This is the conclusion of the first comprehensive review of gaps in risk assessments for “adjuvants” – ingredients added to pesticide formulations to enhance the function or application of the active ingredient. Ignoring the potential dangers of other ingredients in commonly used commercial pesticides leads to inaccuracies in the safety profile of the pesticide solution, as well as confusion in scientific literature on pesticide effects, finds the review published in Frontiers in Public Health.

“Exposure to environmental levels of some of these adjuvant mixtures can affect non-target organisms – and even can cause chronic human disease,” says Dr Robin Mesnage from King’s College London, who co-wrote the review with Dr Michael Antoniou. “Despite this, adjuvants are not currently subject to an acceptable daily intake and are not included in the health risk assessment of dietary exposures to pesticide residues.”

Pesticides are a mixture of chemicals made up of an active ingredient – the substance that kills or repels a pest – along with a mixture of other ingredients that help with the application or function of the active ingredient. These other ingredients are known as adjuvants, and include dyes, anti-foaming agents and surfactants.

Inadequate testing

Regulatory tests for pesticide safety are currently only done on the active ingredient, which assumes the other ingredients have no effects. This means the full toxicity of a pesticide formulation – including those used in both agriculture and domestic gardens – is not known.

“Currently, the health risk assessment of pesticides in the European Union and in the United States focuses almost exclusively on the active ingredient,” explains Dr Mesnage. “Despite the known toxicity of adjuvants, they are regulated differently from active principles, with their toxic effects being generally ignored.”

Based on a review of current pesticide literature, the authors describe how unregulated chemicals present in commercial formulations of pesticides could provide a missing link between pesticide exposure and observed negative outcomes.

Formulations more toxic than the active ingredient alone

The researchers focused on glyphosate-based herbicides, the most used pesticide worldwide. They point out that this weed killer has so many different adjuvant formulations that a safety test of one weed killer does not test the safety of another.

“Studies comparing the toxicity of commercial weed-killer formulations to that of glyphosate alone have shown that several formulations are up to 1,000 times more toxic than glyphosate on human cells. We believe that the adjuvants are responsible for this additional toxic effect,” says Dr Mesnage.

The authors also looked at neonicotinoid insecticides – strongly suspected to be involved in the collapsing of bee colonies – as another example of adjuvant toxicity affecting non-target organisms. An adjuvant used in these insecticides to increase the penetration of the active ingredient has been shown to cause varying toxic effects in bees. On top of this, residues of the toxin have also been found in honey, pollen and beeswax produced by contaminated bees.

The need for precaution

In some investigations into chemical toxicity, the additive effect described in this study is known as the ‘cocktail effect’ – where combinations of chemicals can become more toxic than the sum of each individual chemical in the mix.

The authors hope their review will stimulate discussion on the toxicity of commonly used pesticides and encourage more thorough regulations.

“Testing of whole pesticide formulations instead of just active ingredients alone would create a precautionary approach, ensuring that the guidance value for the pesticide is valid for the worst-case exposure scenario,” says Dr Mesnage.

Their findings have already had a considerable impact. The European Food Safety Authority is now reassessing the validity of pesticide risk assessment in the EU, and authors hope that this reassessment can extend to entire commercial formulations of pesticides and their other ingredients.

So how do you know if a test, treatment of procedure is appropriate and helpful? An interesting new initiative in the US called Choosing Wisely aims to promote conversations between physicians and patients by helping patients choose care that is:

• Supported by evidence
• Not duplicative of other tests or procedures already received
• Free from harm
• Truly necessary

The initiative challenged 17 national organisations representing different medical specialities to identify five tests or procedures commonly used in their field, whose necessity should be questioned.

The resulting lists of Five Things Physicians and Patients Should Question, which are available to download, are fascinating and applicable to medical practice throughout the world. They should spark discussion about the need – or lack thereof – for many frequently ordered tests or treatments.

Included amongst the lists are:

• Taking antibiotics for sinus infections. Most are caused by viruses, which aren’t affected by antibiotics.
• Induced labour or caesarean section.  Unless there’s a proven medical necessity, babies should go to full term and be delivered naturally, since those delivered before 39 weeks can have lung problems, learning disabilities, and other problems.
• Stress tests if you have no symptoms of heart disease. Asymptomatic, low-risk patients account for up to 45% of unnecessary screening.
• Routine annual Pap test if you’re under age 21 or over age. Once every three years is fine unless you’ve had an abnormal test result.
• DEXA (dual-energy X-ray absorptiometry) screening for osteoporosis in women under 65 or men under 70. Unnecessary unless there are signs of bone loss.
• CT scans for children with minor head injuries: Commonly used, but unnecessary.
• EEG (electroencephalography) for patients with recurrent headaches. It has no advantage over clinical evaluation in diagnosing headache, does not improve outcomes and increases cost.
• Imaging for lower back pain. Unnecessary unless the pain has lasted more than six weeks or special circumstances like neurological deficits are involved.
• Antibiotics for pinkeye (conjunctivitis). This is usually a viral disease, so won’t respond to antibiotic treatment.
• PET or CT scans to screen for cancer in healthy people. There is little chance such tests will detect anything.

