2921996 2 17 329 7 3551997 10 9 328 4 3511998 3 11 346 1 3611999 8 7 302 3172000 4 10 312 6 3322001 4 7 254 1 2662002 5 5 280 2902003 5 8 226 1 2402004 7 5 201 1 2142005 1 1 176 1782006 3 7 166 1 1772007 3 2 170 175

Total 109 186 4794 48 5137

510 EPIDEMIOLOGICAL STUDIES OF ANTICHOLINESTERASE PESTICIDE POISONING IN TAIWAN

37.2.3 Types of OP Exposures

In the literature, most OP exposures occurring in Asiainvolved acute ingestions by adult males (Aygun et al.,2002; Eddleston, 2000; Eddleston et al., 1998; Fernando,2002; He et al., 1998; Lin et al., 2004; Lin et al., 2008;Litchfield, 2005; Munidasa et al., 2004; Roberts et al.,2003; Srinivas Rao et al., 2005; Yang et al., 1996). InTaiwan, acute exposures (98.36%) were the most common,leading health-care professionals to consult with Taiwan’snetwork of PCCs.

37.2.4 Locations of Callers to PCCs

Of 5137 OP exposures, 4916 (95.70%) were reported byhealth-care professionals at hospitals. Hospitals were themost common sites of callers consulting with the PCCs.Only 0.25% of the calls came directly from the general

public. Locations were not recorded for 13 OP exposures(0.25%) shown in Table 37.4.

The majority of OP exposure calls made to PCCs inthe United States were not from health-care providersin health-care facilities; instead they were mainly fromthe general public (Lai et al., 2006). Only 28.52% of OPexposures reported to PCCs in the United States werefrom health-care providers in health-care facilities (Laiet al., 2006). As is shown in Table 37.5, this empiricalobservation in Taiwan may arise because most OP expo-sures were related to suicidal ingestions, which requireemergency medical services (EMS) intervention and trans-portation to hospital for emergency medical care, ratherthan simply asking for exposure advice over the phone.This is in contrast to most OP exposures in the UnitedStates, which are unintentional and do not require medicalcare in a health-care facility (Blondell, 2007; Lai et al.,2006; Lin et al., 2008).

TABLE 37.2 Gender Distribution of Cases with OP Exposures Related to Age

Age (years)

Gender ,6 6–9 .19 Unknown Total Percentage

Male 75 107 3161 32 3375 65.70Female 34 76 1618 8 1736 33.79Unknown 3 15 8 26 0.51

Total 109 186 4794 48 5137 100.00

Percentage 2.12 3.62 93.32 0.93 100.00

TABLE 37.3 Types of OP Exposures Related to Patient Age

Age (years)

Type ,6 6–19 .19 Unknown Total Percentage

Acute 106 181 4718 48 5053 98.36Chronic 1 1 39 41 0.80Unknown 2 4 37 43 0.84

Total 109 186 4794 48 5137 100.00

Percentage 2.12 3.62 93.32 0.93 100.00

TABLE 37.4 Sites of Callers Consulting with the PCC Related to Patient Age

Age (years)

Caller ,6 6–9 .19 Unknown Total Percentage

Health-care facility 101 174 4602 39 4916 95.70Non-health-care facility 8 12 181 7 208 4.05Unknown 11 2 13 0.25

Total 109 186 4794 48 5137 100.00

Percentage 2.12 3.62 93.32 0.93 100.00

37.2 OP POISONING 511

37.2.5 Reasons for Exposures

The reasons for exposures are detailed in Table 37.5.Although intentional exposure accounted for 3235 casesin adults (or 67.50%), unintentional exposures accountedfor 89.00% of calls concerning those younger than6 years of age. Suicides were the leading causes of expo-sures in adults and those an age between 6 and 19 years.Occupational exposures were the most common uninten-tional exposures in adults. Accidental exposures resulted inthe majority of unintentional exposures in those youngerthan 6 years.

37.2.6 Routes of OP Exposures

Ingestion was the most common route of exposure (73.51%),followed by inhalation (10.67%). All routes of exposure aredetailed in Table 37.6.

37.2.7 Coingestants of OP Exposures

The maximum recorded number of coingestants was nine butsingle exposures were the most common (Table 37.7).

