Organophosphates

I. Introduction

       Organophosphate insecticides have become one of the most used groups of pest control chemicals. In 1989 almost 40% of the 6.2 billion global insecticide market was composed of organophosphates (OPs) (Phillips and McDougall 1990). The toxicity induced by Organophosphates results from inhibiting the enzymes acetylcholinesterases (ChE), in the nervous system of the exposed organisms. These enzymes remove acetylcholine (ACh) which carries electrical signals across the synapse. Diazinon prevents the ChE from removing the ACh and thus synapses get jammed with ACh, this results in rapid twitching of voluntary muscles and finally paralysis. Three compounds, diazinon, chlorpyrifos and fenamiphos, chosen to represent the class of organophosphates have been used to make comparisons between the compounds, and evaluate the overall trends of OPs as a class. 

     Diazinon is the common name of a synthetic organophosphate insecticide that does not occur naturally. The chemical name is O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate, while other commercial names include Alfa-tox, AG 500, Garden Tox and Knox-out. Diazinon is used to control pest insects in soil, on ornamental plants, and on fruits and vegetables. 

     Fenamiphos is an insecticide originally developed by Bayer Agricultural for the control of soil and leaf nematodes. Its chemical name is Ethyl 3-methyl-4-(methylthio)phenyl (1-methylethyl) phosphoramidate but it is commonly known by its trade name, Nemacur. It is most often used in the form of emulsifiable concentrate against nematodes on field crops, vegetables and turf. 

     Chlorpyrifos, chemical name 0,0-diethyl 0-(3,5,6-trichloro-2-pyridyl) phospothorothioate, is an organophosphate insecticide used for agricultural and domestic use. It is used on the farm to control pests in turfgrass and ornamentals and is used in the home to control cockroaches, fleas, and termites. Formulations of chlorpyrifos include: emulsifiable concentrate, dust, granular wettable powder, microcapsule, pellet, and sprays. Chlorpyrifos is widely used as an active ingredient in many commercial insecticides such as Dursban and Lorsban. 

II. Chemical/Physical Properties

        Organophosphorus compounds tend to have structural similarities within the class. All naturally occurring phosphorus compounds have the characteristic, "phosphoryl" bond, P=O. With only a few exceptions, all organophosphorus pesticides also have either the phosphoryl bond or thiophosphoryl bond, P=S. Because of their structure, many organophosphorus pesticides are able to form enantiomers with the phosphorus atom acting as an asymmetric center creating optically active compounds (Eto 1974). Consequently, the structure of these compounds affects their chemical and physical properties. Several of these properties are listed in Table 1 for the three organophosphates of interest. Structures for the compounds are drawn below.

     Chlorpyrifos has the highest molecular weight and the largest density both of which slow down the transfer rates from one compartment to the other. It would also be most likely to settle in the sediment due to gravity effects. When looking at the compounds’ solubilities, we see that Fenamiphos is much more soluble than the other two compounds, and it also has the lowest vapor pressure. This means that fenamiphos would more likely be found in the water column than would diazinon and chlorpyrifos. The vapor pressure of both chlorpyrifos and diazinon are within the same order of magnitude, but chlorpyrifos has the higher K_H value due to its lower solubility, which gives it a higher tendency to volatilize from the water. All of the compounds have high Kow and Koc values indicating that they all have a tendency to sorb to the sediment. Chlorpyrifos has a shorter half-life in air than does diazinon, but it persists much longer than both diazinon and fenamiphos in the soil.

