Mipafox

182.18

182.18

206-742-3

24MJP5H3YN

8924

DTXSID5042160

Crystals from petroleum ether

50.94000

2.84180

1.2 g/cm³ @ Temp: 25 °C

65 °C

125-126 °C @ Press: 2 Torr

81.7ºC

1.415

74.07g/L(temperature not stated)

0.00 mmHg|0.001 mm Hg at 15 °C

ODORLESS

-2.71±0.70

Henry's Law constant = 3.0X10-9 atm-cu m/mole at 15 °C /Estimated/

Hydroxyl radical reaction rate constant = 9.2X10-11 cm cu/molec-sec at 25 °C /Estimated/|Decomposition by acid & alkali; commercial product hygroscopic

III

6.1(b)

2783

39/26/27/28

13-45

T+

Stable alone or in anhydrous ester solvents.

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.

|Danger|H370 **: Causes damage to organs [Danger Specific target organ toxicity, single exposure]|P260, P264, P270, P307+P311, P321, P405, and P501|H370: Causes damage to organs [Danger Specific target organ toxicity, single exposure]

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.

The effects of aldicarb and verapamil on mipafox (371868) induced inhibition of neuropathy-target-esterase (NTE) activity in human neuroblastoma cells were examined. Differentiated SY-5Y (SY5Y) cells, a cell line derived from SK-N-SH-human neuroblastoma cells, were incubated with 0 or 5x10(-5) molar (M) mipafox in the presence or absence of 5x10(-3)M aldicarb or 1x10(-7)M verapamil for 2 to 10 minutes. The cultures were assayed for NTE activity. The ability of 25 millimolar isonitroacetophenone (INAP) to reactivate NTE activity was evaluated 2, 5, or 10 minutes after mipafox exposure. A similar experiment was performed in chicken brain homogenates. Mipafox caused a similar time dependent decrease of NTE activity in SY5Y cells and chicken brain homogenates. INAP was capable of reactivating NTE activity; however, the degree of reactivation decreased with increasing time between mipafox and INAP treatment. Aldicarb and verapamil countered the inhibitory effect of mipafox in both SY5Y cells and the brain homogenates. The authors conclude that NTE activity in SY5Y cells and chicken brain homogenates, the accepted model for organophosphate induced delayed neuropathy (OPIDN), is inhibited to a similar extent by mipafox. Aldicarb and verapamil exert inhibitory effects on the mipafox induced suppression of NTE activity in both preparations.|The toxic effects of phenylmethylsulfonyl-fluoride (329986) (PMSF) and Mipafox (371868), administered either singly or combined, were studied in 60 day old male Long-Evans-rats. Animals were treated with: 250 milligrams per kilogram (mg/kg) PMSF; 15mg/kg Mipafax; 250mg/kg PMSF followed 4 hours later by 15mg/kg Mipafax; 15mg/kg Mipafox followed 4 hours later by 250mg/kg PMSF; or 250mg/kg PMSF followed 14 days later by 15mg/kg Mipafax. Animals receiving single doses of either compound were sacrificed 1, 4, 24, 48, or 72 hours after administration and others were sacrificed 14 to 21 days postexposure. Assays were conducted to determine evidence of neuropathy, target enzyme, and damage to cervical cord. Animals receiving PMSF only were incapacitated for 48 hours and then resumed normal activity; no mortality occurred. Mipafox only animals experienced mild tremors and diarrhea; no mortality occurred in this group either. Animals receiving Mipafox 4 hours after PMSF had a 50 percent mortality rate and remained immobile for 48 hours after treatment. Animals receiving PMSF 4 hours after Mipafox had tremors which were eliminated after PMSF treatment which immobilized them for 48 hours; a 25 percent mortality rate occurred. There were no deaths among animals receiving Mipafox 14 days after PMSF, although the animals were similarly incapacitated.