37.2.8 Characteristics of Single OP Exposures

Of the 4024 cases caused by exposure to a single OP, mevin-phos (17.99%), chlorpyrifos (17.79%), methamidophos(7.93%), dimethoate (5.24%), and fenitrothion (4.72%)were the top five exposures to a specific, single OP(Table 37.8). The order was the same as in our previousreport (Lin et al., 2008).

Of 4024 OP exposures, 615 (15.28%) involving onlyone OP could not be specifically identified (Table 37.8).This compares with a Sri Lankan study where the top fivespecific OP exposures were to monocrotophos, malathion,profenophos, pirimiphos, and dimethoate (Van der Hoeket al., 1998). Another Sri Lankan study found that the topfive specific OP exposures were to dimethoate, methamido-phos, malathion, monocrotophos, and fenthion (Karallieddeet al., 1988). The four most common specific OP exposuresin a Chinese study were to parathion, omethoate, dimethoate,and dichlorvos (He et al., 1998). The top two OP exposuresin a Turkish study were to methamidophos and parathion(Aygun, 2004).

Within the standard WHO Pesticide Hazard Classes,1872 cases (46.52%) were due to WHO Pesticide HazardClass I OPs, 1350 cases (33.55%) were due to WHOPesticide Hazard Class II OPs, 161 cases (4.00%) were dueto a WHO Pesticide Hazard Class III OP, eight cases(0.20%) were due to a WHO Pesticide Hazard Class whoseactive ingredients were obsolete or discontinued, and 633cases (15.73%) were due to OPs the names of which wereunknown and could not be classified (Table 37.8)(International Programme on Chemical Safety, 2000–02;World Health Organization).

From a chemical structure classification of OP exposuresfrom our cases, 2126 (52.83%) were due to dimethylOPs, 1054 (26.19%) from diethyl OPs, 205 (5.09%) frommixed OPs, 16 (0.40%) from diphenyl OPs, eight (0.20%)from a dipropyl OP, and 615 (15.28%) from OPs whosenames were unknown and whose chemical structure couldnot be classified (Table 37.8) (Eyer, 2003; InternationalProgramme on Chemical Safety, 2000–02; United States

TABLE 37.5 Reasons for OP Exposures Related to Patient Age

Age (years)

Reasons for OP exposures ,6 6–9 .19 Unknown Total Percentage

IntentionalSuicide 4 111 3139 20 3274 63.73Malicious 4 2 14 20 0.39Intentional unknown 1 82 3 86 1.67

UnintentionalOccupational 1 5 842 11 859 16.72Accidental 91 57 532 9 689 13.41Environmental 4 5 36 45 0.88Misuse due to ignorance 10 10 0.19Homicide 1 1 0.02Unintentional unknown 1 1 29 31 0.60

Adverse reactionFood contamination 1 1 0.02

Unknown 4 3 109 5 121 2.36

Total 109 186 4794 48 5137 100.00

Percentage 2.12 3.62 93.32 0.93 100.00


National Library of Medicine; World Health Organization).The distribution of deaths based on the chemical structuresof OPs was statistically significant ( p , 0.001).

The majority of deaths (n) resulting from exposuresthat involved only a single, specific OP were caused bymevinphos (138) (WHO Pesticide Hazard Class Ia), metha-midophos (68) (Class Ib), dimethoate (36) (Class II), chlor-pyrifos (32) (Class II), parathion (25) (Class Ia), andmonocrotophos (25) (Class Ib) (Table 37.8; InternationalProgramme on Chemical Safety, 2000–02; World HealthOrganization). Of the OP exposures with the largest numbers

of deaths (n), four were also among the top five exposuresinvolving only one OP (Table 37.8). The sequence was alsoconsistent with what we observed in our previous report(Lin et al., 2008).

In total, of 541 deaths caused by exposure to a singleOP within the standard WHO Pesticide Hazard Classes,327 (60.44%) were under the category of WHO PesticideHazard Class I OPs, 93 (17.19%) were Class II, 10 (1.85%)were Class III, and one (0.18%) was related with a WHOPesticide Hazard Class for which the active ingredientswere obsolete or discontinued; 110 (20.33%) due to expo-sure to OPs were unidentified, and unclassified withinthe standard WHO Pesticide Hazard Classes (Table 37.8;International Programme on Chemical Safety, 2000–02;World Health Organization). This distribution of deathsbased on WHO Pesticide Hazard Classes was statisticallysignificant ( p , 0.001).

