Recent and projected changes in global climate may increase nicotine absorption and the risk of green tobacco sickness

The study investigates how anthropogenic climate change—specifically increases in temperature and rainfall variability—may amplify dermal nicotine absorption among tobacco harvest workers, elevating the risk of green tobacco sickness (GTS). GTS is an occupational illness caused by transdermal nicotine exposure from green tobacco leaves, leading to symptoms such as chills, diarrhea, weakness, salivation, dizziness, and vomiting, with onset within hours of exposure and lasting up to several days. The condition is underrecognized and underreported, with substantial prevalence noted among farmworkers and an estimated >300,000 affected children globally each season. Two key abiotic determinants of nicotine absorption are moisture (from rain/dew and sweat) and high ambient temperatures that increase skin blood flow and preconditioning during labor. While temperature and rainfall are known to affect nicotine transfer, their recent and future changes due to climate change had not been systematically evaluated in relation to GTS. This study assesses recent (since the 1970s) trends and CMIP6-based future projections of harvest-season temperature and precipitation for major tobacco-growing regions (southern Brazil, Yunnan Province in China, Andhra Pradesh in India, and North Carolina, USA) and uses temperature-dependent transdermal nicotine patch data as a proxy to estimate potential changes in nicotine absorption. The purpose is to quantify how climate trends could exacerbate nicotine uptake and GTS risk, with implications for occupational health—particularly among vulnerable groups such as adolescents and young workers.

Study regions: Major tobacco-producing areas with adequate long-term meteorological records were included: southern Brazil (Santa Catarina and Rio Grande do Sul), Yunnan Province (China), Andhra Pradesh (India), and Eastern North Carolina (USA). Indonesia was excluded due to insufficient long-term data. Periods: Recent trends were evaluated over approximately 50 years (circa 1972/1975–2022) during each region’s primary tobacco harvest season. Climate variables: For each site and harvest period, the following were derived from daily data: (1) cumulative maximum temperature (cumulative Tmax), (2) number of high-temperature days above region-specific thresholds (e.g., 35–38 °C, based on early-period exceedances), (3) cumulative rainfall (cm), and (4) number of rain days (occurrence). Projections: Future climate was assessed using CMIP6 ScenarioMIP Tier 1 scenarios (SSP126, SSP370, SSP585) via the KNMI Climate Explorer, using multi-model mean monthly maximum temperature and precipitation on a 1°×1° grid for 2020–2100 and summarized for each region’s harvest season. Nicotine absorption proxy: Because direct measurements of temperature-dependent nicotine absorption from tobacco leaves are unavailable, published relationships for transdermal nicotine patches were used as a proxy to estimate relative percent change in absorption with temperature increases. Comparators included typical harvest conditions, acknowledging long-duration dermal contact with leaves or sweat-soaked clothing over 10–12 hours. A reference nicotine content equivalency was noted (e.g., 22.5 cm² patch with 7–21 mg nicotine; comparable tobacco leaf area at ~4% nicotine contains ~5.7 mg). Statistical analysis: For recent trends, first- or second-order regression (best fit) models were used to estimate temporal changes in cumulative Tmax, high-temperature day counts, cumulative rainfall, and rain-day occurrence during harvest seasons. Seasonal means and slopes over time were calculated; significance was assessed (reported where applicable with correlation coefficients R and P-values). For projections, differences in average monthly maximum temperature and rainfall during harvest seasons were evaluated across SSP scenarios, and corresponding percent changes in nicotine absorption were estimated using the temperature–absorption proxy. Data and tools: Observational meteorology from regional weather stations (n≈4 per region) and CMIP6 outputs were accessed and processed using KNMI Climate Explorer. Source data and analysis code are available via the cited GitHub repository and Zenodo archive.