Consumer friendly information sheets are currently being developed from this early data. In the meantime more than 35 speciality societies have now joined the campaign, and these first 17 lists complete with references and rationales for the choices made,  represent the beginning of an important conversation about evidence based medicine.

The report which is well-timed to support the Just Label It campaign in the US and inform the vicious battle over Proposition 37 in California, is set to add fuel to the debate over the safety – or otherwise – of GM crops.

In an unusual move, the research group behind the research did not seek outside comment on their paper before its publication in the peer-reviewed journal Food and Chemical Toxicology.

This is thought to be because of very real fears (see below) that the biotech company whose maize they used, would seek to suppress their findings.

Professor Gilles-Eric Séralini and colleagues at the University of Caen in France  found that rats fed on a diet containing NK603 – a seed variety from crop giant Monsanto made tolerant to repeated spraying of the best-selling weedkiller Roundup – or given water containing Roundup at levels permitted in the United States died earlier than those on a standard diet.

The researchers were looking for chronic effects from the GM feeding regime, but found more than they bargained for.  Animals on the GM diet suffered hormone imbalance and more and bigger breast tumours, as well as severe liver and kidney damage. The researchers said 50% of males and 70% of females died prematurely, compared with only 30% and 20% respectively in the control group.

A thorough investigation

The new paper is supported by the independent research organization, Committee for Research and Independent Information on Genetic Engineering (CRIIGEN).

Dr Michael Antoniou, molecular biologist at Kings College, London, and a member of the CRIIGEN scientific council, said:

“This is the most thorough research ever published into the health effects of GM food crops and the herbicide Roundup on rats. It shows an extraordinary number of tumours developing earlier and more aggressively – particularly in female animals.  I am shocked by the extreme negative health impacts.”

“The rat has long been used as a surrogate for human toxicity. All new pharmaceutical, agricultural and household substances are, prior to their approval, tested on rats. This is as good an indicator as we can expect that the consumption of GM maize and the herbicide Roundup, impacts seriously on human health.”

Dr Antoniou and other experts discuss the findings of the study in this video.

Where are the regulators?

In the UK Lawrence Woodward from Citizens Concerned About GM said: “These results are extremely worrying. Health problems associated with GM Round Up Ready crops have been reported before, but this is the first time research has so clearly demonstrated that genetic engineering itself can cause health risks”.

He added that the research raises significant questions about the rigour of the GM regulatory process. “The European Food Standards Authority (EFSA) does not require tests that are as extensive as these, and it’s clear they are missing things. These findings mean that EFSA’s handling of GM is inadequate.”

A lifetime of data

Séralini is part of a team that flagged previous safety concerns based on a shorter rat study in a scientific paper published in December 2009.

That study was a comparative analysis of blood and organ system data from trials with rats fed three main commercialised genetically modified (GM) maize (NK 603, MON 810, MON 863), which are present in food and feed in the world. The analysis showed that all three GMOs were associated with the kidney and liver damage, though other effects were also noticed in the heart, adrenal glands, spleen and on stem cells.

This study is important, however, because it takes things a step further by tracking the animals throughout their two-year lifespan.

According to the researchers, the first large detectable tumours appeared after four and seven months in males and females respectively but only after 14 months in the female control group and 23 months in a control male. However, the majority of tumours were only detectable after 18 months. In other words, the damage was slow to develop.

As with previous negative studies on GM, we can expect a furious response to the data from pro-GM pundits, and yet every year more and more research shows that, at best, we cannot simply assume that GM is safe and, at worst, it is dangerous to consume.

EU urged to act

In a joint statement, in response to the research, Agriculture Minister Stephane Le Foll, Ecology Minister Delphine Batho and Health and Social Affairs Minister Marisol Touraine said they had asked the National Agency for Health Safety (ANSES) to investigate the finding.

“Depending on ANSES’s opinion, the government will urge the European authorities to take all necessary measures to protect human and animal health,” they said.

“(The measures) could go as far as invoking emergency suspension of imports of NK603 corn to Europe pending a re-examination of this product on the basis of enhanced assessment methods.”

