Organophosphorus Compounds

Abstract

Organophosphate pesticides are a highly diverse group of chemicals to which workers may be exposed during manufacture and formulation and during or after application for their intended uses. They are all characterized by their ability to inhibit the enzyme acetylcholinesterase (AChE) that deactivates the neurotransmitter acetylcholine (ACh). Compounds in this class are numerous and have been categorized in many ways according to the nature of the substituents. Gallo and Lawryk, for example, categorized them into four main categories (Groups I‐IV) based on the characteristics of the leaving group (X). Group I compounds, phosphorylcholines, have a leaving group that contains a quaternary nitrogen and are among the most potent organophosphates (e.g., Shradan). Group II compounds, fluorophosphates, have a fluoride leaving group and are also generally highly toxic (e.g., diisopropyl fluorophosphate). Group III compounds have leaving groups that contain cyanide or a halogen other than fluoride and are generally less potent than Groups I or II (e.g., Parathion). Group IV contains most of the organophosphates used as insecticides today. These compounds have alkoxy, alkylthio, aryloxy, arylthio or heterocyclic leaving groups and a wide variety of other substituents. Another classification scheme is based on the nature of the atoms that immediately surround the central phosphorus atom and results in 14 different categories. According to this scheme, phosphates are the prototype for the entire class and are those compounds where all four atoms that surround the phosphorus atom are oxygen (e.g., dichlorvos, mevinphos). Sulfur‐containing organophosphate compounds (phosphorothioates; phosphorothiolates; phosphorodithioates; phosphorodithiolates) are far more numerous than phosphates and include well recognized organophosphate insecticides such as parathion, diazinon, chlorpyrifos, etc. Other groups contain nitrogen (phosphoramides and phosphorodiamides), nitrogen and sulfur (phosphoramidothionates and phosphoramidothiolates), carbon (phosphonates and phosphinates), or carbon and sulfur (phosphonothionates, phosphonothionothiolates and phosphinothionates). All aspects of organophosphate chemistry, toxicity, analysis, and exposure potential have been previously reviewed. Additionally information regarding the toxicity of this class of compounds has expanded greatly in recent years as a result of toxicity data supplied by registrants to the U.S. EPA's Office of Pesticides to support reregistration. These data are being made publically available by the U.S. EPA on their internet web site. The following discussion draws heavily from recent reviews but also includes summaries of relevant toxicity data submitted to the U.S. EPA available when this chapter was completed. Due to space limitations detailed data reviews are included here for only 30 organophosphate pesticides. Information on other pesticides registered or undergoing reregistration in the United States can be readily obtained from the previously mentioned website.

Organophosphorus Pesticides

“…Organophosphate pesticides have generally not shown reproductive or developmental effects in animal studies (5). In those few cases where effects have been observed, they occurred at exceeding levels resulting in decreased acetylcholinesterase.…”

“…In October 2001, EPA finalized the Reregistration Eligibility Document (RED) for azinphos-methyl that includes summaries of acute, subchronic, chronic, carcinogenicity, and other studies provided by the registrant (158). Detailed summaries of studies provided by registrants are summarized in a separate document available on a special docket (176 (5,158,159). An oral LD 50 value of 7 mg/kg and an LD 01 of 4-5 mg/kg in male and female mice, respectively, demonstrated that the dose-lethality curve is very steep.…”

“…Toxicity of coumaphos reported by the registrant and others has been summarized previously (5,254). In 2000, EPA finalized the RED for coumaphos (255).…”

“…Toxicity of methyl parathion reported by the registrant and others has been summarized previously (5,456,(461)(462)(463). In May 2003, the EPA finalized the RED for methyl parathion that includes summaries of acute, subchronic, chronic, carcinogenicity, and other studies provided by the registrant (455).…”

“…All aspects of organophosphate pesticide chemistry, toxicity, analysis, and exposure potential have been previously reviewed (1)(2)(3)(5)(6)(7)(8). Information regarding the toxicity of organophosphate pesticides has expanded greatly in recent years largely as a result of toxicity data supplied by registrants to the U.S. EPA Office of Pesticide Programs (OPP) to support reregistration of pesticides that were originally registered prior to 1984.…”