Recommended safe practices for using the neurotoxin MPTP in animal experiments.
The metabolism and distribution of the parkinsonian syndrome inducing neurotoxin MPTP has been studied in non-human primates and mice housed in controlled environmental chambers. 14C6-MPTP was prepared and injected at concentrations normally employed for lesioning experiments (30 mg/kg in mice, 0.3 mg/kg in monkeys). All interior surfaces of the chambers which could be reached by animals or their excreta were contaminated with radiolabeled metabolites. Vapor born unmetabolized MPTP was negligible, although significant amounts of MPTP were found in the excreta of mice (less than or equal to 15% injected dose) and small amounts from rhesus monkeys (less than 2%). Procedures to minimize contact with animal fur, bedding and excreta should protect investigators working with MPTP over extended periods. Permanganate oxidation effectively detoxifies solutions of MPTP. MPTP, MPP+, common synthetic intermediates, and the products of MPTP's oxidation are not mutagenic as measured by a Salmonella-microsome assay.
Yang
S C
SC
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20982.
Markey
S P
SP
Bankiewicz
K S
KS
London
W T
WT
Lunn
G
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006799:Housing, Animal; D007756:Laboratory Animal Science; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009784:Occupational Diseases / Q000139:chemically induced* / Q000517:prevention & control; D010084:Oxidation-Reduction; D011196:Potassium Permanganate / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism* / Q000633:toxicity / Q000652:urine
D011725:Pyridines; D011196:Potassium Permanganate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine