ISP Lecture Summary

Summarised by Lim Li Ching

Malcolm Hooper asked if we are slowly poisoning ourselves by eating herbicides and pesticides with GM and other foods. He highlighted the herbicides and pesticides that are closely related organic compounds of phosphorus - the organophosponates, including the herbicides glyphosate and glufosinate; and the organophosphates, including some pesticides.

Hooper explained that the problem lies in the fact that numerous processes in the body involve phosphate groups. They are used as switches to turn on and off all kinds of things. As such, processes such as gene activation, glucose transport, hormone response and energy production could be potentially damaged.

While drugs are usually highly specific with a unique target, herbicides and pesticides have a universal target in weeds and insects, respectively. Their goal is a target system(s) that is widespread in insects and plants, so as to kill as many insects and plants as possible. Hooper warned that the unexpected always happens, such as side-effects and the lack of discrimination between ‘good’ and ‘bad’ plants, and pests and organisms, especially humans.

Glufosinate ammonium (the herbicide used in conjunction with Aventis’ Liberty Link GM crops) inhibits glutamine synthetase. Hooper explained that glutamine synthetase is involved in the pathway that converts glutamate and ammonia to glutamine. Glufosinate blocks this pathway, which is the only way most plants remove ammonia. As ammonia is highly toxic to plants, it kills weeds. However, the pathway is universal and is found in humans, insects and micro-organisms. In humans and animals, ammonia is also toxic, but mainly removed by a different pathway.

Nonetheless, the glutamine synthetase pathway is involved in other essential processes. Glutamine maintains homeostatic balance, especially in the brain, immune system and gut. It is the body’s most abundant free amino acid. The gut utilises 40% of the body’s glutamine, which is also the major fuel for the brain, immune cells, kidneys and liver. Therefore, if the pathway and synthesis of glutamine were stopped, it would have enormous potential for damage and destructive imbalance of the system. Glutamine is also involved in detoxification processes, increases resistance to infection, regulates glucose metabolism, plays a key role in nucleic acid synthesis, is an anabolic protein in skeletal muscle and protects against burns, traumas and illness.

The other part of the pathway - glutamate - is also very important. As glufosinate blocks the conversion of glutamate to glutamine, levels of glutamate will increase, potentially creating problems. Glutamate plays key roles in humans and mammals; it is an excitatory neurotransmitter, an excitatory transmitter in the gut and enteric nervous system and an inhibitory transmitter in the gut and brain. It is involved in foetal brain development and is important in memory and learning.

Hooper concluded that it would be difficult to conceive of a more potentially damaging target that would be destructive to human health and well-being than the glutamate-glutamine-glutamine synthetase system. He stressed that any disruption of this finely balanced and essential system by compounds such as glufosinate will have far-reaching and long-term consequences.

He then cited evidence of the effects of acute, high dosage of glufosinate in humans: neurotoxicity, convulsions, mental disturbance and memory loss. Its metabolite is also neurotoxic. Congenital malformations and respiratory failure have been recorded. Furthermore, the surfactant in the formulation is cardio-toxic.

However, the manufacturer dismisses these concerns, claiming that ultra high doses are not relevant to toxic effects associated with proper usage. Nonetheless, high doses are commonly used to tease out major toxicological effects. In the drug industry, high doses would be tested, and the impacts serve as warnings to highlight the problems.

Hooper also outlined the negative effects of glufosinate on mice, such as convulsions, release of nitric oxide (affects many bodily processes), teratogenesis, brain functional abnormalities and increased mortality. All this is in agreement with human data. Furthermore, insects, butterflies, fish, soil bacteria, fungi, clams, oysters and beneficial predatory insects are affected by glufosinate. Inhibition of beneficial soil bacteria, reduction in activity of nitrogen-fixing bacteria, reduced cellulose decomposition and more resistant plant pathogens have been recorded. What would be the knock-on effects on the complex food web?

The accumulation of glufosinate residues on food is cause for concern. Whilst these levels are generally described as too low to cause any harm, the cumulative dose received from eating multiple foods, including meat, cannot be ignored. WHO/FAO figures of residues in food need to be critically assessed, as they are usually taken from manufacturers and the US (Environment Protection Agency) EPA, with not much independent verification. Hooper contended that the amounts in food are high and that combined effects of other residues should also be considered.

Additionally, the EPA describes glufosinate as a persistent and mobile contaminant. It persists in soils from three to 42 days depending on the nature of the soil, and its metabolite leaches twenty times faster from soil.

Hooper stressed that there are many big gaps in our knowledge that need filling. He was concerned that commerce is winning out over science in the consideration of hazards.

