Isofenphos (ISO)

log Kow= 4.12

4.12

Readily soluble in n-hexane, dichloromethane, 2-propanol, toluene

In water, 22.1 mg/l @ 20 °C

0.0221 mg/mL at 20 °C

When heated to decomposition it emits toxic fumes of /phosphorus oxides, sulfur oxides, & nitrogen oxides/.

DT50 for aqueous hydrolysis /is/ 2.8 yr (pH 4), >1 yr (pH 7), >1 yr (pH 9) (22 °C).

Less than -12 °C

-12 °C

0.000003 [mmHg]

3.00X10-6 mm Hg @ 25 °C

Isofenphos is a colorless oil. Non corrosive. Used as an insecticide.

Liquid; [Merck Index] Colorless liquid; [CAMEO]

Liquid

2033；2045；2060.1；2018；2048.1；2039.3；2038.6

2060；2064；2066；2062；2060；2055.5；2063.8；2064.1；2070.9；2070.5；2046.5；2065；2035.8

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]；H311: Toxic in contact with skin [Danger Acute toxicity, dermal]；H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P262, P264, P270, P273, P280, P301+P316, P302+P352, P316, P321, P330, P361+P364, P391, P405, and P501 (click each P-code to see the statement)

Danger

Isofenphos is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

2002/2076

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

IMAP assessments - Benzoic acid, 2-[[ethoxy[(1-methylethyl)amino]phosphinothioyl]oxy]-, 1-methylethyl ester: Environment tier I assessment；IMAP assessments - Benzoic acid, 2-[[ethoxy[(1-methylethyl)amino]phosphinothioyl]oxy]-, 1-methylethyl ester: Human health tier I assessment

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:；Combustible material: may burn but does not ignite readily. Containers may explode when heated. Those substances designated with a (P) may polymerize explosively when heated or involved in a fire. Runoff may pollute waterways. Substance may be transported in a molten form. (ERG, 2024)

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:；Highly toxic, may be fatal if inhaled, ingested or absorbed through skin. Contact with molten substance may cause severe burns to skin and eyes. Avoid any skin contact. Fire may produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause environmental contamination. (ERG, 2024)

Not irritating to skin and mildly irritating to eyes of rabbits; No evidence of delayed neuropathy in intramuscular injection study with hens; [HSDB] No developmental effects in studies with rats at doses that caused cholinesterase inhibition in mothers; No available studies on human reproductive effects or effects on lactation; [REPROTOX] No clinical or histopathological evidence of delayed neurotoxicity in three studies with hens (at doses up to 2 mg/kg bw for 90 days and single oral doses up to 74 mg/kg bw after antidotal treatment); Observations of delayed neurotoxic effects in one study with hens two weeks following (dosage of 100 mg/kg bw achieved with antidotal treatments); [Reference #2] The average of two baseline respective cholinesterase activity determinations three days apart, with no exposures to enzyme inhibiting pesticides for at least 30 days, is recommended for each worker prior to exposure to cholinesterase inhibitors because of large inter-individual differences in published baseline values. To be established at least once a year. Removal from workplace exposures is recommended until the cholinesterase activity returns to within 20% of baseline. [TLVs and BEIs]

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Isophenphos is found on List B. Case No: 2345; Pesticide type: insecticide, herbicide; Case Status: PreRED - OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): isopropylsalicylate,O-ester with O-ethyl isopropylphosphoramidothioate; Data Call-in (DCI) Date(s): 05/10/91, 03/03/95, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

Organothiophosphates, such as ISOFENPHOS, are susceptible to formation of highly toxic and flammable phosphine gas in the presence of strong reducing agents such as hydrides. Partial oxidation by oxidizing agents may result in the release of toxic phosphorus oxides.

