Green Tobacco Sickness

Environmental Pathograph 5 Occupational Disease Nicotine Poisoning

Green tobacco sickness (GTS) is an occupational illness caused by dermal absorption of nicotine from contact with wet tobacco leaves. It predominantly affects tobacco farmworkers during harvesting, topping, and curing activities. The condition is a form of acute nicotine poisoning presenting with nausea, vomiting, dizziness, headache, and weakness. Symptoms typically onset 3-17 hours after exposure and resolve within 1-3 days with supportive care. GTS prevalence varies from 8.2 to 47% globally among tobacco harvesters.

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5
Pathophys.
12
Phenotypes
5
Pathograph
4
Treatments
2
Differentials
8
References
1
Deep Research
⚙

Pathophysiology

5
Transdermal Nicotine Absorption
Nicotine dissolved in dew, rainwater, or perspiration on tobacco leaf surfaces penetrates the skin upon direct contact, bypassing first-pass hepatic metabolism. The rate of absorption increases with moisture on leaves, ambient temperature, duration of skin contact, physical exertion, and compromised skin integrity. High ambient temperatures increase skin absorption and plasma nicotine concentrations by 30-45%. Physical labor shunts blood to the skin, further increasing dermal nicotine absorption.
Downstream
Nicotinic Acetylcholine Receptor Overstimulation Absorbed nicotine enters systemic circulation and binds to nicotinic acetylcholine receptors throughout the body.
Show evidence (4 references)
PMID:29618907 SUPPORT Human Clinical
"It is caused by the absorption of nicotine through the skin while the workers are engaged in handling the uncured tobacco leaves."
Review article establishing that GTS is caused by dermal nicotine absorption from handling uncured tobacco.
PMID:29618907 SUPPORT Human Clinical
"Laborers working in hot, wet conditions are more likely to develop GTS because the wetness and high humidity causes nicotine to reside on the surfaces of the leaves, while the high ambient temperature increases skin absorption, thereby increasing plasma nicotine concentrations by 30–45%."
Describes the role of heat and moisture in enhancing transdermal nicotine absorption.
PMID:12791526 SUPPORT Human Clinical
"this analysis showed that nicotine causes GTS: 25 workers had 31 occurrences of GTS. Among nonsmokers, each increment increase in the natural log of cotinine increased the odds of GTS 2.11 times, adjusting for task and wet conditions."
Prospective study demonstrating dose-response relationship between salivary cotinine and GTS occurrence.
+ 1 more reference
Nicotinic Acetylcholine Receptor Overstimulation
Absorbed nicotine binds to nicotinic acetylcholine receptors (nAChRs) at autonomic ganglia, neuromuscular junctions, and in the central nervous system, causing initial stimulation followed by desensitization and blockade. This produces the characteristic constellation of gastrointestinal, neurological, and cardiovascular symptoms. Smokers and tobacco users may develop tolerance to nicotine effects via chronic nAChR desensitization, providing partial protection against GTS.
Cholinergic Synaptic Transmission link ↑ INCREASED
Downstream
Autonomic Ganglia Dysfunction Overstimulation of ganglionic nAChRs causes excessive parasympathetic and sympathetic activation leading to gastrointestinal and cardiovascular symptoms.
Central Nervous System Effects Nicotine crosses the blood-brain barrier and acts on central nAChRs, triggering the chemoreceptor trigger zone and altering cerebrovascular tone.
Neuromuscular Junction Disruption Overstimulation and subsequent desensitization of nAChRs at the neuromuscular junction impairs voluntary muscle function.
Show evidence (4 references)
PMID:30650314 SUPPORT Human Clinical
"Mecamylamine (Inversine®, Vecamyl®), a nicotinic acetylcholine receptor (nAChR) antagonist, should be tested as a remedy for green tobacco sickness."
The proposal to use nAChR antagonists as treatment supports that GTS pathophysiology involves nicotinic receptor overstimulation.
PMID:30650314 SUPPORT Model Organism
"Mecamylamine has been demonstrated to block nicotine-induced seizures and lethality in mice [27, 28, 41, 42]"
nAChR antagonism blocks nicotine toxicity in mice, supporting the role of nAChR overstimulation in nicotine poisoning.
PMID:30650314 SUPPORT Model Organism
"nicotine-induced seizures in rats [43, 44, 45]"
nAChR antagonism blocks nicotine-induced seizures in rats, corroborating the nAChR mechanism across species.
+ 1 more reference
Autonomic Ganglia Dysfunction
Nicotine-induced overstimulation of nAChRs at autonomic ganglia produces simultaneous parasympathetic and sympathetic hyperactivation. Parasympathetic effects include nausea, vomiting, diarrhea, increased salivation, and abdominal cramps via vagal and enteric nerve stimulation of gastrointestinal smooth muscle and secretory glands. Sympathetic effects include tachycardia, hypertension, and diaphoresis. The simultaneous overdrive of both branches produces the contradictory symptom profile characteristic of acute nicotine poisoning.
Response to Nicotine link
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The nicotine alters part of the brain, causing reflex vomiting, and excites nerves in the gastrointestinal tract that bring about nausea and abdominal cramping."
Describes the peripheral autonomic mechanism of GTS gastrointestinal symptoms including vagal and enteric nerve excitation.
Central Nervous System Effects
Nicotine crossing the blood-brain barrier acts on central nAChRs, directly stimulating the chemoreceptor trigger zone (area postrema) to produce reflex vomiting independent of peripheral gastrointestinal stimulation. Central nicotinic effects also alter cerebrovascular tone and vestibular processing, contributing to headache and dizziness. These central effects are mechanistically distinct from the peripheral autonomic ganglia dysfunction, though both contribute to the overall symptom profile.
Cholinergic Synaptic Transmission link ↑ INCREASED
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The nicotine alters part of the brain, causing reflex vomiting, and excites nerves in the gastrointestinal tract that bring about nausea and abdominal cramping."
Explicitly describes central brain effects of nicotine causing reflex vomiting, distinct from the peripheral GI nerve excitation mentioned in the same sentence.
Neuromuscular Junction Disruption
Nicotine overstimulates nAChRs at the neuromuscular junction (the synapse between motor neurons and skeletal muscle fibers), initially causing excessive muscle activation followed by receptor desensitization and depolarization block. This produces generalized weakness, prostration, and impaired respiratory muscle function contributing to breathlessness. This mechanism is analogous to the depolarizing block produced by succinylcholine and is mechanistically distinct from the autonomic and central nervous system effects.
Neuromuscular Synaptic Transmission link ↓ DECREASED
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
This comprehensive symptom list explicitly includes weakness, prostration, and breathlessness — all consistent with neuromuscular junction disruption causing skeletal muscle impairment and respiratory muscle dysfunction.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Green Tobacco Sickness Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

12
Cardiovascular 1
Hypotension OCCASIONAL Hypotension (HP:0002615)
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
Occasional blood pressure lowering described as a GTS symptom.
Digestive 2
Nausea and Vomiting VERY_FREQUENT Nausea and vomiting (HP:0002017)
Show evidence (2 references)
PMID:29618907 SUPPORT Human Clinical
"The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
Comprehensive review listing nausea and vomiting as primary symptoms of GTS.
PMID:30650314 SUPPORT Human Clinical
"Signs and symptoms include nausea, vomiting, headache, and abdominal cramps."
Expert review confirming nausea and vomiting as cardinal features of GTS.
Diarrhea OCCASIONAL Diarrhea (HP:0002014)
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
Diarrhea listed among the recognized symptoms of GTS.
Head and Neck 1
Excessive Salivation OCCASIONAL Excessive salivation (HP:0003781)
Show evidence (1 reference)
PMID:30650314 SUPPORT Human Clinical
"The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
Increased salivation listed among GTS symptoms.
Integument 2
Diaphoresis FREQUENT Hyperhidrosis (HP:0000975)
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
Increased perspiration listed among GTS symptoms.
Pallor FREQUENT Pallor (HP:0000980)
Show evidence (1 reference)
PMID:30650314 SUPPORT Human Clinical
"The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
Pallor listed as the second most prevalent sign of GTS.
Musculoskeletal 1
Weakness FREQUENT Muscle weakness (HP:0001324)
Show evidence (1 reference)
PMID:30650314 SUPPORT Human Clinical
"The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
Weakness listed among the most prevalent symptoms of GTS.
Nervous System 1
Headache FREQUENT Headache (HP:0002315)
Show evidence (1 reference)
PMID:30650314 SUPPORT Human Clinical
"Signs and symptoms include nausea, vomiting, headache, and abdominal cramps."
Headache identified as a cardinal symptom of GTS.
Respiratory 1
Breathlessness OCCASIONAL Dyspnea (HP:0002094)
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
Breathlessness listed among respiratory complaints of GTS.
Constitutional 2
Abdominal Pain FREQUENT Abdominal pain (HP:0002027)
Show evidence (1 reference)
PMID:30650314 SUPPORT Human Clinical
"Signs and symptoms include nausea, vomiting, headache, and abdominal cramps."
Abdominal cramps identified as a cardinal symptom of GTS.
Chills OCCASIONAL Chills (HP:0025143)
Show evidence (1 reference)
PMID:30650314 SUPPORT Human Clinical
"The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
Chills listed among GTS symptoms.
Other 1
Dizziness VERY_FREQUENT
Show evidence (1 reference)
PMID:30650314 SUPPORT Human Clinical
"The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
Dizziness and lightheadedness listed among the most prevalent GTS symptoms.
💊

