Pesticides, Herbicides, Fungicides and Insecticides

Barium

  • Sources
    • Rodenticide/insecticide and depilatories
    • Barium sulfate (contrast)
  • Effects/MOA
    • Causes hypokalemia due to redistribution – inh Ca-activated K rectifier channels → QT prolong
  • Clinical Manifestations
    • Paralysis
    • Severe hypoK within 2 hours
    • Parkinsonism findings on MRI
  • MGMT/Notes
    • White powder that resembles FLOUR
    • Pulmonary 
    • ORAL sodium sulfate or Mg sulfate (not IV- converts to barium sulfate=bad)
    • HD

Methyl bromide

  • Effects/MOA
    • Oral and dermal routes 
    • Direct cytotoxic (intact methyl bromide) and alkylating agent
    • BUT
    • Neuro effects occur without antecedent irritant effects
    • Greenhouse workers at risk
  • Clinical Manifestations
    • Neuro sx (cns depression) followed by agitation, seizure, coma, death
    • Convulsions, rapid CV collapse (ARDS leading to CV collapse is most common cause of death)
  • MGMT/Notes
    • BAL+NAC
    • HD for bromide
    • DECON!/PPE! – adheres to rubber, leather
    • OSHA PEL (permissible exposure limit)
    • 3x heavier than air
    • Metabolized to formaldehyde and methanethiol (neuro and visual changes)

Dichloropropene

  • Sources
    • Chlorinated hydrocarbon
  • Effects/MOA
    • Inhalation is the primary exposure route
  • Clinical Manifestations
    • Similar to CCl4 and chloroform (liver) met in the liver by 2E1 to electrophilic products
    • Similar to CCl4/APAP, liver tox (but also independent renal tox can occur)
  • MGMT/Notes
    • OSHA TWA TEL (time-weighted average, toxic exposure limit)
    • Extremely volatile – easy to be exposed (lung primary inj site) – normally in soybean oil (prevents volatilization)

Metal phosphides and Phosphine

  • Effects/MOA
    • Aluminum phosphide, Zinc/Mg/Ca phosphide – release phosphine gas(PH3) when exposed to atmospheric moisture (faster when exposed to HCl)
    • Met Acid w gap common
    • Providers should don PPE/N95
    • PH3 exposure as a byproduct of Meth production using RED Phosphorus (white phosphorus=phossy jaw, hypocalcemia, hyperkalemia)
    • Can be absorbed transdermal but low and rare
  • Clinical Manifestations
    • PH3- protoplasmic toxin, inhibits cytochrome c-oxidase (also decreases mitochondrial complexes I, II, IV and V)
    • PH3 is corrosive – mucous membrane burns/alveoli (ARDS)
    • Irritation to Shock, cv collapse
    • AlP – pts will have high jugular venous pressure
  • MGMT/Notes
    • DECON
      • N95 mask does NOT protect against PH3
    • IV NAC using PO apap regimen + IM vitamin E
    • Consider MgSO4 IV
    • Vegetable oil decon (orally) but limited due to risk of aspirating hydrocarbon/oil? Or hyperinsulinemia 
    • Maybe High dose insulin for AlP
    • KMnO4 (Potassium permanganate) or Boron added to GI decon NOT recommended 
    • No AC
    • AlP has greenish-grey color, garlicky odor. 3g tablet = 1g PH3, Ammonia and CO2
    • ZnP – rotten fish, quadrilateral crystalloid tablet
    • NIOSH (IDLH 50 ppm) – 
    • Blood testing not helpful – PH3 rapidly hydrolyzed

White phosphorus

  • Effects/MOA
    • Reacts with oxygen to form phosphous pentoxide → reacts with water to produce EXOTHERMIC reaction and phosphoric acid (corrosive)
  • Clinical manifestations
    • 3 Phase tox
      1. Vomiting/ hematemesis, hypotension, death
      2. Transient resolution
      3. Hepatic injury
  • MGMT/Notes
    • Exothermic, acid-producing, dehydrating reactions
    • Hepatic zone 1 necrosis -> fatty infiltrates within 6 hours
    • Vomitus can be luminescent and/or smoking and can spontaneously combust -> keep it and clothing under water
    • Can use copper sulfate ONCE (0.5%-1% solution)-> contaminated areas turn BLACK (copper phosphide). Similarly diluted silver nitrate can be alternative
    • IV NAC for liver
    • 1mg/kg lethal
    • Absorbed in skin/inhalation/GI (co-ingestants with fat, EtOH, liquids increase toxicity)

Sulfuryl fluoride

  • Effects/MOA
    • Measurable fluoride concentrations after exposure – fluorosis (look at Ca, Mg)
  • Clinical Manifestations
    • Respiratory, CNS and CV are primary targets
  • MGMT/Notes
    • Used for termites (Ca, Fl, Wa)
    • TLV-TWA (threshold limit value, time-weighted average)

