In my series 17 Questions about Glyphosate, question 5. deals with questions I have encountered about how to prepare for and anticipate potential problems which we may have too little knowledge of to foresee at present. In other words, should we apply the precautionary principle and ban glyphosate altogether? For comparison points for such precaution, people often point to thalidomide and DDT. No regulation, as in the time of DDT, versus today, with extensive regulation that requires almost a decade of testing before approval, have dramatically changed the landscape when it comes to unknown risks from pesticides. Question 6. compares toxicity of glyphosate to other pesticides and household chemicals, looks at how dangerous pesticides used to be, and how far we have come from the situation we had but a few decades ago.

5. Could glyphosate be another case like DDT or Thalidomide?

Hearing science-speak conclusions like “failure to show adverse effects”, or “no correlation found”, or “not likely to pose risk” often leaves a layman out cold in the mists of the inherent scientific uncertainty. For our everyday logic, there is a threshold of such little perceived risk, where we simply declare something safe. But science holds fast to the humble intellectual honesty of saying “despite all our best efforts, there is still a very slim chance of an effect that could become evident in some unknown context in the future”. That may make our everyday brains feel uneasy.

An oft surfacing thought amongst the sea of possibilities is along the lines of: isn’t it better to be safe than sorry? It’s happened before – we have realised too late that an approved of chemical has turned out to have unexpected harmful effects. Two specific arguments frequently offered in support of the value in precautionary thinking include the examples of DDT and thalidomide.

The problem is that ‘something has at some point caused harm’ is not a useful way to guide our actions, unless there are reasonable grounds that the mechanism of said harm is similar. If there are no significant similarities, then how do we choose where to apply our absolute better-safe-than-sorry caution? Should we apply it to any medicine? Any household chemical? What about natural pesticides produced by plants themselves, half of which also have carcinogenic potential? We need to find some reasonable basis for our caution.

5a) Are there parallels between glyphosate and the case of thalidomide?

As an exercise in evaluating relevance, let’s first look at Thalidomide and glyphosate. Firstly, Thalidomide is in a special class of compounds (chiral molecules), which have special properties depending on the stereoisomer – like our left and right hands, these stereoisomers are very alike, almost identical, but they have such 3-d structure that they can’t be superimposed onto each other. The S and R Thalidomide molecules are distinct mirror images of each other, and one of these forms causes drastic harmful effects for a developing foetus.

The hydrogen and nitrogen atom bonds, described with a wedge vs dashed, point in different directions, a bit like the thumbs of right and left hand bend in different directions if viewed superimposed.

Glyphosate however is not chiral. It does not belong to this group of molecules at all.

Thalidomide was a drug used by humans, particularly pregnant women. Glyphosate is not a drug, it isn’t taken in a dose aimed at having a tangible effect on humans, instead it is found only in our food in trace amounts – only modern wonders of measurement technique can detect these levels. Thalidomide was taken in large doses by pregnant women before it had been tested for teratogenicity (birth defects). Glyphosate is not taken at all, but it’s effects have been tested by a whole body of research.

Thalidomide was used, off-label, by a group of people during two years, and problems arose immediately. When they did, a clear molecular mechanism of its harmful action was found. At this time Thalidomide had still not in fact been approved for that use. It was undergoing regulatory evaluation, but select doctors were prescribing it for their patients prematurely before FDA approval.

Glyphosate, on the other hand, has been approved for use and indeed used for 40 years, and rodent tests as well as epidemiological human studies have found no cause for concern. No clear mechanism of action has been proposed.

The lack of similarities makes it equally relevant to compare glyphosate to any substance within the mountains of medical compounds that have been brought to market and have saved countless of lives.

5b) But what about DDT?

DDT or Dichloro-Diphenyl-Trichloroethan

It’s a pesticide, just like glyphosate. It was approved for use and turned out to linger in the ecosystem. It is about ten to forty times more toxic than glyphosate measured in LD50 (113-450 mg/kg for DDT vs 4900 mg/kg for glyphosate). What is more important, is that DDT is a so called Persistent Organic Pollutant (POP) which is biomagnified in living organisms – it is not cleared, but accumulates in the body. Had its use not been discontinued, it could have caused great harm for animals higher up in the feeding chain.

This was the absolute key to the problem with DDT: it persists in the environment. It is not cleared from our bodies, and neither is it broken down by sunlight, plant or animal metabolism, or soil microbial activity. This is also where the similarities with glyphosate end. Glyphosate is readily broken down in plants and in the soil, and the minute residues we encounter are cleared from our bodies through normal metabolism. Agricultural geneticist Kevin Folta has written an informative piece on glyphosate where he lays out the math:

glyphosate is degraded, both in the plant and in the soil, so that 83 mg per square meter (…”Speaking metrically, that’s 340 g of active ingredient per acre.”…) is going away as soon as it is applied. It is not taken up by roots, so what is not applied to the plant itself goes into the soil and is degraded with a half life of 3-130 days depending on soil type and other factors.

Jeffrey Smith’s Institute for Responsible Technology says that it persists for 22 years, which is certainly possible when a half life is 130 days. After 22 years there likely are a few molecules still hanging around at least if the math is right.

A word on persistent vs non-persistent pesticides

Neuroscientist Alison Bernstein, who has studied the role of pesticides in Parkinson’s disease, wrote the following analysis of persistent vs non-persistent pesticides on her Facebook page, Mommy, PhD:

Persistence and toxicity are interrelated and bioaccumulation is critical when considering toxicity. […] The answer is, for a non-persistent pesticide, [at the allowed level of residue] you could not possibly eat enough produce to get to a dose that is toxic. Add to the fact that since the pesticide is not persistent, it is also cleared from the body. So the exposure is low and then it is cleared. In short, you cannot eat enough to approach doses that have acute toxicity and the chemical doesn’t stick around long enough to have any chronic effects.

[…] The switch from persistent to non-persistent pesticides is major progress for reducing our toxic exposures. We have come a long way since thinking that DDT was good for us.

Glyphosate has not been found to persist, or bioaccumulate, in living organisms, and neither has its breakdown product, AMPA (you can find a review here). In fact, a recent study on dairy cow metabolism found that 61 % of glyphosate was excreted, 8 % removed in urine, none found in milk, and found that a significant portion of both glyphosate and AMPA may become biodegraded in the rumen.

Regulatory (r)evolution – why DDT could not happen today

DDT was used as an insecticide starting around 1945, its effect on mosquitos helped eradicate malaria in North America, as well as control typhus and malaria during WW2. During this time in the US, there was no established regulation of pesticides – they did not have to be registered or tested, and their use was not controlled. The first attempt to even introduce marketing control (to ensure the companies sell what they promise) came 1947, and the first concerns for safety were introduced to regulation between 1954-1959, such as establishing safe levels, not allowing carcinogens, and requiring pesticides to be registered (find out more in the Wikipedia outline on pesticide regulation history).

The sixties and seventies saw more political and regulatory hurdles aimed at increasing control, largely thanks to the spread of awareness of the harm from pesticides, most notably from DDT, which was banned in the US in 1972, one year after the Environmental Protective Agency (EPA) was founded. Through seventies and eighties the agency struggled to get on its legs and working properly, including things such as having adequate funding, revealing fraud in an important independent testing company, political twisting on different amendments, and actually getting down to the task of evaluating all chemicals already in use (and farmers have been using methods of chemical pest control at least since the time of ancient Rome, more about that in this piece on pesticide history by entomologist K. Delaplane).

In the nineties important amendments were finally in place, such as the Food Quality Protection Act 1996. Neuroscientist Alison Bernstein, who studies the effect of pesticides on Parkinson’s disease, notes several other amendments which have continued improving the process in her article on pesticides:

Other laws (the Food Quality Protection Act of 1996, the Pesticide Registration Improvement Act of 2003, the Pesticide Registration Improvement Renewal Act of 2007 and the Pesticide Registration Improvement Extension Act of 2012) have amended this process.

Under these laws, new pesticides need to be registered before the can be sold and distributed. Existing pesticides must be reevaluated every 15 years to incorporate new data and ensure that they continue to meet current safety standards. All pesticides registered prior to the introduction of the Food Quality Protection Act in 1996 were also reassessed.

In other words, nowadays all pesticides must go through extensive testing before they can become registered and taken into use. From the Food Quality Protection Act 1996:

These tests include: acute toxicity test (short-term toxicity test) and chronic toxicity test (long-term toxicity test). These tests evaluate: whether the pesticide has the potential to cause adverse effects (including cancer and reproductive system disorders) on humans, wildlife, fish, and plants, including endangered species and non-target organisms; and possible contamination of surface water or ground water from leaching, runoff, and spray drift.[9] The registration process can take upwards of 6 to 9 years, and the cost of registration for a single pesticide is in the range of millions of dollars (Toth, 1996).