     Diazinon is a phosphorothioate with a pyrimidine ring attached to it. Even though there are polar bonds in the molecule, such as the S=P bond, the non-polar pyrimidine ring with its alkyl substituents make this compound relatively hydrophobic. This is reflected in the compound’s low water solubility at room temperature, which was found to be around 40 mg/L using a shake flask method followed by GC analysis (Kanazawa 1981). Diazinon is readily soluble in alcohols, ethers, benzene, cyclohexane and similar hydrocarbons. As expected, Diazinon has relatively high Kow, Kd and Koc values due to its low water solubility. This gives it a great tendency to sorb to natural organic matter and sediments. Bowman and Sans used a shake flask method followed by GC analysis to determine Kow experimentally and came up with Log Kow = 3.81 (Bowman and Sans 1983). As for a value of Koc, Sharom reported an average value from three soils of log Koc = 2.28 (Sharom 1980). From a list of vapor pressure data, the mean value appears to be around 8.25E-5 torr at 25° C (Mackay et al. 1997). The henry’s law constant value we used was 1.09E-7 atm-m³/mol, we chose this value because it was most frequently listed (Mackay et al. 1997). 

     Diazinon undergoes rapid chemical hydrolysis under both acidic and alkaline conditions. The products resulting from both mechanisms are the same, and are less toxic than diazinon. The main hydrolysis product is 2-isopropyl-4-methyl-6-hydroxypyrimidine. However, if not enough water is present under acidic conditions, tetraehtyl dithio- and thiopyrophosphates are produced, both of which are extremely toxic. 

     Fenamiphos is described as a colorless or tan waxy solid, which may have a mild sulfur odor. As seen in its structure above, it has a phosphoryl bond, P=O, but does not have a P=S bond like the other two compounds. As seen in the table, fenamiphos’ vapor pressure is quite small reflecting the compound’s low volatility. On the contrary, its solubility in water is much higher. Therefore, it is not surprising that the only K_H value found, is small (ARS Pesticide Properties). Fenamiphos is readily soluble in dichloromethane, isopropanol, and toluene and sparingly soluble in hexane. It appears to have a high affinity for the soil, apparent in its high Kd, Kow, and Koc values. Fenamiphos is stable in pH’s from 5 to 7 and is hydrolyzed by strong acids and bases. 

     The compound is readily oxidized to fenamiphos sulfoxide (FSO), which is then further oxidized at a slower rate to fenamiphos sulfone (FSO₂). In the field, this first oxidation occurs rapidly in aerobic soil through biotic and abiotic processes. The second oxidation occurs more slowly because it is performed predominantly by microbes (Simon, et al. 1992). In certain enhanced soils, such as some sandy soils, fenamiphos may oxidize to FSO, which will rapidly hydrolyze to FSO phenol (FSO-OH) and then degrade to CO2 and H20, without ever going to FSO₂ (Cyung, et al. 1996). 

     Chlorpyrifos, like diazinon, is a phosphorothioate attached to a pyrimidine ring containing three chlorines, which makes this compound very hydrophobic in nature. Chlorpyrifos has two major metabolites: 3,5,6-trichloro-2 pyridinol (TCP) and 3,5,6-trichloro-2 methoxy pyridine (TMP). It has a melting point above ambient temperatures ranging from 41-44° C and thus is a solid in pure form (Rigterink and |Kenaga 1966). TCP has a higher melting point and TMP exists as a liquid at ambient temperatures. Chlorpyrifos and TCP have moderate volatility with a measured vapor pressure between 1.8 * 10^-5 and 2.0 * 10^-5 mmHg at 25 degrees C (Brust 1964). The rate at which chlorpyrifos volatilizes in the environment is greatly influenced by the nature of the environmental matrix in which it is present. TM P, however, has a vapor pressure of 9.68* 10^-3 mmHg and is therefore about 500 times as volatile as chlorpyrifos of TCP. The nonpolar nature of chlorpyrifos is also seen in its low water solubility, which has been reported to be about 0.94 to 2 ppm at 23-25 degrees C (Hummel and Crummet 1964). Chlorpyrifos is not persistent in the water because it is highly volatile and adsorbs strongly to particulate matter. Chlorpyrifos has a high Kow value, which also demonstrates its affinity towards organic phases in the environment. TMP is nearly as non polar as chlorpyrifos, but TCP in anionic form is more polar in nature as seen in it’s high solubility at a pH of 7 (Meikle and Hamaker 1981). 

     All three compounds appear to be typical for the class of organophosphates. 

