Arsenic is a naturally occurring metalloid found in groundwater, soil, and certain crops across much of the world, and chronic exposure is well established as a risk factor for cardiovascular disease, cancers, and skin lesions. Once absorbed, inorganic arsenic does not simply accumulate unchanged. The body metabolizes it in two successive methylation steps, enzymatically attaching methyl groups to convert inorganic arsenic into monomethylated arsenic, or MMA, and then into dimethylated arsenic, or DMA. These methylated forms are excreted in urine, and for decades the methylation process was considered detoxifying, since the fully dimethylated product is generally less reactive at the cellular level than its predecessors. But this conventional wisdom has been increasingly challenged by studies hinting that trivalent intermediates formed along the pathway may be more toxic than the parent compound itself.

The MANOS research team, led by Margaret Quaid of Boston University School of Public Health together with collaborators at institutions in the United States, El Salvador, and Nicaragua, set out to examine whether specific arsenic metabolism profiles were associated with blood pressure among working men in a region where both arsenic exposure and an unexplained kidney disease overlap. The study included 393 male participants drawn from the broader occupational cohort, and the researchers measured the concentrations of inorganic arsenic, MMA, and DMA in urine samples, expressing each species as a percentage of the total inorganic and methylated arsenic. Blood pressure outcomes included systolic pressure, diastolic pressure, pulse pressure, and mean arterial pressure, all adjusted for age, body mass index, worksite, pesticide use, smoking status, and water consumption.

The results revealed a pattern that at first glance seems counterintuitive. Participants with higher percentages of DMA, the end product of complete arsenic methylation, tended to have higher systolic blood pressure and wider pulse pressure. In the conventional models, each percentage point increase in DMA was associated with a 0.17 millimeter of mercury increase in systolic pressure and a 0.14 millimeter of mercury increase in pulse pressure. Conversely, participants with higher percentages of MMA, indicating incomplete methylation, showed lower systolic and pulse pressures, with each percentage point increase in MMA corresponding to a 0.37 and 0.31 millimeter of mercury decrease respectively. In other words, the men whose bodies pushed arsenic metabolism further along the detoxification pathway were the ones showing elevated cardiovascular readings, not those who stalled at an intermediate step.

Because the three urinary metabolite percentages are mathematically interdependent, the researchers took care to disentangle their individual contributions using two additional analytical strategies. In leave-one-out models, they evaluated the relative effect of two species while statistically holding the third constant. These models reinforced the initial findings: higher DMA at the expense of MMA was associated with increased systolic blood pressure, with an effect estimate of 0.33 millimeters of mercury per percentage point, and increased pulse pressure of 0.29 millimeters of mercury per percentage point. A third approach using principal components analysis, a statistical technique that compresses correlated variables into independent axes representing the two methylation steps, provided converging evidence. The component capturing the second methylation step, the conversion of MMA to DMA, was associated with a 0.93 millimeter of mercury increase in systolic pressure and a 0.74 millimeter of mercury increase in pulse pressure.

The consistency of the effect across three distinct modeling frameworks lends weight to the authors’ conclusion that efficient methylation of inorganic arsenic all the way to DMA is associated with higher blood pressure compared with partial methylation to MMA. This finding complicates the simplistic narrative of methylation as unambiguously protective. It aligns instead with a growing body of research suggesting that the methylation process may generate intermediate trivalent species, such as monomethylarsinous acid, which are highly reactive and can disrupt cellular signaling, endothelial function, and oxidative stress pathways. If the second methylation step is inefficient at clearing these intermediates, or if individuals who methylate rapidly accumulate different arsenic species in tissues, the downstream cardiovascular consequences could differ in ways that conventional toxicity rankings fail to capture.

The biological mechanisms linking arsenic metabolism to blood pressure remain under active investigation, but several plausible pathways have been proposed. Arsenic exposure has been associated with impaired nitric oxide signaling, increased oxidative stress, vascular inflammation, and alterations in arterial stiffness, all of which can elevate systolic pressure and widen pulse pressure, a marker of arterial aging. The methylation process itself consumes methyl groups supplied by S-adenosyl methionine, drawing on one-carbon metabolism, a biochemical network that also regulates homocysteine levels and DNA methylation. Variation in the arsenite methyltransferase gene, known as AS3MT, and in nutritional factors such as folate and B vitamins can shift an individual’s metabolic profile substantially, meaning that two people exposed to identical arsenic levels may carry very different internal arsenic species distributions. The MANOS findings suggest these individual differences are not mere biochemical trivia but may carry meaningful cardiovascular consequences.

