Low-level exposures to organophosphorus esters and peripheral nerve function

This review evaluates the epidemiological and clinical evidence linking low-level and prolonged exposures to organophosphorus esters, used as insecticides or nerve agents, to peripheral nerve dysfunction. The clinical effects of large doses of these chemicals-including the cholinergic syndrome, the intermediate syndrome, and the delayed polyneuropathy-are all well established and are summarized. Based on these clinical observations and experimental studies, dose-effect relationships indicate that peripheral neuropathy always develops after cholinergic toxicity. However, several studies have suggested that this relationship may be different after low-level prolonged exposures, as, for instance, those experienced by Gulf War veterans and British sheep farmers, thereby leading to the development of peripheral neuropathy without preceding cholinergic toxicity. A critical assessment of these studies, involving subjects with either current or past exposures, indicates that changes in peripheral nerve function were mild, inconsistent, and unexplained and that most studies lack exposure data. Suggestions made about individual hypersusceptibility to delayed polyneuropathy lack support. It is concluded that there is no evidence of peripheral nerve dysfunction caused by low-level prolonged exposures to organophosphate insecticides or nerve agents. (C) 2002 Wiley Periodicals, Inc.