Of the 541 deaths caused by exposure to a single OPclassified by chemical structure, 342 (63.22%) were due todimethyl OPs, 67 (12.38%) to diethyl OPs, 23 (4.25%)to mixed OPs, one (0.18%) to a diphenyl OP, and none(0.00%) to a dipropyl OP; 108 (19.96%) deaths were dueto OPs whose names were unknown and whose chemicalstructure could not be classified (Table 37.8) (Eyer,2003; International Programme on Chemical Safety,2000–02; United States National Library of Medicine;World Health Organization). This distribution of deaths

TABLE 37.6 Routes of OP Exposures Related to Patient Age

Age (years)

Route ,6 6–9 .19 Unknown Total Percentage

Ingestion 73 146 3525 32 3776 73.51Ingestion þ dermal 9 1 13 23 0.45Ingestion þ inhalation 1 6 7 0.14Ingestion þ inhalation þ dermal 6 6 0.12Ingestion þ inhalation þ ocular þ dermal 1 1 0.02Ingestion þ ocular 4 4 0.08Ingestion þ ocular þ dermal 1 1 0.02Ingestion þ parenteral 1 1 0.02Inhalation 7 19 514 8 548 10.67Inhalation þ dermal 4 7 371 5 387 7.53Inhalation þ dermal þ other 1 1 0.02Inhalation þ dermal þ parenteral 1 1 0.02Inhalation þ ocular 4 4 0.08Inhalation þ ocular þ dermal 5 5 0.10Inhalation þ parenteral 1 1 0.02Dermal 11 10 232 1 254 4.94Ocular 12 12 0.23Ocular þ dermal 1 8 9 0.18Parenteral 13 13 0.25Unknown 4 2 75 2 83 1.62

Total 109 186 4794 48 5137 100.00

Percentage 2.12 3.62 93.32 0.93 100.00

TABLE 37.7 Coingestants of OP Exposures

No. of InvolvedSubstance Case No. Percentage

1 4024 78.332 692 13.473 309 6.024 66 1.285 31 0.606 6 0.127 5 0.109 1 0.02Unknown 3 0.06

Total 5137 100.00


TABLE 37.8 Characteristics of Single OP Exposures

Chemical Type of OPa Generic Name

Exposures toa Single OP

(n)

DeathsCaused by


(n)

Mortality RatesDue to Exposures

to a Single OP(%)

WHOPesticideHazardClassb

Dimethyl Mevinphos 724 138 19.06 IaDiethyl Chlorpyrifos 716 32 4.47 IINC Unknown OPs 615 108 17.56 NCDimethyl Methamidophos 319 68 21.32 IbDimethyl Dimethoate 211 36 17.06 IIDimethyl Fenitrothion 190 7 3.68 IIDiethyl Parathion 176 25 14.20 IaMixed: ethyl & nitrophenyl EPN 129 20 15.50 IaDimethyl Monocrotophos 112 25 22.32 IbDimethyl Malathion 94 7 7.45 IIIDimethyl Parathion-methyl 87 14 16.09 IaDimethyl Demeton-S-methyl 83 13 15.66 IbDimethyl Fenthion 75 11 14.67 IIDiethyl Phorate 73 3 4.11 IaMixed: ethyl & 4-bromo-2-

chlorophenylProfenofos 51 1 1.96 II

Dimethyl Acephate 43 3 6.98 IIIDimethyl Omethoate 36 7 19.44 IbDimethyl Dichlorvos 31 4 12.90 IbDimethyl Methidathion 29 5 17.24 IbDimethyl Phenthoate 27 3 11.11 IIDiethyl Ethion 26 3 11.54 IIDiethyl Terbufos 25 1 4.00 IaMixed: ethyl &

