The most hazardous operations in conducting MPTP animal experiments are the preparation, handling, and injection of concentrated solutions of MPTP. The concentration of MPTP in the solution used for ICA administration is very low (0.05 to 0.07 mg/ml) and therefore is relatively safe. However, the solutions for IV or IM administration (even in small volumes) are much more concentrated, and additional caution will be taken during its handling. Management of these risks requires that solutions be prepared in a ventilated fume hood with precautions to catch and dispose of any spilled solution and that personnel wear appropriate personal protective equipment at all times.
The second primary hazard from these experiments is the potential for exposure of personnel to MPTP or its metabolites that have been excreted by an animal in the days following MPTP administration. Management of this risk requires an understanding of how MPTP is metabolized and excreted following its administration. It is worth emphasizing here that MPTP is the excreta of highest concern because only MPTP can cross the blood-brain barrier and thus endanger personnel who are exposed to it. The metabolite MPP+ is highly toxic to dopamine neurons when it is injected directly into the brain, but when injected peripherally, only very high doses of MPP+ (e.g., 25 mg/kg i.p.) produce detectable toxicity and then only peripherally. Studies have shown that following MPTP administration to a monkey, only the interior surfaces of the animal’s cage and surfaces that the animal and/or its excreta can physically touch (e.g., bedding, food hoppers, drinking bottles) are contaminated with MPTP and its metabolites. At two days post-injection, 70% of the total injected dose of MPTP and its metabolites can be recovered from inside the cage, from urine, and from feces. Of this, only 2% consists of MPTP itself, while the rest consists of metabolites such as MPP+. Unmetabolized MPTP is excreted primarily in the first day post-administration, while metabolites are excreted up to 3 days post-injection. There is no evidence that MPTP or its metabolites are still being excreted after 3 days post-MPTP administration. MPTP is excreted primarily in the urine in an ionized (i.e., non-volatile) form. Thus, excreted MPTP is well absorbed by animal bedding material and/or absorbent pads. Less than 0.01% of the total injected dose of MPTP can be detected as volatile MPTP. In summary, the potential risks of exposure to MPTP following its administration are through direct contact with the animal, the inner surfaces of the animal’s cage, and its soiled bedding material. There is minimal risk from exposure due to airborne forms of MPTP. The period of maximal risk of MPTP contamination is from the moment of injection to 3 days post-MPTP injection.