Isofenphos

Marine pollutant

Acute Tox. 3 (97.6%)；Acute Tox. 3 (97.6%)；Acute Tox. 1 (92.9%)；Aquatic Acute 1 (100%)；Aquatic Chronic 1 (100%)

Acute toxicity - category 3；Acute toxicity - category 3；Hazardous to the aquatic environment (acute) - category 1；Hazardous to the aquatic environment (chronic) - category 1

Acute toxicity (Oral) - Category 1；Acute toxicity (Dermal) - Category 2；Acute toxicity (Inhalation: Dusts and mists) - Category 2；Skin corrosion/irritation - Category 3；Serious eye damage/eye irritation - Category 2B；Reproductive toxicity - Category 2；Specific target organ toxicity - Single exposure - Category 1 (nervous system)；Specific target organ toxicity - Repeated exposure - Category 1 (nervous system, testis)；Hazardous to the aquatic environment (Acute) - Category 1；Hazardous to the aquatic environment (Long-term) - Category 1

Acute Tox. 3 *；Acute Tox. 3 *；Aquatic Acute 1；Aquatic Chronic 1

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:；SMALL FIRE: Dry chemical, CO2 or water spray.；LARGE FIRE: Water spray, fog or regular foam. If it can be done safely, move undamaged containers away from the area around the fire. Dike runoff from fire control for later disposal. Avoid aiming straight or solid streams directly onto the product.；FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks in direct contact with flames. For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn. (ERG, 2024)

Biological Exposure Indices (BEI) [ACGIH] - Acetylcholinesterase activity in red blood cells = 70% of individual's baseline; Butylcholinesterase activity in serum or plasma = 60% of individual's baseline; Sample at end of shift; [TLVs and BEIs]

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:；ELIMINATE all ignition sources (no smoking, flares, sparks or flames) from immediate area. Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Cover with plastic sheet to prevent spreading. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2024)

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.；SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

Excerpt from ERG Guide 152 [Substances - Toxic (Combustible)]:；Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer when there is NO RISK OF FIRE. Structural firefighters' protective clothing provides thermal protection but only limited chemical protection. (ERG, 2024)

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values from 633 to 1,474 on four soils(2) indicate that isofenphos is expected to have low mobility in soil(SRC). Volatilization of isofenphos from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 4.15X10-8 atm-cu m/mole(3). Isofenphos is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 3.00X10-6 mm Hg(4). Isophenophos degrades on soil exposed to light with a half-life of 72 days(2). In a week-long incubation study using 6 soils with a history of isofenphos use and 19 soils with no previous use, an increased rate of mineralization in the soils with previous use history (35.9 +/- 2.4% of the parent mineralized to CO2) was found compared with the nonhistory soils (2.4+/-1.0%)(2). In a 4-week incubation study, 62.8% of the parent was recovered from a soil with no history of use and only 12.9% from a soil that was previously treated with isofenphos(2). Mineralization of the aromatic ring was evident(2). Isofenphos oxygen analog (also called isofenphos oxon) was identified as degradation product(2).

TERRESTRIAL FATE: In turf plots in Georgia and Minnesota and soil plots in Georgia and California, isofenphos dissipated from the upper 6 inches of soil with first-order half-lives of 7 to 81 days and DT50s (the time in which 50% of the pesticide dissipates from the surface of the soil) ranging from 10 to 63 days(1). In California, a rapid initial dissipation (half-life = 7 days) was followed by a plateau and a secondary dissipation half-life of >63 days(1). When both isofenphos and the structurally-similar oxon analog are considered together, the dissipation half-lives range from 21 to 170 days(1). The studies only tracked isofenphos and the formation of its oxygen analog, but did not evaluate the formation of other degradates (including volatiles) or incorporation/ binding within the soil(1). The pesticide use history was unknown in the Georgia turf and soil plots(1). Isofenphos use was not reported in the previous 5 years on the other sites(1). Supplemental field studies covering 23 sites reported dissipation half-lives ranging from less than 2 weeks to more than 1 year, depending on factors such as formulation, location, and number of applications(1). Isofenphos and its oxygen analog were not detected below 12 inches in the Georgia and Minnesota turf studies or below 6 inches in the Georgia bareground study(1). Isofenphos was detected to 18 inches and the oxygen analog to 30 inches in the California bareground study(1). The soils in the California study had a much lower organic matter content (<0.5%) than did the other three sites(1). The results suggest that while isofenphos is not highly mobile through the soil profile, under certain conditions it may move into the subsurface(1).