LD50 Guinea pig oral 80 mg/kg|LD50 Rabbit oral 100 mg/kg|LD50 Mouse ip 14 mg/kg|LD50 Rat sc 75 mg/kg|LD50 Rat ip 90 mg/kg

Mipafox's former production and use as an insecticide(1) resulted in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 8.8(SRC), determined from a water solubility of 80,000 mg/L(2) and a regression-derived equation(3), indicates that mipafox is expected to have very high mobility in soil(SRC). Volatilization of mipafox from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant for mipafox of 3.0X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 0.001 mm Hg(4), and water solubility(2). Mipafox is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 8.8(SRC), determined from a water solubility of 80,000mg/L(2) and a regression-derived equation(3), indicates that mipafox is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant for mipafox of 3.0X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 0.001 mm Hg(4), and water solubility(2). According to a classification scheme(6), an estimated BCF of 1(SRC), determined from its water solubility(5) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Mipafox is reported to hydrolyze slowly under environmental conditions; a half life of 200 days was observed at pH 6(4). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), mipafox, which has a vapor pressure of 0.001 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase mipafox 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 4.2 hrs(SRC), calculated from its rate constant of 9.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Mipafox does not contain chromophores that absorb at wavelengths >290 nm and therefore would not be expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of mipafox with photochemically-produced hydroxyl radicals has been estimated as 9.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4.2 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Mipafox is reported to hydrolyze slowly under environmental conditions; a half life of 200 days was observed at pH 6(2). Mipafox does not contain chromophores that absorb at wavelengths >290 nm and therefore would not be expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 1 was calculated for mipafox(SRC), determined from a water solubility of 80,000 mg/L(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of mipafox is estimated as 8.8(SRC) using a water solubility of 80,000 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that mipafox is expected to have very high mobility in soil.

The Henry's Law constant for mipafox is estimated as 3.0X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 0.001 mm Hg(1), and water solubility, 80,000 mg/L(2). This Henry's Law constant indicates that mipafox is expected to be essentially nonvolatile from water surfaces(3). Mipafox's estimated Henry's Law constant indicates that volatilization from moist soil surfaces is not expected to occur(SRC). Mipafox is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

Occupational exposure and general population exposure should be low or non-existent since mipafox is no longer produced or used. In the past, mipafox was applied directly to plants as an insecticide and exposure to this compound was primarily by inhalation and dermal contact. (SRC)

Food and Environmental Agents: Effect on Breast-Feeding: Reported Sign or Symptom in Infant or Effect on Lactation: Fluorides: None. /from Table 7/

4. 4= Very toxic: probable oral lethal dose (human) 50-500 mg/kg, between 1 teaspoon & 1 oz for 70 kg person (150 lb).

/Direct cholinesterase inhibitors/...group includes...mipafox.../and/ compounds exerting direct inhibitory action...are rapidly hydrolyzed both physically and enzymically as soon as they reach tissues.

...Decomposition... by enzymes of plants... half life is 7-8 days.

...Cholinesterase inhibitor.|The neurotoxic esterase fraction of hen brain microsomal phenyl-valerate-hydrolyzing activity is the target for mipafox.|A direct method of assaying neurotoxic esterase (NTE) activity, using 4-nitrophenyl valerate, was described. The technique was used to determine the bimolecular rate, phosphorylation and affinity constants for the reaction of chicken brain microsomal NTE with mipafox.|A number of... compounds such as... Mipafox... have the ability to bind tenaciously to the active site of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) to produce an irreversibly inhibited enzyme by a mechanism known as aging. The aging process is dependent on the size and configuration of the alkyl (R) substituent, with the potency of the ester increasing in the order of diethyl, dipropyl, and dibutyl for such analogs as DFP and mipafox. The aging process is generally accepted as being caused by the dealkylation of the intermediate dialkylphosphorylated enzymes by one of two possible mechanisms. The first involves the hydrolysis of a P-O bond following a nucleophile (base) attack on the phosphorus atom. The second mechanism involves the hydrolysis of an O-C bond by an acid catalysis, resulting in the formation of a carbonium ion as the leaving group. The aging process is believed to fix an extra charge to the protein, causing some perturbation to the active site and thereby preventing dephosphorylation. While the exact nature of this reaction has not been demonstrated for AChE and NTE, evidence from experiments with saligenin cyclic phosphorus esters (derivative of TOTP) and alpha-chymotrypsin points to the possibility of two stabilized forms of "aged" enzyme. Both of the reactions utilize the imidazole group of a neighboring histidine. In one reaction, the hydroxylated substituent is released and the phosphorylated enzyme is stabilized by a hydrogen on the imidazole group. In the other reaction, the leaving substituent becomes attached to the imidazole, yielding a N-C hydroxylated derivative of the phosphorylated enzyme.