Treatments

4
Chemical Exposure Avoidance
Action: chemical exposure avoidance MAXO:0000071
Immediate cessation of contact with wet tobacco leaves and removal of contaminated clothing. Washing exposed skin with soap and water to remove residual nicotine. Washing can reduce skin nicotine by 96%.
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"Washing with soap and water immediately after working is recommended to reduce exposure to nicotine. Washing can reduce the amount of nicotine that is on skin by 96%."
Documents the effectiveness of washing in removing nicotine from skin.
Supportive Care
Action: supportive care MAXO:0000950
Symptomatic treatment including antiemetics for nausea/vomiting, IV fluid rehydration for dehydration from vomiting, and rest. GTS is self-limiting and symptoms typically resolve within 1-3 days.
Show evidence (1 reference)
PMID:8367763 SUPPORT Human Clinical
"No fatalities have been reported, and treatment is supportive."
Establishes that GTS treatment is supportive with no reported fatalities.
Protective Clothing
Action: chemical exposure avoidance MAXO:0000071
Wearing waterproof gloves, long-sleeved shirts, and rain suits when handling wet tobacco to prevent dermal nicotine absorption. Chemical-resistant gloves and water-resistant clothing are recommended. Clothing must remain dry to be effective.
Show evidence (2 references)
PMID:8367763 SUPPORT Human Clinical
"Prevention, by covering exposed skin, seems to be the most effective way of dealing with GTS."
Identifies skin protection as the primary prevention strategy.
PMID:29618907 SUPPORT Human Clinical
"The use of personal protective equipment like water-resistant clothing, chemical-resistant gloves, plastic aprons, and rain-suits with boots should be used by the tobacco farmers to prevent its occurrence."
Specific PPE recommendations for GTS prevention.
Mecamylamine (Proposed)
Action: Pharmacotherapy NCIT:C15986
Mecamylamine, a nicotinic acetylcholine receptor antagonist approved for hypertension, has been proposed as a potential pharmacotherapy for GTS treatment and prevention. Varenicline and nicotine vaccines have also been proposed as potential therapeutics but have not been tested for this indication.
Show evidence (1 reference)
PMID:30650314 PARTIAL Human Clinical
"Mecamylamine (Inversine®, Vecamyl®), a nicotinic acetylcholine receptor (nAChR) antagonist, should be tested as a remedy for green tobacco sickness."
Proposed pharmacotherapy based on the nicotinic mechanism of GTS, but not yet tested in clinical trials for this indication.
🌍

Environmental Factors

4
Wet Tobacco Leaf Contact
exposure to tobacco link
Direct skin contact with wet or dew-covered green tobacco leaves during harvesting, topping, or handling. Moisture dissolves nicotine from leaf surfaces and facilitates transdermal absorption. Harvesting carries the greatest risk, followed by barning.
Show evidence (2 references)
PMID:11464390 SUPPORT Human Clinical
"Task (e.g., priming ID, 4.04; topping ID, 1.86; barning ID, 0.62) and working in wet clothing (25% of workdays ID, 2.97; fewer than 25% of workdays ID, 1.29) had the largest effect."
Prospective study quantifying the effect of task type and wet conditions on GTS incidence.
PMID:24526387 SUPPORT Human Clinical
"Among men, age, being a non-smoker, hanging tobacco sticks in the barn, harvesting wet leaves, and exposure to physical exertion were risk factors for GTS."
Brazilian study confirming wet leaf harvesting as a key risk factor.
Lack of Protective Clothing
Workers who do not wear waterproof gloves, long sleeves, or rain gear while handling wet tobacco have significantly higher risk of GTS. Washing with soap and water after work reduces skin nicotine by 96%.
Show evidence (2 references)
PMID:8367763 SUPPORT Human Clinical
"Prevention, by covering exposed skin, seems to be the most effective way of dealing with GTS."
Early clinical description identifying skin protection as the primary prevention strategy.
PMID:16236669 SUPPORT Human Clinical
"Our study appears to reinforce the GTS prevention recommendations made by investigators in other tobacco growing regions, specifically the importance of minimizing close skin contact with tobacco leaves and avoiding dermal contact with the plants when they are wet."
Shade-tobacco study reinforcing the importance of minimizing skin contact with wet tobacco.
Heat and Physical Exertion
High ambient temperatures and strenuous physical labor increase cutaneous blood flow, significantly enhancing transdermal nicotine absorption. Perspiration also dissolves additional nicotine from leaf surfaces.
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"The combination of high ambient temperatures and hard physical labor shunts blood to the skin to help lower body temperature. The resultant increase in surface blood flow also significantly increases dermal absorption of nicotine."
Describes the physiological mechanism by which heat and exertion increase nicotine absorption.
Work Inexperience
Workers with less experience in tobacco farming are at higher risk for GTS. This may reflect attrition of susceptible individuals from the workforce and lack of acquired nicotine tolerance.
Show evidence (1 reference)
PMID:11464390 SUPPORT Human Clinical
"Greater work experience (5+ years, ID = 0.87; first year ID = 2.41) and tobacco use (ID of 1.18 vs 2.39) were negatively associated with green tobacco sickness."
Prospective study showing inexperienced workers have nearly 3-fold higher GTS incidence.
🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Green Tobacco Sickness:

Organophosphate Pesticide Poisoning
Overlapping Features Shares symptoms of nausea, vomiting, and diarrhea with GTS, but organophosphate poisoning additionally presents with lacrimation, miosis, pulmonary edema, and cholinesterase depression not seen in GTS.
Distinguishing Features
  • Organophosphate poisoning causes lacrimation, miosis, and pulmonary edema not seen in GTS
  • GTS occurs on farms not using pesticides and was documented before widespread pesticide use
  • Cholinesterase levels are normal in GTS
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"many of the symptoms of organophosphate poisoning (including increased lacrimation, pulmonary edema, and miosis) have not been associated with GTS."
Review distinguishing GTS from organophosphate poisoning.
Heat Exhaustion
Overlapping Features Shares symptoms of nausea, weakness, and dizziness with GTS. However, GTS occurs in cool conditions and symptoms typically onset hours after work cessation, unlike heat exhaustion.
Distinguishing Features
  • GTS symptoms appear hours after work cessation (median 10 hours), unlike heat exhaustion
  • GTS has occurred during cool weather conditions
  • Heat exhaustion patients feel overheated while GTS patients often report chills
Show evidence (1 reference)
PMID:29618907 SUPPORT Human Clinical
"Although tobacco is typically harvested during hot weather, GTS symptoms have also appeared during cool conditions when harvester reported feeling chilled rather than overheated."
Differentiates GTS from heat exhaustion by the presence of chills and occurrence in cool conditions.
{ }