Who is Séralini?

Gilles Eric Séralini has worked tirelessly to expose the health hazards of Monsanto’s GM maize varieties, its herbicide Roundup, and the inadequacies of the EU regulatory system for GMOs and pesticides.

In 2005 he reported that human placenta cells were very sensitive to the herbicide Roundup, even at doses much lower than those used in agriculture. Like other scientists before him he was severely criticised by the GM establishment and his work and professional reputation pilloried in the media, which accused him of being more of an ecological fundamentalist than a serious scientist.

The main complaint of the pro-GM brigade was that laboratory studies using cells prove little and that only feeding studies using animals or humans were worth paying attention to.

It’s an interesting argument given that most of the medicines we take today, and indeed much of the ‘safety’ of GM, as defined by the biotech companies that produce it, depends on laboratory studies on cell cultures.  Indeed cell culture studies are seen as a first step in any scientific process. Should such studies turn up meaningful data, the next step is to see if the effects can be replicated in lab animals or humans.

It is also a not entirely unpredictable irony that early responders to this current study have moved their own goal posts, protesting that animal studies aren’t predictive of human risk. Though again, if this is the case, one could question the basis on which almost every drug currently in use has been passed by government regulators.

A year earlier,in 2004 Séralini, was on the committee that reviewed MON 863 for the French government.

Monsanto sought approval in Europe to introduce a rootworm resistant MON 863 maize. Critics argued that Monsanto’s data was biased and incomplete and that regulatory bodies had been unduly influenced by biotech companies. The GMO Panel of the European Food Safety Authority (EFSA) stated that it had no reservations about approving MON863.

And yet, contained in the report were references to data that Monsanto provided, which suggested changes in some blood cell parameters and in kidney weights of rats that were tested, though these studies were not publicly available.

Gagged

As a condition of the peer review process, Monsanto placed a gagging order on the studies, preventing reviewers from disclosing their details. One of these reviewers was Dr Arpad Pusztai whose own animal feeding studies had previously shown major damage to the gut walls of  animals fed GM potatoes.

Environmental group Greenpeace sued for release of data that Monsanto had locked away. A German court eventually ordered its release in June 2005.

With the gagging order lifted Séralini and his team, were able to fully review the data. His reanalysis of a Monsanto feeding trial, which was eventually published in 2007 showed serious damage to the liver and kindeys of laboratory animals and raise serious questions about the regulatory process for GM.

At the time Professor Seralini commented: “These revelations are profoundly disturbing from a health point of view. They are certainly sufficient to require new and more carefully conducted feeding studies and an immediate ban from human or animal consumption of GM maize MON 863 and all its hybrids. This maize cannot now be considered safe to eat. We are now calling urgently for a moratorium on other approved GMOs while the efficacy of current health testing methods is reassessed.”

Libelled

In 2010 Séralini sued  the French Association for Plant Biotechnology (AFBV) for libel following a smear campaign which he alleged began with that organisation and which had damaged his reputation, reducing his opportunities for work and his chances of getting funding for his research. In January 2011 he won his case.

That same year Séralini and colleagues reviewed 19 animal based studies, some of which showed that consuming genetically modified corn or soybeans led to the organ disruptions, with male kidneys responding the worst.

A number of male rats who were fed Monsanto’s MON 863 corn developed smaller kidneys with significant inflammation among other markers of disruptive kidney filtration and function problems. Some animals experienced changes in metabolic rates in the liver. Female genital cancers increased in the second generation, and some of the animals who were fed genetically modified organisms had altered body weights in at least one gender, which is considered to be a very strong predictor of side effects displaying in various organs related to toxins in the diet.

Earlier this year Séralini and his colleagues announced the results of another laboratory study which examined the effects of two Bt toxins (in the presence and absence of the herbicide Roundup) on cultured embryonic kidney cells. The results suggested the GM toxins could cause serious damage to kidneys.

Consumers have a right to know – and to say ‘no’

And so we’ve come full circle. Yet another feeding study has shown that animals fed GM maize get sick and die more quickly than those that are not fed GM maize.

If anyone ever wondered why Californians are fighting so hard to get proposition 37, the mandatory labelling of GM food, passed this November the work of Séralini, Pusztai and others, who without support and too often without the lavish funding that is given to pro-GM scientists, is the reason.

If anyone ever doubted the GM food should be labelled, for our safety and to allow consumers to choose, and more importantly to refuse to eat GM, they must now think again.

• Copies of the study can downloaded here.
• This story was updated on September 20, 2012.

In this system, the appearance of the tongue is one of the measures used to classify the overall physical status of the body, or zheng.

