Health burden of sugarcane burning on agricultural workers and nearby communities

Abstract

Sugarcane is the most widely cultivated crop in the world, with equatorial developing nations performing most of this agriculture. Burning sugarcane is a common practice to facilitate harvest, producing extremely high volumes of respirable particulate matter in the process. These emissions are known to have deleterious effects on agricultural workers and nearby communities, but the extent of this exposure and potential toxicity remain poorly characterized. As the epidemicof chronic kidney disease of an unknown etiology (CKDu) and its associated mortality continue to increase along with respiratory distress, there is an urgent need to investigate the causes, determine viable interventions to mitigate disease andimprove outcomes for groups experiencing disproportionate impact. The goal of this review is to establish the state of available literature, summarize what is known in terms of human health risk, and provide recommendations for what areas should be prioritized in research.

Keywords:

• Particulate matter
• silica
• environmental health
• biomass burning
• chronic kidney disease
• CKDu
• mesoamerican nephropathy
• climate

Introduction

Sugarcane is a majorcrop in the global agricultural landscape, essential for meeting the world’s growing demand for sugar and bioenergy. Most of this agriculture is performed in equatorial developing nations with workers that have been economically marginalized performing the most difficult and hazardous jobs. Sugarcane agriculture workers often face extreme labor conditions including excessive physical exertion in extreme heat that results in dehydration and kidney injury (García-Trabanino et al. 2015; Leite, Zanetta, Trevisan, et al. 2018; Glaser et al. 2020). Furthermore, these workers are exposed to a variety of potential toxicants (i.e. pesticides, heavy metals, and ash) with minimal personal protective equipment (PPE)(Schaeffer et al. 2020; Imbulana and Oguma 2021). These occupational exposures have gained recent attention as rates of injury and disease among this population increase (Leite, Zanetta, Trevisan, et al. 2018). Concerns regarding worker conditions have grown as climate change and demand for more efficient harvests put added pressure on agricultural communities.

One such concern is exposure to sugarcane ash generated during the conventional practice of pre-harvest burns. Sugarcane fields are routinely burned to facilitate manual cropharvesting. Most of the ash from burning is respirable and represents a major respiratory exposure for both field workers and nearby communities. As such, it is no surprise that sugarcane ash has been suspected of being a contributor to poor health outcomes among nearbyagricultural communities (Le Blond et al. 2017). Determining this has proven difficult however, due to minimal scientific literature, variable sugarcane ash composition, limited understanding of physicochemical properties, unknown extent of human exposure, and a lack of medical resources in the areas where exposure is most common. Filling these gaps in knowledge is becoming increasingly urgent, as risks of exposure are likely to grow alongside the demand for sugar and interest in sugarcane biomass for green chemistry applications. To support public health and protect at-risk populations, it is crucial to understand the potential consequences of sugarcane ash exposure.

The goal of this review is to consolidate and summarize current literature on the properties of sugarcane ash, scope of human exposure and health outcomes, and potential mechanisms of toxicity. In doing so, the most pressing gaps in literature can be identified and recommendations can be made for how the scientific community can best proceed.

Sugarcane burning

Sugarcane production has increased over the past several decades from roughly 0.6 million tons in the early 1970s to approximately 1,800 million tonsin 2017 and generating approximately 279 million metric tons of biomass (Figure 1) (Chandel et al. 2012; de Matos et al. 2020). Crops are primarily grown in tropical and subtropical regions between 22° N and S of the equator: with most growth in Brazil (40%), India (20%), and China (6%) but also many other countries in Central America, the United States and other parts of Asia (Souza et al. 2012; FAO FAOSTAT). To generate end-stage products (biomass and subsequent industrial/commercial materials), most sugarcane fields undergo preharvest burning, though shifts toward mechanical harvesting where burn is not required are beginning and utilized in more developed countries (Souza et al. 2012).

Figure 1. FAOSTAT estimation of global sugarcane crop biomass b-urned each year measuredaskilo tons of dry matter.

The burning process removes leaf surplusfrom the stalk and slows the degradation of sucrose allowing more time for harvest. This burning generates sugarcane straw ash (SCSA) and is responsible for notable increases in particulate matter (PM) into the atmosphere. Leaves, prior to burning, contain between 0.45 and 1.8% wt of silica (SiO₂) depending on soil quality, concentrations of soil silicon, sugarcane cultivar, fertilizer, and climate (Le Blond et al. 2010; Bortolotto Teixeira et al. 2021). After burning, total silica content of SCSA by % weight is approximately 70% (Villar-Cociña et al. 2008). While most of the silica found in sugarcane crops is of the amorphous form, crystalline silica can be found up to 3.5% of total silica content with increases possible if burning reaches 1000°+C when amorphous silica can transition to crystalline forms (Le Blond et al. 2010).

Physicochemical properties

Of the major contributing components from the burning process, PM is critically important. Particulate matter can be roughly divided into three categories: (i) particulates capable of getting into the thoracic regions (nose and mouth), (ii) those inhalable and able to reach to the bronchi, (iii) and those respirable and able to reach the deepest parts of the lung where gas exchange occurs. Crop burning increases ultrafine PM (PM_2.5)from approximately 8 µg/m³ prior to harvesting to roughly 23.58 µg/m³ in nearby towns and greater than 60 µg/m³ in the fields where most workers remain during the harvest process (Prado et al. 2012). Burning occurs in two combustion phases: flaming, where temperatures are higher and a reaction between a homogenous gas and an oxidizer occurs, releasing additional heat; and smoldering, where flameless, lower heat leads to a heterogenous reaction between a solid fuel and an oxidizer, usually leading to more toxic compounds getting released (Santoso et al. 2019). Particulate matter from preharvest burning contains silica, carbonaceous material, KCl, NaCl, oxides such as Mg and Fe, unburned hydrocarbons (UHC), and some fibrous materials, each emitted during both flaming and smoldering phases (Le Blond et al. 2017). A recent study, matching closely with other similarly performed analyses, showed that average values of emission factors (g/kg of burned dry biomass) of CO₂, CO, NO_x, UHC, and PM_2.5 were 1303, 65, 1.5, 16, and 2.5, respectively (França et al. 2012). Of the total mass of PM, roughly 16% of SCSA is considered respirable while 2% of PM from bagasse ash is respirable (Le Blond et al. 2017).

