Paths from Pesticides to Parkinson's

Sir Colin Berry1, P. Botham2, C. Breckenridge2, L. Smith3

Kamel’s (1) perspective on Parkinson’s disease (PD) is highly selective, does not acknowledge significant methodological issues in epidemiological studies, and promulgates an over-simplistic appreciation of mechanistic toxicology. Kamel cited a case-control study nested within the AHS study (2) where an elevated association between paraquat (PQ) use and incident + prevalent PD cases was reported (OR =2.5; 95% CI: 1.4-4.7) yet did not cite her own cohort study (3) where the incidence odds ratio associated with ever/never using PQ was 1.0 (95% CI: 0.5-1.9). An association between PD and pesticide use was cited based upon meta-analysis even though 3 of 5 cohort studies (4) were not significantly different from null and 2 of these studies (5, 6) identified cases based upon patient/death records (6) or neurological examination and use of prescription medication (5). A case-control study having a low participation rate and using an un-validated geo-coded, area measure of infrequent ever/never exposure to PQ over 26 years was cited as additional evidence of an association between PQ use and PD (7).

Kamel stated that PQ is structurally similar to MPTP and its active metabolite MPP+, ignoring research indicating that their chemical properties & mechanisms of toxicity are very different (8,9,10). It was stated that chronic low-dose exposure to PQ was claimed to result in many features of PD (11) yet recent short (12) and long duration studies (13) have not found any evidence of changes in dopamine level, neuronal degeneration or gliosis in the SNpc or striatum of PQ-treated C57BL/6J mice.

1 colin@sircolinberry.co.uk 2 Syngenta Crop Protection 3 LLS Services

1. F. Kamel, Science 341,723(2013). 2. C.M. Tanner et al., Environ. Health Perspect. 119,866(2011). 3. F. Kamel et al., Am. J. Epidemiol. 165,364(2007). 4. G. Pezzoli, E. Cereda, Neurol. 80,2035(2013). 5. H. Petrovitch et al., Arch. Neurol. 59,1787(2002). 6. A.L. Feldman et al., Parkinsonism Relat. Disord. 17,677(2011). 7. A. Wang et al., Eur. J. Epidemiol. 26,547(2011). 8. S.P. Markey, A. Weisz, and J.P. Bacon, J. Anal. Toxicol. 10,257(1986). 9. J.R. Richardson JR, et al., Toxicol. Sci. 88,193(2005). 10. S. Ramachandiran, Toxicol. Sci. 95,1(2007). 11. J.R. Cannon, J.T. Greenamyre, Neurobiol Dis. 57,38(2013). 12. C.B. Breckenridge et al., Neurotoxicol. 37,1(2013). 13. N. Sturgess et al., The Toxicologist. 132,10 (#55)(2013).