Alachlor/Butachlor/Propanil

  • Effects/MOA
    • Methemoglobinemia due to dichlorophenyhydroxylamine oxidizing Fe2+ to Fe3+
    • But not just MetHg since fatalities occur with levels <40% (usually requires >50-70% for death)
    • Pesticide exposure with intoxication and metheoglobinemia
  • Clinical manifestations
    • Mild, nonspecific findings to seizure coma death.
  • MGMT/Notes
    • Rhabdo is a feature
    • Numerous toxic metabolites via CYP450
    • Can cause sedation due to hydrocarbon (intoxication+methemoglobin=propanil)
    • Euglycemia! Adequate glucose needed to detoxify methemoglobin
    • AC reasonable
    • Methylene blue
    • Alternatives: NAC, cimetidine (used for dapsone), ascorbic acid

Paraquat/Diquat

  • Effects/MOA
    • Induces redox cycling: Paraquat oxidized to paraquat radical (intracellular) then reduced by diaphorase + NADPH back to paraquat + superoxide radical
    • When NADPH+Oxygen run out, cell death → nonspecific cell necrosis
    • Cortinarius orellanus mushrooms contain biprydil like compound similar to paraquat (primarily known for nephrotoxicity due to orellanine)
  • Clinical Manifestations
    • Lung and Kidney common organs affected
    • Topical exposures- painful (ulceration -> desquamation)
    • Seizures with Diquat
  • Hemoperfusion/HD
    • AC/NAC/VitC/Cyclophosphamide/Xuebijing
    • SIPP (Severity Index of Paraquat Poisoning)
      • Paraquat level x hours since ingestion
        • SIPP < 10 = survival
        • SIPP 10-50 = death by lung fibrosis
        • SIP > 50 = death
    • Rate of increase in Scr predicts prognosis
      • < 0.3 mg/dL/hr over 5 hours = survival
      • > 0.5 mg/dL/hr over 12 hours = death
    • Poorly bioavailable, but F of 5% sufficient to cause death. As little as 10mL of 20% solution = death.
    • Can penetrate skin
    • Rapid distribution to all tissues, then redistribution to plasma.
    • Not metabolized almost fully renally eliminated
    • Diquat = pulmonary fibrosis in survivors
    • Urinary dithionite= Paraquat blue, diquat green
      • NO COMMON FALSE POSITIVES
      • If light blue or negative @ 24 hours, good prognosis. Repeat in 6 hours to see if color change occurs.
    • Jones, Proudfoot and Scherrerman-Proudfoot

Glufosinate

  • Effects/MOA
    • Structurally similar to glutamate
  • Clinical Manifestations
    • Interferes with glutamine synthase leading to hyperammonemia
    • Seizures
    • Metabolic acidosis
  • MGMT/Notes
    • Surfactants may contribute more to toxicity than glufosinate

Glyphosate

  • Effects/MOA
    • May disrupt cell membrane and cause uncoupling of ox phos
  • MGMT/Notes
    • WHO U classification – unlikely to cause harm

Phenoxy compounds

2,4-D, 2,4,5-T; MCPA, MCPP, Mecoprop; Ioxynil, Bromoxynil

  • Effects/MOA
    • Uncoupling ox phos
    • Inhibits voltage-gated chloride channel-1 (ClC-1) – muscle and renal tissue
    • Disrupts blood-brain barrier AND neuronal membrane transport mechanisms
  • Clinical Manifestations
    • Corrosive – causes direct injury to GI
    • Ox phos uncoupler
    • Myotonia (ClC-1 inh)
    • Organophosphate like effects
  • MGMT/Notes
    • Alkalinize urine/HD, HP
    • Good PO absorption, poor dermal/inhal absorption
    • Extensively bound to albumin
    • T1/2 of 2,4-D is 20-30 hours
    • Non-linear kinetics – dose-dependent changes in absorption/protein binding, clearance
    • As pH decreases, toxicity increases
    • Can initially have tachypnea w resp alkalosis

Triazine compounds

  • Effects/MOA
    • Uncoupling ox phos
  • Clinical manifestations
    • Ox phos uncoupled
  • MGMT/Notes
    • Supportive care

Pentachlorophenol

  • Uses/source
    • Wood preservative
  • Clinical manifestations
    • Uncoupling ox phos
  • MGMT/Notes
    • Can use LIPID (log D ~ 3)
    • Manufacturing leads to production of dioxins

Hexachlorobenzene

  • Uses/Source
    • Rubber/wood preservative
  • Clinical Manifestations
    • Inhibits uroporphyrinogen decarboxylase activity leading to accumulation of uroporphyrin and the induction of aminoleuvulinic acid synthase (Lead causes inc in delta-ala and protoporphyrin 9)
    • Porphyria cutanea tarda (PCT)
  • MGMT/Notes
    • Hydroxychloroquine – normalizes urinary porphyrin excretion and improves skin lesions
    • PCT outbreak in Turkey in the 1950s of 5000 cases
    • Bioaccumulates in adipose tissue