2,4-dichlorophenylProthiophos 17 2 11.76 NC

Diphenyl Edifenphos 16 1 6.25 IbDimethyl Pirimiphos-methyl 14 0 0.00 IIIDimethyl Trichlorfon 14 0 0.00 IIDimethyl Formothion 11 0 0.00 IIDiethyl Diazinon 9 0 0.00 IIDiethyl Isoxathion 9 2 22.22 IbDipropyl Iprobenfos 7 0 0.00 IIIDiethyl Phosalone 5 0 0.00 IIDimethyl Phosmet 5 0 0.00 IIDiethyl Pyrazophos 5 0 0.00 IIDiethyl Triazophos 5 0 0.00 IbDimethyl Naled 4 0 0.00 IIDimethyl Azinphos-methyl 3 1 33.33 IbMixed: ethyl &

4-methylmercapto-3-methylphenyl

Fenamiphos 3 0 0.00 Ib

Dimethyl Oxydemetonmethyl

3 0 0.00 Ib

Diethyl Pyridaphenthion 3 0 0.00 IIIDimethyl Thiometon 3 0 0.00 IbDimethyl Vamidothion 3 0 0.00 IbMixed: methyl &

2,5-dichloro-4-bromophenylLeptophos 2 0 0.00 DC

Diethyl Mephospholan 2 1 50.00 DCDimethyl Tolclofos-methyl 2 0 0.00 DC

(Continued)


TABLE 37.8 Continued

Chemical Type of OPa Generic Name


(n)

DeathsCaused by


(n)

Mortality RatesDue to Exposures

to a Single OP(%)

WHOPesticideHazardClassb

Mixed: diethyl &dichlorophenyl

Chlorthiophos 1 0 0.00 NC

Dimethyl Dicrotophos 1 0 0.00 IbMixed: ethyl & phenyl Disulfoton 1 0 0.00 IaMixed: ethyl & phenyl Fonofos 1 0 0.00 IaDipropyl IPSP 1 0 0.00 DCDimethyl Menazon 1 0 0.00 DCDimethyl Temephos 1 0 0.00 II

Total 4024 541 13.59

aFrom United States National Library of Medicine and Eyer, 2003.bExtremely hazardous (Class Ia); Highly hazardous (Class Ib); Moderately hazardous (Class II); Slightly hazardous (Class III); DC, active ingredients believed tobe obsolete or discontinued for use as pesticides; NC, not classified as one of the above by the World Health Organization (WHO); from World HealthOrganization (WHO), 2003.

TABLE 37.9 Clinical Outcomes of OP Exposures Related to Patient Age

Age (years)

Outcome ,6 6–19 .19 Unknown Total Percentage

Minor effect 43 78 2071 19 2211 43.04Moderate effect 17 48 1078 11 1154 22.46Major effect 7 26 674 9 716 13.94Death 3 12 608 8 631 12.28No effect 37 14 158 1 210 4.09Unknown 2 6 112 120 2.34No follow-up 2 93 95 1.85

Total 109 186 4794 48 5137 100.00

Percentage 2.12 3.62 93.32 0.93 100.00

TABLE 37.10 Antidote Use for OP Exposures Related to Patient Age

Age (years)

,6 6–19 .19 Unknown Total Percentage

Antidote 45 114 2882 24 3065 59.67No treatment 39 32 751 12 834 16.24Supportive care 1 12 13 0.25Unknown 24 40 1149 12 1225 23.85

Total 109 186 4794 48 5137 100.00

Percentage 2.12 3.62 93.32 0.93 100.00


based on the chemical structures of OPs was statistically sig-nificant ( p , 0.001).

Specifically, 13 (56.52%) of the 23 identified WHOPesticide Hazard Class I OPs in this study were also dimethylOPs and 13 (48.15%) of the 27 identified dimethyl OPs werealso WHO Pesticide Hazard Class I OPs (Table 37.8). WHOPesticide Hazard Class I OPs are not necessarily dimethylOPs, and dimethyl OPs are not necessarily WHO PesticideHazard Class I OPs (Lin et al., 2008).

37.2.9 Clinical Outcomes of OP Exposures

The majority of clinical outcomes were 2211 minor effects(43.04%). The mortality rate for all 5137 OP exposures was12.28% (Table 37.9). The mortality rates for OP exposureswith only one involved OP were 13.59%, as detailed inTable 37.8.

37.2.10 Antidote Use in OP Exposures

Of the 5137 OP exposures, 3065 patients (59.67%) receivedatropine and/or pralidoxime. The clinical outcomes of OPexposures in Taiwan are detailed in Table 37.10.