The high concentration of silica in sugarcane ash is a primary concern as inhalation of silica is known to lead to adverse respiratory health, perturbations in kidney function, and potential cancer risk (Leung et al. 2012). Crystalline silica maintains long-range order throughout its atomic structure and therefore has a predictable density allowing for deformations to be precisely located and biochemical interactions to be better predicted (Table 2). Contrary to the crystalline form, amorphous silica contains short-range order where predictability of atomic structure is lost; deformations appear random; and reactivity, specifically at the surface, may increase (Figure 3)(Lunt et al. 2018). Both crystalline and amorphous silica exist at nano and micron scales, with increased surface to volume ratios at the nano scale leading to increased reactivity in biological conditions.

Crystalline silica has been well-characterized and studied with a vast array of knowledge of physicochemical properties as well adverse health outcomes. Unlike crystalline forms, however, there is still comparatively little known of the potential adverse outcomes of amorphous silica (Dong et al. 2020). Recent studies have indicated a mostly size and dose-dependent cytotoxic response to amorphous silica, most likely related to the increased propensity for chemically reactive surface groups (Waters et al. 2009; Li et al. 2011; Li et al. 2016; Li et al. 2019).

Of the surface moieties onsilica, hydroxyl groups, termed silanols, are of increased interest in recent decades for their high chemical reactivity. Silanols are formed either through condensation polymerization or rehydroxylation of dehydroxylated silica (Zhuravlev 2000). New research has shown that disorganization of the long-range spatial arrangement of silanols on the silica surface could induce toxicity leading to membrane lysis, inflammatory cytokine release from macrophages, reactive oxygen species (ROS) generation, and lung damage in rats (Pavan et al. 2020).

Bioenergetic potential

The remaining biomass after burning can be further refined to produce liquid fuels, chemicals, and synthetic materials (e.g. ethanol, xylitol, acids, and enzymes) (Chandel et al. 2012; Zhu and Pan 2022). Because of the renewable and carbon neutral aspects of biomass, sugarcane production is expected to increase by 21.3% over the next decade (de Matos et al. 2020; Favero et al. 2020).

While sugar and ethanol are the primary products of sugarcane processing, the potential for additional streams of energy exist in residual biomass fractions like (i) straw ash, (ii) bagasse ash, (iii) vinasse, and (iv) filter cake from sugarcane juice clarification (Formann et al. 2020). The products of these biomasses have been studied and have diverse applications ranging from adsorbents, resins, cements, and polymers and they have the potential to drastically decrease global energy demand while improving sustainability and increasing environmental conservation (Ajala et al. 2021).

Occupational and community exposure

The harvest of sugarcane requires several distinct jobs with different degrees of sugarcane ash exposure risk. Field workers are generally considered to be at much higher risk of this occupational ash exposure than support staff or positions in subsequent processing and refinement, thus most public health studies have focused on this group. Among field workers, those performing the job of burned cane cutter have been found to experience the greatest inhalation burden due to initiating harvest burns, cutting/stacking burnt sugarcane stalks, and spreading the ash back over the field (Figure 2). The height of PM exposure occured during burning, with a 1-h time weighted average (TWA) of 1807 µg/m³ for fine PM (PM₁₀)(Le Blond et al. 2017). While workers do not exclusively labor during active burn times, PM₁₀ concentrations remain relatively high during routine cutting with 1-h TWAs of 123 µg/m³(Le Blond et al. 2017). The majority of these particles seem to be respirable, with PM_2.5 values found to be consistently in the range of 100 µg/m³ during harvest (Leite et al. 2015; Leite, Zanetta, Antonangelo, et al. 2018). It is important to note these exposures are chronic (recurring each harvest season) and further exacerbated by non-mechanized harvest methods, requiring heavy manual labor and elevated breathing rates in close proximity to ash sources.

Figure 2. Photograph of burnt cane harvesters in Nicaragua demonstrating the high potential for ash inhalation.

Figure 3. TEM Images of particles demonstrate the highly uniform nature of pristine manufactured SiNPs compared to the much more heterogeneous structure of environmentally relevant SiNPs derived from sugarcane ash.

Sugarcane fields are rarely far from agricultural communities, while this is beneficial for harvest efficiency and worker convenience, it also exposes the local population to emissions from sugarcane burning. Sugarcane burning has been found to negatively impact air quality in cities across Central America, South America, South Africa, and Asia (Flores-Jiménez et al. 2019; Shikwambana et al. 2021; Sahu et al. 2021; Souto-Oliveira et al. 2023). Ambient levels of PM₁₀ in nearby cities during the harvest season have been found to be around ∼60µg/m³ and PM_2.5 exceeding 45 µg/m³, with the majority of particles determined to be of sugarcane origin (Lara et al. 2005; Vasconcellos et al. 2010; Souza et al. 2014; Le Blond et al. 2017; Adegboye 2022). In more rural communities, PM₁₀ averaged ∼45 µg/m³ with PM_2.5 measuring ∼25µg/m³ in local towns and ∼60µg/m³ on the plantations themselves (Prado et al. 2012; Leite, Zanetta, Antonangelo, et al. 2018). Even in the southern United States, where more stringent regulations may mitigate effects, PM₁₀increased ∼50% during the harvest season and sugarcane fires contributed an amount of PM_2.5 comparable to motor vehicles (Gullett et al. 2006; Sevimoglu and Rogge 2015; Hiscox et al. 2015; Sevimoglu and Rogge 2016; Nowell et al. 2022; Adegboye 2022; Pinakana et al. 2023).