Source YAML

click to show 
name: Green Tobacco Sickness
creation_date: "2026-03-23T00:00:00Z"
updated_date: "2026-05-09T03:15:56Z"
category: Environmental
description: >
  Green tobacco sickness (GTS) is an occupational illness caused by dermal absorption
  of
  nicotine from contact with wet tobacco leaves. It predominantly affects tobacco
  farmworkers
  during harvesting, topping, and curing activities. The condition is a form of acute
  nicotine
  poisoning presenting with nausea, vomiting, dizziness, headache, and weakness. Symptoms
  typically onset 3-17 hours after exposure and resolve within 1-3 days with supportive
  care.
  GTS prevalence varies from 8.2 to 47% globally among tobacco harvesters.
disease_term:
  preferred_term: green tobacco sickness
parents:
- Occupational Disease
- Nicotine Poisoning
notes: >
  No specific MONDO term exists for green tobacco sickness or nicotine poisoning.
  MONDO:0029000 (poisoning) is the closest ancestor but too broad to be a useful mapping.
  ECTO:0100013 (exposure to tobacco) is used for the environmental exposure context.
tracked_issues:
- url: https://github.com/monarch-initiative/mondo/issues/10054
  title: New term request — green tobacco sickness / nicotine poisoning
  tracked_issue_role: ontology_term_request
  tracked_issue_status: OPEN
  notes: Upstream MONDO term request; until resolved, this entry has no specific MONDO mapping.
pathophysiology:
- name: Transdermal Nicotine Absorption
  description: >
    Nicotine dissolved in dew, rainwater, or perspiration on tobacco leaf surfaces
    penetrates the skin upon direct contact, bypassing first-pass hepatic metabolism.
    The rate of absorption increases with moisture on leaves, ambient temperature,
    duration of skin contact, physical exertion, and compromised skin integrity.
    High ambient temperatures increase skin absorption and plasma nicotine concentrations
    by 30-45%. Physical labor shunts blood to the skin, further increasing dermal
    nicotine absorption.
  chemical_entities:
  - preferred_term: Nicotine
    term:
      id: CHEBI:17688
      label: "(S)-nicotine"
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It is caused by the absorption of nicotine through the skin while the workers are engaged in handling the uncured tobacco leaves."
    explanation: Review article establishing that GTS is caused by dermal nicotine absorption from handling uncured tobacco.
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Laborers working in hot, wet conditions are more likely to develop GTS because the wetness and high humidity causes nicotine to reside on the surfaces of the leaves, while the high ambient temperature increases skin absorption, thereby increasing plasma nicotine concentrations by 30–45%."
    explanation: Describes the role of heat and moisture in enhancing transdermal nicotine absorption.
  - reference: PMID:12791526
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "this analysis showed that nicotine causes GTS: 25 workers had 31 occurrences of GTS. Among nonsmokers, each increment increase in the natural log of cotinine increased the odds of GTS 2.11 times, adjusting for task and wet conditions."
    explanation: Prospective study demonstrating dose-response relationship between salivary cotinine and GTS occurrence.
  - reference: PMID:18181197
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Self-reported rash increased the odds of having GTS in the bivariate (OR 2.29, 95% CI 1.21, 4.35), and multivariate analyses (OR 3.30, CI 2.17, 5.02)."
    explanation: Demonstrates that compromised skin integrity increases GTS risk via enhanced transdermal nicotine absorption.
  downstream:
  - target: Nicotinic Acetylcholine Receptor Overstimulation
    description: >
      Absorbed nicotine enters systemic circulation and binds to nicotinic
      acetylcholine receptors throughout the body.
- name: Nicotinic Acetylcholine Receptor Overstimulation
  description: >
    Absorbed nicotine binds to nicotinic acetylcholine receptors (nAChRs) at
    autonomic ganglia, neuromuscular junctions, and in the central nervous system,
    causing initial stimulation followed by desensitization and blockade. This
    produces the characteristic constellation of gastrointestinal, neurological,
    and cardiovascular symptoms. Smokers and tobacco users may develop tolerance
    to nicotine effects via chronic nAChR desensitization, providing partial
    protection against GTS.
  biological_processes:
  - preferred_term: Cholinergic Synaptic Transmission
    term:
      id: GO:0007271
      label: synaptic transmission, cholinergic
    modifier: INCREASED
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mecamylamine (Inversine®, Vecamyl®), a nicotinic acetylcholine receptor (nAChR) antagonist, should be tested as a remedy for green tobacco sickness."
    explanation: The proposal to use nAChR antagonists as treatment supports that GTS pathophysiology involves nicotinic receptor overstimulation.
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Mecamylamine has been demonstrated to block nicotine-induced seizures and lethality in mice [27, 28, 41, 42]"
    explanation: nAChR antagonism blocks nicotine toxicity in mice, supporting the role of nAChR overstimulation in nicotine poisoning.
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "nicotine-induced seizures in rats [43, 44, 45]"
    explanation: nAChR antagonism blocks nicotine-induced seizures in rats, corroborating the nAChR mechanism across species.
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "nicotine-induced seizures in cats [46]"
    explanation: nAChR antagonism blocks nicotine-induced seizures in cats, further supporting the nAChR overstimulation mechanism.
  downstream:
  - target: Autonomic Ganglia Dysfunction
    description: >
      Overstimulation of ganglionic nAChRs causes excessive parasympathetic
      and sympathetic activation leading to gastrointestinal and cardiovascular symptoms.
  - target: Central Nervous System Effects
    description: >
      Nicotine crosses the blood-brain barrier and acts on central nAChRs,
      triggering the chemoreceptor trigger zone and altering cerebrovascular tone.
  - target: Neuromuscular Junction Disruption
    description: >
      Overstimulation and subsequent desensitization of nAChRs at the
      neuromuscular junction impairs voluntary muscle function.
- name: Autonomic Ganglia Dysfunction
  description: >
    Nicotine-induced overstimulation of nAChRs at autonomic ganglia produces
    simultaneous parasympathetic and sympathetic hyperactivation. Parasympathetic
    effects include nausea, vomiting, diarrhea, increased salivation, and
    abdominal cramps via vagal and enteric nerve stimulation of gastrointestinal
    smooth muscle and secretory glands. Sympathetic effects include tachycardia,
    hypertension, and diaphoresis. The simultaneous overdrive of both branches
    produces the contradictory symptom profile characteristic of acute nicotine
    poisoning.
  biological_processes:
  - preferred_term: Response to Nicotine
    term:
      id: GO:0035094
      label: response to nicotine
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The nicotine alters part of the brain, causing reflex vomiting, and excites nerves in the gastrointestinal tract that bring about nausea and abdominal cramping."
    explanation: Describes the peripheral autonomic mechanism of GTS gastrointestinal symptoms including vagal and enteric nerve excitation.
- name: Central Nervous System Effects
  description: >
    Nicotine crossing the blood-brain barrier acts on central nAChRs, directly
    stimulating the chemoreceptor trigger zone (area postrema) to produce reflex
    vomiting independent of peripheral gastrointestinal stimulation. Central
    nicotinic effects also alter cerebrovascular tone and vestibular processing,
    contributing to headache and dizziness. These central effects are mechanistically
    distinct from the peripheral autonomic ganglia dysfunction, though both
    contribute to the overall symptom profile.
  biological_processes:
  - preferred_term: Cholinergic Synaptic Transmission
    term:
      id: GO:0007271
      label: synaptic transmission, cholinergic
    modifier: INCREASED
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The nicotine alters part of the brain, causing reflex vomiting, and excites nerves in the gastrointestinal tract that bring about nausea and abdominal cramping."
    explanation: Explicitly describes central brain effects of nicotine causing reflex vomiting, distinct from the peripheral GI nerve excitation mentioned in the same sentence.
- name: Neuromuscular Junction Disruption
  description: >
    Nicotine overstimulates nAChRs at the neuromuscular junction (the synapse
    between motor neurons and skeletal muscle fibers), initially causing excessive
    muscle activation followed by receptor desensitization and depolarization
    block. This produces generalized weakness, prostration, and impaired
    respiratory muscle function contributing to breathlessness. This mechanism
    is analogous to the depolarizing block produced by succinylcholine and is
    mechanistically distinct from the autonomic and central nervous system effects.
  biological_processes:
  - preferred_term: Neuromuscular Synaptic Transmission
    term:
      id: GO:0007274
      label: neuromuscular synaptic transmission
    modifier: DECREASED
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
    explanation: This comprehensive symptom list explicitly includes weakness, prostration, and breathlessness — all consistent with neuromuscular junction disruption causing skeletal muscle impairment and respiratory muscle dysfunction.
phenotypes:
- name: Nausea and Vomiting
  category: Gastrointestinal
  frequency: VERY_FREQUENT
  description: >
    Nausea is the most commonly reported symptom, often accompanied by vomiting.
    These result from stimulation of the chemoreceptor trigger zone and vagal
    afferents by circulating nicotine.
  phenotype_term:
    preferred_term: Nausea and vomiting
    term:
      id: HP:0002017
      label: Nausea and vomiting
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
    explanation: Comprehensive review listing nausea and vomiting as primary symptoms of GTS.
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Signs and symptoms include nausea, vomiting, headache, and abdominal cramps."
    explanation: Expert review confirming nausea and vomiting as cardinal features of GTS.
- name: Dizziness
  category: Neurological
  frequency: VERY_FREQUENT
  description: >
    Dizziness and lightheadedness are common, resulting from nicotine effects
    on the central nervous system and possibly transient blood pressure changes.
  phenotype_term:
    preferred_term: Dizziness
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
    explanation: Dizziness and lightheadedness listed among the most prevalent GTS symptoms.
- name: Headache
  category: Neurological
  frequency: FREQUENT
  description: >
    Headache frequently accompanies other symptoms, likely due to direct
    central nervous system effects of nicotine and autonomic dysfunction.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Signs and symptoms include nausea, vomiting, headache, and abdominal cramps."
    explanation: Headache identified as a cardinal symptom of GTS.
- name: Weakness
  category: Musculoskeletal
  frequency: FREQUENT
  description: >
    Generalized weakness and prostration are common, resulting from nicotinic
    receptor effects at neuromuscular junctions and general autonomic dysfunction.
  phenotype_term:
    preferred_term: Muscle weakness
    term:
      id: HP:0001324
      label: Muscle weakness
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
    explanation: Weakness listed among the most prevalent symptoms of GTS.
- name: Abdominal Pain
  category: Gastrointestinal
  frequency: FREQUENT
  description: >
    Abdominal cramping and pain result from parasympathetic stimulation of
    gastrointestinal smooth muscle by nicotine.
  phenotype_term:
    preferred_term: Abdominal cramps
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Signs and symptoms include nausea, vomiting, headache, and abdominal cramps."
    explanation: Abdominal cramps identified as a cardinal symptom of GTS.
- name: Diaphoresis
  category: Dermatological
  frequency: FREQUENT
  description: >
    Excessive sweating due to sympathetic cholinergic activation by nicotine.
  phenotype_term:
    preferred_term: Excessive sweating
    term:
      id: HP:0000975
      label: Hyperhidrosis
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
    explanation: Increased perspiration listed among GTS symptoms.
- name: Pallor
  category: Dermatological
  frequency: FREQUENT
  description: >
    Pallor is a frequently reported sign, likely related to nicotine-induced
    peripheral vasoconstriction and autonomic dysfunction.
  phenotype_term:
    preferred_term: Pallor
    term:
      id: HP:0000980
      label: Pallor
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
    explanation: Pallor listed as the second most prevalent sign of GTS.
- name: Diarrhea
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: >
    Diarrhea results from parasympathetic stimulation of gastrointestinal motility.
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
    explanation: Diarrhea listed among the recognized symptoms of GTS.
- name: Chills
  category: Constitutional
  frequency: OCCASIONAL
  description: >
    Chills and feeling cold are reported by affected workers, likely due to
    autonomic dysregulation of thermoregulation.
  phenotype_term:
    preferred_term: Chills
    term:
      id: HP:0025143
      label: Chills
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
    explanation: Chills listed among GTS symptoms.
- name: Hypotension
  category: Cardiovascular
  frequency: OCCASIONAL
  description: >
    Occasional lowering of blood pressure or heart rate may occur due to
    vagal stimulation by nicotine.
  phenotype_term:
    preferred_term: Hypotension
    term:
      id: HP:0002615
      label: Hypotension
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
    explanation: Occasional blood pressure lowering described as a GTS symptom.
- name: Excessive Salivation
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: >
    Increased salivation results from parasympathetic stimulation of
    salivary glands by nicotine acting on autonomic ganglia.
  phenotype_term:
    preferred_term: Excessive salivation
    term:
      id: HP:0003781
      label: Excessive salivation
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The signs and symptoms, in order of prevalence, included vomiting, pallor, weakness, dizziness, light-headedness, headache, increased sweating, abdominal pain, cold, chills, and increased salivation."
    explanation: Increased salivation listed among GTS symptoms.
- name: Breathlessness
  category: Respiratory
  frequency: OCCASIONAL
  description: >
    Breathlessness and labored respiration may occur as a respiratory
    complaint in GTS, likely due to nicotine effects on respiratory
    center and chest wall musculature.
  phenotype_term:
    preferred_term: Breathlessness
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The symptoms include nausea, vomiting, pallor, dizziness, headaches, increased perspiration, chills, abdominal pain, diarrhea, increased salivation, prostration, weakness, breathlessness, and occasional lowering of blood pressure."
