Acute Toxicity of Pesticides: An Overview

Objectives
  • To appreciate the complexity of monitoring, managing, preventing acute pesticide managing, preventing acute pesticide exposures
  • To briefly focus on specific pesticide classifications of concern for acute exposures
Poison Control Center Statistics in
  • 2.4 million human exposures reported in 2002
    • 92.3% residential exposures
    • 2.2% of exposures in a workplace
    • 51.6% of cases involved children < 6 years of age
    • 96,112 human exposures to pesticides
      • 4% of total exposures reported to poison centers
        • Most frequently implicated pesticides.

Table 17A. Substances Most Frequently Involved in Human Exposures

Substance
No.
%*
Analgesics 256,843 10.8
Cleaning substances 225,578 9.5
Cosmetics and personal care products 219,877 9.2
Foreign bodies 119,323 5.0
Sedatives/hypnotics/anti psychotics 111,001 4.7
Topicals 105,815 4.4
Cough and cold preparations 100,612 4.2
Antidepressants 99,860 4.2
Bites/envenomations 98,585 4.1
Pesticides 96,112 4.0
Plants 84,578 3.6
Food products, food poisoning 75,813 3.2
Alcohols 69,215 2.9
Antihistamines 69,107 2.9
Antimicrobials 63,372 2.7
Cardiovascular drugs 61,056 2.6
Hydrocarbons 59,132 2.5
Chemicals 54,623 2.3

Note: Despite a high frequency of involvement, these substances are not necessarily the most toxic, but rather may only be the most readily accessible.

*Percentages are based on the total number of human exposures (2,380,028) rather than the total number of substances.

Watson WA et al., (2003): 2002 Report of the AAPCC, TESS Am J Emerg Med 21(5)

Table 18. Categories with Largest Numbers of Deaths

Substance
No.
% of All Exposures in Category
Analgesics 659 .257
Sedative/hypnotics/psychotics 364 .328
Antidepressants 318 .318
Stimulants and street drugs 242 .528
Cardiovascular drugs 181 .296
Alcohols 139 .200
Chemicals 50 .091
Anticonvulsants 65 .181
Gases and fumes 44 .106
Antihistamines 71 .103
Muscle relaxants 52 .260
Hormones and hormone antagonists 33 .062
Cleaning substances 33 .013
Automotive products 30 .213
Cough and cold preparations 22 .022
Pesticides 18 .019

Note: Tables 18, 22A and 22B are based on an unlimited number of substances coded per exposure, while Table 21 only includes up to 3 substances per case.

Pesticides implicated in fatal cases (2002): Sulfuryl fluoride Paraquat Strychnine Brodifacoum Dinitrophenol(?) OP’s

Strengths, Limitations of Poison Center Strengths, Limitations of Poison Center Data: Acute Pesticide Exposures Data: Acute Pesticide Exposures

  • Strengths
    • Number of cases
    • Ease of access
      • 24 hour/day service Toll-free access in U.S.
    • Consistency of reporting mechanism
    • Current initiatives in toxicosurveillance
      • Electronic reporting of acute pesticide exposures from PCC's to State Health Depts.
      • Real-time data uploading and analysis by CDC
        • Temporal, spatial trends
  • Limitations
    • May not be capturing occupational exposures
      • High-risk population
    • Limited specificity of reporting
      • Identity of active ingredient
      • EPA Reg. #
      • Details on circumstances surrounding exposure
        • Important for unintentional exposures
Table 1. Oregon PC Pesticide - Related Calls 1994 - 1998

  1994 1995 1996 1997 1998 Total
Arsenates 13 9 9 9 6 46
Organophosphate 215 183 152 151 168 869
OP + carbamate 10 18 7 18 14 67
OP + chlorinated HC 2 1 2 2 1 8
OP + other substance 9 17 11 15 12 64
OP + carbamate + chlorinated HC 2 0 1 0 0 3
Carbamate 49 42 32 44 33 200
Carbamate + other 11 4 5 5 7 32
Chlorinated HC 45 47 63 75 39 269
Chlorinated HC + other 2 3 4 2 0 11
Borates 69 69 35 50 67 290
Piperonyl butoxide + pyrethrins 82 106 64 84 94 430
Pyrethrins 64 100 64 92 82 402
Rotenone 3 2 1 2 2 10
Metaldehyde 20 18 31 25 42 136
Piperonyl Butoxide 1 3 3 1 2 10
Nicotine 0 1 1 0 0 2
Misc repellents 68 126 67 71 48 380
Other insecticides 24 17 20 26 25 112
Veterinary insecticide 61 54 41 50 47 253
Unknown 58 56 40 54 60 268
             