In addition to particulate matter, sugarcane fires are known to produce a vast array of harmful emissions including volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), carbon and nitrogen oxides, and various other compounds (de Andrade et al. 2010; Silva et al. 2010; Cristale et al. 2012; Pestana et al. 2017; Sahu et al. 2021; Nowell et al. 2022; Geldenhuys et al. 2023). Sugarcane fires have also been associated with elevated silica in nearby groundwater and silicon in the urine of local population (Smpokou et al. 2019; Nikagolla et al. 2020). This is unsurprising as amorphous silica is the primary component of sugarcane ash, but is concerning given silica’s posited role in anepidemic of kidney diseaseof unknown etiology (CKDu) and its impact on increased mortalityamong agricultural workers in these areas (Mascarenhas et al. 2017; Schaeffer et al. 2020; Imbulana and Oguma 2021; Seroka et al. 2022a, 2022b; Rogers et al. 2023).

Biomass use and increasing exposure risks

The process of sugarcane harvest produces a large volume of byproducts, the most abundant of these being the burnt remains of biomass not suitable for sugar or ethanol refinement. This residual waste ash is known as bagasse and is largely used to fertilize the fields in preparation for the next crop. Recently, however, there has been discussion about how this material could prove useful in a variety of green chemistry applications. Sugarcane bagasse has been used as a construction material for quite some time, serving as an environmentally friendly and economical supplement in cement (Xu et al. 2018; Bheel et al. 2022). This supplementation results in a cementitious material with durability and physical properties at least equivalent to standard cement, making it highly desirable (Ferreira-Ceccato et al. 2011; Amin et al. 2020; Farrant et al. 2022). Sugarcane bagasse biomass also has value in energy production, paper mills, and adsorbent applications (Ezeonuegbu et al. 2021; Mahmud and Anannya 2021; Ajala et al. 2021; Elshabrawy et al. 2023). Even the silica which has been investigated as a potential contributor toCKDu, has highly prized physicochemical properties for use in everything from medicine to dye once it is purified from bagasse (Chindaprasirt and Rattanasak 2020; Seroka et al. 2022a, 2022b; Malpani and Goyal 2023). While these are commendable applications for a material often considered “waste”, they also represent new potential inhalation exposures. If new industries begin to emerge centered around sugarcane bagasse processing, it could result in a new wave of occupational and community exposures with the accompanying risks discussed in previous sections. This is precisely why it is important that we achieve a better understanding of the potential toxicity of sugarcane ash exposure.

Sugarcane ash is already considered to be a substantial respiratory burden for sugarcane fieldworkers, but the extent of such exposures beyond those in the immediate vicinity and the full range of potential health effects are still being investigated. Initial studies focused on sampling respirable particles during sugarcane burning and ambiently throughout the harvest season, demonstrating clear occupational exposure risks for nearby workers. However, subsequent investigations found evidence of elevated particulate matter in cities miles away from sugarcane fires, revealing a greater scope of exposure than was originally considered. These sugarcane emissions have been linked to a range of poor health outcomes in the cardiopulmonary and renal systems of exposed populations (Figure 4). It is feasible that sugarcane smoke could be carried a great distance from the source fires and still represent a significant health hazard. These exposure risks become increasingly salient as climate change results in increased temperatures and drought risks, particularlyin the areas where sugarcane is harvested, which could exacerbate heat stress, dehydration, PM exposure, and other conditions which compound the risk of ash exposure. At the same time, the growing demand for sugar and bioenergy places additional pressure on agricultural communities for more efficient harvests, expanding populations at risk of exposure. Together, these factors make for a potential health crisis, with most of this burden falling on under-resourced communities.

Figure 4. Potential exposure routes of silica nanoparticles and observed health effects.

Health outcomes

Pulmonary effects

In the case of biomass burning and ash inhalation, the respiratory system is the first line of defense and lung damage is a common outcome. Sugarcane fires are thought to be linked to adverse pulmonary effects in local residents as they are often accompanied by symptoms of respiratory distress, acute respiratory illness, and increased hospital admissions (Arbex et al. 2007; de Aragão Umbuzeiro et al. 2008; Riguera et al. 2011; Mnatzaganian et al. 2015). These emissions are associated with increased mortality, contain mutagenic compounds, and seem to be of similar toxicity as those produced by traffic (de Aragão Umbuzeiro et al. 2008; Mazzoli-Rocha et al. 2008; Nowell et al. 2022). These effects are particularly pronounced among susceptible populations such as the young/elderly or those with preexisting respiratory disorders, further exacerbating episodes of respiratory distress (Long et al. 1998; Boopathy et al. 2002; Cançado et al. 2006; Mazzoli-Rocha et al. 2008). It is likely that this is a general response to PM exposure rather than a more specific allergic reaction, as workers in a sugarcane processing factory that were exposed to bagasse were found to demonstrate similar signs of respiratory distress (shortness of breath, rhinitis symptoms, etc.) and impaired pulmonary function without increased levels of IgE or indications of atopy (Patil et al. 2008; Gascon et al. 2012; Debela et al. 2023).