    explanation: Breathlessness listed among respiratory complaints of GTS.
prevalence:
- population: Global tobacco harvesters
  percentage: "8.2-47%"
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The prevalence of GTS varies from 8.2 to 47% globally."
    explanation: Review article summarizing the wide range of GTS prevalence across global studies.
- population: Latino farmworkers in North Carolina, USA
  percentage: "24.2%"
  evidence:
  - reference: PMID:11464390
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The green tobacco sickness prevalence was 24.2%, whereas the ID was 1.88 days per 100 days worked."
    explanation: Prospective surveillance study documenting GTS prevalence and incidence density.
- population: Male tobacco farmers in southern Brazil
  percentage: "6.6%"
  evidence:
  - reference: PMID:24526387
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "GTS prevalence among men in the previous month was 6.6%, while among women it was 11.9%."
    explanation: Cross-sectional study in Brazil showing sex-stratified GTS prevalence.
- population: Female tobacco farmers in southern Brazil
  percentage: "11.9%"
  evidence:
  - reference: PMID:24526387
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "GTS prevalence among men in the previous month was 6.6%, while among women it was 11.9%."
    explanation: Higher GTS prevalence among female tobacco farmers in Brazil.
progression:
- phase: Onset
  notes: >
    Symptom onset occurs 3-17 hours after exposure, with a median onset of
    approximately 10 hours after cessation of tobacco contact.
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "most of those stricken with GTS became ill after they had gone home for the day (median onset = 10 hours)."
    explanation: Documents the delayed onset characteristic of GTS, with symptoms appearing hours after exposure.
- phase: Resolution
  duration: "1-3 days"
  notes: >
    GTS is self-limiting. Symptoms typically resolve within 1-3 days with
    supportive care. Median illness duration is 2.4 days.
  evidence:
  - reference: PMID:8367763
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No fatalities have been reported, and treatment is supportive."
    explanation: Confirms the self-limiting nature of GTS and supportive treatment approach.
environmental:
- name: Wet Tobacco Leaf Contact
  description: >
    Direct skin contact with wet or dew-covered green tobacco leaves during
    harvesting, topping, or handling. Moisture dissolves nicotine from leaf
    surfaces and facilitates transdermal absorption. Harvesting carries the
    greatest risk, followed by barning.
  exposure_term:
    preferred_term: exposure to tobacco
    term:
      id: ECTO:0100013
      label: exposure to tobacco
  effect: Primary route of nicotine exposure causing GTS symptoms
  evidence:
  - reference: PMID:11464390
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Task (e.g., priming ID, 4.04; topping ID, 1.86; barning ID, 0.62) and working in wet clothing (25% of workdays ID, 2.97; fewer than 25% of workdays ID, 1.29) had the largest effect."
    explanation: Prospective study quantifying the effect of task type and wet conditions on GTS incidence.
  - reference: PMID:24526387
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among men, age, being a non-smoker, hanging tobacco sticks in the barn, harvesting wet leaves, and exposure to physical exertion were risk factors for GTS."
    explanation: Brazilian study confirming wet leaf harvesting as a key risk factor.
- name: Lack of Protective Clothing
  description: >
    Workers who do not wear waterproof gloves, long sleeves, or rain gear
    while handling wet tobacco have significantly higher risk of GTS. Washing
    with soap and water after work reduces skin nicotine by 96%.
  effect: Increased dermal exposure to dissolved nicotine
  evidence:
  - reference: PMID:8367763
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Prevention, by covering exposed skin, seems to be the most effective way of dealing with GTS."
    explanation: Early clinical description identifying skin protection as the primary prevention strategy.
  - reference: PMID:16236669
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our study appears to reinforce the GTS prevention recommendations made by investigators in other tobacco growing regions, specifically the importance of minimizing close skin contact with tobacco leaves and avoiding dermal contact with the plants when they are wet."
    explanation: Shade-tobacco study reinforcing the importance of minimizing skin contact with wet tobacco.
- name: Heat and Physical Exertion
  description: >
    High ambient temperatures and strenuous physical labor increase cutaneous
    blood flow, significantly enhancing transdermal nicotine absorption.
    Perspiration also dissolves additional nicotine from leaf surfaces.
  effect: Enhanced transdermal nicotine absorption
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The combination of high ambient temperatures and hard physical labor shunts blood to the skin to help lower body temperature. The resultant increase in surface blood flow also significantly increases dermal absorption of nicotine."
    explanation: Describes the physiological mechanism by which heat and exertion increase nicotine absorption.
- name: Work Inexperience
  description: >
    Workers with less experience in tobacco farming are at higher risk for
    GTS. This may reflect attrition of susceptible individuals from the
    workforce and lack of acquired nicotine tolerance.
  effect: Higher GTS susceptibility
  evidence:
  - reference: PMID:11464390
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Greater work experience (5+ years, ID = 0.87; first year ID = 2.41) and tobacco use (ID of 1.18 vs 2.39) were negatively associated with green tobacco sickness."
    explanation: Prospective study showing inexperienced workers have nearly 3-fold higher GTS incidence.
epidemiology:
- name: Global Affected Population
  description: >
    An estimated 8 million individuals worldwide are afflicted with GTS,
    including women and children. Prevalence has shifted from the United States
    and Europe to China, India, and Brazil.
  evidence:
  - reference: PMID:30650314
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Worldwide 8 million individuals are afflicted, including women and children."
    explanation: Estimate of global GTS burden.
differential_diagnoses:
- name: Organophosphate Pesticide Poisoning
  description: >
    Shares symptoms of nausea, vomiting, and diarrhea with GTS, but
    organophosphate poisoning additionally presents with lacrimation, miosis,
    pulmonary edema, and cholinesterase depression not seen in GTS.
  distinguishing_features:
  - Organophosphate poisoning causes lacrimation, miosis, and pulmonary edema not seen in GTS
  - GTS occurs on farms not using pesticides and was documented before widespread pesticide use
  - Cholinesterase levels are normal in GTS
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "many of the symptoms of organophosphate poisoning (including increased lacrimation, pulmonary edema, and miosis) have not been associated with GTS."
    explanation: Review distinguishing GTS from organophosphate poisoning.
- name: Heat Exhaustion
  description: >
    Shares symptoms of nausea, weakness, and dizziness with GTS. However,
    GTS occurs in cool conditions and symptoms typically onset hours after
    work cessation, unlike heat exhaustion.
  distinguishing_features:
  - GTS symptoms appear hours after work cessation (median 10 hours), unlike heat exhaustion
  - GTS has occurred during cool weather conditions
  - Heat exhaustion patients feel overheated while GTS patients often report chills
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although tobacco is typically harvested during hot weather, GTS symptoms have also appeared during cool conditions when harvester reported feeling chilled rather than overheated."
    explanation: Differentiates GTS from heat exhaustion by the presence of chills and occurrence in cool conditions.
treatments:
- name: Chemical Exposure Avoidance
  description: >
    Immediate cessation of contact with wet tobacco leaves and removal of
    contaminated clothing. Washing exposed skin with soap and water to remove
    residual nicotine. Washing can reduce skin nicotine by 96%.
  treatment_term:
    preferred_term: chemical exposure avoidance
    term:
      id: MAXO:0000071
      label: chemical exposure avoidance
  evidence:
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Washing with soap and water immediately after working is recommended to reduce exposure to nicotine. Washing can reduce the amount of nicotine that is on skin by 96%."
    explanation: Documents the effectiveness of washing in removing nicotine from skin.
- name: Supportive Care
  description: >
    Symptomatic treatment including antiemetics for nausea/vomiting, IV fluid
    rehydration for dehydration from vomiting, and rest. GTS is self-limiting
    and symptoms typically resolve within 1-3 days.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:8367763
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "No fatalities have been reported, and treatment is supportive."
    explanation: Establishes that GTS treatment is supportive with no reported fatalities.
- name: Protective Clothing
  description: >
    Wearing waterproof gloves, long-sleeved shirts, and rain suits when
    handling wet tobacco to prevent dermal nicotine absorption. Chemical-resistant
    gloves and water-resistant clothing are recommended. Clothing must remain
    dry to be effective.
  role: preventive
  treatment_term:
    preferred_term: chemical exposure avoidance
    term:
      id: MAXO:0000071
      label: chemical exposure avoidance
  evidence:
  - reference: PMID:8367763
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Prevention, by covering exposed skin, seems to be the most effective way of dealing with GTS."
    explanation: Identifies skin protection as the primary prevention strategy.
  - reference: PMID:29618907
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The use of personal protective equipment like water-resistant clothing, chemical-resistant gloves, plastic aprons, and rain-suits with boots should be used by the tobacco farmers to prevent its occurrence."
    explanation: Specific PPE recommendations for GTS prevention.
- name: Mecamylamine (Proposed)
  description: >
    Mecamylamine, a nicotinic acetylcholine receptor antagonist approved for
    hypertension, has been proposed as a potential pharmacotherapy for GTS
    treatment and prevention. Varenicline and nicotine vaccines have also been
    proposed as potential therapeutics but have not been tested for this indication.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  evidence:
  - reference: PMID:30650314
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Mecamylamine (Inversine®, Vecamyl®), a nicotinic acetylcholine receptor (nAChR) antagonist, should be tested as a remedy for green tobacco sickness."
    explanation: Proposed pharmacotherapy based on the nicotinic mechanism of GTS, but not yet tested in clinical trials for this indication.
  notes: >-
    These are proposed therapeutics not yet tested in clinical trials for GTS.
references:
- reference: DOI:10.1016/j.shaw.2017.06.007
  title: Green Tobacco Sickness Among Tobacco Harvesters in a Korean Village
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: Green Tobacco Sickness Among Tobacco Harvesters in a Korean Village
    supporting_text: Green Tobacco Sickness Among Tobacco Harvesters in a Korean Village
- reference: DOI:10.1038/s43856-024-00584-x
  title: Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness
    supporting_text: Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness
- reference: DOI:10.1080/00039896.1995.9935972
  title: 'Green Tobacco Sickness: Occupational Nicotine Poisoning in Tobacco Workers'
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: 'Green Tobacco Sickness: Occupational Nicotine Poisoning in Tobacco Workers'
    supporting_text: 'Green Tobacco Sickness: Occupational Nicotine Poisoning in Tobacco Workers'
- reference: DOI:10.1080/17512433.2019.1570844
  title: 'Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics'
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: 'Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics'
    supporting_text: 'Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics'
- reference: DOI:10.11606/s1518-8787.2018052000287
  title: Urinary cotinine in tobacco farmers in Southern Brazil
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: To describe urinary cotinine levels in tobacco farmers.
    supporting_text: To describe urinary cotinine levels in tobacco farmers.
    evidence:
    - reference: DOI:10.11606/s1518-8787.2018052000287
      reference_title: Urinary cotinine in tobacco farmers in Southern Brazil
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: To describe urinary cotinine levels in tobacco farmers.
      explanation: Deep research cited this publication as relevant literature for Green Tobacco Sickness.
- reference: DOI:10.1300/j096v10n02_05
  title: Cotinine Levels and Green Tobacco Sickness Among Shade Tobacco Workersx
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: Cotinine Levels and Green Tobacco Sickness Among Shade Tobacco Workersx
    supporting_text: Cotinine Levels and Green Tobacco Sickness Among Shade Tobacco Workersx
- reference: DOI:10.1590/s0102-311x2010001200005
  title: First reported outbreak of green tobacco sickness in Brazil
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: Dermal absorption of nicotine by people harvesting tobacco may cause an acute intoxication called green tobacco sickness.
    supporting_text: Dermal absorption of nicotine by people harvesting tobacco may cause an acute intoxication called green tobacco sickness.
    evidence:
    - reference: DOI:10.1590/s0102-311x2010001200005
      reference_title: First reported outbreak of green tobacco sickness in Brazil
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Dermal absorption of nicotine by people harvesting tobacco may cause an acute intoxication called green tobacco sickness.
      explanation: Deep research cited this publication as relevant literature for Green Tobacco Sickness.
- reference: DOI:10.3390/ijerph21050606
  title: Qualitative Study to Explore the Occupational and Reproductive Health Challenges among Women Tobacco Farm Laborers in Mysore District, India
  found_in:
  - Green_Tobacco_Sickness-deep-research-falcon.md
  findings:
  - statement: Tobacco farm laborers are primarily women and children working for very low wages.
    supporting_text: Tobacco farm laborers are primarily women and children working for very low wages.
    evidence:
    - reference: DOI:10.3390/ijerph21050606
      reference_title: Qualitative Study to Explore the Occupational and Reproductive Health Challenges among Women Tobacco Farm Laborers in Mysore District, India
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Tobacco farm laborers are primarily women and children working for very low wages.
      explanation: Deep research cited this publication as relevant literature for Green Tobacco Sickness.
📚

