Environmental pharmacology: how safe is our chemical jungle?

By Christopher Connolly, University of Dundee

CC-image2The human population has grown from 1 billion in the 1800’s, to 7 billion in 2012 and is estimated to reach 10 billion by 2050. Feeding this burgeoning population, as cheaply as possible, has driven the global industrialisation of agriculture. Now large monocultures replace a diverse natural habitat. In so doing, the natural ecosystem balance has been damaged and in defence of our food supplies we have opted for the easy solution – chemical warfare against pest species.

Industrial scale pesticide use

To protect our crops against insect pest species, fungal attack and competition from weeds, we trust the use of insecticides, fungicides and herbicides. In total, between 1990 and 2005, the UK used an average of 33,155,000 kg of pesticide per year. This has now been reduced to an estimated 17,817,809 kg of pesticide in 2015. However, using this as evidence for a reduced chemical load is disingenuous, as it ignores potency. Imagine halving your daily alcoholic consumption from 3 pints of beer to just one pint of whisky! Many of today’s pesticides are highly potent, requiring small quantities to achieve the same goal.

In addition to increased potency, the area of land treated has steadily increased, from 44,981,520 hectares (ha) in 1990 to 80,274,553 ha in 20151. The total area of the arable land in the UK is 6,400,000 ha, yet it is estimated that 79,449,062 ha is treated with pesticides. This discrepancy is because multiple applications (an average of 12.4) are applied to the same field. One report suggested that twenty chemical applications in a field may be common.

Beyond agriculture, pesticides are also used on local amenity sites (eg. parks and golf courses), most ornamental garden centre plants and on livestock/pets to control ticks and fleas. Finally, adding to this chemical load is the large amount of waste therapeutic drugs that are discarded or excreted into the environment. Therefore, our total chemical exposure is vast, complex and chronic. Do we know that such exposure is safe?

Pesticide recording

There is a risk-benefit relationship that we must consider. For example, chemotherapy is highly toxic and no healthy person would want to be exposed to these toxic chemicals. However, for a cancer patient, the toxicity may be a price worth paying. The same risk-benefit analysis should be considered for all chemical uses, whether it be for environmental or personal benefits.

In contrast, the overuse of chemicals leads to diminishing returns (benefits) and higher side-effects (risks). Their chronic overuse can back-fire and lead to the development of resistance, which is a major problem for insecticides in the control of pest species of crops, and antibiotics in the control of bacterial pathogens.  In the case of pesticides, some chemicals like the neonicotinoids are widely used prophylactically, as an insurance against possible future attack. In these situations, there is widespread environmental contamination, little benefit, chronic toxicity and developing pest resistance.

In the UK, pesticide use data is extrapolated from data gathered at pilot farms every two years1. However, this data is just an indicator of usage and does not provide any local information that might inform on its consequential effects on the environment or human health. Under EU regulations (EC No. 1107/2009), all farmers must record their chemical use. However, this information is not gathered and so epidemiological studies to identify correlations between chemical cocktail use and the local consequences of such use is not possible. This is an important opportunity lost, as knowledge of the impact of chronic exposure, or exposure to chemical cocktails, is difficult to obtain in the laboratory due to the large number of chemicals and combinations possible.

Chronic exposure

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Bumblebee in flight (Tracey Dixon, University of Dundee)

The additional risk from chronic exposure may be a consequence of molecular adaptations that lead to increased sensitivity and even preference seeking. For example, in man, chronic nicotine exposure leads to receptor upregulation that drives preference seeking behaviour in smokers. In bees, the acute response to neonicotinoids is hyperactivity. Within minutes, neurons become non-responsive to normal stimulation and neuronal function is lost. These acute effects are reversible. However, following chronic exposure to neonicotinoids, bees also experience increased preference seeking and suffer a heightened vulnerability to future exposure, presumably due to receptor upregulation.

Cocktails

Several hundred pesticides and about a hundred different broad categories of therapeutic drugs are available, making the opportunity for chemical cocktail exposure enormous. Increased toxicity from chemical cocktails is the basis of combined therapy approaches (eg. in targeting cancer). When chemical cocktail exposure occurs via our food, drink or therapeutic use, each compound is below its safety limit, but tests are not performed on chemical combinations.

Future directions

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Queen honeybee attended by worker bee (Tracey Dixon, University of Dundee)

There have been recent calls for better pesticidovigilance and possible monitoring of biological accumulation of these chemicals by sampling local honey. Likewise, polypharmacy needs wider consideration and better evidence gathering of identified drug interactions.

Once we have a full record of chemical or therapeutic exposure, and its consequences, we can perform epidemiological studies to identify potentially toxic cocktails that can direct experimental ‘cause and effect’ studies. The industrialisation of the use of pesticides and therapeutics requires that we apply the basic principles of pharmacology to learn about the risk and how to mitigate against it.

Further reading:

  1. Data provided by DEFRA. http://pusstats.fera.defra.gov.uk/myindex.cfm

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