- Recent (1972/1975–2022) harvest-season trends: - Southern Brazil: Significant increases in all four metrics—days above 35 °C (R=0.49, P<0.01), cumulative Tmax (R=0.58, P<0.01), cumulative rainfall (R=0.34, P<0.025), and rain occurrence (R=0.52, P<0.001). - Yunnan, China: Increases observed in days >30 °C, cumulative maximum temperature, and cumulative rainfall across 1972–2022. - Andhra Pradesh, India: Significant increases in cumulative rainfall and number of rain days; temperature thresholds analyzed (including days >38 °C) indicate warming. - Eastern North Carolina, USA: Recent trends in days >30 °C, cumulative Tmax, and concurrent rainfall changes documented (Fig. 7 referenced). - Future projections (CMIP6): - Southern Brazil: Significant increases in average monthly maximum temperatures for SSP370 and SSP585; average monthly rainfall shows an increasing trend, significant under SSP585. - Yunnan, China: Significant increases in average monthly maximum temperatures through 2100 for SSP370 and SSP585; average monthly rainfall projected to increase under all SSPs. - Andhra Pradesh, India: Significant increases in monthly maximum temperatures for SSP370 and SSP585; rainfall projections equivocal. - Eastern North Carolina, USA: Projected increases in maximum temperatures and changes in rainfall during harvest season (figural results presented). - Estimated percent increases in nicotine absorption (temperature–patch proxy) associated with projected Tmax increases during harvest: - Brazil: SSP126 +0.5 °C → +5.5%; SSP370 +4.2 °C → +41.15%; SSP585 +5.5 °C → +49.89%. - China (Yunnan): SSP126 +1.0 °C → +9.9%; SSP370 +4.1 °C → +40.49%; SSP585 +5.4 °C → +49.11%. - India (Andhra Pradesh): SSP126 +0.4 °C → +3.9%; SSP370 +2.9 °C → +28.78%; SSP585 +3.9 °C → +38.89%. - USA (Eastern NC): SSP126 +0.7 °C → +7.1%; SSP370 +3.7 °C → +36.56%; SSP585 +4.6 °C → +49.99%. - Overall implication: Across continents, recent warming and rainfall increases during harvest, together with projected warming under SSP370/SSP585, are consistent with substantial increases in dermal nicotine absorption. Under SSP585, absorption increases approach ~50% by late century, implying elevated GTS risk, particularly for younger workers.

The findings support the hypothesis that climate change—through higher ambient temperatures and altered precipitation patterns during tobacco harvest—will increase conditions that favor dermal nicotine transfer, thereby elevating the risk and potential burden of green tobacco sickness (GTS). Observed increases in extreme heat days, cumulative thermal load (cumulative Tmax), and moisture exposure (rainfall totals and rain-day frequency) in key tobacco-growing regions already coincide with factors known to enhance transdermal absorption (greater skin blood perfusion with heat, increased moisture from dew/rain and sweat). Projections under CMIP6 pathways (notably SSP370 and SSP585) indicate continued increases in harvest-season maximum temperatures across regions, with rainfall also increasing in several cases. Using temperature-dependent transdermal patch data as a proxy, the study quantifies how incremental warming could substantially elevate nicotine absorption (often >35% under higher-emissions scenarios by 2100), directly translating to increased GTS risk. These results are particularly relevant for vulnerable populations such as children and adolescents, who have heightened sensitivity to heat, limited thermoregulation, and potentially greater skin permeability, and who may face additional risks like dehydration from GTS-related vomiting. The underrecognition and underreporting of GTS further complicate public health responses, while factors such as experience, age, skin exposure, PPE availability and use, and workplace practices modulate individual risk. The study highlights the need for targeted occupational health interventions (e.g., heat mitigation, moisture management, PPE, education about GTS), improved surveillance, and adaptation planning in tobacco-farming communities to address the compounding risks from a warming climate.

This study links recent and projected climate changes during tobacco harvest seasons to increased potential nicotine absorption and elevated risk of green tobacco sickness across multiple major producing regions. By integrating long-term observational trends with CMIP6 projections and a temperature–absorption proxy, the work provides quantitative estimates of how warming—especially under higher-emission scenarios—could raise GTS risk by up to ~50% by late century. The findings underscore the urgency of enhancing occupational protections, training, and access to PPE; improving recognition and reporting of GTS; and prioritizing the health of child and adolescent workers. Future research should: (1) directly measure temperature-dependent nicotine absorption from tobacco leaves in field settings; (2) refine exposure models by incorporating demographics, work practices, skin exposure, and PPE effectiveness; (3) expand multi-sectoral impact assessments (e.g., ISIMIP) integrating climate, labor, and health data; and (4) evaluate and implement adaptation strategies to reduce heat and moisture exposure during harvest.

- Proxy for absorption: Temperature effects on nicotine absorption were estimated using transdermal patch data rather than direct measurements from tobacco leaf contact; actual field conditions (variable contact area, intermittent wetting, sweat, clothing) may differ. - Underreporting and poor case ascertainment: GTS incidence and severity are not well characterized, limiting validation of climate-linked risk estimates. - Model and scenario uncertainties: CMIP6 projections carry inherent uncertainties; rainfall projections, in particular, were equivocal in some regions (e.g., Andhra Pradesh), and local microclimates may differ from gridded outputs. - Regional data limitations: Analyses relied on approximately four weather stations per region; observational coverage and quality may affect trend estimates. - Heterogeneity in thresholds and seasons: Temperature thresholds (e.g., 30–38 °C) and harvest periods vary by region; comparisons across sites may be affected by differing baselines. - Individual-level modifiers: Factors such as age, acclimatization, skin integrity, smoking history, and PPE use were not directly modeled but can substantially influence absorption and GTS risk.