III. Commercial Uses

A) Diazinon 

     Diazinon is produced by reacting 2-isopropyl-4-hydroxy-6-methylpyrimidine and O,O-diethyl phosphorochloridothioate. There are several facilities that produce Diazinon in the United States, but since the production of this compound involves proprietary information, exact amounts produced in a certain year along with details about the manufacturing process are virtually impossible to obtain. According to title III of the Superfund Amendments and Reauthorization Act of 1986, Diazinon was added to the list of chemicals that manufacturing and processing facilities have to report on in the toxic release inventory database (TRI). According to the TRI of 1997, in 1995 107,510 Ibs of production related waste was generated. Releases from facilities to the environment totaled 11,498 lbs, most of which was in the form of stack emissions (TRI95). 

     Since it was first registered for use in the United States in 1956, Diazinon has been used to control soil insects and pests of fruit trees, vegetables, grasslands and other crops. Nowadays it is also used to control flies around animal facilities, greenhouses, fair grounds, and other businesses and public places where food or animal wastes might accumulate (Williams et al. 1985). In addition, Diazinon is the active ingredient added to most pet collars and ear tags to control biting insects or skin parasites on pets and livestock. For home and garden applications (i.e. to control crickets and cockroaches), Diazinon is applied in the form of strips placed near entryways, or is sprayed near certain areas. 

     Due to the vast number of different applications, Diazinon has to be formulated in many different ways. Some of these formulations include wettable powders, emulsifiable concentrates, pressurized sprays, dusts, and granules (Tox. Profile of Diazinon 1996). 

     Diazinon can enter the environment either due to its application, or due to emissions from facilities during manufacturing and processing. The total releases from facilities, which are mostly by stack or fugitive emissions, are minimal when compared to the amounts of Diazinon used in all the different fields. The latest estimated Diazinon use in the United States was 10 million pounds in 1985 (EPA 1990). This amount is several orders of magnitude bigger than the amount released by facilities as indicated in the TRI database. Since Diazinon has been replacing several more toxic organochloride pesticides such as chlordane, the amount used in the US in 1997 is probably even greater than the estimated figure of 1985. 

     The pathway by which most of the Diazinon gets released to the atmosphere is by volatilization from the soil after application, and from drifting during spray applications. Runoff from agricultural areas, rinsing of Diazinon containers, and direct discharges all release the compound into the surface and ground waters. Diazinon enters the soil mainly through field applications. Partitioning tendencies of Diazinon and the other two organophosphates towards certain environmental compartments will be examined later using the EXAMS model. 

B) Fenamiphos 

     Bayer, Inc (also known as Miles, Inc.) is the principle manufacturer of fenamiphos. The amino derivative of fenamiphos is produced by reacting 3-methyl 4-methylthiophenol with phosphoryl chloride to the dichloidate. A second step occurs in which there is nucleophilic displacement of the chlorine atoms by sodium ethylate and isopropyl amine yielding fenamiphos. The technical grade of fenamiphos is manufactured in Leverkusen, Germany. According to Bayer, it is diluted to a 60% solution, shipped to the United States, and then formulated into a liquid and granular product. Like diazinon, the exact amounts of fenamiphos that are produced in the US are difficult to obtain, partly because different amounts are produced each year. Furthermore, Bayer is not required to report this information or information on feedstocks and byproducts to the public. 

     Today, fenamiphos is used as a systemic and contact insecticide, that is used to control several genera of nematodes from field and fruit crops, vegetables, and turf grasses, including bananas, pineapples, citrus fruit, pome fruit, stone fruit, vines, hops, cotton, cocoa, coffee, okra, groundnuts, soy beans, curcurbits, tomatoes, potatoes, vegetables, sugar beets, ornamentals, and tobacco. The compound also has secondary activity against sucking insects and spider mites (Agrochmicals Handbook 1991). Fenamiphos is used in the form of emulsifiable concentrate, granules or oil in water emulsion by itself or can be mixed with isofenphos, carbofuran, or disofultan. The pesticide can be applied broadcast, in-the-row, in band, by drench, before or at planting time, or to established plants (fenamiphos page-web). 