AQUATIC FATE: Based on a classification scheme(1), Koc values from 633 to 1,474 on four soils(2) indicate that isofenphos is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(SRC) based upon a Henry's Law constant of 4.15X10-8 atm-cu m/mole(3). According to a classification scheme(4), BCF values in fish tissues of 94.5 (fillet), 469 (viscera), and 277 (whole body)(2), suggests bioconcentration in aquatic organisms is high(SRC). Isophenphos is stable to hydrolysis at pHs 5 and 7 and degrades slowly at pH 9 with a half-life of 131 days(2). Isophenophos is stable to photolysis in water(2). Using non- sterilized, filtered river water at pH 7.3, isofenphos degraded in 97 and 175 days at 22 and 6 °C, respectively(5). In seawater at pH 8.1, isofenphos degraded in 118 and 224 days at 22 and 6 °C, respectively(5). In filtered estuarine water (pH 7.8, salinity 20 g/l) from the Ebre River, Spain, the degradation half-life for isofenphos ranged from 9.8-11.9 days(6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), isofenphos, which has a vapor pressure of 3.00X10-6 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere(SRC). Vapor-phase isofenphos is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.4 hrs(SRC), calculated from its rate constant of 2.75X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase isofenphos may be removed from the air by wet and dry deposition(SRC).

In Canada between 1992-1994, isofenphos was found in 1 of 105 broccoli (fresh) samples and 1 of 211 cauliflower (fresh) samples at concns <0.05 ppm(1). In Canada between 1989-1991, isofenphos was found in 1 of 1,044 samples of potato (fresh) and 2 of 187 samples of broccoli (fresh) at concns of 0.05 ppm(2).

... A unique case of attempted suicide /was reported/ by intramuscular injection of the organophosphate isofenphos which resulted in a muscarinic and nicotinic syndrome lasting 15 days and requiring prolonged mechanical ventilation and hospitalization. The patient, who demonstrated no signs of delayed polyneuropathy on hospital day 25, subsequently died of pneumonia. Toxicological investigations showed isofenphos plasma decay and confirmed the intramuscular route of poisoning. It appears that continuous isofenphos absorption resulted in the prolonged intoxication observed in this patient.

Late progressive polyneuropathy followed by pyramidal findings in a 20-year old agricultural laborer who ingested Isofenphos solution during his work, is presented. The patient was confined to a wheelchair within 6 weeks, regained walking ability within 6 months, and a 23 months' follow up revealed slight additional clinical improvement with minimal progression of the pyramidal signs. The neuropathic clinical manifestations, the EMG and the nerve conduction studies were compatible with a pathology of a distal, mainly axonal, mainly motor neuropathy.

The organophosphate pesticide, isofenphos, is associated with human myeloid leukemia. In this study we describe metabolic changes in K562 myeloid blast cells from exposure to varying concentrations of isofenphos using the stable [1,2-13C(2)]glucose isotope as the single tracer and biological mass spectrometry. Isofenphos (1, 10, 100 microg/ml/72 hr) treated K562 cells showed increases of 10.7, 33.8 and 39.7% in lactate production as well as a 14.2% increase (1 microg/ml/72 hr) in 13C incorporation into nucleic acid ribose from glucose. Concomitantly, we observed a decrease in glucose oxidation and the synthesis of glutamate, palmitate and stearate from glucose. Our results demonstrate that this organophosphate pesticide exerts a leukemogenic effect by the recruitment of glucose carbons for nucleic acid synthesis thus promoting proliferation simultaneous with poor differentiation. The imbalanced metabolic phenotype with a severe defect in glucose oxidation, lipid and amino acid synthesis concurrent with de novo synthesis of nucleic acids in response to isofenphos treatment conforms to the invasive proliferating phenotype observed in TGF-beta treated lung epithelial carcinoma cells.

AEROBIC: Isofenphos degrades slowly (half-life of 352 days) under aerobic soil conditions(1). Although isofenophos is persistent when first applied to soils, microbial adaptations enhance degradation in subsequent years(1). In a week-long incubation study using 6 soils with a history of isofenphos use and 19 soils with no previous use, an increased rate of mineralization in the soils with previous use history (35.9 +/- 2.4% of the parent mineralized to CO2) was found compared with the nonhistory soils (2.4+/-1.0%)(1). In a 4-week incubation study, 62.8% of the parent was recovered from a soil with no history of use and only 12.9% from a soil that was previously treated with isofenphos(1). Mineralization of the aromatic ring was evident(1). Isofenphos oxygen analog (also called isofenphos oxon) was identified as degradation product(1). If both isofenphos and the structurally similar isofenphos oxon are considered together, the aerobic soil metabolism half-life is on the order of 3 years(1). Isofenphos oxon accumulated only in a nonhistory soil(1). Repeated annual treatments of isofenphos increased the enhanced degradation activity in soil(1). Enhanced degradation activity was still apparent in soils more than 162 weeks after the last treatment(1). Exposure of soil to salicylic acid, a secondary hydrolysis product, resulted in enhanced degradation of isofenphos(1). The formation of salicylic acid in soil may be a key factor in triggering the susceptibility of isofenphos to enhanced degradation(1). It is not clear whether the presence of other organophosphates may trigger enhanced degradation(1).

AEROBIC: Using non-sterile, filtered river water at pH 7.3, isofenphos degraded in 97 and 175 days at 22 and 6 °C, respectively(1). In seawater at pH 8.1, isofenphos degraded in 118 and 224 days at 22 and 6 °C, respectively(1). In filtered estuarine water (pH 7.8, salinity 20 g/l) from the Ebre River, Spain, the degradation half-life for isofenphos ranged from 9.8-11.9 days(2).

ANAEROBIC: Isofenphos is stable under anaerobic aquatic conditions(1). In an anaerobic aquatic metabolism study, the distribution of applied isofenphos residues increased from 30% to >60% in the pond water and decreased from 69% to <30% in the sediment after 1 year (isofenphos comprised 90% of the residues)(1). This data suggests, at least in stagnant waters, a significant portion of applied isofenphos will remain in the water column(1).

BCFs of 94.5 (fillet), 469 (viscera), and 277 (whole body) in fish tissues were measured for isofenphos(1). According to a classification scheme(2), these BCF values suggests the potential for bioconcentration in aquatic organisms is high(SRC).

The Henry's Law constant for isofenphos is 4.15X10-8 atm-cu m/mole(1). This Henry's Law constant indicates that isofenphos is expected to be essentially nonvolatile from water surfaces(2). Isofenphos is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 3.00X10-6 mm Hg(3).

Not irritating to skin, slightly irritating to eyes (rabbits).

In 1990 an outbreak of ataxia occurred in over 700 pigs in the north of England. /Follow up/ studies demonstrated that the disorder was associated with the consumption of feed from a particular supplier and that one component (wheat screenings) was common to the batch of feed with which the ataxia was associated. An analysis of the feed demonstrated the presence of an organophosphorus pesticide, later identified as isofenphos, a pesticide not approved for use in the United Kingdom. The wheat screenings had been imported from France and the warehouse in which they had been stored was contaminated with isofenphos, which is approved for restricted use in France. Isofenphos is known to cause delayed neuropathy. The dose to which the pigs were theoretically exposed would be expected to have resulted in neuropathy (manifested as ataxia).

The neuropathic potential of acute and repeated exposures of the phosphoramidates tabun (GA) and isofenphos (IFP), of diisopropyl fluorophosphate (DFP) and paraoxon (PO) were examined in the hen with treatments for up to 90 days via intramuscular injections of the highest tolerated doses with atropine protection. Plasma acetylcholinesterase (AChE), non-specific butyrylcholinesterase (BChE) and creatine kinase (CK) activities were measured in order to monitor whether the compounds were present at biologically active concentrations. Locomotor behavior was observed and tissues from the peripheral and central nervous systems were examined for signs of organophosphate-induced delayed neuropathy (OPIDN). No behavioral or histological evidence of OPIDN was observed after treatments with GA, IFP, PO, saline or atropine sulfate. DFP-treated birds displayed locomotor and neuropathological signs of OPIDN with a no effect level (NOEL) between 25 and 50 micrograms/kg.