During the harvest season, sugarcane field workers were found to have significantly impaired nasal mucociliary clearance, altered mucus properties, and impaired respiratory system barriers that could increase susceptibility to particle exposure (Goto et al. 2011; Ferreira-Ceccato et al. 2011). In both sugarcane workers and nearby town residents, mucus became more acidic and mRNA levels of MUC5AC, MUC1, and MUC16 increased over the harvest season (Matsuda et al. 2020). Such changes are consistent with a protective response to PM exposure and have been found to occur following increased oxidative stress, resulting in pro-inflammatory responses (Kim et al. 2017). Indeed, antioxidant enzyme activity (i.e. catalase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase) have all been found to decrease among sugarcane workers and nearby residents during the harvest season (Prado et al. 2012). This was accompanied by symptoms of respiratory distress, increased plasma malonaldehyde (a lipid peroxidation product), and, in the case of sugarcane workers, elevated urinary 1-hydroxypyrene indicating PAH exposure (Prado et al. 2012; Paula Santos et al. 2015). Sugarcane farmers also seem to be at increased risk of developing lung cancer (Amre et al. 1999).

Adverse pulmonary responses to sugarcane ash inhalation are worth monitoring and characterizing, but thus far do not seem to be distinct from general PM induced effects. Fine particulate matter (PM_2.5) generated from fossil fuel combustion (e.g. automotive and factory emissions) can be deposited in the lungs following inhalation, induce respiratory distress, and exacerbate respiratory diseases (Pope et al. 2002; Kyung and Jeong 2020). The primary mechanisms of PM induced health effects are comparable to those seen in ash exposed populations, including ROS generation, reduced antioxidant activity, induction of lipid peroxidation, increased inflammation, and altered MUC5ACexpression (Rogers and Cismowski 2018; Leikauf et al. 2020; Hu et al. 2023). The one distinction between exposure to fine PM and sugarcane ash was change in concentration of CC16, an anti-inflammatory protein whose deficiency is associated with impaired lung function (Voraphani et al. 2023). Sugarcane harvesting was associated with reduced CC16 concentration in urine and plasma, while acute exposure to PM has been associated with increased serum CC16 concentration (Wang et al. 2017; Leite, Zanetta, Antonangelo, et al. 2018). This may be due to differences in chemical composition, whereas elemental composition of ambient PM is far more heterogeneous, while sugarcane ash is primarily comprised of amorphous silica (Xu et al. 2018; Zhang et al. 2020). Interestingly, reduced serum CC16 was found to occur in other silica-exposed workers, which could indicate the silica in sugarcane ash yields a distinct response and should be further investigated (Bernard et al. 1994).

Cardiovascular effects

While literature is limited, available studies investigating PM exposure and health effects among sugarcane workers have found some evidence of cardiovascular perturbation. Sugarcane workers have been found to lose weight and increase peak VO₂ (cardiovascular fitness indicator) over the harvest season (Barbosa et al. 2012). Despite this, workers also demonstrated increased resting heart rates, higher blood pressure, and evidence of increased blood viscosity (Barbosa et al. 2012; Leite et al. 2015; Leite et al. 2018). Hematocrit was also found to decrease over the harvest season, both acutely and chronically, consistent with previous indications of alveolar inflammation (Leite et al. 2015; Leite, Zanetta, Antonangelo, et al. 2018). Pro-inflammatory state was further indicated by increased concentrations of monocytes and neutrophils (Paula Santos et al. 2015; Leite et al. 2015; Leite, Zanetta, Antonangelo, et al. 2018). Increased oxidative stress and inflammatory mediators, as demonstrated in both these studies, are known to induce negative cardiovascular effects (Barbosa et al. 2012; Basith et al. 2022). Thus it is unsurprising that sugarcane fires are associated with increased cardiovascular-related hospitalizations (Pestana et al. 2017). However, it is once again unclear whether any of these effects are specific to sugarcane burning or are just a function of the well documented cardiovascular risks of PM exposure (Du et al. 2016). Agricultural workers experience a wide range of potentially hazardous occupational exposures, because of this, more literature is desperately needed to determine the contribution of sugarcane ash inhalation to the potential cardiovascular impacts (Leite et al. 2018).

Renal effects

The majority of information regarding health effects of ash exposure in sugarcane workers is the association with deleterious effect on the kidney (Schaeffer et al. 2020). Sugarcane workers experience disproportionate rates of chronic kidney disease (CKD), particularly chronic kidney disease of unknown etiology (CKDu) which is unrelated to traditional risk factors such as age, diabetes or hypertension (López-Marín et al. 2014; Wesseling et al. 2015; Wesseling et al. 2016; Johnson et al. 2019). Kidney biopsies have found the disease presents with varying degrees of glomerulosclerosis, tubulointerstitial nephritis, fibrosis, and an absence of immune deposits (López-Marín et al. 2014; Selvarajah et al. 2016; Wijkström et al. 2017; Fischer et al. 2017). Field workers, especially cane cutters, have been found to have higher rates of proteinuria, increased serum creatinine, decreased estimated glomerular filtration rate (eGFR), and other biomarkers consistent with chronic kidney injury (Peraza et al. 2012; Laws et al. 2015; Paula Santos et al. 2015; Laws et al. 2016; Kupferman et al. 2018; López-Gálvez et al. 2021; Raines et al. 2023). Serum creatinine and eGFR are the most consistent reported markers, but neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), and IL-18 were frequently found to be elevated as well (Laws et al. 2016; Wesseling, Aragón, González, Weiss, Glaser, Bobadilla, et al. 2016; Wesseling et al. 2016). Decreasing hematocrit, which has been associated with sugarcane harvest, is yet another feature which has been observed in CKDu and impaired renal function (Hsu et al. 2001; Leite et al. 2015; Leite, Zanetta, Trevisan, et al. 2018; Gunawickrama et al. 2022). The cause of these renal effects remains unclear, with heat stress, dehydration, and exertional injuries often cited as primary contributors (García-Trabanino et al. 2015; Wesseling, et al. 2016; Wijkström et al. 2017; Chapman et al. 2021).