     Fenamiphos tends to enter natural systems after application. The pesticide is known to leach through soil and has been found in groundwater as a result of agricultural use (Crop Protection Reference). Also, emulsion formulations leave a deposit of crystalline pesticide on the plant (Davis et al. 1996). If fresh applications are exposed to short but intense rainfall, runoff of material to neighboring waters will occur. 

C) Chlorpyrifos 

     The major manufacturer of chlorpyrifos is Dow Elanco, which is the corporate successor to the Dow Chemical Company. Chlorpyrifos is commercially prepared by several methods, the most common of which includes reacting TCP with 0,0-diethyl phosphorochloridothioate under basic conditions with dimethyl formamide, as the final synthetic step. The synthesis of chlorpyrifos was first described by Rigterink (1966) and Rigterink and |Kenaga (1966). 

     The most common formulations of chlorpyrifos include: emulsifiable concentrates, granulers, and wettable powders, but other formulations available are dust, microcapsule, pellet, and sprays. The purpose of each formulation is based on delivery and pest control as to maximize product stability and availability to the target pest with a minimum of human exposure. 

     Chlorpyrifos was first introduced into the non-crop specialty market in the late 1960’s in order to control pests in turfgrass, in ornamental plants and shrubs, and to control indoor pests. In 1980, chlorpyrifos was registered as a termiticide, which added to its use. The primary users of specialty insect control products are professional pest control workers, however, various products are also registered for the use of homeowners. Agricultural commercial products were introduced in the 1970’s. Chlorpyrifos is mostly used as a foliar pesticide which can be applied by ground or aerial equipment, depending on crop type, to primarily control a variety of surface-feeding insects. There is no information in the Toxic Release Inventory (TRI) database on the total environmental release of chlorpyrifos from production facilities because chlorpyrifos is not included under SARA, Title 3 and therefore is not one of the chemicals that facilities are required to report. Data from usage surveys conducted by the USDA, EPA, and the Department of Food and Agriculture of the State of California, indicates that the estimated usage of chlorpyrifos is about 7,023,190 pounds of active ingredient per year. Agriculture accounts for most of its usage. Chlorpyrifos is nationally ranked twelfth in frequency of indoor pesticide application and fifth in frequency of outdoor pesticide application. 

     Chlorpyrifos enters the atmosphere resulting from it’s use as an insecticide Volatilization during foliage or soil application by ground or air broadcast equipment, allows chlorpyrifos to be released into the atmosphere (Racke 1993). This process, along with runoff or leaching, can also result in chlorpyrifos being released into the water, which contaminates both surface and ground water. In the past, chlorpyrifos was applied aerially over water in swamps to control mosquitoes, however chlorpyrifos is no longer registered for this use. Chlorpyrifos is applied to agricultural, home, and garden soil during direct soil or foliar treatment, and from waste disposal in hazardous waste sites containing chlorpyrifos (HSDB 1994). Much of the chlorpyrifos-containing waste in these contaminated sites may come from manufacturer’s waste. 

IV. Environmental Risk and Prevention

A) Diazinon 

     Since Diazinon is considered a toxic chemical under Section 313 of the Emergency Planning and Community Right-To-Know Act (EPA 1995), sufficient time should be allowed between applications. As a general rule, enough time should be allowed for diazinon to break down to harmless compounds before another application. Since degradation depends on the formulation applied and the medium (soil, water, etc), each case has different regulations. The general safety period varies from 1 to 21 days (web page). Diazinon should never be used in cases where potential contact with humans or pets exists. In case indoor use is necessary, precautions must be taken to avoid direct exposure. 

     Large amounts of dazinon should be disposed off in an EPA approved incinerator with an effluent gas-scrubbing unit. For smaller amounts, controlled hydrolysis or bioremediation techniques may be used. These disposal techniques can also be used for remediation and cleaning up spills. 