37.3 CM POISONING

37.3.1 Incidence of CM Exposures Each Year

There were 2375 human CM poisoning exposures reported tothe Taiwan’s network of PCCs from July 1985 throughDecember 2007. The yearly case numbers of CM poisoningexposures are shown in Table 37.11.

37.3.2 Demographic Data

Out of 2375 cases, the overall ratio of males to females was2.59 (71.92% versus 27.79%), with gender unidentifiedin seven cases (0.29%) (Table 37.12). The mean patient age(+s.d.) were 47.28+ 17.90 years. The youngest patientwas 1 year old. The oldest patient was 90 years old. Casesover 19 years old (91.79%) comprised the most popularexposure group.

37.3.3 Types of CM Exposures

In the literature, most CM exposures were caused by acuteingestions (Fernando, 2002; Lai et al., 2006; Yang et al.,1996). In Taiwan, acute exposures (98.19%) were themost common type of exposure (Table 37.13), which ledhealth-care professionals to consult with Taiwan’s networkof PCCs.

37.3.4 Locations of Callers to PCCs

Of 2375 CM exposures, 2132 (89.77%) were reported byhealth-care professionals at hospitals. Table 37.14 shows

TABLE 37.12 Gender Distribution of Cases with CM Exposures Related to Age

Age (years)

Gender ,6 16–19 .19 Unknown Total Percentage

Male 43 45 1585 35 1708 71.92Female 30 30 594 6 660 27.79Unknown 1 1 5 7 0.29

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00

TABLE 37.11 Yearly Incidence of CM Poisoning ExposuresRelated to Age

Age (years)

Year ,6 6–9 .19 Unknown Total

1985 1 11986 1 11 121987 1 6 24 2 331988 2 5 54 1 621989 3 3 76 1 831990 7 7 69 831991 2 1 115 2 1201992 6 1 102 5 1141993 4 66 2 721994 8 4 53 1 661995 2 7 82 911996 5 2 113 3 1231997 3 4 60 2 691998 3 3 123 3 1321999 5 9 141 1 1562000 5 7 186 5 2032001 5 3 145 2 1552002 3 3 158 1 1652003 3 2 173 2 1802004 2 4 90 2 982005 3 3 108 4 1182006 1 102 6 1092007 1 128 1 130

Total 74 75 2180 46 2375


that hospitals were the most common sites of calls toPCCs, with only 10.23% of calls coming directly from thegeneral public.

37.3.5 Reasons for Exposures

The reasons for exposures are detailed in Table 37.15.Although intentional exposure accounted for 902 cases inadults (41.38%), unintentional exposures accounted for90.54% of calls for those younger than 6 years. Suicides

were the leading causes of exposures in adults and casesaged between 6 and 19 years old. Occupational exposureswere the most common unintentional exposures in adults.Accidental exposures resulted in the majority of unintentionalexposures in those younger than 6 years.

37.3.6 Routes of Exposures

Ingestion was the most common route of exposure (50.57%).Inhalation was the second most common route of

TABLE 37.13 Types of CM Exposures Related to Patient Age

Age (years)

Type ,6 6–19 .19 Unknown Total Percentage

Acute 73 75 2141 43 2332 98.19Chronic 23 2 25 1.05Unknown 1 16 1 18 0.76

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00

TABLE 37.14 Sites of Caller to PCCs Related to Patient Age

Age (years)

Caller ,6 6–19 .19 Unknown Total Percentage

Health-care facility 65 63 1967 37 2132 89.77Non-health-care facility 9 12 213 9 243 10.23

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00

TABLE 37.15 Reasons for CM Exposures Related to Patient Age

Age (years)

Reasons for CM Exposures ,6 6–19 .19 Unknown Total Percentage

IntentionalSuicide 1 28 869 10 908 38.23Malicious 1 8 9 0.38Intentional unknown 1 2 25 28 1.18

UnintentionalOccupational 5 822 18 845 35.58Accidental 64 26 354 10 454 19.12Environmental 2 25 2 29 1.22Misuse 2 2 0.08Homicide 3 5 34 42 1.77Unintentional unknown 4 3 13 2 22 0.93

Adverse reactionFood contamination 1 1 0.02Unknown 1 3 28 4 36 1.52

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00

37.3 CM POISONING 517

exposure (20.97%). All routes of exposures are detailed inTable 37.16.