References & Deep Research

References

8
DOI:10.1016/j.shaw.2017.06.007
Green Tobacco Sickness Among Tobacco Harvesters in a Korean Village
1 finding
Green Tobacco Sickness Among Tobacco Harvesters in a Korean Village
"Green Tobacco Sickness Among Tobacco Harvesters in a Korean Village"
DOI:10.1038/s43856-024-00584-x
Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness
1 finding
Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness
"Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness"
DOI:10.1080/00039896.1995.9935972
Green Tobacco Sickness: Occupational Nicotine Poisoning in Tobacco Workers
1 finding
Green Tobacco Sickness: Occupational Nicotine Poisoning in Tobacco Workers
"Green Tobacco Sickness: Occupational Nicotine Poisoning in Tobacco Workers"
DOI:10.1080/17512433.2019.1570844
Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics
1 finding
Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics
"Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics"
DOI:10.11606/s1518-8787.2018052000287
Urinary cotinine in tobacco farmers in Southern Brazil
1 finding
To describe urinary cotinine levels in tobacco farmers.
"To describe urinary cotinine levels in tobacco farmers."
Show evidence (1 reference)
DOI:10.11606/s1518-8787.2018052000287 SUPPORT Human Clinical
"To describe urinary cotinine levels in tobacco farmers."
Deep research cited this publication as relevant literature for Green Tobacco Sickness.
DOI:10.1300/j096v10n02_05
Cotinine Levels and Green Tobacco Sickness Among Shade Tobacco Workersx
1 finding
Cotinine Levels and Green Tobacco Sickness Among Shade Tobacco Workersx
"Cotinine Levels and Green Tobacco Sickness Among Shade Tobacco Workersx"
DOI:10.1590/s0102-311x2010001200005
First reported outbreak of green tobacco sickness in Brazil
1 finding
Dermal absorption of nicotine by people harvesting tobacco may cause an acute intoxication called green tobacco sickness.
"Dermal absorption of nicotine by people harvesting tobacco may cause an acute intoxication called green tobacco sickness."
Show evidence (1 reference)
DOI:10.1590/s0102-311x2010001200005 SUPPORT Human Clinical
"Dermal absorption of nicotine by people harvesting tobacco may cause an acute intoxication called green tobacco sickness."
Deep research cited this publication as relevant literature for Green Tobacco Sickness.
DOI:10.3390/ijerph21050606
Qualitative Study to Explore the Occupational and Reproductive Health Challenges among Women Tobacco Farm Laborers in Mysore District, India
1 finding
Tobacco farm laborers are primarily women and children working for very low wages.
"Tobacco farm laborers are primarily women and children working for very low wages."
Show evidence (1 reference)
DOI:10.3390/ijerph21050606 SUPPORT Human Clinical
"Tobacco farm laborers are primarily women and children working for very low wages."
Deep research cited this publication as relevant literature for Green Tobacco Sickness.

Deep Research

1
Falcon ▸
Green Tobacco Sickness (GTS) — Comprehensive Disease Characteristics Report
Edison Scientific Literature 30 citations 2026-05-08T18:34:41.478389

Green Tobacco Sickness (GTS) — Comprehensive Disease Characteristics Report

Target Disease

  • Disease name: Green Tobacco Sickness (GTS)
  • Category: Environmental / occupational intoxication
  • MONDO ID: Not identified from the retrieved sources in this run (gap).

1. Disease information

Overview (current understanding)

Green tobacco sickness is an acute occupational nicotine intoxication occurring primarily during handling/harvest of green (uncured) tobacco, especially when leaves/clothing are wet, leading to transdermal nicotine absorption and systemic cholinergic/toxic effects. It is generally self-limited (often resolving within ~1–2 days), but may require medical care for dehydration or physiologic instability. (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)

Synonyms / alternative names

  • “Green tobacco sickness” (most common)
  • “Green tobacco disease” / “doença da folha verde do tabaco” (Portuguese-language literature term for the same syndrome) (oliveira2010firstreportedoutbreak pages 1-2)

Key identifiers

  • ICD-10/ICD-11, MeSH, MONDO: Not recoverable from the full-text evidence obtained in this run (gap).

