Why Paraquat is claimed to be associated with Parkinson’s Disease

1. Why Paraquat is claimed to be associated with Parkinson’s Disease

2. Parkinson’s Disease: Association with paraquat • 1. Objective : • Explain Parkinson’s disease and why there is an increase in reports of an association between this disease and exposure to paraquat. • The presentation is not a review of the risk assessment of paraquat, nor an explanation of the regulatory impact of this issue.

3. Parkinson’s Disease • A loss of neurones in an area of the brain (substantia nigra) often associated with motor nerve activity (ie muscle activity). • Usually a disease of ‘old age’. Has a prevalence of 2 per 1000. But over 65 years a prevalence of 1.8 per 100 (Europe). • It is a disease involving both genetic and environmental factors. • The most certain environmental factor is cigarette smoke, which is strongly associated with a lower incidence of Parkinson’s.

4. Background of Paraquat association with Parkinson’s Disease • In the early 1980’s a chemist synthesised the compound MPTP while attempting to synthesise recreational drugs. • Those who injected MPTP developed symptoms very similar to Parkinson’s Disease and subsequently died within a few years.

5. MPTP MPP+ Charged, neurotoxic metabolite of MPTP Monoamine, uncharged lipophilic molecule Paraquat Hydrophilic, charged di-cation Background of Paraquat association with Parkinson’s Disease ‘cyperquat’

6. Background of Paraquat association with Parkinson’s Disease /continued • In the 1980’s, Canadian scientists (Barbeau et al) claimed there was an association between pesticide use and Parkinson’s. This was not substantiated. • In the early 2000’s scientists in the USA showed that paraquat plus MANEB when given to mice caused loss of neurones in the substantia nigra. • Following the above, several studies have been reported showing paraquat can cause the loss of neuronal cells in the brain.

7. Background of Paraquat association with Parkinson’s Disease /continued • There is no certainty that humans, even when exposed to paraquat will lose neurones in the substantia nigra. • We know additional studies are underway in several laboratories to investigate the effect of paraquat on the substantia nigra in several species of experimental animal. • The data from epidemiological studies are conflicting. Some epidemiological studies show an association between pesticide use, and in particular paraquat, and the development of Parkinson’s Disease.

8. Timelines for Syngenta • We are in the process of reviewing all the relevant experimental data and epidemiological studies on paraquat and Parkinson’s Disease with the help of external experts (end August 2007). • A risk assessment will be carried out to establish Syngenta’s position on completion of this review (Sept 2007). • We shall identify studies that could resolve unanswered questions (end Sept 2007). • At present we have every reason to maintain our position that there is no causative association between the development of Parkinson’s Disease and exposure to paraquat. However, we are likely to receive increasing challenges on this.

9. No. of Publications referencing Paraquat and Parkinson's (1980 - 2006)

10. Managing the Paraquat, Parkinsons’s Disease Issue Strategy Establish if paraquat can cause Parkinson’s symptoms in humans and if it can, under what circumstances of dose and time Capability and capacity: Identify what needs to be done, how it can be achieved and who can do it • Project Management: • Use expert committees on: • Experimental studies • Epidemiological studies • To investigate further the issue Science: Review the experimental data on the effect of paraquat on the brain of mice and the epidemiology studies that claim there is an association between exposure to pesticides and Parkinson’s disease Outcome: Establish whether there is a qualitative, or quantitative difference in the effect of paraquat in the mouse compared with humans and, if relevant, the extent of the quantitative difference