Sugarcane ash induction of renal damage is intriguing as the relationship between PM exposure and kidney function is not well explored. If PM is small enough, it does have the potential to penetrate the circulatory system and be distributed throughout the body (Magalhaes et al. 2018). Such particles could easily reach the nephron, evade glomerular filtration and be taken up by renal tubular cells, potentially damaging renal function (Kim 2017). While there is some association between PM_2.5 exposure and occurrence of CKD, many studies demonstrate contradictory results and CKD events generally occur alongside the traditional risk factors of age and diabetes (Bowe et al. 2018; Rasking et al. 2022). This appears distinct from the increased risk of CKDu among sugarcane workers which occurs predominantly among young and otherwise healthy individuals, suggesting that increased CKDu prevalence may go beyond PM exposure or be unique to sugarcane ash. Heat stress, dehydration, and exertion are known to cause kidney injury and may be contributing to this disease, but such factors are not unique to sugarcane workers. Previous studies have investigated occupational heat stress and dehydration in similar occupations and found their CKDu risk to be significantly lower than farmers (De Silva et al. 2022). Wildland firefighters are exposed to high levels of smoke exposure, at risk for dehydration, and perform strenuous activities in extreme heat (Horn et al. 2013; Walker et al. 2016; Navarro et al. 2019). While this group has demonstrated increase cardiopulmonary risks consistent with sugarcane ash findings, there is no such evidence of increased risk of kidney disease (Navarro et al. 2019; Navarro 2020; Pinkerton et al. 2022). However, there are ongoing studies which are currently investigating this topic (Navarro et al. 2022). CKDu has also been found in individuals without significant heat stress. Interestingly, the histopathology appears distinct from chronic dehydration injuries and several studies have argued that an environmental toxicant is likely to contribute to pathogenesis (Herath et al. 2018; Broe and Vervaet 2020; Pett et al. 2022; Schreurs et al. 2023).

Silica content in sugarcane ash is far higher than wildfire ash making this a major distinction in the exposure among sugarcane workers anda potential contributor to increased risk of CKDu (Harper et al. 2019; Seroka et al. 2022a, 2022b). Indeed, silica nanoparticles have been recently reported to be found in the kidney of sugarcane agricultural workers (Rogers et al. 2023). These findings are consistent with elevated silica in agricultural communities’ water sources and higher silicon levels in the urine of individuals at risk of CKDu (Smpokou et al. 2019; Nikagolla et al. 2020). This also indicates that a major route of sugarcane ash exposure could be ingestion, such as groundwater contamination or ash deposition. Alternative exposures to ash inhalation may explain why observed pulmonary symptoms are often subclinical and relatively minor compared to CKD. The potential role of sugarcane ash in the CKDu epidemic is particularly concerning as kidney diseases are particularly devastating to those of low socio-economic status, who experience disproportionate exposure rates and financial barriers limiting access to appropriate medical care (Mckee and Paasche-Orlow 2012; Krinsky and Levine 2014; Aguilar and Madero 2019; Ranasinghe et al. 2019; Abdissa 2020; Kovesdy 2022).

Toxicological effects of sugarcane ash exposure

Current understanding of sugarcane ash toxicity relies heavily on observational studies and risk factor associations. Such investigations have been invaluable in the initial identification of an issue, but this body of literature is lacking in terms of mechanistic insights. As discussed in previous sections, occupational and public health studies have demonstrated clear hazards of sugarcane ash inhalation such as increased rates of cardiovascular disease, pulmonary distress, kidney injury, and systemic inflammation. Experimental studies are now required to further our understanding of potential mechanisms responsible for observed health changes. In vivo and clinical investigations will be needed to perform in-depth characterization of pathophysiological changes and to maintain physiologic relevance. While in vitro experimentation allows for a more controlled environment and is ideal for examining toxicity of different components of sugarcane ash as well as specific mechanisms and pathways. Bridging these knowledge gaps will help to identify key risk factors, early warning signs, and design effective interventions to better protect the disproportionately affected.

Clinical investigations

Most research into sugarcane ash toxicity is relatively recent, despite sugar production and processing having been a major industry for quite some time. Interestingly, medical concerns about bagasse exposure occurred as early as 1941, with clinicians reporting a respiratory condition in factory workers who experienced a high degree of bagasse inhalation (Lemone et al. 1947). The term “bagassosis” was used to describe this disease and it was thought to be due to particulate matter, microorganisms, silica, allergic reactions, or some combination thereof (Madu and Sharman 2023). Cases began to emerge across the world and were the subject of several clinical investigations, yet the specific cause remained unknown (Gillison and Taylor 1942; Sodeman 1967). This disease nearly vanished in the 1970s, likely due to different storage methods, improved ventilation, increased mask use, and other improved safety measures which reduced bagasse dust exposure (Lehrer et al. 1978; Madu and Sharman 2023). Similarly, interventions have been attempted with sugarcane workers, to reduce rates of kidney injury (Sorensen et al. 2019; Glaser et al. 2020). However, such approaches have not been fully successful, indicating the need for more experimental studies to improve mechanistic understanding and better designed workplace interventions.

