Isazophos

Insecticides

Active substance -> EU Pesticides database: Not approved

Pesticides -> Organophosphate Insecticides

log Kow = 3.82

2.99

Amber liquid

Yellowish liquid

Yellow liquid

Miscible with methanol, chloroform, benzene, hexane

In water, 69 mg/l at 20 °C

Decomposes above 200 degrees C.

When heated to decomposition it emits very toxic fumes of /hydrogen chloride/, nitrous oxides, phosphorous oxides, and sulfoxides.

0.000087 [mmHg]

8.70X10-5 mm Hg at 25 °C

Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]

P260, P261, P262, P264, P270, P271, P272, P273, P280, P284, P301+P316, P302+P352, P304+P340, P316, P319, P320, P321, P330, P333+P317, P361+P364, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Danger

H301 (97.6%): Toxic if swallowed [Danger Acute toxicity, oral]

P260, P261, P262, P264, P270, P271, P272, P273, P280, P284, P301+P316, P302+P352, P304+P340, P316, P319, P320, P321, P330, P333+P317, P361+P364, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Caused inhibition of cholinesterase activity but no gross or histopathological changes observed in long term feeding studies with rats and dogs; No evidence of increase in tumor frequency in long term feeding studies with rats; Caused developmental toxicity in rats at dose levels maternally toxic; No evidence of delayed neurotoxicity in oral studies with birds; No evidence of any mutagenic effects from the California EPA (2003); Marked increase in spontaneous mutation frequency observed with Salmonella and increase in mitotic indices and chromosome aberrations seen in bone marrow cells of mice (Mutation Research in Amsterdam 1998); [HSDB] 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]

Acute Tox. 3 (97.6%)

Specific target organ toxicity (repeated exposure) - category 2

Acute Tox. 2 *

49 216 74; Organophosphorus pesticide, liquid, not otherwise specified (compounds and preparations) (insecticides, other than agricultural, NEC)

49 216 75; Organophosphorus pesticide, liquid, not otherwise specified (compounds and preparations) (agricultural insecticides, NEC, liquid)

49 105 44; Organophosphorus pesticide, liquid, not otherwise specified (compounds and preparations) (insecticides, other than agricultural, NEC)

49 105 45; Organophosphorus pesticide, liquid, not otherwise specified (compounds and preparations) (agricultural insecticides, NEC, liquid)

49 216 76; Organophosphorus pesticide, solid, not otherwise specified (compounds and preparations) (insecticides, other than agricultural, NEC)

49 216 77; Organophosphorus pesticide, solid, not otherwise specified (compounds and preparations) (agricultural insecticides, NEC, other than liquid)

No person may /transport,/ offer or accept a hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./

The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials.

The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article.

UN 3018; Organophosphorus pesticides, liquid, toxic, not otherwise specified

UN 3017; Organophosphorus pesticides, liquid, toxic, flammable, not otherwise specified, flashpoint between 23 °C and 61 °C

UN 2783; Organophosphorus pesticides, solid, toxic, not otherwise specified

UN 2784; Organophosphorus pesticides, liquid, flammable, toxic, not otherwise specified, flashpoint less than 23 °C

For more Shipping Name/ Number DOT/UN/NA/IMO (Complete) data for ISAZOFOS (6 total), please visit the HSDB record page.

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]

If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical or carbon dioxide. /Organophosphorus pesticides, liquid, flammable, toxic; Organophosphorus pesticides, liquid, toxic/

If material on fire or involved in fire: Use water in flooding quantities as fog. Extinguish fire using agent suitable for type of surrounding fire. (Material itself does not burn or burns with difficulty.) /Organophosphorus pesticides, solid, toxic/

Environmental considerations: Air spill: Apply water spray or mist to knock down vapors. /Organophosphorus pesticides, liquid, flammable, toxic; Organophosphorus pesticides, liquid, toxic; Organophosphorus pesticides, solid, toxic/

Environmental considerations: Water spill: Use natural barriers or oil spill control booms to limit spill travel. Remove trapped material with suction hoses. /Organophosphorus pesticides, liquid, flammable, toxic; Organophosphorus pesticides, liquid, toxic; Organophosphorus pesticides, solid, toxic/

Environmental considerations: Land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, cement powder, or commercial sorbents. /Organophosphorus pesticides, liquid, flammable, toxic; Organophosphorus pesticides, liquid, toxic; Organophosphorus pesticides, solid, toxic/

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. /Organophosphorus pesticides, solid, toxic

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue personnel hazard. Use water spray to knock-down vapors. /Organophosphorus pesticides, liquid, toxic/

If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Use water spray to knock-down vapors. /Organophosphorus pesticides, liquid, flammable, toxic/

For more Preventive Measures (Complete) data for ISAZOFOS (10 total), please visit the HSDB record page.

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

The combination of certain herbicides with insecticides can inhibit crop growth. Greenhouse studies were conducted to evaluated interaction effects of herbicides and insecticides with/without protectant, on corn and weed species. 'Northrup King 9283' hybrid corn showed greater sensitivity to acetanilide herbicides than 'Cargill 7567'. Neither the insecticides terbufos nor isazofos appeared to enhance this sensitivity....