Total Carbamates 65 51 44 50 41 251
Total Organophosphates 238 219 173 186 195 1011
Total OP + carbamates 303 270 217 236 236 1262
Total Insecticides 808 876 653 776 749 3862
             
Carbamate 5 5 7 1 1 19
Mercurial 0 0 0 0 0 0
Non-mercurial 9 8 8 4 5 34
Unknown 19 13 19 8 13 72
Phthalimide 6 4 2 2 2 16
Total Fungicides 39 30 36 15 21 141
             
Strychnine 7 5 1 8 5 26
Short-acting anticoagulant 5 5 6 7 7 30
Long-acting anticoagulant 193 130 74 90 119 606
Others 12 8 12 8 7 47
Total Rodenticides 217 148 93 113 138 709
             
2,4- or 2,4,5-T 99 112 85 82 112 490
Paraquat 2 2 4 3 6 17
Diquat 2 4 1 2 4 13
Others 113 144 108 138 93 596
Total Herbicides 216 262 198 225 215 1116
             
Total Pesticides 1280 1316 980 1129 1123 5828

BZ Horowitz, S Griffin, CL Thomsen (2002): Pesticide-Related Illnesses: Are Poison Centers Reporting to the State Health Department?
Vet Hum Toxicol; 44(1):49-51.
  • Over 5-year period, Oregon Poison Center receives ~1,000 calls/year for acute pesticide exposures
  • Insecticides most frequently implicated
    • OP’s, OP/carbamates, pyrethrin, pyrethroids
  • % of OPC cases reported to State Health Department ….?
Pesticides of Relevance to Acute Toxicity: Fumigants



  • Active ingredient exists as a gas
    • Relevant to inhalation pathways of exposure
  • Diverse chemical structures
  • Utilized to control pests in enclosed spaces, soil, and structures
  • Many are restricted use
  • Modern epidemiological data suggest fewer exposure cases than other pesticide classes
  • Higher case-severity and case-fatality rate than fungicides
    • Many exposures are accidental
      • Applicators, workers, non-occupational (residential)
  • Scenarios of concern: Inadequate ventilation of a treated structure, unanticipated cross-ventilation from a treated structure
Fumigants: Toxicology of Acute Overexposure (Methyl Bromide)



  • Highly lipid soluble
    • Well-absorbed via inhalation pathways
  • Wide volume of distribution
    • CNS, liver, kidneys are target organs
  • Me-Br is strong alkylating agent
    • Cell membrane disruption
    • Inhibition of critical enzyme function
  • Metabolism of MeBr occurs rapidly
  • Parent compound (MeBr MeBr) not usually detectable in tissues
  • Management of overexposure is supportive
    • No antidotes are available
Fumigants: Toxicology of Acute Overexposure (Phosphides)

  • Decomposition products of phosphide fumigants include phosphine gas, phosphoric acid
  • Phosphine inhibits electron transport chain
    • Mechanism similar to cyanide
      • Unlike cyanide, there are no specific antidotes for gas
      • Reliable biomarkers of exposure are not readily available
  • Acute inhalation overexposure
    • Pulmonary injury, cardiogenic shock, neurological depression
NIOSH Alert: Preventing Phosphine Poisoning and Explosions



  • http://www.cdc.gov/niosh/docs/99-126/
  • A review of 205 occupational exposure cases
  • Common accidental exposure scenarios
    • Lack of proper handling during fumigant application
    • Failure to monitor air concentrations during application
    • Failure to use appropriate respiratory equipment
    • Improper disposal of unused fumigant products
    • Incidental exposure from nearby fumigant application
  • Majority of exposures associated with agricultural applications
  • Most symptomatic exposures occurred among non-applicators
    • Workers in proximity to or entering recently treated areas