37.3.7 Coingestants of CM Exposures

The maximum recorded number of coingestants was five butsingle exposures were more common (Table 37.17).

37.3.8 Characteristics of Single CM Exposures

Of the1844 cases caused by exposure to a single CM, meth-omyl (39.32%), carbofuran (38.99%), carbaryl (3.69%), iso-procarb (1.74%), and propoxur (1.30%) were the top five(Table 37.18). The majority of the 150 deaths (n) fromexposures that involved only a single, specific CM were

caused by methomyl (99), carbofuran (24) and carbaryl (1).Of these CM exposures with the largest numbers of deaths(n), three were also among the top five exposures involvingonly one CM. The highest mortality rates from exposuresthat involved only a single, specific CM were for methomyl(13.66%), thiofanox (10.00%), vernolate (6.67%), carbaryl(4.41%), and propoxur (4.17%) (Table 37.18).

37.3.9 Clinical Outcomes of CM Exposures

The majority of clinical outcomes were minor effects (1403,59.07%). The mortality rate for all 2375 CM exposures was7.33% (Table 37.19). Mortality rates for CM exposureswith only one involved CM were 8.13%, as detailed inTable 37.18.

TABLE 37.16 Routes of Exposures Related to Patient Age

Age (years)

Route ,6 6–19 .19 Unknown Total Percentage

Ingestion 52 58 1071 20 1201 50.57Ingestion þ dermal 4 4 7 1 16 0.67Ingestion þ inhalation þ dermal 2 2 0.08Ingestion þ inhalation þ ocular þ dermal 1 1 0.04Ingestion þ parenteral 1 1 0.04Inhalation 3 486 9 498 20.97Inhalation þ dermal 3 2 389 8 402 16.93Inhalation þ ocular 4 4 0.17Inhalation þ ocular þ dermal 1 1 0.04Dermal 10 7 190 6 213Ocular 5 5 0.21Ocular þ dermal 4 4 0.17Other 3 3 0.13Parenternal 3 3 0.13Unknown 3 1 15 2 21 0.88

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00

TABLE 37.17 Coingestants of CM Exposures Related to Patient Age

Age (years)

No. ,6 6–19 .19 Unknown Total Percentage

1 68 73 1666 37 1844 77.642 4 2 471 8 485 20.423 2 37 1 40 1.684 5 5 0.215 1 1 0.04

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00


TABLE 37.19 Clinical Outcomes of CM Exposures Related to Patient Age

Age (years)

Severity ,6 6–19 .19 Unknown Total Percentage

Minor effect 40 50 1288 25 1403 59.07Moderate effect 8 13 376 6 403 16.97Major effect 7 4 176 5 192 8.08Death 1 2 169 2 174 7.33No effect 14 4 52 3 73 3.07Unknown 4 2 119 5 130 5.47

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00

TABLE 37.18 Characteristics of Single CM Poisoning Exposure

CM Generic NameExposures to a Single

CM (n)Deaths Caused by Exposures

to a Single CM (n)Mortality Rates Due to

Exposures to a Single CM (%)

Methomyl 725 99 13.66Carbofuran 719 24 3.34Unknown 170 20 11.76Carbaryl 68 3 4.41Isoprocarb 32 1 3.13Propoxur 24 1 4.17Vernolate 15 1 6.67Benomyl 14 0 0.00Carbosulfan 12 0 0.00Oxamyl 10 0 0.00Thiofanox 10 1 10.00Aldicarb 9 0 0.00Carbendazim 9 0 0.00Pirimicarb 8 0 0.00Mancozeb 6 0 0.00Fenobucarb 4 0 0.00Metiram 2 0 0.00Propamocarb

hydrochloride2 0 0.00

Thiobencarb 2 0 0.00Fenothiocarb 1 0 0.00Thiodicarb 1 0 0.00XMC 1 0 0.00

Total 1844 150 8.13

TABLE 37.20 Antidote use in CM Exposures Related to Patient Age

Age (years)

Antidote ,6 6–19 .19 Unknown Total Percentage

Antidote 26 42 825 11 904 38.06No treatment 27 12 536 18 593 24.97Supportive care 3 5 74 1 83 3.49Unknown 18 16 745 16 795 33.49

Total 74 75 2180 46 2375 100.00

Percentage 3.12 3.16 91.79 1.94 100.00

37.3 CM POISONING 519

37.3.10 Antidote Use in CM Exposures

Of the 2375 carbamate exposures, 904 patients (38.06%)received atropine. Clinical outcomes of CM exposures inTaiwan are detailed in Table 37.20.