Evidence source type

Evidence is derived primarily from: - Human outbreak investigations and case-control studies (e.g., Brazil outbreak) (oliveira2010firstreportedoutbreak pages 1-2) - Occupational cohort/survey studies among farmworkers/harvesters (quandt2000migrantfarmworkersand pages 1-2, fassa2018urinarycotininein pages 1-3, ballard1995greentobaccosickness pages 1-3) - Narrative/expert reviews synthesizing multiple studies (mcmahon2019greentobaccosickness pages 1-6, mcmahon2019greentobaccosickness pages 14-18)

2. Etiology

Disease causal factors (environmental/occupational)

Primary cause: systemic nicotine toxicity from transdermal absorption of nicotine during contact with wet tobacco leaves (and wet clothing contaminated with leaf nicotine). (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)

Key mechanistic note: nicotine can diffuse through the stratum corneum into the bloodstream; absorption increases with skin moisture and damaged skin. (quandt2000migrantfarmworkersand pages 1-2)

Risk factors

Across studies and reviews, risk is increased by: - Harvesting/handling wet leaves and wet clothing/shoes (fassa2018urinarycotininein pages 1-3, ballard1995greentobaccosickness pages 1-3) - Heat/humidity (increasing sweating and dermal absorption; also reduces PPE tolerance) (mcmahon2019greentobaccosickness pages 1-6, ziska2024recentandprojected pages 5-6) - High-intensity contact tasks (e.g., harvesting wet leaves; barn tasks; transporting bales; bundling/tying) (fassa2018urinarycotininein pages 1-3) - Non-smoking status (observed in Brazil outbreak; also seen in other epidemiologic work) (oliveira2010firstreportedoutbreak pages 1-2, fassa2018urinarycotininein pages 1-3) - Younger age and working in wet conditions (Kentucky outbreak) (ballard1995greentobaccosickness pages 1-3)

Genetic risk factors / gene–environment interactions

  • A genetic-polymorphism study exists in the retrieved corpus but genotype-specific associations were not extractable from the evidence snippets available in this run; overall, GTS is best supported as an exposure-driven occupational intoxication rather than a Mendelian disease in the retrieved evidence. (mcmahon2019greentobaccosickness pages 1-6)

Protective factors

  • Avoiding work when plants are wet and reducing skin contact with leaves. (trapecardoso2005cotininelevelsand pages 1-3, ballard1995greentobaccosickness pages 1-3)
  • Personal protective equipment (PPE) (water-resistant/chemical-resistant gloves, aprons, rain suits/boots) and prompt changing of wet clothing are repeatedly recommended in occupational health contexts. (ravi2024qualitativestudyto pages 1-2)
  • Nicotine tolerance from prior nicotine use (e.g., smoking) is sometimes described as potentially protective but is inconsistent and should not be relied upon. (mcmahon2019greentobaccosickness pages 1-6, mcmahon2019greentobaccosickness pages 14-18)

3. Phenotypes

Core clinical phenotype (symptoms/signs)

Common symptoms across outbreak reports and surveys include: - nausea, vomiting - dizziness, headache - weakness/asthenia - pallor and sweating; sometimes hypersalivation

Brazil outbreak report (human outbreak investigation) explicitly lists: “dizziness, weakness, vomit, nausea and headache” as the main observed signs/symptoms. (oliveira2010firstreportedoutbreak pages 1-2)

A 2024 qualitative study (women tobacco laborers, India) summarizes reported symptoms including: “nausea, dizziness, increased salivation, poor appetite, insomnia, and increased sweating.” (ravi2024qualitativestudyto pages 2-3)

Additional/severe manifestations

Severe cases can involve dehydration and physiologic instability; earlier U.S. outbreak work reported hospitalizations and ICU admissions (see epidemiology section). (ballard1995greentobaccosickness pages 1-3)

Temporal pattern

Symptoms typically occur several hours after exposure, often later the same day, and resolve in ~1–2 days; one expert review reports onset often around ~10 hours after exposure and mean duration ~2.4 days. (mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2)

Suggested HPO terms (examples)

  • Nausea (HP:0002018)
  • Vomiting (HP:0002013)
  • Dizziness (HP:0002321)
  • Headache (HP:0002315)
  • Asthenia / Weakness (HP:0025406)
  • Hyperhidrosis (HP:0000975)
  • Sialorrhea (HP:0002307)
  • Abdominal pain (HP:0002027)
  • Diarrhea (HP:0002014)
  • Dehydration (HP:0001944)

(oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3, ravi2024qualitativestudyto pages 2-3)

Quality-of-life impact

Workforce studies emphasize lost work time and functional impairment during symptomatic episodes; among migrant farmworkers, most self-managed but some sought care and missed work. (quandt2000migrantfarmworkersand pages 1-2)

4. Genetic / molecular information

Causal genes / pathogenic variants

  • Not applicable as a primary disease model based on retrieved evidence. GTS is an exposure-mediated intoxication syndrome.

Molecular entities (CHEBI)

  • Nicotine (CHEBI:18723) — principal toxicant in this syndrome (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
  • Cotinine (CHEBI:39941) — primary nicotine metabolite used as exposure biomarker (oliveira2010firstreportedoutbreak pages 1-2, fassa2018urinarycotininein pages 1-3)

5. Environmental information

Environmental/occupational exposure

  • Direct exposure to green tobacco leaves, especially wet leaves, is the key environmental driver; moisture increases dermal uptake. (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)

Lifestyle factors

  • Smoking status is repeatedly associated with differing risk patterns, plausibly via tolerance; however, it is not a recommended preventive strategy. (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6)

Infectious agents

  • Not applicable.

6. Mechanism / pathophysiology

Causal chain (trigger → manifestations)

  1. Trigger: harvesting/handling wet tobacco leaves; sweat/wet clothing increases dermal transfer. (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
  2. Exposure: nicotine crosses the stratum corneum into systemic circulation; absorption varies by body site and increases with moisture/skin damage. (quandt2000migrantfarmworkersand pages 1-2)
  3. Downstream physiology: systemic nicotine affects nicotinic acetylcholine receptor pathways and autonomic function, producing GI symptoms (nausea/vomiting/abdominal symptoms), neurologic symptoms (headache/dizziness/weakness), and sometimes cardiovascular instability. (mcmahon2019greentobaccosickness pages 1-6, ballard1995greentobaccosickness pages 1-3)

Biomarker kinetics / interpretation

  • Cotinine (urine/saliva/plasma) is widely used to assess nicotine exposure, but symptom–biomarker correlation can be imperfect due to timing and tolerance.
  • In a large Brazilian study with urine sampling, overall urinary cotinine means did not differ between symptomatic and asymptomatic groups, but among non-smokers, recent picking was associated with higher cotinine and there was symptom-day–dependent decline patterns. (fassa2018urinarycotininein pages 1-3)

Suggested GO terms (biological processes; high-level)

  • Response to nicotine (GO concept; exact GO ID not validated in this run)
  • Cholinergic signaling
  • Xenobiotic transport and metabolism

Suggested CL (cell types; high-level)

  • Keratinocyte (epidermal barrier/absorption interface)

7. Anatomical structures affected

Primary interface (route of entry)

  • Skin (UBERON concept: skin; epidermis/stratum corneum). (quandt2000migrantfarmworkersand pages 1-2)

Systems affected (clinical manifestations)

  • Gastrointestinal system (nausea/vomiting/abdominal symptoms) (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6)
  • Nervous system (headache, dizziness, weakness) (oliveira2010firstreportedoutbreak pages 1-2, quandt2000migrantfarmworkersand pages 1-2)
  • Cardiovascular/autonomic (occasionally blood pressure/heart-rate instability in severe cases) (ballard1995greentobaccosickness pages 1-3)

8. Temporal development

  • Onset: acute/subacute after work exposure, often later the same day or evening (quandt2000migrantfarmworkersand pages 1-2)
  • Course/duration: self-limited, often ~1–2 days; review estimate mean ~2.4 days (mcmahon2019greentobaccosickness pages 1-6, ballard1995greentobaccosickness pages 1-3)
  • Pattern: episodic, linked to harvesting periods and wet/heat conditions (ballard1995greentobaccosickness pages 1-3, ziska2024recentandprojected pages 5-6)

9. Inheritance and population

Inheritance

  • Not a genetic inheritance condition in the primary disease model; exposure-driven.

Epidemiology (recent data prioritized when available)

Quantitative estimates vary by population, design, and tobacco type: - Kentucky, USA (1992–1993 outbreak): crude incidence 10.0 per 1,000 tobacco workers (1992) and 14.0 per 1,000 (1993); 12 hospitalizations and 2 ICU admissions reported in 1992. (ballard1995greentobaccosickness pages 1-3) - Southern Brazil (cross-sectional, 2014): previous-month prevalence 6.6% (men) and 11.9% (women). (fassa2018urinarycotininein pages 1-3) - Northeastern Brazil (outbreak investigation, 2010): 107 case-patients identified, using urinary cotinine >10 ng/mL in the case definition; cases had higher median urinary cotinine than controls (p<0.05). (oliveira2010firstreportedoutbreak pages 1-2) - North Carolina migrant/seasonal farmworkers (survey): 41% reported GTS at least once during a summer season. (quandt2000migrantfarmworkersand pages 1-2) - Global prevalence ranges (review-level): estimates across settings commonly range roughly 8.2%–47% (review synthesis). (mcmahon2019greentobaccosickness pages 1-6, ravi2024qualitativestudyto pages 1-2)

Demographics / geography

  • Occurs in multiple major tobacco-growing regions (Americas, Asia).
  • Vulnerable groups include migrant/seasonal laborers and children/younger workers (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3), and women workers with PPE access inequities (ravi2024qualitativestudyto pages 1-2).

