For Brenda Eskenazi, what once seemed merely a rich vein of epidemiological knowledge has turned out to be a mother lode.

Eskenazi, who runs the Center for the Health Assessment of Mothers and Children of Salinas study (known as CHAMACOS, Mexican Spanish slang for “little kids”), has tracked pairs of mothers and their children for more than 20 years. She’s collected hundreds of thousands of samples of blood, urine and saliva, along with exposure and health records. This treasure trove of data has produced unprecedented insights into the effects of environmental hazards on children living in California’s Salinas Valley, an agricultural region often called the “world’s salad bowl.” 

So when Charles Limbach, a doctor at a Salinas health clinic, saw an explosion of fatty liver disease in his young patients and found a study linking the condition in adults to the weed killer glyphosate, he contacted Eskenazi.

Eskenazi, who also heads the Center for Environmental Research and Children’s Health at the University of California, Berkeley, offered to pull samples from her freezer to test Limbach’s suspicions about glyphosate, the main ingredient in Roundup and the most popular herbicide on the planet. The pair enlisted the help of Paul Mills, chief of U.C. San Diego’s Behavioral Medicine Division, who led the glyphosate study in adults, along with several other scientists at Eskenazi’s center.

The results of the team’s study of Eskenazi’s children, published in the peer-reviewed journal Environmental Health Perspectives earlier this month, echoed what Mills had found in older patients. 

”We show an association between early life exposure to glyphosate and liver inflammation and metabolic disease in young adults,” said Eskenazi, who led the study. 

These conditions can be precursors for more serious diseases, including liver cancer and cardiometabolic diseases like stroke and diabetes, she said. “And these are only 18-year-olds.”

The metabolic and liver conditions the researchers found in 18-year-olds living in Salinas farmworker communities were once diseases found mostly in much older adults. But the national prevalence of childhood metabolic syndrome and obesity has increased at an alarming rate, the team notes in their study, particularly among populations of color.

The study’s results are of “great concern,” Eskenazi said. “We’re seeing an epidemic of liver problems and metabolic disease in children and young adults, and we need to understand why we’re seeing this huge increase.”

The team measured levels of glyphosate and its main breakdown product, AMPA (short for aminomethylphosphonic acid), in urine samples from mothers during pregnancy and in their children at 5, 14 and 18 years old. They also analyzed records of glyphosate use near study participants’ homes.

Teenagers who had metabolic syndrome and markers of liver disease at age 18 had higher urinary concentrations of AMPA and glyphosate between ages 5 and 18 years.  Metabolic syndrome in the 18-year-olds was also associated with agricultural use of glyphosate near their homes during early childhood. 

Kids who ate more cereal, fruits, vegetables and bread had higher urine concentrations of glyphosate and AMPA, suggesting that diet was a major source of their exposures.

Most glyphosate passes through the body unchanged, research shows. That means the AMPA in kids’ urine had likely already degraded in the environment, Eskenazi said. “So I might be exposed to AMPA either by being near where glyphosate was sprayed or by foods that had converted it to AMPA.”

AMPA is also a byproduct of compounds found in other products, including fire retardants and detergents. “But other studies have shown that the lion’s share, a much, much larger proportion of AMPA is due to glyphosate,” Eskenazi said.

The liver and metabolic conditions the researchers saw could be related to other causes, such as poor diet or excess weight. But the associations between AMPA and glyphosate remained when they controlled for those factors.

The findings are not surprising, considering the other studies showing liver toxicity and microbiome effects in animal models, said Bruce Blumberg, an expert on obesity and related metabolic disorders at the University of California, Irvine who was not involved in the new study. (The “microbiome” refers to the trillions of bacteria, viruses and fungi that live in animals’ intestinal tracts.)

“We don’t really know much about how glyphosate may be eliciting such effects yet,” said Blumberg. “With funding so tight and glyphosate so controversial, it may take some time before we develop a mechanistic understanding of how glyphosate, Roundup and/or AMPA are eliciting the effects they are associated with.”

Eskenazi’s CHAMACOS study previously linked pesticides and other harmful exposures to neurodevelopmental disorders, lower IQ, preterm birth, respiratory problems and obesity, among other health problems.

The CHAMACOS study is amazing in that it started with pregnant women and has followed their children for more than two decades, said Caroline Cox, a glyphosate expert and former senior scientist at The Center for Environmental Health who was not involved in the research. “You just don’t find that very often.”

Instead of asking people to recall potential pesticide exposures, as older studies used to do, the CHAMACOS researchers follow people through their lives, taking biological samples along the way. And because California requires farmers to report pesticide use, the researchers can gauge residential exposures. 