Dithiocarbamates (methyl isothiocyanate)

  • Effects/MOA
    • Metam sodium (dithiocarbamate) quickly degrades in soil or water to produce methyl isothiocyanate
    • Active metabolites: carbon disulfide (all dithocarbamates; thiram); methyl isocyanate (metam sodium)
  • Clinical Manifestations
    • Contact dermatitis
    • Metam sodium potent mucosal irritant
    • Disulfiram rxn possible
  • MGMT/Notes
    • Decon
    • In the same class as disulfiram (disulfiram is 2 molecules of DDC which then metabolized to CS2 and diethylamine.
    • NOT THE SAME AS CARBAMATES – dithiocarbamates have no acetylcholinesterase activity
    • Bhopal was methyl isocyanate NOT methyl isothiocyanate

Copper sulfate

  • Effects/MOA
    • Liver failure (centrilobular necrosis)
    • Intravascular hemolysis
    • Methemoglobinemia
  • Clinical Manifestations
    • MM irritation
    • Corrosive injury
    • Greenish blue emesis, hematemesis
  • MGMT/Notes
    • BAL, CaNaEDTA

Organotin compounds

Tributyltin oxide (TBTO); Triphenyltin; Cyhexatin

  • Effects/MOA
    • TBTO used as an anti-mildew control agent in interior and exterior paint
  • Clinical Manifestations
    • Potent irritant effects
    • Immunotoxic effects can occur
  • Notes
    • Prevents barnacles, algae, marine organisms

N-HEXANE aka Methyl-n-butyl ketone (MBK)

  • Effects/MOA
    • Axonopathy due to decreased phosphorylation of neurofilament proteins with disruption of the axonal cytoskeleton
  • Clinical Manifestations
    • PERIPHERAL NEUROTOXIC
    • Begins in distal extremities and progresses proximally

BUTANONE aka Methyl ETHYL ketone (MEK)

  • Uses/Notes
    • In cigarettes
    • 1, 3, 0 on NFPA
  • Clinical Manifestations
    • Irritant

Chlorinated hydrocarbons

  • Effects/MOA
    • Hepatotoxic: CCl4, benzene, pentene, vinyl chloride
    • Nephrotoxic: TOLUENE (renal tubule acidosis)
  • MGMT/Notes
    • Toluene associated with Good pasture syndrome

Methylene chloride

  • Carbon monoxide (paint thinner)

Chlorhexidine

  • Systemic absorption via GI can occur and convert chlorhexidine to p-chloranaline and induce metHg

Hydrogen peroxide

  • Effects/MOA
    • Home use is 3%-8%, but is also available as  35% for “hyperoxygenation therapy”
  • Clinical Manifestations
    • 1ml of 35% liberates 100mL of Oxygen so “two sips” can lead to cerebral gas embolization
  • MGMT/Notes
    • Patients with evidence of gas embolization, place in TRENDELENBURG to prevent gas from obstructing RV flow 
    • MGMT – venous aspiration of gas, HBO

Iodine

  • Effects/MOA
    • Povidone-iodide – caustic (pH~2.4)
  • MGMT/Notes
    • Oral ingestion – starch, to convert iodine to iodide → will turn effluent dark purple.
      • If no starch available, use MILK or sodium THIOSULFATE 3%

Phenol

  • Clinical Manifestations
    • Skin decon with PEG 400 and WATER (NOT PEG 3350)
    • Can use isopropyl
  • MGMT/Notes
    • Rabbit syndrome – EPS like movements and chewing that resembles a rabbit
    • Burns, CNS stimulation (seizures)

Ethylene oxide

  • Uses/Notes
    • Sterilant for medical equipment
    • Risk for healthcare workers (USP 800 and IARC carcinogen)

Glutaraldehyde

  • Uses/Notes
    • Cold sterilant
    • Similar to formaldehyde exposure

FIFRA

  • Federal Insecticide, Fungicide, and Rodenticide Act of 1962
  • Established criteria for “signal word” on the insecticide which implies the degree of toxicity based on LD50
    1. Danger: Lowest LD 50 and corrosive to eyes/skin
    2. Warning: Eye issues resolve 8-21 days, severe skin irritation @ 72 hours
    3. Caution: Eye issues resolve 7 days, moderate skin irritation @ 72 hours
    4. None: Eye irritation cleared wn 24 hours and mild skin irritation

1,1-difluoroethane (DUSTING)

  • Uses
    • Keyboard dusting spray
  • Clinical Manifestations
    • Skeletal fluorosis
    • Burns (frostbite)

 

For more chapters, visit the ABAT Study Guide homepage

Chemicals, Pesticides, Herbicides, Fungicides and Insecticides Chemicals, Pesticides, Herbicides, Fungicides and Insecticides Chemicals, Pesticides, Herbicides, Fungicides and Insecticides Chemicals, Pesticides, Herbicides, Fungicides and Insecticides