     Diazinon itself is not a ChE inhibitor, however, in animals it is converted to diazoxon , a very strong enzyme inhibitor. Diazoxon differs from diazinon in that an oxygen molecule substitutes the sulfur molecule. The range of doses that result in toxic effects varies widely with formulation and exposed individuals. Some of the common symptoms associated with diazinon poisoning in humans include headaches, weakness, blurred vision, nausea, diarrhea, and muscle cramps. At very high levels of exposure, death might also occur. In humans, the no-effect dose is about 0.02 mg/kg/day. The maximum drinking water contamination is set at 0.014 mg/l, while the reference dose for humans is 0.00009 mg/kg/day (all numerical values where taken from Entoxnet). As for the LD50s, a range from 2.75 mg/kg/day to nearly 450 mg/kg/day for rats where reported by Howard (Howard 1991). 

     Based on a study in which rats where exposed to diazinon by different pathways, it was established that diazinon is neither a mutagen nor a carcinogen (Entoxnet). 

     As for ecological effects, Birds are the most susceptible species to diazinon poisoning. Bird kills associated with diazinon use have been reported in every area of the country and at all times of the year. The Ld50s for birds range from 2.75 to 40.8 mg/kg/day (Bartsch, 1974). Bioconcentration ratios are low when compared to compounds such as DDT, therefore diazinon is not expected to significantly bioconcentrate in animals or humans. In fact, the half-life of the pesticide in animals is 12 hours. The metabolites account for around 70% of the total amount excreted. 

B) Fenamiphos 

     Fenamiphos has a restricted use status, meaning it can be purchased and applied only by a certified applicator (Entoxnet). The organophosphate is regulated by several government agencies such as OSHA and its risk is categorized by federal legislature, such as SARA Title III and CERCLA. In consequence, there are several standards applied to fenamiphos. The time weighted average (TWA) for skin recorded by OSHA and ACGIH is 0.10 mg/m³ at 15% concentration (MSDS). 

     Fenamiphos is highly toxic to humans and several animals in the environment. For humans, based on EPA toxicity category criteria, this compound is highly toxic by the oral route of exposure and mildly toxic by the dermal routes of exposure. Its routes of entrance into the body are inhalation, skin contact, skin absorption, and eye contact. Symptoms of acute poisoning develop during the exposure or within 12 hrs of contact (MSDS). These symptoms include breathing difficulty, diarrhea, urination, slowness of heart, muscle twitching and tremors. Some of its toxicity standards are a dermal LD50 equal to 178 to 225 mg/kg (rabbit, technical), an oral LD50 of 8.1 to 9.6 mg/kg (rat, technical) and an inhalation LC50 of 110 ug/l/60 min (male rat)(Nemacur page-web). Fenamiphos has an oral RfD equal to 0.00025 mg/kg/day (MSDS:Nemacur). Its LEL is 0.05 mg/kg/day and its NOEL is 0.025 mg/kg/day. Both of these values were obtained from a two-year dog study (IRIS). 

     A number of long-term studies have been conducted with fenamiphos on several different animals to determine its chronic toxicity. Repeated exposure to small amounts of this material have been known to result in an unexpected cholinesterase depression causing symptoms such as malaise, weakness, and anorexia that resemble other illnesses, such as influenza. Other studies have shown that the compound appears to have almost no related reproductive effects and is not a carcinogen or mutagen (Nemacur MSDS). 

     Fenamiphos has other ecological impacts. It is acutely toxic to birds and fish, depending on the species. Fortunately, the compound is not expected to bioaccumulate appreciably in aquatic organisms (Entoxnet). 

     In terms of remediation, if fenamiphos is spilled, it should be carefully swept into a pile. The contaminated area should be scrubbed with detergent and bleach solution and rinsed with water. Dry absorbent material such as clay granules can be used to absorb and collect wash solution for disposal. Further, contaminated soil may have to be removed and disposed. Fenamiphos can be buried in an EPA approved landfill or burned in an incinerator approved for pesticide destruction if necessary (MSDS). 