37.4 CONCLUSIONS

Most OP poisoning exposures were caused by acute (98.36%)ingestions (73.51%) of a single OP (78.33%) to attemptsuicide (63.73%) in adults (93.32%). Males were the mostcommon gender (65.70%) in this study. In Taiwan, 1872 of4024 cases (46.52%) were most commonly caused byexposure to a single WHO Pesticide Hazard Class I OP. In327 of 541 deaths (60.44%), they were caused by expo-sure to a single WHO Pesticide Hazard Class I OP. Of4024 cases, 2126 (52.83%) were most commonly causedby exposure to a single dimethyl OP. Exposure to a singledimethyl OP resulted in 342 of 541 deaths (63.22%). Thissuggests that banning the use of WHO Pesticide HazardClass I OPs and dimethyl OPs in Taiwan would significantlycut the number of deaths due to OP exposures. This wouldbe an important public health initiative in Taiwan (Linet al., 2008).

Similar for the situation with OPs, most CM exposureswere acute (98.19%) ingestions (50.57%) of a single CM(77.64%) in an attempt to commit suicide (38.23%) byadults (91.79%), who were predominantly male (71.92%).Methomyl was the most common specific, single CM, andwas also the leading cause of death. It is important to regulateand/or control methomyl in an appropriate way to minimizethe potential morbidity and mortality of related CMpoisonings.

ACKNOWLEDGMENTS

The authors would like to thank all the staff in the Taiwan’snetwork of PCCs for collection of the data from July 1985 throughDecember 2007 and also they gratefully thank the TaiwanDepartment of Health for its support.

REFERENCES

Aygun D (2004) Diagnosis in an acute organophosphate poisoning:report of three interesting cases and review of the literature. Eur JEmerg Med 11: 55–58.

Aygun D, Doganay Z, Altintop L, Guven H, Onar M, Deniz T, andSunter T (2002) Serum acetylcholinesterase and prognosis ofacute organophosphate poisoning. J Toxicol Clin Toxicol 40:903–910.

Blondell JM (2007) Decline in pesticide poisonings in the UnitedStates from 1995 to 2004. Clin Toxicol (Phila) 45: 589–592.

Chuang FR, Jang SW, Lin JL, Chern MS, Chen JB, and Hsu KT(1996) QTc prolongation indicates a poor prognosis in patientswith organophosphate poisoning. Am J Emerg Med 14: 451–453.

Eddleston M (2000) Patterns and problems of deliberate self-poisoning in the developing world. QJM 93: 715–731.

Eddleston M, Sheriff MH, and Hawton K (1998) Deliberate selfharm in Sri Lanka: an overlooked tragedy in the developingworld. BMJ 317: 133–135.

Eyer P (2003) The role of oximes in the management of organo-phosphorus pesticide poisoning. Toxicol Rev 22: 165–190.

Fang TC, Chen KW, Wu MH, Sung JM, and Huang JJ (1995)Coumaphos intoxications mimic food poisoning. J ToxicolClin Toxicol 33: 699–703.

Fernando R (2002) The National Poisons Information Centre in SriLanka: the first ten years. J Toxicol Clin Toxicol 40: 551–555.

Good AM, Kelly CA, and Bateman DN (2007) Differences intreatment advice for common poisons by poisons centres—aninternational comparison. Clin Toxicol 45: 234–239.

He F, Xu H, Qin F, Xu L, Huang J, and He X (1998) Intermediatemyasthenia syndrome following acute organophosphates poison-ing—an analysis of 21 cases. Hum Exp Toxicol 17: 40–45.

Hsiao CT, Yang CC, Deng JF, Bullard MJ, and Liaw SJ (1996)Acute pancreatitis following organophosphate intoxication.J Toxicol Clin Toxicol 34: 343–347.