Now, University of Missouri researchers have developed computer software that puts this ancient technique to the test.

For the study, 263 gastritis patients and 48 healthy volunteers had their tongues analysed. The gastritis patients were classified by whether they showed infection by a certain bacteria, known as Helicobacter pylori, as well as the intensity of their gastritis symptoms.

In addition, most of the gastritis patients had been previously classified with either hot or cold zheng. This allowed the researchers to verify the accuracy of the software’s analysis.

The computer programme used in the study, which was published in the journal Evidence Based Complementary and Alternative Medicine, successfully classified people based on their zheng status.

Useful and accurate screening tool

“Knowing your zheng classification can serve as a pre-screening tool and help with preventive medicine,” said Dong Xu, chair of MU’s computer science department in the College of Engineering and one of the authors of the study.

The software the researchers used analyses images based on the tongue’s colour and coating to distinguish between tongues showing signs of “hot” or “cold” zheng. Shades of red and yellow are associated with hot zheng, whereas a white coating on the tongue is a sign of cold zheng.

“Hot and cold zheng doesn’t refer directly to body temperature,” said Xu, who is also on the faculty of the Bond Life Sciences Center. “Rather, it refers to a suite of symptoms associated with the state of the body as a whole.”

For example, a person with cold zheng may feel chills and coolness in the limbs and show a pale flushing of face. Their voice may have a high pitch. Other symptoms of cold zheng are clear urine and loose stool. They also may prefer hot foods and drinks and desire warm environments.

A future for smartphone diagnosis?

The software used in the trial combines ancient wisdom – tongue analysis is practised in both traditional Chinese medicine  and Ayurvedic systems of medicine – with modern technology  providing an automated system for analysing images of the tongue.

“As we continue to work on the software we hope to improve its ability,” said study co-author Ye Duan, associate professor of computer science at MU. “Eventually everyone will be able to use this tool at home using webcams or smartphone applications. That will allow them to monitor their zheng and get an early warning about possible ailments.”

The paper appears in the prestigious Journal of the American Medical Association (JAMA) and discusses the potential harms of screening tests and reviewed the attitudes about these harms, which has shifted within medicine in recent years.

These include iatrogenic, or medically induced complications (for example perforation from colonoscopy), anxiety over abnormal results, and a cascade of follow-up tests and treatments. Screening can also precipitate over-diagnosis and therefore unnecessary drug and surgical treatments.

“People assume that getting screened for a disease is a ‘no-brainer,’” said co-author Steven H. Woolf, MD, MPH, professor in the Virginia Commonwealth University Department of Family Medicine and director of the VCU Center on Human Needs.

“There is presumably much to gain and little to lose by detecting diseases early. A common perception is that anyone objecting to screening must be worrying about costs, but most guidelines that set limits on screening are concerned about potential harms,” he said.

Not always good for your health

According to Woolf, the article draws attention to the “stark reality that screening tests are not always good for public health,” as well as discussing the increasing concerns being raised by the American Cancer Society and other professional organizations about screening tests.

“Being more mindful of limitations and downsides will make patients more informed consumers,” Woolf said. “They may still choose to be screened, but being armed with the full story will prepare them should they experience complications or later discover that the disease went undetected even with screening.”

Even breast cancer screening can cause harm

The JAMA study comes at the same time as the publication of a new book ‘Mammography Screening Truth Lies and Controversy’ by Prof Peter Gøtzsche, director of the Nordic Cochrane Centre, Copenhagen. In his new book Prof Gøtzsche argues that women undergoing breast cancer screening are being “misinformed” and are not told about the risks of over-diagnosis.

In September 2011 Gøtzsche co-authored a paper published in the Journal of the Royal Society of Medicine, (JRSM).

The paper, ‘The Breast Screening Programme and Misinforming the Public’, which looked specifically at breast screening programmes in the UK called for “more honesty” from the NHS. It argued that harm has been “downplayed” and that the information given to women about screening has remained largely unaffected by “repeated criticism and pivotal research” which has questioned its benefits and documented how it can lead to substantial over-diagnosis.

Doctors stuck in the past

The paper noted that many doctors beliefs had not changed in 25 years and that the lack of accurate balanced information means that, “Women therefore cannot make an informed choice whether to participate in screening.”

“The claim that death rates have fallen ‘in part from earlier diagnosis associated with screening’ is astonishingly misleading,” says Gøtzsche.

“Deaths from breast cancer are falling because treatment is improving. There’s been a similar fall in the age-groups not invited to screening.” What is more, he added, “Danish data has demonstrated that because of over-diagnosis, screening increases the use of mastectomies substantially.”