Progress and Prospects in Parkinson's Research/Causes/Toxins/Maneb

Background
Maneb is a member of the ethylene bisdithiocarbamate (EBDC) group of fungicides, which includes the related active ingredients mancozeb and metiram. Its full name is Manganese ethylene-1,2-bisdithiocarbamate, polymer. It was first registered in the United States in 1962 for use on food and ornamental crops. It is designed to protect crops from fungi both during their growing and storage stages. In 1977 the registration body – the Environmental Protection Agency (EPA)– initiated a review based on reports that the product contained a contaminant, and in 1982 issued a Final Determination requiring the implementation of risk reduction measures.Further reports were issued in 1985, 1989 and 1992.

A second Final Determination was issued in 1987 warning against the use of the product in connection with the growing of apricots, carrots, celery, collards, mustard greens, nectarines, peaches, rhubarb, spinach, succulent beans, and turnips. There is no mention of potential neurological damage in the EPA Fact Sheet dated August 1985.

The product was implicated as a toxic precursor to Parkinson’s Disease as the result of a series of experiments carried out on mice by Thiruchelvam et al (2000). . Corroboration came from a similar study carried out in California in 2009 by Beate Ritz and Sadie Costello of UCLA and another by Zhonghua (2011).

Maneb was included in a biocide ban proposed by the Swedish Chemicals Agency and approved by the European Parliament on January 13, 2009.

Research
2000

Mona Thiruchelvam, PhD and Gail Zeevalk of the Robert Wood Johnson Medical School, New Jersey have made the observation that hormone replacement therapy can reduce the risk of PD in postmenopausal women. Studies in animal models of PD have shown a difference in susceptibility between genders, with males more vulnerable to dopaminergic neurotoxicants such as Paraquat and Maneb. This appears to be due to the protective effect of increased levels of oestrogen. They are evaluating the possibility of producing non-feminizing analogues of oestrogen as a form of vaccination against PD. Warning See Below

2010

Ahmad et al demonstrated the effect of Maneb and Paraquat on rat livers.

2011

Roede et al found that Maneb and Paraquat used in combination were particularly toxic.

Grosicka et al demonstrated that N-acet-L-cysteine offered protection against the toxic effects of Maneb (in Chinese hamster cells).

Singhal et al demonstrated that silymarin and melatonin offer nigrostriatal dopaminergic neuroprotection against Maneb and Paraquat-induced PD  (in rats) by the modulation of oxidative stress and apoptotic machinery.

2012

Mona Thiruchelvam, PhD committed research misconduct by fabricating data, according to an investigation by the university and the Department of Health and Human Services Office of Research Integrity (ORI). The ORI, which announced its findings on Thursday (June 28), determined that Mona Thiruchelvam falsified cell count data published in two papers in 2009 in Environmental Health Perspectives and Journal of Biological Chemistry, both of which she has agreed to retract. One of the papers slated for retraction investigated the neurological response to the combined pesticides paraquat and maneb. The false data were used to create several summary bar graphs, which Thiruchelvam modified to support the hypothesis that proteasomal dysfunction is higher in males than females with PD, and that exposure to paraquat and maneb enhances this effect.