International Programme on Chemical Safety (2000–02) The WHOrecommended classification of pesticides by hazard and guide-lines to classification, World Health Organization, Geneva,Switzerland.

Karalliedde L and Senanayake N (1988) Acute organophosphorusinsecticide poisoning in Sri Lanka. Forensic Sci Int 36: 97–100.

Lai MW, Klein-Schwartz W, Rodgers GC, Abrams JY, Haber DA,Bronstein AC, and Wruk KM (2006) 2005 Annual Reportof the American Association of Poison Control Centers’ nationalpoisoning and exposure database. Clin Toxicol 44: 803–932.

Lee F and Lin JL (2006) Intermediate syndrome after organo-phosphate intoxication in patient with end-stage renal disease.Ren Fail 28: 197–200.

Lin CL, Yang CT, Pan KY, and Huang CC (2004) Most commonintoxication in nephrology ward organophosphate poisoning.Ren Fail 26: 349–354.

Lin TJ, Walter FG, Hung DZ, Tsai JL, Hu SC, Chang JS, Deng JF,Chase JS, Denninghoff K, and Chan HM (2008) Epidemiologyof organophosphate pesticide poisoning in Taiwan. ClinToxicol (Phila) 46: 794–801.

Litchfield MH (2005) Estimates of acute pesticide poisoning in agri-cultural workers in less developed countries. Toxicol Rev 24:271–278.

Liu JH, Chou CY, Liu YL, Liao PY, Lin PW, Lin HH, and Yang YF(2008) Acid-base interpretation can be the predictor of outcomeamong patients with acute organophosphate poisoning beforehospitalization. Am J Emerg Med 26: 24–30.

Munidasa UA, Gawarammana IB, Kularatne SA, Kumarasiri PV,and Goonasekera CD (2004) Survival pattern in patients withacute organophosphate poisoning receiving intensive care.J Toxicol Clin Toxicol 42: 343–347.


Roberts DM, Karunarathna A, Buckley NA, Manuweera G, SheriffMH, and Eddleston M (2003) Influence of pesticide regulationon acute poisoning deaths in Sri Lanka. Bull World HealthOrgan 81: 789–798.

Srinivas Rao C, Venkateswarlu V, Surender T, Eddleston M, andBuckley NA (2005) Pesticide poisoning in south India: opportu-nities for prevention and improved medical management. TropMed Int Health 10: 581–588.

Tsai MJ, Wu SN, Cheng HA, Wang SH, and Chiang HT (2003) Anoutbreak of food-borne illness due to methomyl contamination.J Toxicol Clin Toxicol 41: 969–973.

Tsai MH, Tsai NW, Chen SF, Tsai HH, Lu CH, Huang CR, andChang WN (2006) Organophosphate intoxication-relatedcoital-like involuntary movements: report of a case. ActaNeurol Taiwan 15: 34–37.

Tsao TC, Juang YC, Lan RS, Shieh WB, and Lee CH (1990)Respiratory failure of acute organophosphate and carbamatepoisoning. Chest 98: 631–636.

United States National Library of Medicine. ChemlDplusAdvanced, World Health Organization (WHO).

Van der Hoek W, Konradsen F, Athukorala K, and Wanigadewa T(1998) Pesticide poisoning: a major health problem in SriLanka. Soc Sci Med 46: 495–504.

Wang AG, Liu RS, Liu JH, Teng MM, and Yen MY (1999)Positron emission tomography scan in cortical visual loss inpatients with organophosphate intoxication. Ophthalmology106: 1287–1291.

World Health Organization (WHO) (2003) WHO Pesticide List.National Poison Control and Information Service 2003, WorldHealth Organization (WHO).

Yang PY, Tsao TC, Lin JL, Lyu RK, and Chiang PC (2000)Carbofuran-induced delayed neuropathy. J Toxicol ClinToxicol 38: 43–46.

Yang CC, Wu JF, Ong HC, Hung SC, Kuo YP, Sa CH, Chen SS, andDeng JF (1996) Taiwan National Poison Center: epidemiologicdata 1985–1993. J Toxicol Clin Toxicol 34: 651–663.

REFERENCES 521

anticholinesterase pesticides (metabolism, neurotoxicity, and epidemiology) || epidemiological...

Documents