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 91.3 to 385(2), indicate that isazofos is expected to have high to moderate mobility in soil(SRC). Isazophos has a pKa of 4; in soils with lower pH, Koc values are expected to be higher as protonated species are readily sorbed to exchange sites in the soil(5). Volatilization of isazofos from moist soil surfaces is expected(SRC) given a Henry's Law constant of 5.21X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 8.7X10-5 mm Hg(4), and water solubility, 69 mg/l(4). Isazofos is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). Isazofos was reported to have a half-life in soil of 10 days in laboratory studies(3). Field half-lives of 34 days(4) and 2.5 to 48.4 days, have been reported(2). A half-life of 40 days at 25 deg has been reported for photolysis of isazofos on soil (pH 5)(2).

AQUATIC FATE: Based on a classification scheme(1), Koc values in the range of 91.3 to 385(7), indicates that isazofos may be expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(8) based upon a Henry's Law constant of 5.21X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 8.7X10-5 mm Hg(2), and water solubility, 69 mg/l(2). Using this Henry's Law constant and an estimation method(8), volatilization half-lives for a model river and model lake are 270 and 2000 days, respectively(SRC). According to a classification scheme(3), an estimated BCF of 170(SRC), from its log Kow of 3.82(4) and a regression-derived equation(5), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Isazofos is hydrolyzed more rapidly in alkali than in acids; half-lives were calculated at 20 °C as 85 days (pH 5), 48 days (pH 7), and 19 days (pH 9)(6). A half-life of 4 days at 25 deg has been reported for photolysis of isazofos in water (pH 7.5)(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), isazofos, which has a vapor pressure of 8.7X10-5 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase isazofos 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 3.8 hours(SRC), calculated from its rate constant of 9.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase isazofos may be removed from the air by wet and dry deposition(SRC). While isazofos is susceptible to photolysis in water and on soil(4), no data were found regarding the direct photolysis in air of isazofos by sunlight(SRC).

Isazofos is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.

Measurement of whole blood-AChE is the most widely adopted method for monitoring the effects of occupational exposure to organophosphorus insecticides. Physiological variations in blood ChE levels occur in a healthy person and are seen among a population. It has been estimated that the coefficient of variation for AChE activity in samples from an individual is 8-11%, and that a decrease of 23% below pre-exposure level may, therefore, be considered significant. If the average of several pre-exposure values were available, then a decrease of 17% would be significant. It has been recommended that, if measured activity is reduced by 30% or more of the pre-exposure value, AChE measurements should be repeated at appropriate intervals to confirm the results. Depressions of AChE or ChE in excess of 20-25% are considered diagnostic of exposure but not, necessarily, indicative of hazard. Depressions of 30-50% or more are considered indicators for removal of an exposed individual from further contact with pesticides until levels return to normal. /Organophosphorus Pesticides/

...Organophosphorus pesticides may undergo hydrolysis in vivo to yield substituted phosphoric acids that are subsequently excreted in urine. Advances in gas chromatography and combined gas chromatography/mass spectrometry (GC/MS) have made it possible to analyse the urine of exposed persons for the presence of appropriate metabolites. It is usually necessary to preserve the sample by the addition of chloroform, to concentrate or extract the metabolite(s), and to convert them to suitably-volatile derivatives that can be detected by GC. Obviously, access to a well-equipped analytical laboratory, capable of the quick processing of samples, is a necessary factor if monitoring by urine analysis is proposed. However, in some cases, simpler and sensitive colorimetric tests are available for screening the urine of exposed persons. Thus, 4-nitrophenol can be measured directly in the urine of workers exposed to parathion. Consideration of the concentration of metabolite(s) in the urine can be helpful in determining patterns of exposure, and these concentrations can be calibrated against the effects on AChE for a particular pesticide. However, the time-course and peak of excretion of metabolites appears to vary according to dose, so that serial sampling and analyses of urine are desirable. Levels of metabolite alone cannot be considered a guide to hazard. This is obvious when it is realized that pesticides that have very different toxicities may yield identical acidic metabolites. Thus, the level of metabolites in urine, after exposure to sufficient amounts of the very toxic parathion-methyl to depress blood-AChE to 50%, will be much lower than that of the identical metabolites, following exposure to the related fenitrothion, which is about 40 times less toxic. /Organophosphorus Pesticides/

SRP: Workers should undergo an annual medical exam. Contraindications for work with organophosporous pesticides are organic diseases of the CNS, mental disorders and epilepsy, and pronounced endocrine disorders. Blood cholinesterase, both plasma and RBC, must be determined before work starts. In the event of prolonged work periods, this activity should be determined at intervals of 3-4 days. Persons exhibiting a fall in cholinesterase activity of 25% or more must be transferred to other work where they are not exposed until cholinesterase activity is restored. /Organophosphorous pesticides/

Koc values of 52.9, 91.3, 139, and 385 have been reported for isazofos in sand (pH 6.5, 0.9% organic matter), sandy loam (pH 8.5, 1.0% om), clay (pH 5.9, 4.8% om), and silt loam (pH 7.5, 1.0% om)(1). According to a classification scheme(2), Koc values in the ranges of 50-150 and 150-500 indicate high and moderate mobility, respectively. In a study using 1.2 meter deep soil monolith lysimeters with a turf cover, isazofos was not detected (detection limit=16 ug/l) in the percolate during the study, Sept 1991-Oct 1993(3). Isazofos was determined to be mobile in a Kentucky bluegrass turf managed as a golf course fairway(4).