The context of the study population adds an important dimension to the findings. MesoAmerican nephropathy, also referred to as chronic kidney disease of unknown etiology, is an epidemic affecting agricultural workers along the Pacific coast of Central America, and arsenic exposure has been proposed among the candidate causes, alongside heat stress, dehydration, and pesticide exposures. By focusing on working men in sugarcane communities in El Salvador and Nicaragua, the MANOS investigators examined arsenic metabolism in a real-world setting of intense occupational and environmental stressors, rather than in a general population survey. The cross-sectional design means the study captures a single moment in time and cannot establish whether arsenic metabolism patterns cause the blood pressure differences or reflect some underlying physiological state. The authors are careful to frame the results as an association, and reverse causation or residual confounding cannot be excluded, particularly in a workforce with high rates of kidney impairment that could alter arsenic excretion.

Nevertheless, the study carries practical implications for how researchers and clinicians think about arsenic risk. Most environmental health surveillance measures total urinary arsenic, treating exposure as a single number. The MANOS results argue that the speciation profile, meaning the relative proportions of inorganic arsenic, MMA, and DMA, conveys additional information about cardiovascular vulnerability that total exposure alone would miss. If future longitudinal studies confirm that the second methylation step is genuinely associated with elevated blood pressure, then arsenic metabolism biomarkers could become part of cardiovascular risk assessment in exposed populations, helping to identify individuals who, despite similar exposure levels, face different health trajectories. Such work would also sharpen the search for modifiable factors, such as nutrition and one-carbon metabolism support, that shape methylation capacity and might therefore mediate arsenic’s cardiovascular effects.

For now, the study stands as a reminder that the body’s handling of a poison can be as consequential as the poison itself. In the cane fields of Central America, where arsenic, kidney disease, and hypertension intersect in an unfolding public health crisis, understanding the chemistry of methylation may prove essential to protecting the hearts and kidneys of the people who live and labor there. The researchers emphasize the importance of arsenic metabolism profiles in cardiovascular risk assessment, and their findings open a clear path for follow-up studies that follow exposed workers over time, track their metabolic profiles, and test whether the blood pressure patterns observed here translate into hypertension, arterial disease, and cardiovascular events in the years ahead.

Subject of Research: The association between arsenic metabolism profiles and blood pressure in MesoAmerican agricultural workers

Article Title: The association of arsenic metabolism and blood pressure: a cross-sectional analysis in the MesoAmerican Nephropathy Occupational Study (MANOS)

Article References: Quaid, M., Rodgers, K., Velázquez, J. J. A., García-Trabanino, R., Jarquin, E., Lopez-Pilarte, D., Leibler, J., Brooks, D., Glabonjat, R. A., Navas-Acien, A., Argos, M., & Scammell, M. K. (2026). The association of arsenic metabolism and blood pressure: a cross-sectional analysis in the MesoAmerican Nephropathy Occupational Study (MANOS). Environmental Health. https://doi.org/10.1186/s12940-026-01333-4

Image Credits: AI Generated

DOI: 10.1186/s12940-026-01333-4

Keywords: arsenic, arsenic metabolism, blood pressure, methylation, MMA, DMA, hypertension, MesoAmerican nephropathy, El Salvador, Nicaragua, environmental health, cardiovascular risk

For decades, seismic hazard assessment in most parts of the world has concentrated on horizontal ground motion, driven by the observation that lateral forces are usually the primary cause of structural collapse. Yet engineers have increasingly recognized that vertical shaking can impose severe axial demands on columns, beams, and connections, particularly in reinforced concrete frames, bridges, and base-isolated structures. Laboratory testing and post-earthquake investigations have repeatedly shown that reinforced concrete columns subjected to combined horizontal and vertical accelerations lose load-carrying capacity faster than those facing lateral motion alone, and that vertical ground motion has been implicated in damage to historical structures and modern buildings alike. Until now, El Salvador’s building codes and hazard maps have lacked a rigorous, nationally calibrated basis for quantifying that vertical threat.

The new work presents time-independent probabilistic seismic hazard maps expressed in terms of vertical peak ground acceleration and spectral ordinates at periods of 0.2 and 1 seconds, computed for 5 percent of critical damping. These values were produced for rock site conditions and flat topography across five return periods: 50, 95, 475, 975, and 2475 years. The return-period framework mirrors the conventions used in modern design standards, allowing engineers to select ground-motion intensities appropriate to the importance and intended lifespan of a structure. A 475-year return period, corresponding to roughly a 10 percent probability of exceedance in 50 years, is the traditional benchmark for ordinary buildings, while the rarer 2475-year event informs the design of critical facilities such as hospitals and emergency centers.

To construct the hazard models, Salazar employed two complementary approaches: the classical area source method and the smoothed seismicity method. The area source approach divides a region into discrete zones assumed to share uniform seismicity characteristics, a technique rooted in Cornell’s foundational 1968 formulation of engineering seismic risk analysis. The smoothed seismicity method, pioneered by Gordon Woo in the 1990s, dispenses with rigid zonation boundaries and instead spreads earthquake occurrence spatially using kernel functions, letting the historical record itself shape the hazard landscape. Using both methods within a logic tree framework allows the analysis to capture epistemic uncertainty, the uncertainty arising from incomplete scientific knowledge about where and how frequently earthquakes occur.

The seismicity evaluation draws on a homogenized earthquake catalog spanning nearly five centuries, from 1528 to 2023, with moment magnitudes ranging from 5.0 to 8.1. Bringing nearly 500 years of historical and instrumental records into a consistent magnitude scale is one of the most labor-intensive aspects of hazard analysis in developing countries, where early accounts may consist only of damage descriptions in colonial archives. From this catalog the study derived classical Gutenberg-Richter frequency-magnitude relationships, which describe the predictable inverse relationship between earthquake size and occurrence rate, as well as average kernel bandwidth distances, a measure of the typical spacing among epicenters of earthquakes of the same size that parameterizes the smoothed seismicity calculations.

A distinctive strength of the study lies in its empirical testing of vertical ground-motion prediction equations against actual accelerometer recordings from El Salvador itself. The candidate equations were evaluated against data from the two destructive earthquakes of 2001: the January 13 event of magnitude 7.7, which ruptured within the Cocos plate subduction zone offshore, and the February 13 event of magnitude 6.5, which struck in the volcanic chain zone where shallow crustal faults cut across the densely populated interior. Both earthquakes caused catastrophic losses, and their contrasting tectonic settings make them ideal calibration points for distinguishing how subduction interface and upper-crustal earthquakes transmit vertical energy to the surface. Salazar also accounted for hanging-wall effects, the amplification of shaking that occurs at sites located above the up-dip edge of a dipping fault rupture, which can substantially elevate ground motions at near-fault locations.

The weighting of competing ground-motion models in the logic tree was informed directly by how well each vertical prediction equation reproduced the observed Salvadoran recordings, rather than being assigned arbitrarily or borrowed wholesale from other regions. This data-driven calibration matters because vertical-to-horizontal spectral ratios vary widely across tectonic regimes, and models developed for Japan, Italy, Taiwan, or the Mediterranean do not necessarily transfer cleanly to Central America’s unique combination of a rapidly subducting oceanic plate and an active volcanic arc. By anchoring the model selection to local data, the study reduces one of the largest sources of uncertainty in vertical hazard estimates.

Among the study’s most practical outputs are proposed relations between horizontal and vertical map accelerations, expressed across all the return periods considered. These vertical-to-horizontal ratios provide an efficient bridge for practicing engineers: instead of requiring new vertical hazard computations for every site, designers can derive vertical design forces directly from the horizontal hazard values already in use, scaled by the locally calibrated ratios. Given that international design provisions, including the American Society of Civil Engineers’ ASCE 7-22 standard, increasingly demand explicit treatment of vertical seismic effects, such locally derived conversion factors are precisely what national code committees need to modernize requirements without embarking on a parallel hazard analysis from scratch.

The implications extend beyond structural engineering practice. El Salvador’s seismic vulnerability was starkly demonstrated in 1986, when the San Salvador earthquake destroyed thousands of buildings, and again in 2001, when the two major quakes within a month devastated communities already struggling with recovery. Recent geodetic work using GNSS and InSAR has continued to map the accumulating tectonic deformation across the country, underscoring that the forces driving the hazard remain fully active. Regional hazard models developed for sovereign parametric insurance also depend on the kind of robust, probabilistic ground-motion characterization this study provides, meaning the new vertical maps could ultimately inform not only building design but financial instruments that transfer catastrophe risk at the national scale.

For a country that sits atop one of the planet’s most active seismic engines, the message of this research is clear: the ground does not only move sideways, and the engineering community must plan for the full three-dimensional character of earthquake shaking. By combining a five-century earthquake catalog, dual seismicity modeling methods, empirically tested vertical ground-motion equations validated against Salvadoran strong-motion records, and practical hazard maps spanning return periods from 50 to 2475 years, the study gives El Salvador a technical foundation that few nations of its size possess. The work was supported by research grants from the Catholic University of El Salvador and made use of Woo’s KERFRACT Fortran code for smoothed seismicity, and it stands as a template for how data-scarce, high-hazard countries can leverage both historical archives and modern instrumental networks to quantify the risks beneath their feet.

Subject of Research: Probabilistic seismic hazard mapping of vertical earthquake ground motion components in El Salvador

Article Title: Seismic hazard maps for El Salvador: the vertical component of motion

Article References: Salazar, W. (2026). Seismic hazard maps for El Salvador: the vertical component of motion. Bulletin of Earthquake Engineering. https://doi.org/10.1007/s10518-026-02665-9

Image Credits: AI Generated

DOI: 10.1007/s10518-026-02665-9

Keywords: seismic hazard, El Salvador, vertical ground motion, probabilistic seismic hazard analysis, ground-motion prediction equations, smoothed seismicity, subduction zone, earthquake catalog, logic tree, return period, vertical-to-horizontal ratio, Bulletin of Earthquake Engineering