Animal studies found that dosing mice or rats with sugarcane ash particles via intranasal installation resulted in pathophysiologic changes. Respiratory mechanics were impaired (promoting alveolar collapse), lung parenchyma were injured, and increased macrophage infiltration occurred in the lung (Mazzoli-Rocha et al. 2014). In another study alveolar spaces were reduced, conjunctive tissue thickness in the trachea reduced, and release of inflammatory cytokines was promoted (Ferreira et al. 2014). Direct inhalation exposure to sugarcane burning emissions in rats resulted in tracheal inflammation, interstitial edema, and cell infiltration (Matos et al. 2017). Sugarcane ash has also been found to induce liver toxicity in certain species of fish (Gonino et al. 2019). As discussed above, sugarcane ash is a highly heterogenous mixture and it remains unclear which components might be responsible for the observed effects. Amorphous silica nanoparticles (SiNPs) are often posited as a key toxicant, as silica is the predominant component and SiNPs have demonstrated similar toxicological effects (McCarthy et al. 2012). Administration of sugarcane ash in rats was found to induce CKD pathophysiology and result in accumulation of silica in several organs (Roncal-Jimenez et al. 2024). Exposure to SiNPs has resulted in liver and kidney damage in mice, as well as histopathological changes indicative of CKD in rats (Boudard et al. 2019; Sasai et al. 2022). Elevated SiNPs have even been seen in the kidney biopsies of sugarcane farmers, consistent with the increased risk of CKDu experienced by sugarcane agricultural workers (Rogers et al. 2023). Such findings suggest that silica may be a key factor in sugarcane ash toxicity and should be thoroughly investigated.

In vitro investigations

Toxicology studies of sugarcane ash in cell culture are rare, but available literature indicates varying biological response across ash components. Sugarcane ash in its natural state demonstrated minimal toxicity when directly exposed to cells, inducing some degree of ROS generation and hemolysis, but relatively low cytotoxicity (Le Blond et al. 2014). Ash was also found to reduce mitochondrial membrane potential and increase mitochondrial respiration in human kidney cell cultures (Stem et al. 2023). It is possible that this cell response is ameliorated by ash being in its initial state and that in-vivo biological reactions could digest the ash into more toxic components, requiring further investigation of these potential toxicants. PAHs and SiNPs are two such toxicants that have been thought to be responsible for adverse effects of sugarcane ash exposure. One study found that sugarcane ash induced significant ROS generation, DNA damage, and cell death in HeLa cells; suggesting that it could be due to the PAHs found in the ash samples (Verma et al. 2019). SiNPs purified from sugarcane ash have been found to be extremely cytotoxic, inhibiting mitochondrial respiration and perturbing energy metabolism (Stem et al. 2023). Interestingly, synthetic amorphous SiNPs did not demonstrate comparable cytotoxicity, suggesting different physicochemical properties which may limit relevance of invitro studies utilizing such SiNPs to determine potential toxicity of sugarcane ash. Synthetic amorphous SiNPs toxicity is highly variable and dependent on particle agglomeration, metabolic activity of cells, and particle size (Chang et al. 2007; Drescher et al. 2011). While smaller particles are consistently found to be more cytotoxic, overall understanding remains poor due to inconsistent standards and limited characterization in most literature (Murugadoss et al. 2017; Dong et al. 2020; Croissant et al. 2020). Determining silica’s contribution to sugarcane ash toxicity will require further investigation, ideally with particles derived from sugarcane ash directly.

Potential mechanisms

There are several mechanisms that likely contribute to the adverse health effects associated with sugarcane ash exposure (Table 1). Particulate matter, particularly PM_2.5, is known to impair cardiopulmonary function, potentially through ROS generation and promotion of inflammation (Thangavel et al. 2022). There is also an increasing body of evidence suggesting deleterious effect on kidney function, though the mechanism remains unknown (Rasking et al. 2022). Sugarcane ash has also been found to be a source of PAHs, which are associated with lung, heart, and kidney damage, consistent with the primary health effects reported in sugarcane ash exposure (Mallah Manthar et al. 2022). The high carbon content in the ash has also been posited as a potential contributor, as carbonaceous particles are known to impair lung function (Le Blond et al. 2014). Silica is yet another component which has high potential for toxicity, sugarcane is primarily amorphous silica with crystalline silica remaining low despite the burning process (Le Blond et al. 2010). However amorphous silica is not without risk, amorphous SiNPs have a large surface area for their size and high adsorbent potential, making them quite capable of undesirable endogenous reactions and formation of a biocorona (Frost et al. 2017). Their structure also facilitates passage through biological barriers, such as cell membranes, which could be particularly harmful if carrying other toxicants (Häffner et al. 2021). One of the best predictors for silica nanoparticle toxicity appears to be presence of silanol groups, which can catalyze ROS generating reactions (Lehman et al. 2016). Nanoparticles with a high number of silanol groups on the surface have the potential for increased free radical production and subsequent oxidative stress (Rubio et al. 2019). If this oxidative stress is sufficient to perturb the redox environment of the cell (e.g. glutathione depletion), it can induce a range of harmful effects such as lipid peroxidation and DNA damage (Pizzino et al. 2017). Downstream effects of these could explain the symptoms observed in cardiopulmonary and renal systems of populations exposed to sugarcane ash but would require the SiNPs to be present in the tissue (Figure 5). While such particles have been found in the kidney biopsies of sugarcane workers, no other such evidence yet exists. The toxicity of sugarcane ash is likely multifactorial and there remains much work to be done to determine key mechanisms.

Figure 5. Hypothesized mechanism of SiNP-mediated kidney disease.

Table 1. Summary of primary literature investigating sugarcane fire emissions and key findings.