10. Diagnostics

Clinical diagnosis (typical approach)

A practical clinical approach combines: 1) recent occupational exposure to green tobacco (especially wet leaves/clothing), 2) compatible symptom cluster, 3) supportive biomarker evidence (cotinine), while considering key differentials such as pesticide poisoning and heat illness. (oliveira2010firstreportedoutbreak pages 1-2, ballard1995greentobaccosickness pages 1-3)

Laboratory tests / biomarkers

  • Cotinine measurement in urine, saliva, or blood/plasma is the most common biomarker approach. (oliveira2010firstreportedoutbreak pages 1-2, trapecardoso2005cotininelevelsand pages 1-3, fassa2018urinarycotininein pages 1-3)
  • In the Brazil outbreak investigation, a case-patient definition used urinary cotinine >10 ng/mL (assayed by HPLC) plus clinical diagnosis of acute intoxication during the period. (oliveira2010firstreportedoutbreak pages 1-2)

Differential diagnosis

  • Organophosphate/carbamate pesticide poisoning (symptom overlap)
  • Heat illness/heat exhaustion
  • Acute gastroenteritis or other intoxications

Diagnostic confusion is explicitly raised in occupational studies. (ballard1995greentobaccosickness pages 1-3)

Genetic testing

  • Not indicated as standard-of-care; exposure-mediated condition.

11. Outcome / prognosis

  • Generally self-limited with recovery in ~1–2 days (ballard1995greentobaccosickness pages 1-3).
  • Morbidity can be significant (dehydration, medical visits, lost work); severe outbreaks included hospitalizations and ICU care. (ballard1995greentobaccosickness pages 1-3)

12. Treatment

Supportive management (current practice)

  • Immediate removal from exposure, rest, symptomatic treatment.
  • Rehydration (oral/IV) and antiemetic management as needed.
  • Medical evaluation/admission for severe dehydration or instability. (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)

Experimental / proposed pharmacologic strategies (not standard)

An expert review proposes evaluating nicotine-receptor–targeting agents (e.g., mecamylamine, varenicline, cytisine) and nicotine immunization strategies as research tools/potential therapeutics; these are not established standard care for GTS. (mcmahon2019greentobaccosickness pages 14-18)

Suggested MAXO terms (examples)

  • Supportive care
  • Fluid replacement therapy
  • Antiemetic therapy
  • Occupational exposure cessation

13. Prevention

Primary prevention (most important)

  • Avoid harvesting/handling when leaves are wet where feasible.
  • Use PPE (water-resistant/chemical-resistant gloves; protective outerwear; boots) and change out of wet clothing quickly.
  • Worker education and occupational health training. (ravi2024qualitativestudyto pages 1-2)

System-level implementations

  • Training clinicians to recognize GTS and distinguish it from pesticide poisoning.
  • Occupational surveillance (e.g., poison-center detection reported historically in the U.S. context). (ballard1995greentobaccosickness pages 1-3)

14. Other species / natural disease

No veterinary/animal natural disease analogs were identified in the retrieved sources; GTS is primarily characterized as a human occupational intoxication.

15. Model organisms

No dedicated model organism systems for “green tobacco sickness” as a distinct disease entity were identified in the retrieved sources.

Recent developments and latest research (2023–2024 prioritized)

Climate change as an emerging risk multiplier (2024)

A 2024 paper in Communications Medicine analyzed historical and projected harvest-season climate patterns across major tobacco-growing regions (Brazil, China, India, North Carolina USA) using CMIP6 scenarios and estimated that higher temperatures could increase dermal nicotine absorption. Projected nicotine-uptake increases (proxy-based) were on the order of ~28.7% to ~49.6% under moderate-to-high emissions scenarios, depending on location. (ziska2024recentandprojected pages 5-6)

Interpretation: While based on proxy modeling (therapeutic nicotine patch temperature relationships), the study reframes GTS as a climate-sensitive occupational illness and provides quantitative scenario estimates relevant for long-term planning and worker protections. (ziska2024recentandprojected pages 2-5, ziska2024recentandprojected pages 5-6)

Women’s occupational health and reproductive context (2024)

A 2024 qualitative study of women tobacco farm laborers in Mysore District, India reported GTS symptoms (e.g., headaches, gastric complaints, weakness) and emphasized barriers to PPE access/use and occupational health education, particularly around menstruation, pregnancy, and the postnatal period. (ravi2024qualitativestudyto pages 16-17, ravi2024qualitativestudyto pages 1-2)

Summary artifact for knowledge base population

The following table compiles the most KB-ready facts (definition/synonyms, epidemiology, risks/protection, phenotypes with HPO, diagnostics, management/prevention with MAXO, and chemicals with CHEBI IDs):