Isofenphos is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

2002/2076

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Isophenphos is found on List B. Case No: 2345; Pesticide type: insecticide, herbicide; Case Status: PreRED - OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): isopropylsalicylate,O-ester with O-ethyl isopropylphosphoramidothioate; Data Call-in (DCI) Date(s): 05/10/91, 03/03/95, 10/13/95; AI Status: The producers of the pesticide has made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

A preparation of liver mixed-function oxidases and brain NTE was used to rapidly detect activations of OPs. The compounds (0.1 mM or less) to be tested were incubated with microsomes isolated from livers of phenobarbital-treated chick embryos (P-450 content averaged 1.81 + or - 0.27 nmol/mg protein, means + or - SD, N = 5) and NTE (average of 13.8 nmol/min/mg protein) from untreated chick embryo brains. The NTE was separated by calcium precipitation and its activity assayed as usual. The low inhibitions of NTE of compounds that were not neurotoxic (parathion, Diazinon) did not increase in the presence of NADPH; inhibitions of NTE of compounds that required activation (leptophos, S,S,S-tri-n-butyl phosphorotrithioate, and tri-o-cresyl phosphate) greatly increased with NADPH. Both the recently identified neuropathic OP isofenphos (IFP) and its oxon required activation to inhibit NTE (inhibitions of 20 and 80%, respectively).

The degenerative process of the myofibers of the diaphragm of rats intoxicated with the organophosphate isofenphos, a compound that inhibits esterases, was studied at different intervals of intoxication. Early disorganization of the intermyofibrillar network and of the myofilaments, as well as dilatation of organelles, were observed by use of transmission electron microscopy. These changes precede macrophage invasion of the muscle fibers. Early expression of ubiquitin was observed in segments of muscle fibers by immunohistochemistry. Bands of polyubiquitin complexes in muscle homogenates were observed by immunoblotting. These bands disappeared in later stages of intoxication. A 42.5-kDa band corresponds to actin, as observed by immunoblotting using antisarcometric actin. This indicates relatively large amounts of polyubiquitin complex associated with sarcomeric actin in muscle fibers in early stages of intoxication.

Adult male Wistar rats were given oral organophosphate compounds dissolved in glycerol formal: dichlorvos, isofenphos, metamidophos, and diazinon. Half of the animals also received pralidoxime mesylate (20 mg/kg, intraperitoneal). Control animals received only the solvent. Twenty-four hours after treatment, the diaphragm muscle was collected for histological counts of necrotic muscle fibers in transverse sections.

The cytotoxicity of isophenphos, an organophosphorus insecticide that has the potential to cause delayed polyneuropathy, was evaluated in GBK and V79 cells. A 72 hr time course following isophenphos exposure indicated a dose-dependent growth inhibition as determined by cell counts. The administration of isophenphos (20 g/ml) to GBK cells cultured at high densities indicated a decrease in the activities of LDH isoenzymes. Analysis of V79 cells revealed a decrease of LDH3, the only LDH isoenzyme detected in these cells.

The rate of metabolism of [14C]isofenphos (IFP) to isofenphos oxon (IFP-oxon), des N-isofenphos (d-N-IFP), and des N-isofenphos oxon (d-N-IFP-oxon) by rat, guinea pig, monkey, dog, and human liver microsomal p450 enzymes was studied to obtain Vmax and Km values for Michaelis-Menten kinetics. The monkey had the highest Vmax value for the conversion of IFP to IFP-oxon (desulfuration), 162 nmol isofenphos hr-1 per 1.3 nanomoles p450, followed by guinea pig (98), rat (66), dog (43), and human (14). The Km values for the desulfuration of isofenphos were 19.2, 7.4, 14.1, 23.3, and 18.4 microM, respectively, for the monkey, guinea pig, rat, dog, and human. The Vmax values for the dealkylation process (conversion of IFP to d-N-IFP) were 64.6, 17.2, 9.7, and 7.3 nmol isofenphos hr-1 per 1.3 nanomoles P-450 for the monkey, rat, dog, and human, respectively. For the dealkylation process, monkey had the highest Km value, 16.3 microM IFP, followed by human (11.2), rat (9.9), and dog (9.3). The rate of metabolism of IFP-oxon and d-N-IFP to d-N-IFP-oxon were separately studied. The Vmax and Km values obtained in this study for animal and human liver p450 enzymes will be used to develop a PB-PK/PB-PD model to predict the fate and toxicity of isofenphos in animals and man.