“They actually have two different measures of exposure,” Cox said. “That’s pretty remarkable to have both.”

The study design can’t prove glyphosate causes these conditions, but flags an association that warrants further investigation, Eskenazi cautioned. But the fact that there’s such an increase in liver inflammation and metabolic syndrome so early in life in general, she said, “means that we’re setting ourselves up for something catastrophic in our population as they age.” 

Eskenazi expected the levels of glyphosate and AMPA in her Salinas kids to be higher than those reported in the general population—but they’re not.

“That means it’s not just agricultural workers or families of agricultural workers that could be at risk,” Eskenazi said. “It’s the general population.”

A Clouded Past

Monsanto first sold glyphosate under the brand name Roundup in the 1970s, not long after regulators restricted use of another Monsanto herbicide, Agent Orange, based on evidence that it caused birth defects in mice. 

At the time, federal regulators were grappling with the potentially devastating health consequences of dumping millions of gallons of Agent Orange across the Vietnamese countryside to destroy forest cover and crops during the Vietnam War. Scientists have since linked Agent Orange exposure to a laundry list of other health problems, including non-Hodgkin lymphoma and other cancers, liver disorders, diabetes, heart disease and Parkinson’s.

Glyphosate’s toxicity has been the subject of intense debate for years, with concerns growing after the herbicide’s use skyrocketed in the mid-1990s along with plantings of soybeans, cereals, corn and other crops engineered to survive a chemical designed to kill most any plant. 

Those concerns deepened after the World Health Organization’s cancer experts classified glyphosate as a probable human carcinogen in 2015. California health regulators cited that ruling when they added glyphosate to the state’s list of substances known to cause cancer in 2017—a move Monsanto unsuccessfully challenged.

The European Union considered a ban the same year, but ultimately extended its approval through this year. Several U.S. cities have banned or restricted the herbicide. 

Bayer, which bought Monsanto in 2018, has settled more than 100,000 lawsuits worth billions of dollars without conceding plaintiffs’ charges that the companies failed to disclose glyphosate’s cancer risks. 

“Bayer believes it has meritorious defenses and intends to defend the safety of glyphosate and our glyphosate-based formulations vigorously,” the chemical and pharmaceutical giant, valued at $60 billion, said in its latest annual report. Still, starting this year, Bayer plans to replace glyphosate-based herbicides sold in the residential market with alternative ingredients to reduce “future litigation risk.”

Glyphosate-based herbicides have been used safely and successfully for nearly 50 years and are among the most thoroughly studied products of their kind, said Bayer spokesperson Susan Lord. “Leading health regulators around the world have repeatedly concluded that glyphosate-based products can be used safely as directed. The Environmental Protection Agency determined that ‘Glyphosate products used according to label directions do not result in risks to children or adults.’”

One reason the EPA and WHO cancer experts reached opposite conclusions, an expert on Roundup concluded in a 2019 Environmental Sciences Europe study, was because the EPA relied mostly on unpublished regulatory studies commissioned by the manufacturer—99 percent of which found no effect. WHO cancer experts, on the other hand, relied mostly on studies published in publicly available, peer-reviewed journals, the vast majority conducted by scientists not working on behalf of pesticide manufacturers, 70 percent of which found evidence of harm.

More than 80 papers published since 2016 “provide clear and compelling evidence” that both glyphosate and glyphosate-based herbicide products are toxic to DNA, causing damage that can lead to cancer, scientists concluded in an updated review of the 2019 paper, published in the journal Agrochemicals in January.

“Glyphosate is anything but innocuous,” said toxicologist Linda Birnbaum, former director and now scientist emeritus at the National Institute of Environmental Health Sciences.

Most research has focused on glyphosate’s cancer risk. “But the noncancer effects are of significant concern,” Birnbaum said. “And there’s quite a bit of data showing reproductive and developmental effects.”

Monsanto claimed glyphosate would harm only plants because it targets an enzyme people and other animals lack. “Roundup can be used where kids and pets will play, and breaks down into natural materials,” a commercial from the 1990s assured viewers.

That “plant” enzyme, it turns out, is also found in a wide range of microbes, including those essential for health in animals and people. 

Exposing honeybees to glyphosate interferes with their gut microbes, making the pollinators critical to the food supply more likely to die from infections, researchers reported in 2018. Exposing mice to glyphosate appears to disrupt gut microbes that communicate with the brain, making the rodents anxious and listless.

Scientists have just started to study glyphosate’s ability to disrupt the trillions of microorganisms in the human gut that digest food and regulate metabolism, body weight and immune function.

“My first introduction to glyphosate was as this nontoxic alternative to that horrible Agent Orange,” said Cox, the glyphosate expert. 