Topic	Findings	Studies
Sugarcane Burning and Respiratory Symptoms in Nearby Residents	Sugarcane burning was associated with increased acute respiratory illness, asthma and rhinitis symptoms, asthma hospital admissions, and premature mortality.	Long et al. 1998; Boopathy et al. 2002;Cançado et al. 2006; Arbex et al. 2007; Riguera et al. 2011; Mnatzaganian et al. 2015; Nowell et al. 2022
Sugarcane Burning and Cardiovascular Symptoms in Nearby Residents	Sugarcane burning was associated with increased NO2 and cardiovascular related hospital admissions.	Pestana et al. 2017
Sugarcane Bagasse Exposure and Pulmonary Function in Factory Workers	Sugarcane processing workers exposed to bagasse demonstrated reduced pulmonary function parameters withoutindications of allergy.	Gillison and Taylor 1942; Lemone et al. 1947; Sodeman 1967; Patil et al. 2008; Gascon et al. 2012; Debela et al. 2023
Sugarcane Harvesting and Mucociliary Clearance	Sugarcane harvesting was associated with impaired mucociliary clearance and altered mucus properties in workers and nearby residents.	Goto et al. 2011; Ferreira-Ceccato et al. 2011; Matsuda et al. 2020
Sugarcane Harvesting and Oxidative Stress in Field Workers and Nearby Residents	Sugarcane harvesting was associated with decreased antioxidant enzyme activity and increased lipid peroxidation products.	Prado et al. 2012; Paula Santos et al. 2015
Sugarcane Harvesting and Inflammatory Markers in Field Workers	Sugarcane harvesting was associated with reduced CC16 levels and increased inflammatory cell populations.	Paula Santos et al. 2015; Leite et al. 2015; Leite, Zanetta, Antonangelo, et al. 2018
Sugarcane Farmers and Lung Cancer	Sugarcane farmers were found to be at increased risk of developing lung cancer.	Amre et al. 1999
Sugarcane Harvesting and Cardiovascular Changes	Sugarcane workers demonstrated increased heart rates, blood pressure, and blood viscosity over the harvest season. Hematocrit was found to decrease.	Barbosa et al. 2012; Leite et al. 2015; Leite, Zanetta, Antonangelo, et al. 2018
Sugarcane Workers and Renal Function	Sugarcane workers were found to experience higher rates of chronic kidney disease of unknown etiology and demonstrate signs of impaired kidney function. Specific metrics includeddecreased estimated glomerular filtration rate, increased serum creatinine, increased neutrophil gelatinase-associated lipocalin, increased blood urea nitrogen, increased IL-18, and higher rates of proteinuria.	Peraza et al. 2012; Laws et al. 2015; Paula Santos et al. 2015; Laws et al. 2016; Wesseling, Aragón, González, Weiss, Glaser, Bobadilla, et al. 2016; Wesseling, Aragón, González, Weiss, Glaser, Rivard, et al. 2016; Kupferman et al. 2018; López-Gálvez et al. 2021; Raines et al. 2023
Sugarcane Workers and Kidney Biopsy Histopathology	Sugarcane workers with chronic kidney disease of unknown etiology were found to have glomerulosclerosis, tubulointerstitial nephritis, fibrosis, and tubular atrophy.	López-Marín et al. 2014; Wijkström et al. 2017; Fischer et al. 2017
Sugarcane Workersand Silica Nanoparticles	Sugarcane workers with chronic kidney disease of unknown etiology were found to have higher levels of silica nanoparticles present in kidney biopsies.	Rogers et al. 2023
Sugarcane Ash Exposure In-Vivo	Sugarcane ash particles promoted alveolar collapse, injured lung parenchyma, reduced conjunctive tissue thickness in the trachea, interstitial edema, increased cell infiltration in the lung, and release of inflammatory cytokines in mice and rats.Accumulation of silica occurred in several organs. Sugarcane ash also induced liver toxicity in aquatic species.	Mazzoli-Rocha et al. 2008 Mazzoli-Rocha et al. 2014 Ferreira et al. 2014 Matos et al. 2017 Gonino et al. 2019 Roncal-Jimenez et al. 2024
Sugarcane Ash Exposure In-Vitro	Direct sugarcane ash exposure to cells induced reactive oxygen species generation, DNA damage, altered mitochondrial respiration, and resulted in some cytotoxicity. Purification of silica nanoparticles from this ash induced greater cytotoxicity and perturbation to cellular energy metabolism.	Le Blond et al. 2014; Verma et al. 2019; Stem et al. 2023

Table 2. Summary of silica characteristics and sources.

Silica Type		Source: Primary and Occupational	Size Distribution	Structure	Tissue Distribution	Organ Effects of Toxicity
Amorphous (Natural)	Uncalcined	Found in: Rock, Sand, and Stone Foundries Commercial and Residential Materials Job/Career Construction Demolition Glass workers Field/Agriculture workers Manufacturing	2nm—10µm	Disordered, randomly linked silicon and oxygen tetrahedral units, lacking any pattern	Tissue distribution is dependent on particle size and biological reactivity Lungs Kidneys Lymph Nodes Liver Spleen	Lung Granulomas, emphysema, interstitial lung disease, alveolitis, silicosis, cancer Kidney Kidney disease characterized by glomerular injury Cardiovascular System Cardiovascular disease—atherosclerosis, thrombosis, decreased heart contractility, coagulation
	Flux-calcined
	Calcined
	Vitreous
Amorphous (Synthetic)	Pyrogenic		Primary: 5–50nm Aggregate: 0.1–1µm Agglomerate: 1–250µm
	Precipitated		Primary: 5–100nm Aggregate: 0.1–40µm Agglomerate: 1–250µm
	Silica Gel		Primary: 5–100nm Aggregate: 0.1–25µm Agglomerate: N/A
	Colloidal Silica		Primary: 4–60nm Aggregate: 0.1–1µm Agglomerate: 1–250µm
Crystalline	Quartz		0.01–100µm diameter, ≤ 10µm length	Regular, repeating 3D structure with central oxygen atoms shared with 2 tetrahedral Silicon atoms		Lung silicosis, cancer, fibrosis, proteinosis, alveolitis Kidney chronic kidney disease Immune System Scleroderma, Rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis
	Cristobalite
	Tridymite

Influence of climate change

Unfortunately, the very same communities that are experiencing the greatest sugarcane ash exposure are in the same regions which are poised to be most impacted by climate change (Sasai et al. 2021; Geladari et al. 2021). This has the potential to be even more challenging considering that agricultural communities are often resource-poor, and people living in poverty or at-risk of poverty are more likely to experience hardship from climate change (Shonkoff et al. 2011). Investigations into climate’s impact on sugarcane crop yield have found temperature to be non-significant, but do not consider worker conditions (Silva et al. 2020; Ali et al. 2021; Da Cruz and Machado 2023). Climate change also has the potential to increase crop water requirements and drought occurrences, which could prove difficult for agricultural communities that rely on groundwater and well water sources to meet drinking water needs (Gade and Khedkar 2023). Drought and increased temperatures also have the potential to concentrate toxicants already present in water, while perturbed rainfall patterns could redistribute toxicants in the environment. Another concern is how increased temperatures may increase the risk of heat stress and exertional injuries among sugarcane workers, which may be exacerbated by dehydration and put additional strain on water resources (Wegman et al. 2018; Dally et al. 2023). While these issues are not directly related to sugarcane burning, they place additional stress on biological systems and may compromise the ability to respond to respiratory challenges. The influence of climate change on sugarcane fires remains to be determined, but hotter and drier conditions have the potential to increase burn area and fire intensity (Littell et al. 2016). This could lead to more biomass burning and higher levels of particulate matter and other emissions. As climate change results in increased wildfire frequency and air quality hazards, the health effects of sugarcane burning may become even more pronounced (Rossiello and Szema 2019; Senande-Rivera et al. 2022). Thus, it becomes increasingly important to minimize greenhouse gas emissions through alternative non-burning harvest methods and support of environmentally friendly new sugarcane-based technologies (de Figueiredo et al. 2010; Moreira and Pacca 2020).

Transition to green harvesting

Concerns surrounding sugarcane burning emissions and long-term sustainability of the sugar industry have led to increased use of alternative ‘green harvesting’ methods to reduce the practice of sugarcane burning. Brazil began mandating the gradual elimination of pre-harvest burns in the 2000s and, while many regions are still mid-transition, there has already been some evidence of an improvement in local respiratory health (Nicolella and Belluzzo 2015). This method of harvesting also seems to have beneficial effects on soil conditions, with nutrients and other biochemical characteristics being improved under green harvesting conditions relative to conventional burning (Moitinho et al. 2021). Similar results have been reported in Ecuador, Costa Rica, and the United States, however overall harvest efficiency was reduced due to decreased yield and increased cost (Núñez and Spaans 2008; Sandhu et al. 2017). It is possible that improved soil conditions may improve subsequent yields and offset reductions to harvest efficiency, but initial investments in mechanical equipment and decreased cost efficiency are considerations which hinder transition away from pre-harvest burns (da Silva et al. 2021). It is also important to note that the transition to such harvest practices are significantly more difficult in areas where mechanical harvest may not be feasible due to terrain, costs or other factors (Núñez and Spaans 2008; Nicolella and Belluzzo 2015). Despite these difficulties, the shift to green harvesting has continued in Brazil and is gaining increased support in India (Bhuvaneshwari et al. 2019). The outcomes of such initiatives should be closely monitored as they have the potential to be highly valuable for environmental sustainability of the sugarcane industry and improve scientific understanding of sugarcane burning’s effect on public health.

Summary, recommendations, and conclusion

Sugarcane, a major global crop, serves as a critical source of sugar and bioenergy. However, its cultivation, predominantly in equatorial developing nations, poses significant health risks to workers and nearby communities due to the common practice of pre-harvest burning. This produces sugarcane ash, a complex mixture containing respirable particulate matter that is suspected of causing various health ailments. Despite its significance, the depth of exposure and potential hazards of sugarcane ash remain inadequately characterized. Research has shown that both direct (occupational) and indirect (community) exposures to this ash can lead to respiratory, cardiovascular, and renal health issues. The suspected role of sugarcane ash in the rising cases of chronic kidney disease, especially among field workers, highlights the urgency of elucidating toxicological mechanisms. Climate change exacerbates these concerns, potentially increasing the risks associated with sugarcane burning. With sugarcane ash finding new applications in green chemistry and other industries, understanding its health implications becomes even more crucial.

There are several approaches that should be considered to improve scientific understanding and mitigate the risks that such exposures pose, particularly to vulnerable populations. Increased funding and attention should be directed toward studies on the chemical composition of sugarcane ash and its specific toxicological effects on human health. Workplace interventions should be considered, including more thorough monitoring, stricter safety regulations, regular health checkups, and provision of PPE. Initiatives should be undertaken to educate communities residing near sugarcane fields about the potential hazards of sugarcane ash and ways to mitigate exposure (e.g. staying indoors during burning, using masks). Alternative harvest techniques should be employed when possible, minimizing the need for pre-harvest burning. Once more precise mechanisms of toxicity are elucidated, it may be feasible to develop therapeutic interventions to ameliorate the effects of sugarcane ash exposure or at least perform more targeted risk management and preventative care.

While initial studies have shed light on the potential dangers of sugarcane ash inhalation, there remains a pressing need for more in-depth research. Despite its economic importance, sugarcane cultivation brings significant health concerns. As our understanding grows regarding the extent of these health impacts, especially on the respiratory, cardiovascular, and renal systems, it’s evident that immediate actions are required. Combining targeted research with practical interventions will not only protect the health of millions but also ensure the sustainable growth of this crucial agricultural sector.

Acknowledgements

Figures were generated using Biorender.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

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Additional information

Funding

This work was supported by the National Institutes of Health grant R01 DK125351.