Evaluation of C57B1/6 Mice for Motor Abnormalities and Parkinson-Patterned Neuropathology After Paraquat and Maneb Exposure at Human-Relevant Doses

Details

• Personal Author:
  Benkovic A ; Collier M ; Li AA ; McIntosh LJ ; Miller DB ; O'Callaghan JP ; Patten R ; Switzer R
• Description:
  C57Bl/6 mice were dosed daily from PND 5-19 (0.3/1.0 mg/kg PQ/MB) and/or twice weekly from week 28-31 of age (10/30 mg/kg PQ/MB), the levels reported in the literature to cause loss of substantia nigra cells. This high dose was reduced to 5/15 mg/kg PQ/MB following marked clinical reaction in naïve adult males after three injections, leading to termination for welfare reasons. Additionally, two other doses were derived from human PQ exposure models and were administered as a middle dose (0.06/0.18 mg/kg PQ/MB preweaning, 0.6/1.8 mg/kg PQ/MB adult) and a low dose (0.0007/0.002 mg/kg PQ/MB preweaning and adult) representing exposure levels relevant to humans. Animals dosed preweaning only, as adults only, or both, were tested for motor activity and arena behaviour at 32 weeks, and then evaluated for neuropathology at 33 weeks. One additional group dosed preweaning and as adults was retested at 62 weeks and sacrificed at 70 weeks of age. There was an increased incidence of tremors in the high dose males at 32 weeks of age, but not at 62 weeks of age, inconsistent with a progressive disease state. In the 1 h motor activity testing, there was an increase in ambulatory activity and rearing in high dose females at 62 weeks of age only. Staining with GFAP and silver did not detect any degenerative response related to treatment across the entire brain at either 33 or 70 weeks of age in either gender. Stereological analysis and quantitation of TH+ neurons in the substantia nigra is ongoing. [Description provided by NIOSH]
• Subjects:
  Age Factors Environmental Monitoring Laboratories Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Age-factors Cell-biology Exposure-assessment Exposure-levels Exposure-methods Laboratory-animals Laboratory-testing Neurological-reactions Neuromotor-system Neuromotor-system-disorders Neuromuscular-function Quantitative-analysis

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• ISSN:
  0378-4274
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; Tennessee ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  189
• NIOSHTIC Number:
  nn:20035915
• Citation:
  Toxicol Lett 2009 Sep; 189(Suppl 1):S217
• Contact Point Address:
  Laura J. McIntosh, Exponent, Inc., Toxicology and Mechanistic Biology, Menlo Park, CA
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Peer Reviewed:
  False
• Source Full Name:
  Toxicology Letters. Abstracts of the 46th Congress of the European Societies of Toxicology
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:05334a9d5217beab9cdf31cb9cec9111425fd533000ed6e5ad73e8751fc97f50a87c64ef71419b9bd29cb7b9db26178aad064d2ccefb20b524abbc7a1a6dc7dc
• Download URL:
  https://stacks.cdc.gov/view/cdc/187584/cdc_187584_DS1.pdf
• File Type:
  [PDF - 89.31 KB ]