She recalled having trouble finding studies of glyphosate’s toxicity as recently as the early 2000s. “So much of the research was done by Monsanto or paid by Monsanto and never showed any problems,” Cox said. “You’ve probably seen those ads where Monsanto used to advertise that it’s safer than table salt.”

Such claims moved the New York attorney general to charge Monsanto with false advertising in 1996. The company agreed to stop running ads and commercials claiming glyphosate is less toxic to rats than table salt, biodegrades and is “practically non-toxic” to mammals, birds and fish, among other contested claims.

Most of the evidence used by U.S. regulatory agencies to approve glyphosate-based herbicides was produced decades ago—by manufacturers and their consultants. Yet scientists’ ability to detect toxic effects from even low doses of glyphosate, and the other so-called inert ingredients in Roundup, has advanced light years since then.

All the studies that find no evidence of harm—all the industry studies—are with pure glyphosate, Birnbaum said. “But no one is exposed to pure glyphosate.”

Numerous studies clearly show that the commercial products are problematic, Birnbaum said. Many glyphosate herbicides contain other chemicals derived from petroleum that enhance their effectiveness but have proven more toxic, research shows.

A growing body of evidence from independent scientists shows that glyphosate and its metabolites are also likely to target other molecular pathways in animals, resulting in kidney and liver damage, nutrient imbalances and hormonal disruptions, U.C. Irvine’s Blumberg and other scientists warned in a statement of concern published in Environmental Health in 2016.

Government agencies should not be relying on unpublished, non-peer-reviewed data generated by manufacturers, they argued. Instead, they should launch “a fresh and independent” investigation of glyphosate-based herbicides’ toxicity, along with systematic efforts to monitor the weed killer’s levels in people and the food supply—“none of which are occurring today.”

Meanwhile, people’s exposure to the world’s most heavily applied herbicide is rising, the scientists noted.

Widespread Exposures

Applications of glyphosate-based herbicides have increased 100-fold since Monsanto introduced the chemical in 1974. Bayer noted in its 2022 Annual Report that sales in its herbicides division “rose year on year due to higher volumes and prices, especially for our glyphosate-based products.”

Growers sprayed more than 12 million pounds of glyphosate—six times more than the chemical sprayed at the second highest volume—on 5.5 million acres in California alone in 2020, the most recent year of full reporting. 

The rapid growth of the glyphosate market, now valued at $9 billion, was driven mostly by the widespread adoption of “Roundup Ready” crops engineered to survive applications of the plant killer. Even so, non-agricultural applications by homeowners, parks, schools and forest and range managers increased 43-fold between 1974 and 2014. 

Monsanto assured U.S. regulators that weeds wouldn’t evolve resistance to glyphosate when it sought approval for its Roundup Ready soybeans in the early 1990s. Two years later, scientists documented glyphosate resistance in weeds. 

Farmers now spray more frequently at higher rates to control the recalcitrant weeds, applying close to 300 million pounds of glyphosate on average every year. They also must increasingly resort to tilling practices to eradicate weeds, a method that releases climate-warming gases from soil.

And scientists have found the world’s favorite weed killer most everywhere they’ve looked. In house dust, particulate matter carried by the wind, soil, ditches, rivers, streams, lakes, ponds, wetlands, groundwater, dairy cows’ urine and dietary staples like the corn, soy, wheat, legumes and oats used in cereals, baked goods and other processed foods. 

Glyphosate is also in the urine of more than 80 percent of the U.S. population age 6 and older. 

Farmers often spray wheat, barley, oats and other cereal grains to hasten drying before harvest, which can lead to much higher residue levels in the end product. 

With farmers spraying crops like wheat and harvesting it a few weeks later, there has to be some residue on the end product, Blumberg said. “I hope someone is looking at baked goods to see how much is in there.”

CHAMACOS and many others studies have shown that an organic diet reduces urine levels of pesticides, including glyphosate and AMPA.  

“This chemical should be much more tightly regulated, probably not allowed for home use, and certainly under only restricted circumstances,” said Birnbaum, long the nation’s top toxicologist. If the human race is going to survive, she said, “we’ve got to stop using all these highly used chemicals, which poison us, wildlife and the whole ecosystem.”

Scientists say there’s an urgent need to invest in impartial assessments of glyphosate’s potential role in a growing list of diseases, as farmers’ reliance on the ubiquitous chemical continues to grow.

With climate change, we’re going to probably wind up using more pesticides, Eskenazi said.

“The food we eat and the exercise we don’t do play a role in the epidemiology of liver disease and metabolic disease,” she said. “But does glyphosate also contribute? That’s what we need to figure out.”