Does the dose define how chemicals can lead to harm? Yes.
But is the dose the only thing that “makes the poison”? No.
The idea that the dose makes the poison – originally explained as “all things are poison, and nothing is without poison; only the dose permits something not to be poisonous” – was introduced by a 16th-century physician named Paracelsus. It laid the foundation for what is, more than 400 years later, the field of toxicology.
Today the chemical industry and its supporters point to the phrase when claiming health risks only exist above certain chemical exposure levels and some doses are “too low” to be harmful.
It’s generally true that a chemical is more toxic at higher doses. But our understanding of how chemicals and mixtures interact with our bodies has improved considerably over the past 400 years, showing that there’s more to consider than just the amount of a substance.
A complicated mix of factors affect the ‘poison’
Who you are, when and how often you are exposed to something, and what else you’re exposed to all matter. And what is defined as a low dose might, with prolonged exposure, be sufficient to lead to health harms.
Relationships between dose and biological response – how it impacts a body – can be linear, where a higher dose results in a greater response. But scientists have also observed a variety of other, non-linear relationships between dose and response. Depending on the chemical, a higher dose doesn’t necessarily mean a higher response, or more “poison.”
In some cases, both lower and higher doses can trigger certain health harms, while moderate doses do not (see Panel F in Figure 1 below). For other chemicals (like in Panel D), the relationship might be logarithmic, meaning that toxicity might drastically increase at lower dose-ranges but taper off as doses get higher.
Figure 1. A variety of documented dose-response relationships
Source: Ramaiah et al., Figure 1 from Toxicological Pathology
What does ‘dose’ even mean?
The dose is the amount of a substance that is absorbed into the body. But not everything that we come into contact with will be absorbed into the body.
The exposure route can play a large role.
For example, titanium dioxide is an effective active ingredient in sunscreens, an ultraviolet filter that does not cross the skin barrier when applied. But its use in sprays or powders raises concern, since the particles can be inhaled deep into the lungs and harm health.
So the impact of exposure isn’t just about the amount, it’s also about how a person is exposed.
What else matters, apart from the dose?
When you are exposed
Low exposures in utero or during early childhood can have very different effects than the same exposure in adulthood. Even when they’re exposed to the same amounts of a chemical, children may absorb more than adults.
A World Health Organization study found young children can absorb up to five times more lead than adults from the same ingested dose.
And even if the dose is the same, it could have a greater impact on kids than adults because their brains are still developing. They may suffer irreversible damage to the brain and experience developmental impacts later in life.
What else you are exposed to
We know we aren’t exposed to chemicals one by one but instead to mixtures of chemicals over long periods of time. We constantly come into contact with combinations of chemicals from food, water and consumer products.
Research shows that small, seemingly insignificant doses of multiple chemicals can add up or interact together to multiply each other’s effects, creating a total health risk that is measurably more harmful than those from the chemicals acting alone.
Glyphosate, an herbicide, and cypermethrin, an insecticide, are sometimes used together to manage crops. A 2025 study compared the impacts in cells of individual exposures to glyphosate and cypermethrin with exposure to both pesticides at the same time. The authors found that joint exposure triggered early and late cell death, along with overall toxicity in animal models.
When combined, these two pesticides triggered more late cell death than would be expected from simply adding their individual effects together. A decade earlier, another study reported the same pattern – that these chemicals magnify each other’s effects when mixed.
Both pesticides are frequently used together on soy and corn fields, so this mixture analysis is a simulation of real-world exposures.
In 2021, the European Commission and European Food Safety Authority, or EFSA, announced a joint strategy to integrate cumulative risk assessments in pesticide reviews. This new approach incorporates methods to assess the effect of chemical mixtures on human health. EFSA is reviewing the status of multiple approved pesticides in light of toxicity findings from mixtures assessments.
U.S. regulatory safety assessments routinely fail to account for chemical interaction, when the presence of one chemical can unexpectedly amplify the toxicity of another by altering how much is absorbed or metabolized.
The bottom line: It has been known for a while that exposure to chemicals in combination can multiply their effect. In other words, for some chemical mixtures, the sum is greater than its parts.
How often you are exposed
The average person uses between 10 and 14 personal care products a day, spanning several categories. You aren’t exposed just once, you’re exposed every day for years.
This repeated, long-term use leads to what’s called cumulative exposure. While many chemicals are rapidly excreted, they can still have an impact with repetitive low dose exposure.
The issue isn’t just a single dose today. It’s repeated exposure – even at low levels – across months or years that can add up.
Who you are
Individual susceptibility, genetics, and your microbiome matter.
Your genes can act like a personalized instruction manual for how well your body processes toxins. Some people have versions of enzymes that clear chemicals quickly, while others can have versions that allow the same small dose to build up to dangerous levels.
Your immune system and gut microbiome can also change how you respond. A “safe” dose of a given substance could be “poison” to an immunocompromised individual or someone taking a specific medication.
Statins, widely used cholesterol medications, are broken down in the body by an enzyme called CYP3A. Grapefruit juice contains compounds called furanocoumarins that stop CYP3A from doing its job.