Undisturbed soil columns under an irrigation regime similar to agricultural practice (150 ml/day/column) were used to study the mobility of isazophos in soil over 13 weeks(1). 37.15, 1.4, and 0.1% of the initial concn was found in the soil profile, the water leachates and the plant material, respectively(1). Koc values varied with 2190 reported in the top 20 cm and 4320 from the 40 cm depth(1). The pH of the soils used was not provided(1). Mobility of commercial formulations of isazophos was studied using field lysimeters (packed with Honeywood silt loam; 1.5 to 2.8% organic matter) under two moisture regimes(2). Isazophos was eluted from 9 of 12 cores following watering during the first week of the experiment; however, no further elution was reported for the remainder of the experiment(2). Total amounts of isazophos below 10 cm never exceeded 2% of the applied product(2). Kd values of 2.828 and 1.336 were determined(2). Kd values from 0.81 to 2.82 were reported for soils containing organic matter from 2.0 to 4.9%(3). Isazophos has a pKa of 4; in soils with lower pH, Koc values are expected to be higher as protonated species are readily sorbed to exchange sites in the soil(4). Leaching of isazophos was less than 0.1% of the applied amount during a 6 month field study(5).

Persistence of isazophos, as either an emulsifiable concentrate or as granules, was measured in field lysimeters packed with Plainfield sand (1.5% organic matter) and receiving either natural rainfall or supplementary watering(3). Neither isazophos or its metabolite, CGA 17193 (5-chloro-1-isopropyl-3-triazolol), were found in the effluent of lysimeters receiving only rainfall over the 21 week period (223 mm rain fell)(1). Isazophos, applied as an emulsifiable concentrate, was eluted on 22 occasions from the lysimeters; however, when applied as granules, only 4 instances of isazophos elution were reported (total water input of 811 mm)(1).

/HUMAN EXPOSURE STUDIES/ Signs and symptoms of acute intoxication by organophosphorus insecticides include muscarinic, nicotinic, and central nervous system (CNS) manifestations. Symptoms may develop rapidly, or there may be a delay of several hours after exposure before they become evident. The delay tends to be longer in the case of more lipophilic compounds, which also require metabolic activation. Symptoms may increase in severity for more than one day and may last for several days. In severe cases, respiratory failure is a dominant effect. /Organophosphorus Pesticides/

/SIGNS AND SYMPTOMS/ Principal effects /of anticholinesterases as toxic components of insecticides/ on eye, whether from local contact or systemic poisoning, are miosis and spasm of accommodation for near vision. /Anticholinesterases/

Organophosphorus insecticides exert their acute effects in both insects and mammals by inhibiting acetylcholinesterase (AChE) in the nervous system with subsequent accumulation of toxic levels of acetylcholine (ACh), which is a neurotransmitter. In many cases, the organophosphorylated enzyme is fairly stable, so that recovery from intoxication may be slow. /Organophosphorus Pesticides/

Metabolism occurs principally by oxidation, hydrolysis by esterases, and by transfer of portions of the molecule to glutathione. Oxidation of organophosphorus insecticides may result in more or less toxic products. The glutathione transferase reactions produce products, that are, in most cases, of low toxicity. Hydrolytic and transferase reactions affect both thioates and their oxons. /Organophosphorus Pesticides/

Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.

Used as insecticide for turf, maize, rice, and other crops; Also used as soil nematicide for bananas, citrus, and other annual crops; [HSDB]

No longer registered as a pesticide for use in the US; [HSDB]

Farming (Pesticides) [Category: Industry]

For isazofos (USEPA/OPP Pesticide Code: 126901) there are 0 labels match. /SRP: Not registered for current 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./

Insecticide for turf, maize, rice, and other crops.

Isazofos is a soil-applied nematicide with contact and systemic properties.

Semicarbazide hydrochloride + formamide + isopropanol + O,O-diethyl phosphorochlorothioate (amine formation/ dehydrochlorination)

Isazophos is synthesized by reacting ethyl 3-isopropylcarbazate with cyanogen chloride, followed by cyclization with phosgene. Phosphorylation of the triazole with O,O-diethylthiophosphoryl chloride yields isazofos.

Emulsifiable concentrates, granules

Tradenames: 'Brace' * (Ciba-Geigy); 'Miral' * (Novartis); 'Triumph' * (Ciba-Geigy); 'Victor' * (Ciba-Geigy) .

The WHO Recommended Classification of Pesticides by Hazard identifies Isazofos (technical grade) as an active ingredient believed to be obsolete or discontinued for use as a pesticide.

The basic producer of isazophos is Syngenta