     The best way to prevent contamination of fenamiphos is to use and apply it properly. Certain controlled-release formulations have been suggested as a means to decrease pesticide leaching, runoff, and volatilization while increasing persistence. These controlled–release formulations are formulated by the encapsulation of the active ingredient with a polymeric matrix of alginate and appear to reduce leaching in soil and runoff. (Davis, et al. 1996) 

C) Chlorpyrifos 

     The recommended treatment and disposal methods include incineration, adsorption, and landfilling (IRPTC 1989). For small amounts of chlorpyrifos, the recommended disposal is absorption with materials such as sand and burying in locations away from domestic water supplies. The triple rinse and drain procedure is the preferred method of decontaminating containers (IRPTC 1989). The major degradation product of chlorpyrifos is TCP, which can also act as a sensitive marker for exposure. 

     ATSDR has derived an MRL of .003 mg/kg/day for both acute and intermediate oral exposure, based on a NOAEL of .03 mg/kg/day observed in human adult males exposed orally to chlorpyrifos (Coulston et. al.). No inhalation reference concentration data exists at the present time for this chemical. Chlorpyrifos is regulated under "The Emergency Planning and Community Right-to-Know Act of 1986" (EPCRA) (EPA 1988a). This requires owners and operators of certain facilities that manufacture, import, process, or otherwise uses the chemicals on the list to annually report their releases of those chemicals to any environmental media. The EPA has also established tolerances for chlorpyrifos in raw agricultural commodities, foods, and animal feeds as a means of regulation of exposure levels. 

     Symptoms of short-term exposure to low to moderate levels of chlorpyrifos include: dizziness, confusion, salivation, tremors, rapid heart rate, paralysis, loss of consciousness, and muscle weakness which may persist even after the original symptoms have past. The muscle weakness is referred to as organophosphate-induced distal neuropathy (OPIDN) which has been seen in laboratory animals as well as people. Age and sex also play a role in chlorpyrifos toxicity. Children and Infants absorb more chlorpyrifos through their skin than adults do and they cannot get rid of it as fast. Women have also been seen to get rid of chlorpyrifos 2-3 times as slower than do men. This puts women and children at a higher risk. 

     Toxicity is significantly increased when chlorpyrifos is combined with other pesticides. 

V. Fate and Transport (EXAMS) 

Diazinon: The EXAMS model shows that at steady state 90% of the diazinon will be sorbed or complexed in the benthic sediments, while only 10% of the compound will be found in the water column. This 10% includes diazinon sorbed to the organic water in the water. These values agree well with the predictions based on structure, Kd, and solubility from the physical properties section. 

     Twelve months after the loading stopped 70% of the mass initially present in the water column had disappeared, in addition to 62% of the mass present in the benthic sediments. The most likely removal mechanisms are hydrolysis, volatilization, and biotransformation. For the complete output of the EXAMS model look at table 2. 

Fenamiphos: As shown in the EXAMS model, at steady state, fenamiphos will have a greater total concentration sorbed in the benthic sediments than dissolved in the water column of the pond. This is expected due to its fairly high Kd and Kow values. Furthermore, within both compartments, the greatest concentration will be found in the biota or plankton. This is also foreseen because the chemical was designed to be taken up by plants. Only 0.18% of the compound is volatilized, probably due to its low K_H value. Therefore, any removal of the compound is due to other pathways, such as runoff and leaching. Consequently, 61.0% of the compound was removed in 144 days. This number would be smaller if other half-lives, such as hydrolysis, for the different compartments had been taken into account. 

Appendix 1: Citations For Chemical and Physical Parameters  

Diazinon:  

Density 
Melting Point 
Boiling Point 
Vapor Pressure* 
Water Solubility* 
K_H* 
Log Kow* 
Log Koc 
Kd 
pKa 
Log BCF 
Half-Life 
    Air 
    Water 
    Soil 
    Biota 

 
Fenamiphos:

Density 
Melting Point 
Boiling Point 
Vapor Pressure* 
Water Solubility* 
K_H* 
Log Kow* 
Log Koc 
Kd 
Half-Life 
    Soil

Appendix 2: Works Cited

Text and Magazine: 

Internet: