Neurotoxicity human observations

A possible, noneholinesterase-based explanation for the neurotoxic symptoms observed in humans from the examples cited above is that workers were also exposed to a combination of chemicals including heavy metals, solvents, herbicides, and fumigants. The symptoms may actually have been caused by these chemicals and not by the OP (Kamel and Hoppin, 2004). However, the animal data cannot be explained this way because the animals were treated only with OP. In conclusion, OP targets that are not acetylcholinesterase or butyrylcholinesterase are involved in chronic neurotoxicity. These unknown targets bind OP at doses too low to inhibit acetylcholinesterase. 

In summary, the frank neurotoxic effects of endosulfan are apparent only after acute ingestion of relatively high doses in animals. However, long-term decreased psychomotor function, possibly resulting from acute endosulfan exposure, have been reported by two authors (Aleksandrowicz 1979 Shemesh et al. 1988). Such effects cannot be easily measured in animals. Hence, the fact that long-term neurotoxic effects have not been observed in animals does not mean that such effects caimot occur in humans. However, no information was located that indicated that persons exposed to low levels of endosulfan might experience any neurotoxicity. 

The data in animals are insufficient to derive an acute inhalation MRL because serious effects were observed at the lowest dose tested (Hoechst 1983a). No acute oral MRL was derived for the same reason. The available toxicokinetic data are not adequate to predict the behavior of endosulfan across routes of exposure. However, the limited toxicity information available does indicate that similar effects are observed (i.e., death, neurotoxicity) in both animals and humans across all routes of exposure, but the concentrations that cause these effects may not be predictable for all routes. Most of the acute effects of endosulfan have been well characterized following exposure via the inhalation, oral, and dermal routes in experimental animals, and additional information on the acute effects of endosulfan does not appear necessary. However, further well conducted developmental studies may clarify whether this chemical causes adverse developmental effects. 

In more recent studies, it has also demonstrated that administration of 2.5 or 10 mg/kg MDMA twice daily for 4 consecutive days resulted in neurotoxic effects in rhesus monkeys, with decreases in the density of serotonin uptake sites occurring at the higher dose (Johannessen et al. 1988). The neurotoxic effects of MDMA observed in primates included reductions in the content of serotonin and 5-HLAA and marked reductions in the cerebrospinal (CSF) concentrations of 5-HIAA levels that were observed following drug administration. These findings and other reports of neurotoxic effects of MDMA in primates (Ricaurte et al. 1988) raise serious concerns for its potential hazard in humans. 

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