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There is no way something like DDT could pass these tests today. DDT was an endocrine disruptor, it is lipophilic, (it likes to stick to fatty environments such as those found inside organisms), and its half life in humans 6-10 years.

Glyphosate however is not an endocrine disruptor, it is not lipophilic, it is cleared mostly through the gut, and rest through urine. Rats clear all glyphosate from their system within a week, and in known human cases of acute glyphosate poisoning (drinking large amounts of glyphosate), the levels dropped to almost undetectable after 12 hours. The half-life has been estimated to 3 hours, and an analysis of 601 cases of self-poisoning attempts, the fatality rate was 3.2 %, fatalities associated with larger ingested amount and greater age.

Nowadays endocrine disruptor activity, as well as cumulative effects, are some of the standard things that must be tested before something can be approved as a pesticide:

The EPA must find that a pesticide poses a “reasonable certainty of no harm” before that pesticide can be registered for use on food or feed.[9] Several factors are addressed before a tolerance level is established[9]

• the aggregate, non-occupational exposure from the pesticide (this includes exposure through diet, drinking water, and the use of the pesticide in and around the home);
• the cumulative effects from exposure to different pesticides that produce similar effects in the human body;
• whether there is increased susceptibility to infants and children, or other sensitive subpopulations, from exposure to the pesticide; and
• whether the pesticide produces an effect humans similar to an effect produced by a naturally occurring estrogen or produces other endocrine-disruption effects.

Interestingly, from 60s through 80s, European scientists were criticising US for implementing overly cautious regulations more on the basis of public concern rather than scientific evidence, and European regulations were much less restrictive, which might come as a surprise as people are much more used to thinking the opposite. It was only after the eighties when it was Europe’s turn to rely more heavily on precautious principles, even against the better judgement of the scientific community – you can read more about that over at The Regulation of GMOs in Europe and the United States: A Case-Study of Contemporary European Regulatory Politics.

To conclude: people had good cause to raise alarm about the harm from pesticides back in the mid 20th century, as this was the first time the issues were noted with appropriate gravity. The environmental movements of the time were championing for a good cause. As recently as 1980s, there were still hiccups in ensuring a properly meticulous process when it came to regulating pesticides. But when advances are made, it is also important to update one’s information. Many pesticides back in the day were risky, some with potentially grave consequences – but just because all pesticides fall under the same category of usage, it doesn’t mean that a pesticide substance today would be anything like arsenic or DDT.

To get a better understanding of that, let’s look at how glyphosate, and pesticide usage in general today differs from pesticides used before.

6. Is glyphosate an especially dangerous pesticide?

There are many pesticides that have been in use for hundreds of years which carry clear potential for harmful effects for the consumers, such as lead arsenate and other arsenate compounds. The use of these, luckily, has largely been banned or discontinued between 1950s and 1980s. Other pesticides, such as DDT and 2,4,5-T (responsible for much of the ill effects in Agent Orange), were introduced around last mid-century and also became banned a few decades later after clear evidence of harm to humans or the ecosystem had surfaced. The substances introduced during this time (when regulation was non-existent, as outlined above) are probably responsible for much of the reputations pesticides still carry today.

But most of the pesticides in use today are significantly less toxic than those used even a few decades ago, and despite what many might think, glyphosate is actually among the safest of the bunch. If you look at the doses that have proven lethal to half of the laboratory animals tested, the so called Lethal Dose 50 (LD50), you find that some of the most common organic herbicides, such as clove oil, acetic acid, and cinnamon oil, are also more toxic than glyphosate. In fact, when it comes to the lethal dose, even table salt is more toxic than glyphosate formulation or active ingredient (see table below: 3000 vs 4900 mg/kg, or glyphosate active ingredient 5600 mg/kg – toxicity studies on glyphosate LD50 can be found here, and studies determining the No Observable Adverse Effects Level (NOAEL) here). Other common substances and their LD50 values described here.

LD50 values can be interesting, they are not, however, the most relevant ways of looking at glyphosate toxicity. Neuroscientist Alison Bernstein writes in Glyphosate Vs. Caffeine: Acute and Chronic Toxicity Assessments Explained:

Most real human exposures are not acutely lethal but have other, long-term or chronic, effects that may or may not be toxic. Thus, LD50s are not very useful when considering health effects of the large majority of human exposures.

