Organophosphorus (OP) compounds are detectable in the environment for years after use and endanger many populations. Although the effects of acutely toxic doses of many OP compounds are well described, much less is known about repeated low-level exposures. The purpose of these studies was to further evaluate potential toxicological effects of the extensively used OP pesticide chlorpyrifos (CPF) in rats. CPF, across a range of subthreshold doses (i.e., for acute toxicity), reduced rearing and sniffing activity and the magnitude of weight gain over 14 days of repeated exposure. Performance in a spatial learning task was impaired after 14 days of exposure to CPF (18.0 and 25.0 mg/kg) when testing was initiated 24 h after the last injection but not after a 14-day washout. However, inhibition of both fast anterograde and retrograde axonal transport was observed for up to 20 days after exposure to 25.0 mg/kg CPF. Studies using hippocampal cultures indicated that 8 days of continuous exposure to the parent compound, CPF (Ն100 M), resulted in cell toxicity and death. Furthermore, a dose (2.5 mg/kg) of CPF that had no effects on weight gain or memory performance when administered 5 days per week over 38 days impaired forelimb grip strength in the later days of testing. Collectively, these results indicate that repeated exposures to subthreshold doses of CPF may lead to growth retardation, behavioral abnormalities, and muscle weakness. Some of these symptoms may be attributed to effects of the OP on axonal transport.

Persistent behavioral abnormalities have been commonly associated with acute organophosphate (OP) pesticide poisoning; however, relatively little is known about the consequences of chronic OP exposures that are not associated with acute cholinergic symptoms. In this study, the behavioral and neurochemical effects of chronic, intermittent, and subthreshold exposures to the OP pesticide, chlorpyrifos (CPF), were investigated. Rats were injected with CPF s.c. (dose range, 2.5-18.0 mg/kg) every other day over the course of 30 days and then were given a 2-week CPF-free washout period. In behavioral experiments conducted during the washout period, dosedependent decrements in a water-maze hidden platform task and a prepulse inhibition procedure were observed, without significant effects on open-field activity, Rotorod performance, grip strength, or a spontaneous novel object recognition task.After washout, levels of CPF and its metabolite 3,5,6-trichloro-2-pyridinol were minimal in plasma and brain; however, cholinesterase inhibition was still detectable. Furthermore, the 18.0 mg/kg dose of CPF was associated with (brain region-dependent) decreases in nerve growth factor receptors and cholinergic proteins including the vesicular acetylcholine transporter, the high-affinity choline transporter, and the ␣ 7 -nicotinic acetylcholine receptor. These deficits were accompanied by decreases in anterograde and retrograde axonal transport measured in sciatic nerves ex vivo. Thus, low-level (intermittent) exposure to CPF has persistent effects on neurotrophin receptors and cholinergic proteins, possibly through inhibition of fast axonal transport. Such neurochemical changes may lead to deficits in information processing and cognitive function.

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The populations of fiber types in hindlimb muscles of the tree shrew (Tupaia glis), lesser bushbaby (Galago senegalensis), and the slow loris (Nycticebus coucang) were described and an attempt was made to correlate populations of fiber types and locomotor patterns. Muscle fibers were assigned to one of the following groups: fast-twitch glycolytic (FG), fast-twitch oxidative-glycolytic (FOG), and slow-twitch oxidase (SO). Histochemical techniques for the demonstration of alkaline- and acid-stable ATPase, succinic dehydrogenase, and mitochondrial alpha-glycerophosphate dehydrogenase were used in the classification of muscle fibers. Results indicated that the FG fiber type is the predominant fiber type in muscles used for jumping, the FOG fiber type is predominant in muscles used for running, and the SO fiber type occurs in high percentages in postural muscles. The SO fiber was also the most common fiber in muscles of the slow loris-a species that exhibits a slow, deliberate, sustained locomotor pattern. Intramuscular regional variations in populations were seen in some larger muscles of the tree shrew, but not in the lesser bushbaby and slow loris. Our results did not support the contentions of others that analogous muscles in different species have similar populations of fiber types.

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