Fumigants and Acute Toxicity
  • Inhalation pathways of exposure
  • Broad, non-selective mechanisms of toxicity
  • Relevance of major morbidity, mortality from accidental exposures
    • Applicators and non-applicators (bystanders)
  • In most cases, biomarkers are of limited or no utility
  • Specific therapies after overexposure are not available
  • Need for vigilance in prevention
    • Education, training, engineering controls, and appropriate use of PPE
Insecticides and Acute Toxicity



  • Insecticides with a common mechanism of toxicity
    • Inhibitors of acetylcholinesterase
      • Vary in chemical properties, dermal absorption, potency
  • Acute overexposure results in cholinergic signs, symptoms
    • Excess acetylcholine at muscarinic, nicotinic receptors
      • Muscarinic SLUDGE toxidrome: Salivation, Lacrimation, Urinary incontinence,
        D        iarrhea, GI symptoms, Eyes (miosis)
      • Nicotinic signs
        • Fasiculations, weakness, acute paralysis (in worst-case scenario)
Cholinesterase Inhibitors and Acute Toxicity: Measuring Exposure

  • Blood (serum and RBC) monitoring
    • Cholinesterase enzyme activity as a biomarker of effect for OP’s, carbamates
  • Difficulties, and challenges in cholinesterase monitoring as biomarker
    • Reliability (inter-laboratory) Reliability (inter-laboratory)
    • Variation in normal reference ranges
    • Rapid recovery in cholinesterase activity after overexposure to N-methyl carbamates
  • Importance of education, engineering controls, appropriate use of required PPE to reduce unnecessary exposure


Other Insecticides: Pyrethroids and Acute Toxicity

  • Commonly utilized in agriculture, residential settings, public health (vector control)
  • Mechanism of toxicity
    • Prolong deactivation of sodium channels, excitation of nerve fibers
  • Systemic intoxication is rare
  • Local effects from dermal overexposure to concentrated formulations
    • Transient paresthesias (12-24 hours)
    • Usually occur in absence of any signs of skin injury
  • Irritant effects (eye, throat, respiratory irritation) from inhalation overexposure


Insecticides and Acute Toxicity: Misapplication



  • Content of 19 “bug-bombs” released within a 470 sq. foot residence
    • Product label indicated use application for 700 square feet
    • Pilot light ignited the gas that had accumulated, resulting in explosion
  • The Label is the Law
Newer Insecticides



  • Imidacloprid
    • Neonicotinoid family of insecticides
    • Selective for the nicotinic acetylcholine receptor of the insect
      • Targets the insect nervous system
    • Poor penetration across blood-brain barrier in mammals
    • Registered applications in agriculture, structural pest control, pet care (topical structural solution)
    • Experience with human overexposure is very limited

Newer Insecticides

  • A case of intentional (ingestion) poisoning (Wu, 2001)
  • Farmer ingested 100 mL of insecticide formulation
    • 9.7% imidacloprid
    • < 2 % surfactant
    • Remainder: N-methyl pyrrolidone
  • Clinical course: initial drowsiness, dizziness, abdominal pain, vomiting GI endoscopy revealed corrosive injury
    • Mainly upper GI tract
  • Individual recovered, discharged at 4 days post-ingestion
  • Were most significant effects (GI tract injury) caused imidacloprid or N-methylpyrolidone?
    • Authors suggest N-methylpyrolidone as more likely explanatory factor
      • dermal, ocular effects from occupational exposures in humans
      • Low potency of imidacloprid as skin, eye irritant in animal studies
  • Health care providers need to consider the entire formulation when assessing risks after acute overexposure
Pesticides and Acute Toxicity: Medical Case Profiles at NPIC

  • Intended to educate health care providers
    • Importance of exposure history Importance of exposure history
    • Understanding prevention
      • Engineering controls, PPE, decontamination,
    • Clinical assessment
      • Biomarkers of exposure
    • Role of public health surveillance, other State Agencies
  • Examples:
    • Pyrethroids and paresthesias
    • Inhalation risks of phosphide fumigants
    • Pesticide incident reporting
Acute Toxicity of Pesticides: An Overview

Daniel L. Sudakin, M.D., M.P.H.
Assistant Professor
Department of Environmental and Molecular Toxicology
Oregon State University

NPIC: http://www.npic.orst.edu/

Disclaimer and Reproduction Information: Information in NASD does not represent NIOSH policy. Information included in NASD appears by permission of the author and/or copyright holder. More

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