So when ingested with grapefruit, more of the drug can be absorbed than intended. Both substances alone are safe, but the combination can be unexpectedly toxic. This is why some medications warn about consuming grapefruit while taking the medicine.
Some medication labels warn against consuming grapefruit when taking the drugs
The case of hormone disruptors
Endocrine-disrupting chemicals, or EDCs, are a class of chemicals that mimic the body’s natural hormones. Our hormone system is designed to respond to tiny “doses” of substances that act as signals to control how we grow and how our bodies use energy.
One well-known EDC is bisphenol A, or BPA. Results from a 2012 study linked low doses of BPA, legally considered “safe,” to endocrine disruption.
The study emerged from a partnership among the Food and Drug Administration, the National Institute of Environmental Health Sciences, and 14 independent researchers, called CLARITY-BPA.
As a landmark 2007 report in Environmental Health News notes, even exposure to a tiny dose of an EDC can interfere with these signals. Repeated exposure over time can cause health impacts later in life.
The relationship between the amount of an EDC and its effect on health doesn’t always proceed in a straight line or in one direction. When the relationship doesn’t move in one direction only – when the shape of the dose-response relationship does not consistently increase or decrease – the low-dose effects of exposure to EDCs “cannot be predicted by the effects observed at high doses,” one study found.
This study’s results demonstrate how, if only high doses are tested, serious health impacts that only show up at lower doses can be missed.
The researchers tested a cancer-causing chemical called TCDD on rats. At a “high dose” of 0.25 micrograms per kilogram, or µg/kg, TCDD didn’t seem to cause any reproductive problems. But when the dose was tested at a much lower level, 0.064 µg/kg, researchers saw a significant drop in the rats’ daily sperm production.
This doesn’t mean that higher doses are safer. The authors point out that high levels of TCDD are still harmful to many organs and can even be deadly. Instead, the study shows why we can’t just say “the dose makes the poison.” Low levels of exposure can interfere with the body in ways that are not seen at high doses.
Low doses do not mean safe doses
Analysis of the science documents made public through trial discovery led to EWG advocating for increased regulation of the “forever chemical” perfluorooctanoic acid, or PFOA. At the time, PFOA was extensively used as a processing aid in the manufacturing of Teflon.
But industry representatives pushed back, citing the notion that dose makes the poison to argue that health concerns about PFOA were “unfounded.” PFOA detections were “negligible … and within government standards,” they said, characterizing the measured average PFOA concentrations of 4 parts per billion in drinking water as a mere “shot glass … spread among 250 railroad tankers.”
Since 2005, research has repeatedly documented the dangers of exposure to this supposedly “negligible” – and, at the time legal – level of PFOA.
That same concentration would today be 1,000 times the Environmental Protection Agency’s legal limit for PFOA in drinking water, currently set at 4 parts per trillion.
Chemical companies and pesticide manufacturers have long argued that low doses are safe. For example, Dow, a global materials science manufacturer, lists “the dose makes the poison” on its position statement page, arguing that “as a dose increases . . . the likelihood of a toxic response increases as well.”
Despite the wealth of peer-reviewed literature indicating otherwise, Dow maintains that findings of the toxicity of low doses are unsubstantiated.
Outcomes matter in defining safe doses
A “safe” dose is safe only for the specific health outcomes being measured.
Traditional tests often look for obvious signs of harm, like organ damage or a specific birth defect. But they may completely miss changes in other parts of the body, like the immune or nervous systems.
This means a chemical can be labeled safe at a certain level because it doesn’t cause organ damage in animals, even if the same dose is high enough to disrupt hormones or immunity.
What we define as the level at which a chemical becomes a poison depends entirely on which part of the body we’re looking at.
For example, PFAS were long considered safe at levels that didn’t appear to harm the liver. But once scientists researched impacts on immunotoxicity, they found these supposedly safe doses contributed to suppressed immune responses in children, prompting increased research and regulator scrutiny, including restrictions and bans on use and lower limits for allowable water contamination.
When setting a drinking water standard, the EPA evaluated data about all available health outcomes. It found that, in the case of PFOA, low exposure levels could lead to increased cholesterol, decreased birth weight, weakened immune response and liver harm.
The herbicide dimethyl tetrachloroterephthalate, commonly known as DCPA and sold under the brand name Dacthal, was initially approved in 1958 and deemed safe for use. In 2024, the EPA banned it following new findings that linked the pesticide to “irreversible harm to unborn babies’ developing brains,” among several other hormonal issues.
It’s more complicated than just dose
The science now suggests a more refined interpretation of Paracelsus’s statement: the dose matters, but the timing, the individual, and what else one is exposed to are also critical aspects in predicting harm.
While it’s generally true that a chemical is more toxic at higher doses, there are cases where that is not the whole picture. “The dose makes the poison” is overly simplistic and has been used for years to defend the continued use of harmful chemicals. The dose contributes to the poison, but there are many other factors at play.
And that’s why legal does not always mean safe.
