Research finds pesticides toxic at low doses 

Dr Vyvyan Howard is head of the Developmental Toxico-Pathology Research Group in the Department of Human Anatomy and Cell Biology at Liverpool University. At the Pesticide Use Reduction in Europe (PURE) conference, he spoke about measuring how toxic pesticides can be for human cells. John Harvey interviewed Dr Howard.

Field work: looking for insects in rice field. Photo: Thai Education Foundation

JH: Can you say how the work that you and your team are doing parallels the work of Professor Seralini at the University of Caen [see p. 4]?
VH: We have performed some research on combinations of pesticides in a test which is done on embryonal nerve cells. We can transform them so they start to grow out little hair-like processes to communicate with other nerve cells. A measure of the inhibition of that process is predictive of developmental toxicity in the brain.
    This is the work of Dr Janie Axelrad. One of the interesting things she found was that when you looked at the active ingredient, on its own it was less toxic in this test than when you had it in its formulation. That is in parallel with the work at Caen, where they have had very similar findings on a different model.

JH: This work was with glyphosate?
VH: Yes. Now the other thing which Janie Axelrad did was to expose some of the cells that were used for eight weeks to a very low concentration of an organophosphorous compound called diazinon. Then she re-challenged those cells which had been chronically exposed at extremely low dose to some other compounds, including glyphosate. She found that they were much more sensitive to the toxic effects than they would have been if they had not been pre-exposed to this low dose.
    What she was trying to model there was the fact that all of us are carrying low doses of these substances around in our bodies. If we then get hit with a higher dose, the question is does that mean we are more susceptible.
    All this testing has been done in a dish in a lab in vitro and working out what that means in vivo in the intact animal or person needs to be found out. But the fact that our French colleagues have found similar sorts of synergies between glyphosate and mixtures is interesting and requires further investigation.

JH: Why are so few laboratories doing this work when glyphosate is used in so many countries around the world?
VH: There are more labs beginning to look at mixtures, though it has until now been very difficult or nigh impossible to obtain funding for this type of work. Clearly the companies producing pesticides don't want to investigate this problem. But it is a very daunting prospect. We are all walking around with exposures to literally hundreds of groups of chemicals and if you break those down into their individual bits and pieces, we are talking about a mixture which is tens of thousands of different compounds. We do not really have the tools to be able to decipher such a complex mixture.
    Janie Axelrad looked at some 40 pairs of interactions: now that took three years. If you just take 1,000 chemicals and take any three in permutations at one concentration, you are dealing with more than 160 million experiments.
    From a regulatory point of view, our option is very clear: we must reduce our exposure as a population to groups of chemicals which are perceived to be hazardous. By hazardous, I mean they may be developmental neuro-toxicants or they may cause cancer – all these different aspects.
    The manufacturers often ask us to look at chemicals one at a time, prove that this specific chemical is causing that specific condition, then they will remove it. They know as well as we do that that is impossible. So this is not a suitable way forward.
    Demonstrations of chemicals working in a more than additive manner in these tests indicate to us that there may well be problems in complex mixtures. But it does not change the approach currently put forward by Margot Wallstrom, the EU’s Environment Commissioner. An overall hazard reduction programme based on the toxicological data, without any further ado, is a sensible and pragmatic way forward.

JH: If laboratories across Europe are questioning glyphosate use, would you say to EU Commissioner Wallstrom that she should reduce the use of pesticides immediately?
VH: They are in very widespread use. I think the assumption that glyphosate degrades rapidly in the ground has been shown to be wrong. Two countries have now reported that it is getting down into aquifers and drinking water. We should not have it in our drinking water, so steps should be taken to reduce that.
    Further research is required to show whether the interactions we have shown in the lab in vitro are demonstrable in vivo. In the meantime, there seems to be a certain amount of information available to show that we should be acting with caution.

JH: The Caen group also found that by looking at a particular enzyme they could detect effects from glyphosate on the human sexual function.
VH: Most toxicology in the past has been based on Paracelsus’s dictum that ‘the dose makes the poison’. That was aimed at adult, acute toxicity, and says that the more you take, the more poisonous the effect. What we know from many different sources is that when you are looking at foetal development, you cannot assume these straight line dose-response relationships. Retinoic acid is an example: you can have too much or you can have too little and either will lead to adverse effects in the foetus.
    The toxicology that we are worried about now is not just a few bad actors in adults at high dose, but the fact that there seem to be many bad actors which can act at low doses to hijack development. This is occurring within a complex mixture and with current technology there is no way of unravelling it.
    There are adverse effects observable in the pattern of human disease, both in foetal malformations and the increase in the incidence of cancer – particularly in young people – and we can observe that those changes have taken place over the same period of time as the introduction of these novel chemicals. Since many of these are hormone disruptors and carcinogens, it is plausible that there may be a relationship. But that is as far as we can go because we have no analytical tools to directly test it.

Vyvyan Howard, Head of Developmental Toxico-Pathology Group, Department of Human Anatomy and Cell Biology, University of Liverpool, tel: 0151 794 3854 /5958, c.v.howard@Liverpool.ac.uk

[This article first appeared in Pesticides News No. 63, March 2004, page 5]