This does not mean that glyphosate would appear more concerning from the point of view of chronic toxicity. In fact, Dr. Bernstein concludes:

[…] caffeine is 40 times more toxic than glyphosate. However, this is only a useful number if we know our typical exposures. The exposure numbers above show that we don’t give a second thought to consuming caffeine at levels hundreds of times higher than the oral RfD [Reference Dose – European Food Safety Authority uses the term ADI, Acceptable Daily Intake], but are simultaneously worried about exposures to glyphosate that are 100 times lower than the RfD.

This doesn’t mean we don’t have to be careful about glyphosate’s effects – we wouldn’t want to sprinkle salt, coffee, or concentrated plant oils on our fields either without a good understanding of the consequences.

University of Florida Pesticide Information Office compared the toxicity of herbicides and household chemicals. The lower the LD50 (dose at which half of lab animals die) value, the more potent the toxicity of the compound. Glyphosate (LD50 4900) is less toxic than table salt (LD50 3000).

In fact there is a lot more focus on what consequences there are to using pesticides than there used to be. DDT, 2,4,5-T, and lead arsenate have been banned. Farmers in the US no longer treat apple orchards with arsenic-containing pesticides (which still contaminate the grapes of some wineries growing in their place, and whose use continued for longer in other countries, such as China).

This switch to less toxic pesticides, which Alison Bernstein also talked about above, is part of a process which many consumers may not be aware of. During the past several decades, science and regulatory agencies have moved modern agriculture away from persistent and acutely toxic substances. Milder, more targeted, and much less generally toxic pesticides have replaced older, harsher agents. Thanks to wide adoption of Integrated Pest Management and biotech crops, overall pesticide use is also down.

Agricultural scientist and journalist Steve Savage has written in detail about the kinds of pesticides in use today. Using pesticides in California as his example, he illustrates the major shift toward essentially non-toxic substances, and he compares changes in amounts and toxicities of pesticides used between 1990 and today. He writes:

Most pesticides today have oral ALD(Acute Oral Toxicity)50s of more than 5,000 mg/kg (Category IV) and are less toxic than table salt, vinegar, citric acid, vanillin and many other familiar food ingredients.

University of Florida Pesticide Information Office has also put out a report on this trend towards much more harmless herbicides, called Herbicides: How Toxic Are They? In it, they write:

Although there have been pesticides that were toxic and dangerous to handle, most of these products are no longer used and have been replaced by newer chemistry. Pesticides now must go through rigorous testing by the U.S. Environmental Protection Agency (EPA) before they can be sold. This has led to many herbicides that possess little or no mammalian toxicity and are less harmful than many everyday household products (Table 1). Surprisingly, household chemicals that many of us store under the kitchen sink pose more risk to the handler than herbicides.

For other comparisons, see the excellent piece here by Cami Ryan: The Dose Makes the Poison. Her table also illustrates that rotenone (rarely used in organic farming) and copper sulphate (very common in organic farming) are much more toxic than glyphosate. This begs the question, why are so many people worried about glyphosate, and not other, more toxic pesticides?

The Credible Hulk has written a piece documenting the effects of many of the pesticides which glyphosate has directly helped make redundant, many of which we would need to resort to again, should glyphosate become banned in the EU. What we need to consider, is which of the known risks are larger. In his piece, The Credible Hulk writes:

Many people never even hear about the herbicides that were phased out in favor of glyphosate simply because they aren’t pertinent to the anti-agricultural biotech narrative, and because their popularity had waned by the time it had become trendy to demonize GMOs and everything remotely associated with them.
[…]
Weeds are a legitimate problem in farming that has to be dealt with one way or another. In its absence, it would have to be replaced with something else, and it would likely be something more harmful: not less.

The important question is whether there is a realistic basis to worry about a risk – any risk, not just glyphosate. Why should we single out glyphosate as more risky than something else? What about the risks of not using glyphosate (more about that in section 13. Glyphosate and The Environment)? In life we rarely choose from a scenario where there is only the risk of one thing to consider. Choosing not to do something has different consequences, and also carries a risk. Which choice should we apply precautionary principle on?

The best way to find guidance to that question is to rely on the collected wisdom of the best and most comprehensive recent reviews on the research. At present, they show that used appropriately, glyphosate is a very safe option for weed control, with many benefits and little risk.

If you are interested in other environmental or health topics, you can find my other pieces on glyphosate over at 17 Questions about Glyphosate, and further resources under Farming and GMOs, The Environment, and Vaccines and Health. If you would like to have a discussion in the comments below, please take note of my Commenting policy. In a nutshell: