Do pesticides and manganese affect human health

1
Do pesticides and manganese affect human health?

• Henrik Rye Lam
• Department of Toxicology and Risk Assessment
• Danish Institute for Food Safety

2
Do pesticides and manganese affect human health?

• Acute, high dose pesticide exposure affects human
  health
• Long term, low dose pesticide exposure seems
  linked to increased risk for Parkinsons disease
• Manganese affects human health
• There is a potential for combinatory effects of
  manganese and pesticides when co-exposed

3
Studies on manganese and selected pesticides

• Manganese chloride
• Maneb
• Chlorpyrifos
• Combinatory studies
• Funded by the Danish EPA Programme for Pesticide
  Research 2002-2004

4
Working hypotheses

• There are combinatory effects between
  neurotoxicity induced by manganese and certain
  pesticides
• Underlying mechanisms and their combinatory
  effects can be illuminated by neurochemical,
  morphological, and immunohistochemical methods by
  use of the rat as the model

5
Studies in the project

• Manganese (intraperitoneal dosing)
• 1,22 mg manganese (MnO2)/kg bw/day for 8 or
  12 weeks
• 2,5 mg manganese (MnCl2)/kg bw/day for 8 or
  12 weeks
• Maneb (intraperitoneal dosing)
• 7,5, 15 or 30 mg maneb/kg bw/week for 12
  weeks
• Chlorpyrifos (subcutaneous dosing)
• 2,5, 15 or 30 mg chlorpyrifos/kg bw/week for
  12 weeks
• Combinatory studies
• 2,5 mg manganese (MnCl2)/kg bw/day for 12
  weeks
• 15 chlorpyrifos/kg bw/week for 12 weeks
• 10 mg maneb/kg bw/week for 12 weeks

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Manganese concentration(Manganese dosing)
7
Manganese brain concentration(Maneb dosing)
8
Manganese concentrations(Combinatory studies)
9
Concentrations of neurotransmitters(Manganese
dosing)

10
Concentration of neurotransmitters(Maneb dosing)
11
Acetylcholinesterase activity(Maneb dosing)
12
Acetylcholinesterase activity(Chlorpyrifos
dosing)
13
Concentration of neurotransmitters(Combinatory
studies)
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Acetylcholinesterase activity (Combinatory
studies)
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Key conclusions

• Manganese dosing increases the brain manganese
  concentration
• Maneb dosing increases the brain manganese
  concentration
• Co-exposure to manganese and maneb increases the
  brain manganese concentration in an additive
  manner and thereby potentially increases the risk
  for developing Parkinsons disease
• Chlorpyrifos dosing reduces the activity of brain
  acetylcholinesterase
• Manganese, chlorpyrifos, maneb and their
  combinations affect basic neurochemical
  parameters that are early indications of
  neurotoxicity

16
Perspectives

• Because
• Many epidemiological studies document increased
  risk of developing Parkinsons disease when
  exposed to manganese and pesticides
• Several cases report development of Parkinsons
  disease when occupationally exposed to maneb
• Inhalation of manganese can induce parkinsonism
• There is a need for future studies that can
  illuminate or even document the potential for
  combinatory effects of manganese and pesticides
  to obtain increased protection and health

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Ole Ladefoged, Erik Huusfeldt Larsen, Brian
Svend Nielsen, and Henrik Rye Lam acknowledge

• Technical staff
• Amer Mujezinovic, Annette Landin, Kai Vest,
  Lena Kristensen, Trine Gejsing, Vibeke Kegel,
  Vibeke Kjær, Birgitte Koch Herbst, Karen
  Bielefeldt Pedersen, Lisbeth Philkjær
  Christensen, Animal caretakers
• Colaborating parteners
• Prof. Michael Aschner, Wake Forest
  University, NC, USA
• Prof. Poul Henning Jensen, Aarhus
  Universitet
• PhD Karina Petersen, Lundbeck