Glyphosate, the herbicide used in conjunction with Monsanto’s Roundup Ready GM crops, targets the shikimate pathway, essential for the synthesis of aromatic amino acids. Hooper explained that glyphosate inhibits the conversion of shikimate-3-phosphate and phosphoenol pyruvate (PEP) to 5-enolpruvyl-3-phosphate. This pathway is not present in humans, but in other organisms.

However, PEP is involved in many biochemical reactions in humans, so there are many potential areas of damage. It is important for the synthesis of ganglioside, which is a key membrane component in the brain/nerves, liver, spleen and red blood cells. PEP is crucial for all energy processes in human cells and for the synthesis of glucose from non-sugar precursors, especially important for the brain during periods of starvation. Furthermore, surfactants and some components in the formulation are toxic and carcinogenic.

Glyphosate toxicity depends on the route of administration, with the most important route being inhalation and the dermal route also significant. Unfortunately, most of the testing in animals has involved oral administration, so one must question how the tests are being conducted. Lethal suicide attempts are 10-20% successful with as little as 100 ml. However, the manufacturer says that glyphosate’s acute toxicity is very low, like water, or is not as toxic as table salt or aspirin!

Consider these realities: Severe neurotoxicity was observed in a 12-year old girl who swam in a canal with four times the recommended amount of Roundup. She was completely paralysed, and only partially recovered after five years. One man developed Parkinson’s disease after one accidental exposure. This evidence contests the claims that glyphosate is ‘not as toxic’; glyphosate is a serious neurotoxin. The original neurotoxicty tests conducted by Monsanto were actually ruled invalid by the US EPA. Hence, bad science has been used extensively, in many cases, to justify conclusions about the safety of these materials.

Widespread disturbances of many body systems have been reported after exposure to glyphosate at normal use levels. Glyphosate is the most frequent cause of complaints and poisoning in the UK. It has many effects, particularly on the central nervous system. Common symptoms include severe neurological effects; balance disorder and vertigo; reduced cognitive capacity; seizures; impaired vision, smell, hearing and taste; headaches; reduced blood pressure; twitches and tics; muscle paralysis; peripheral neuropathy; loss of motor skills; excessive sweating; severe fatigue; endocrine disorders; suppression of steroid formation; adrenal deficits; digestive problems; nausea; diarrhoea; depression of liver detoxifying enzymes; nasal congestion and swelling of various parts of the body. The surfactant used in the formulation also results in misshapen red blood cells.

Hooper noted that these symptoms are similar to those reported in syndromes such as Gulf War Syndrome, chronic fatigue syndrome (ME), multiple chemical sensitivity, fibromyalgia, multiple sclerosis and HIV-AIDS. He suggested that damage to the brain stem and basal ganglia accounts for many of the symptoms of glyphosate and glufosinate poisoning.

Hooper cited a study by Vogel et al., which used DFP - a tracer compound - to radiolabel pesticide molecules and follow their movement, in an attempt to investigate toxicity of combined pesticides (Vogel et al. Env Health Perspect 2002; 110 suppl: 1-5.) They measured the movement of DFP into the brain and other tissues, following very low exposure to pesticides. They found that DFP concentrations were raised more than 20% by minute quantities of other pesticides. Hence, the data show that common pesticides significantly change the amount of toxin at concentrations commensurate with normal ingestion of sprayed foods, drinking of surface water or use of home pesticides. The levels of the pesticides correspond to the amount that might be found on a single apple following spraying with these pesticides. The study also provided evidence of a novel mechanism for the toxicity of pesticides and synergism even at very low exposure levels. The mechanism involves greater blood-brain barrier permeability, leading to neural damage and the possibility that other toxins and even pathogens may obtain greater access.

Hooper also presented evidence documenting glyphosate’s detrimental effects on human health, to fish, soil organisms, mycorrhizae and nitrogen-fixing bacteria. Additionally, glyphosate is not irreversibly bound to soil, but re-circulates, with high persistence in soil and water.

He stressed that the identification of acceptable daily intake is an example of inadequate science, as the safety factor was arbitrarily determined for a single compound study, ignoring synergistic increases in toxicity that can arise from interactions with other pesticides and agents. This can multiply toxicity by factors of 100 or more. Furthermore, glyphosate accumulates in bone, providing a basis for increasing accumulation of toxin and shows that clearance from the body will be partial. The possibility of major disruption of bone metabolism is also very real.

During the Question and Answer session, Hooper was queried whether GM crops result in less herbicides. He answered that the data on pesticide/herbicide use is contested, and where independent studies have been done, there has been excess use of these chemicals. With the threat of super-weed emergence, even more pesticides might be used. Results have been variable, but much more data and evidence need to be collected.