Domain Item Details Ontology suggestions Evidence
Definition / classification Green Tobacco Sickness (GTS) Occupational/environmental illness; acute nicotine poisoning caused primarily by dermal absorption of nicotine from wet green tobacco leaves; typically self-limited over 1–2 days, though severe dehydration/hospitalization can occur (oliveira2010firstreportedoutbreak pages 1-2, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3) MONDO: not clearly established in retrieved sources; MeSH/ICD: not confirmed in retrieved sources (oliveira2010firstreportedoutbreak pages 1-2, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
Synonyms Alternative names Green tobacco disease; tobacco harvesters’ acute nicotine poisoning; nicotine poisoning from wet tobacco leaves; Portuguese literature uses “doença da folha verde do tabaco” (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6) Related concept: nicotine poisoning (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6)
Epidemiology Prevalence range across studies/reviews Literature review reported prevalence ranging from 6.6% to 56.9% across included studies; another review cited global prevalence 8.2%–47% (mcmahon2019greentobaccosickness pages 1-6, ravi2024qualitativestudyto pages 1-2) Not applicable (mcmahon2019greentobaccosickness pages 1-6, ravi2024qualitativestudyto pages 1-2)
Epidemiology Southern Brazil, 2014 Previous-month prevalence: 6.6% in men and 11.9% in women among tobacco farmers (fassa2018urinarycotininein pages 1-3) Not applicable (fassa2018urinarycotininein pages 1-3)
Epidemiology Northeastern Brazil, 2018 study population Total prevalence 56.9%; women 71.7%, men 35.3% (oliveira2010firstreportedoutbreak pages 1-2) Not applicable (oliveira2010firstreportedoutbreak pages 1-2)
Epidemiology Kentucky, USA, 1992–1993 Incidence 10.0 per 1,000 tobacco workers in 1992 and 14.0 per 1,000 in 1993; 12 hospitalizations and 2 ICU admissions in 1992 outbreak (ballard1995greentobaccosickness pages 1-3) Not applicable (ballard1995greentobaccosickness pages 1-3)
Epidemiology North Carolina migrant/seasonal farmworkers 41% reported GTS at least once during one summer season (quandt2000migrantfarmworkersand pages 1-2) Not applicable (quandt2000migrantfarmworkersand pages 1-2)
Epidemiology Brazil outbreak count 107 laboratory-supported case-patients identified in outbreak investigation (oliveira2010firstreportedoutbreak pages 1-2) Not applicable (oliveira2010firstreportedoutbreak pages 1-2)
Risk factors Exposure-related Harvesting wet leaves; direct skin contact with tobacco; wet clothing/shoes; heat/humidity; physical exertion; leaf bundling/barn tasks/transporting bales; younger age in some studies (mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, fassa2018urinarycotininein pages 1-3, ballard1995greentobaccosickness pages 1-3) Exposure to nicotine (CHEBI: nicotine) (mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, fassa2018urinarycotininein pages 1-3, ballard1995greentobaccosickness pages 1-3)
Risk factors Individual / contextual Non-smoker status in several studies; male sex in some outbreaks; female sex in some prevalence studies; dermatosis/skin damage; long work history; abnormal BMI; concomitant pesticide contact can complicate risk/recognition (oliveira2010firstreportedoutbreak pages 1-2, quandt2000migrantfarmworkersand pages 1-2, fassa2018urinarycotininein pages 1-3) CL/GO not specific; skin barrier compromise relevant (oliveira2010firstreportedoutbreak pages 1-2, quandt2000migrantfarmworkersand pages 1-2, fassa2018urinarycotininein pages 1-3)
Protective factors Behavioral / occupational Avoiding harvest when leaves are wet; reducing skin contact; prompt change from wet clothes; PPE use (water-resistant clothing, gloves, boots, aprons/rain suits); mechanization proposed as exposure-reduction strategy (trapecardoso2005cotininelevelsand pages 1-3, fassa2018urinarycotininein pages 1-3, ravi2024qualitativestudyto pages 1-2) MAXO: personal protective equipment use; exposure avoidance; health education (trapecardoso2005cotininelevelsand pages 1-3, fassa2018urinarycotininein pages 1-3, ravi2024qualitativestudyto pages 1-2)
Protective factors Biological / tolerance Prior nicotine exposure from smoking or other nicotine use may be partially protective via tolerance in some reports, but protection is inconsistent and not reliable (mcmahon2019greentobaccosickness pages 1-6, mcmahon2019greentobaccosickness pages 14-18) Not applicable (mcmahon2019greentobaccosickness pages 1-6, mcmahon2019greentobaccosickness pages 14-18)
Clinical features Core symptom cluster Nausea, vomiting, dizziness, headache, weakness, pallor, sweating/hypersalivation; often begins several hours after exposure and may peak later the same day/evening (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3) HPO: Nausea HP:0002018; Vomiting HP:0002013; Dizziness HP:0002321; Headache HP:0002315; Asthenia/Weakness HP:0025406; Pallor HP:0000980; Hyperhidrosis HP:0000975; Sialorrhea HP:0002307 (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
Clinical features Additional manifestations Abdominal cramps/pain, diarrhea, chills, poor appetite, insomnia, labored respiration; severe cases may involve dehydration, blood pressure/heart-rate instability, seizures, ICU care (trapecardoso2005cotininelevelsand pages 1-3, mcmahon2019greentobaccosickness pages 1-6, ballard1995greentobaccosickness pages 1-3, ravi2024qualitativestudyto pages 2-3) HPO: Abdominal pain HP:0002027; Diarrhea HP:0002014; Chills HP:0025143; Decreased appetite HP:0004396; Insomnia HP:0100785; Dyspnea HP:0002094; Dehydration HP:0001944; Seizure HP:0001250 (trapecardoso2005cotininelevelsand pages 1-3, mcmahon2019greentobaccosickness pages 1-6, ballard1995greentobaccosickness pages 1-3, ravi2024qualitativestudyto pages 2-3)
Temporal development Onset / course Acute onset after harvest exposure; onset often ~10 hours after exposure; self-limited, mean duration about 2.4 days, usually recovery within 1–2 days (mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3) HPO: Acute episode; recurrent/episodic occupational exposure pattern (mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
Diagnostics Clinical recognition No universally standardized diagnostic criteria in retrieved sources; common approach combines recent tobacco harvest exposure + compatible symptoms + nicotine/cotinine biomarker evidence, while excluding pesticide poisoning and heat illness (oliveira2010firstreportedoutbreak pages 1-2, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3) MAXO not applicable (oliveira2010firstreportedoutbreak pages 1-2, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
Diagnostics / biomarkers Cotinine Cotinine is the main nicotine metabolite and widely used biomarker of nicotine exposure; useful in urine, saliva, blood/plasma, but symptom severity does not perfectly track cotinine because tolerance and timing matter (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6, fassa2018urinarycotininein pages 1-3) CHEBI: cotinine (oliveira2010firstreportedoutbreak pages 1-2, mcmahon2019greentobaccosickness pages 1-6, fassa2018urinarycotininein pages 1-3)
Diagnostics / biomarkers Sample types and thresholds Urine: outbreak case definition used urinary cotinine >10 ng/mL; salivary cotinine used in shade tobacco workers; plasma/blood cotinine also studied; urinary cotinine higher soon after symptom onset and declines over days (oliveira2010firstreportedoutbreak pages 1-2, trapecardoso2005cotininelevelsand pages 1-3, fassa2018urinarycotininein pages 1-3) LOINC not established from retrieved sources (oliveira2010firstreportedoutbreak pages 1-2, trapecardoso2005cotininelevelsand pages 1-3, fassa2018urinarycotininein pages 1-3)
Differential diagnosis Key rule-outs Organophosphate/carbamate or other pesticide poisoning, heat illness/heat exhaustion, dehydration, viral gastroenteritis, other acute intoxications (fassa2018urinarycotininein pages 1-3, ballard1995greentobaccosickness pages 1-3, ravi2024qualitativestudyto pages 2-3) Not applicable (fassa2018urinarycotininein pages 1-3, ballard1995greentobaccosickness pages 1-3, ravi2024qualitativestudyto pages 2-3)
Management Acute treatment Primarily supportive care: removal from exposure, rest, oral/IV rehydration, antiemetics/symptom management, medical evaluation for severe dehydration or cardiovascular instability; evidence base for specific pharmacotherapy remains limited (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3) MAXO: supportive care; fluid replacement; antiemetic therapy; hospital admission when severe (quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
Management Experimental / proposed pharmacology Review proposed studying nicotinic receptor antagonists/partial agonists such as mecamylamine, varenicline, cytisine, and nicotine vaccines, but these are not established standard care for GTS (mcmahon2019greentobaccosickness pages 14-18) MAXO: investigational drug therapy (mcmahon2019greentobaccosickness pages 14-18)
Prevention Worker-level prevention Wear chemical-/water-resistant gloves and clothing, boots, aprons/rain suits; avoid working with wet leaves when possible; change wet clothes quickly; reduce duration/intensity of contact; worker education/first-aid knowledge improves preparedness (trapecardoso2005cotininelevelsand pages 1-3, ballard1995greentobaccosickness pages 1-3, ravi2024qualitativestudyto pages 1-2) MAXO: personal protective equipment use; occupational health education; behavior modification (trapecardoso2005cotininelevelsand pages 1-3, ballard1995greentobaccosickness pages 1-3, ravi2024qualitativestudyto pages 1-2)
Prevention System / policy / implementation Train clinicians to distinguish GTS from pesticide poisoning; improve occupational surveillance; expand PPE access and adoption; community campaigns and educational videos increased farmer first-aid knowledge in Indonesia; mechanization suggested where feasible (fassa2018urinarycotininein pages 1-3, ravi2024qualitativestudyto pages 1-2) MAXO: clinician training; surveillance; preventive counseling; mechanized harvesting (fassa2018urinarycotininein pages 1-3, ravi2024qualitativestudyto pages 1-2)
Recent developments (2023–2024) Climate change and GTS risk 2024 analysis projected higher harvest-season temperatures could increase estimated nicotine dermal absorption by ~28.7%–49.6% under moderate/high emissions scenarios across Brazil, China, India, and North Carolina; rainfall and heat may amplify GTS risk (ziska2024recentandprojected pages 2-5, ziska2024recentandprojected pages 5-6) Environmental exposure context (ziska2024recentandprojected pages 2-5, ziska2024recentandprojected pages 5-6)
Recent developments (2024) Women’s occupational health 2024 qualitative study in Mysore, India documented GTS symptoms among women laborers, especially around menstruation/pregnancy/postnatal periods, and highlighted poor awareness, unequal PPE access, and reproductive-health concerns (ravi2024qualitativestudyto pages 16-17, ravi2024qualitativestudyto pages 2-3, ravi2024qualitativestudyto pages 1-2) HPO terms above; MAXO: maternal occupational health support, PPE provision, health education (ravi2024qualitativestudyto pages 16-17, ravi2024qualitativestudyto pages 2-3, ravi2024qualitativestudyto pages 1-2)
Key chemicals Nicotine Principal tobacco alkaloid causing toxicity after dermal absorption from wet leaves; water soluble and readily absorbed through skin (mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3) CHEBI: nicotine (CHEBI:18723) (mcmahon2019greentobaccosickness pages 1-6, quandt2000migrantfarmworkersand pages 1-2, ballard1995greentobaccosickness pages 1-3)
Key chemicals Cotinine Major metabolite of nicotine used as biomarker in urine, saliva, blood/plasma for exposure assessment (oliveira2010firstreportedoutbreak pages 1-2, fassa2018urinarycotininein pages 1-3) CHEBI: cotinine (CHEBI:39941) (oliveira2010firstreportedoutbreak pages 1-2, fassa2018urinarycotininein pages 1-3)

Table: This table compiles the core structured facts needed for a Green Tobacco Sickness knowledge base entry, including definition, epidemiology, risk/protective factors, phenotypes, diagnostics, treatment/prevention, and ontology term suggestions. It emphasizes evidence-backed details and recent 2024 developments relevant to occupational and environmental health.

Key evidence gaps (for curation)

  • ICD-10/ICD-11, MeSH, MONDO identifiers were not retrievable from the collected sources in this run.
  • Standardized diagnostic criteria and validated cotinine thresholds for toxicity remain non-uniform across studies; timing and nicotine tolerance complicate biomarker interpretation. (fassa2018urinarycotininein pages 1-3, ballard1995greentobaccosickness pages 1-3)
  • Limited controlled intervention evidence for PPE/behavioral strategies within the retrieved full texts.

References (URLs and publication dates)

  • de Oliveira PPV et al. First reported outbreak of green tobacco sickness in Brazil. Dec 2010. https://doi.org/10.1590/s0102-311x2010001200005 (oliveira2010firstreportedoutbreak pages 1-2)
  • Park SJ et al. Green tobacco sickness among tobacco harvesters in a Korean village. Mar 2018. https://doi.org/10.1016/j.shaw.2017.06.007 (park2018greentobaccosickness pages 4-4)
  • Trapé-Cardoso M et al. Cotinine levels and green tobacco sickness among shade tobacco workers. Oct 2005. https://doi.org/10.1300/j096v10n02_05 (trapecardoso2005cotininelevelsand pages 1-3)
  • McMahon LR. Green tobacco sickness: mecamylamine, varenicline, and nicotine vaccine as clinical research tools and potential therapeutics. Jan 2019. https://doi.org/10.1080/17512433.2019.1570844 (mcmahon2019greentobaccosickness pages 14-18)
  • Quandt SA et al. Migrant farmworkers and green tobacco sickness: new issues for an understudied disease. Mar 2000. https://doi.org/10.1002/(sici)1097-0274(200003)37:3<307::aid-ajim10>3.0.co;2-z (quandt2000migrantfarmworkersand pages 1-2)
  • Fassa AG et al. Urinary cotinine in tobacco farmers in Southern Brazil. Aug 2018. https://doi.org/10.11606/s1518-8787.2018052000287 (fassa2018urinarycotininein pages 1-3)
  • Ballard T et al. Green tobacco sickness: occupational nicotine poisoning in tobacco workers. Oct 1995. https://doi.org/10.1080/00039896.1995.9935972 (ballard1995greentobaccosickness pages 1-3)
  • Ziska L, Parks R. Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness. Aug 2024. https://doi.org/10.1038/s43856-024-00584-x (ziska2024recentandprojected pages 2-5, ziska2024recentandprojected pages 5-6)
  • Ravi P et al. Qualitative study to explore the occupational and reproductive health challenges among women tobacco farm laborers in Mysore District, India. May 2024. https://doi.org/10.3390/ijerph21050606 (ravi2024qualitativestudyto pages 16-17, ravi2024qualitativestudyto pages 2-3, ravi2024qualitativestudyto pages 1-2)

References

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