Elimination is very quick; almost 95% is excreted within 24 hr, in urine & feces.

... Dermal absorption in man was 3.6 + or - 3.6% of applied dose for 24-hr exposure and 3.6 + or - 0.5% for 72-hr exposure. Skin wash recovery data show that isofenphos evaporates from the skin during the absorption process; the surface dose is minimal (< 1%) by 24 hr. Skin stripping showed no residual isofenphos in stratum corneum. ... Skin surface recovery in vivo with soap and water was 61.4 + or - 10.4% for the first dosing time (15 min). Time-recovery response declined with time to 0.5 + or - 0.2% at 24 hr. In vitro absorption utilizing flow-through diffusion methodology with human cadaver skin and human plasma receptor fluid gave 2.5 + or - 2.0% dose absorbed, an amount similar to in vivo studies. An additional 6.5 + or - 24% was recovered in the skin amples (total of 9%). Skin surface wash at 24 hr recovered 79.7 + or - 2.2% and skin content was 6.5 + or - 2.4% (total dose accountability of 88.7 + or - 4.6%). Neither in vitro absorption nor in vitro evaporation studies predicted the potential skin evaporation of isofenphos. Published dermal studies in the rat had predicted isofenphos absorption at 47% of applied dose (12-fold greater than actual in man).

Used as soil insecticide for turf and ornamentals; [HSDB] Approximately 60% of the US consumption was used on golf courses; [Reference #1]

Voluntarily cancelled by the sole US registrant in 1999; All tolerances revoked; [Reference #1]

Farming (Pesticides) [Category: Industry]

For Isofenphos (USEPA/OPP Pesticide Code: 109401) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Isofenphos, marketed under the basic producer's trade name Oftanol, is currently used in the United States on turf & ornamental trees & shrubs to control white grubs, mole crickets, & other insects (mostly subterranean species). According to recent usage data, about 60% of the Isofenphos active ingredient produced annually is used on golf courses; the remainder is used on residential & public turf sites. Isofenphos ... was first registered in the United States in 1980 by Bayer Corporation for use on corn for control of the corn rootworm. In recent years, all of the food uses & the various residential indoor uses (including the termiticide use) were dropped by the basic producer. ... The remaining turf & ornamental uses of the pesticide are now no longer supported. ... All food tolerances for Isofenphos have been revoked (effective January 1999).

Insecticide; control of cabbage root flies, onion flies, corn rootworms, white grubs, wireworms, and other soil insects. /Former use/

USEPA/OPP Pesticide Code 109401; Trade Names: Amaze, Oftanol, BAY 92114, SRA 12869, Pryfon 6.

Granules, emulsifiable concentrate, wettable powder, powder for deep seed treatment

Mixtures (isofenphos +): thiram; fenamiphos; phoxin; carbonfuran; disulfoton

The acute biocidal effects of organophosphorus pesticides are a central feature of modern agricultural chemistry, and also define the concerns of regulatory toxicology. Less well known, but more complex and idiosyncratic, is the potential for some agents to produce a delayed and progressive polyneuropathy--Organophosphorus Induced Delayed Neurotox-icity (OPIDN). On three occasions during the past ten years, the National Institute for Occupational Safety and Health (NIOSH) had been asked to evaluate human delayed neurotoxicity from three commercially available pesticides. These were leptophos, fenthion, and isofenphos. In each case, human disease was either observed or suggested by specialized toxicity testing. The reasons that federally recommended screening measures failed to identify a potential for human neurotoxicity were not accidental, but stem from a systematic approach that focuses on a traditional definition of acute lethal toxicity. The oral single dose study on one species appears to be insufficient for recognizing the delayed neurotoxic hazard of many representatives of this chemical class. The recent addition of a recommended biochemical assay--neurotoxic esterase (NTE)--to federal guidelines potentially improves sensitivity, but it is purely adjunctive and does not amend underlying ambiguities in selecting the dose and route of administration. It is also quite probable that human neurotoxicity may be a potential hazard from exposure to more than the handful of organophosphorus pesticides that have been described in the literature.