A USask mouse study combining endotoxin and glyphosate exposure found lung changes only synchrotron imaging could detect
A University of Saskatchewan (USask) study has found that combined exposure to two common agricultural contaminants – endotoxin and the herbicide glyphosate – produced lung damage in female mice that standard biomedical testing missed entirely, and that only became visible through synchrotron imaging at the Canadian Light Source (CLS) in Saskatoon. The research, led by Dr. Shelley Kirychuk, director of the Canadian Centre for Rural and Agricultural Health (CCRAH) at USask, was published this year in the journal Scientific Reports.
A gap in the research
Kirychuk’s interest in the question goes back decades. “Our early studies in the late ’90s were showing that the population – so grain farmers versus workers who were in animal confinement, working in animal confinement buildings, compared to blue-collar workers – they had different lung functions,” she said. “And we could see that people who worked with animals in confinement had greater changes in their lung function over time than grain farmers, who had greater changes than blue-collar workers. So workplace exposures were impacting lung health.”
Those early studies, she noted, were overwhelmingly male, reflecting the agricultural workforce of the time. According to the latest Canadian Census of Agriculture, women now make up roughly 30 per cent of Canadian farmers – a shift that has left a gap in exposure and outcome data specific to women. “It’s important that we understand that females respond differently than males, and how we best protect all of the people working,” Kirychuk said.
Testing a mixed exposure
The study used a mouse model – specifically female mice, with a companion paper comparing male and female response still forthcoming – exposed over five days to doses of endotoxin and glyphosate calibrated to levels found in real agricultural dust samples. Four groups were tested: endotoxin alone, glyphosate alone, a saline control, and the combination of both.
“What we could see is that the exposure to both agents, so both endotoxin and glyphosate, caused a stronger reaction than the individual exposure,” Kirychuk said. The mixed-exposure effect was the central question the study set out to isolate. “It’s really hard in hygiene to understand a mixed exposure, a mixed response,” she said. “We were just trying to delineate if the mixed response caused anything different than the singular response.”
Notably, conventional measures – blood markers, lung fluid analysis, direct tissue observation – showed no clear difference between groups after five days. “We couldn’t really, in the females, discern after these five days any real differences,” Kirychuk said. The finding only emerged once researchers turned to the CLS.
What the imaging revealed
Dean Chapman, a professor in the Department of Anatomy, Physiology and Pharmacology at USask and scientific lead for the Biomedical Imaging and Therapy (BMIT) beamline at the CLS, explained why. Conventional X-ray relies on absorption, which makes lung tissue – mostly air – nearly invisible. The CLS instead uses a technique called multiple image radiography (MIR), which detects how X-rays refract, rather than absorb, as they pass through the many air-tissue interfaces inside lung structure.
“With this method, we see lungs typically have the most contrast of anything in the body, including bones, which is somewhat remarkable,” Chapman said. That contrast let his team see what blood work and whole-body plethysmography could not: fluid buildup in the small airways from the combined exposure. “This was really a pilot experiment, and I’m stunned that it worked as well as it did,” Chapman said, noting the low imaging dose makes repeated, longitudinal scans feasible for future occupational research, access permitting.
What it means for protection today
For farmers, Kirychuk’s practical guidance hasn’t changed, though the study sharpens the case for it. N95 masks remain the standard recommendation, particularly in enclosed spaces like grain bins and during high-dust activities such as augering at harvest. “The solution to pollution is dilution, so the more airflow you can get, you have more protection,” she said, adding that she tells farmers to keep a mask in a plastic bag in the truck or tractor cab for when dust plumes appear unexpectedly.
Fit matters too – a challenge many women in physically demanding trades have raised about standard-issue protective equipment generally. Kirychuk pointed to CCRAH’s own mask selection guidance for different exposure types, noting that N95s specifically address dust and aren’t a one-size-fits-all solution for every hazard on a farm.
For Chapman, the study’s significance extends beyond this one result. A high-profile publication, he said, “bodes really well” for the team’s chances at future peer-reviewed beamtime – competitive access that determines whether longitudinal imaging, tracking the same animals across multiple exposure points, becomes possible. “It’s a method looking for applications,” he said, “and that one is one.”