Main impurities of commercial product are hydrolytic products & the Isopropylamide of orthophosphoric acid...

Emergency and supportive measures. Caution: rescuers and health care providers must take measures to prevent direct contact with the skin or clothing of contaminated victims, because secondary contamination and serious illness may result, especially with potent pesticides and nerve agents. Maintain an open airway and assist ventilation if necessary. Pay careful attention to respiratory muscle weakness; sudden respiratory arrest may occur. If intubation is required, note potential interactions between neuromuscular blockers and cholinesterase inhibitors. Administer supplemental oxygen. Treat hydrocarbon pneumonitis, seizures, and coma if they occur. Observe asymptomatic patients for at least 8-12 hours to rule out delayed-onset symptoms, especially after extensive skin exposureor ingestion of a highly fat-soluble agent. /Organophosphates and carbamates/|Specific drugs and antidotes. Specific treatment includes the antimuscarinic agent atropine and the enzyme reactivator pralidoxime. Give atropine ... repeated frequently as needed. Large cumulative doses of atropine ... may occasionally be required in severe cases. The most clinically important indication for continued atropine administration is persistent wheezing or bronchorrhea. Note: Atropine will reverse muscarinic but not nicotinic effects. Pralidoxime is a specific antidote for organophosphate toxicity, that acts to regenerate the enzyme activity at all affected sites (muscarinic, nicotinic, and probably CNS; however, it does not reactivate plasma cholinesterase). Pralidoxime should be given immediately to reverse muscular weakness and fasciculations... . It is most effective if started within the first 24 hours of the exposure before irreversible phosphorylation of the enzyme, but may still be effective if given late, particularly after exposure to highly lipid soluble compounds. Pralidoxime is not generally recommended for carbamate intoxication, because in such cases the cholinesterase inhibition is spontaneously reversible and short-lived. However, if the exact agent is not identified and the patient has significant toxicity, pralidoxime should be given empirically. /Organophosphates and carbamates/|Decontamination. Note: Rescuers must wear chemical-protective clothing and gloves when handling a grossly contaminated victim. If there is heavy liquid contamination with a solvent such as xylene or toluene, clothing removal and victim decontamination should be carried out outdoors or in a room with high-flow ventilation. 1. Skin. Remove all contaminated clothing and wash exposed areas with soap and water, including the hair and under the nails. Irrigate exposed eyes with copious tepid water or saline. 2. Ingestion. a. Prehospital. Administer activated charcoal, if available. Do not induce vomiting because of the risk of abrupt onset of toxicity. b.Hospital. Administer activated charcoal (cathartics are not necessary if the patient already has diarrhea). Perform gastric lavage for large recent ingestions. /Organophosphates and carbamates/|Enhanced elimination. Dialysis and hemoperfusion are not generally indicated because of the large volume of distribution... /Organophosphates and carbamates/|For more Antidote and Emergency Treatment (Complete) data for MIPAFOX (19 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ ...Acetylcholinesterase inhibitor, like parathion. After acute phases of poisoning, degenerative lesions may become apparent in central and peripheral nervous systems.|/SIGNS AND SYMPTOMS/ ...Some cholinesterase-inhibiting organophosphorus compounds can produce permanent paralysis due to /PRC: secondary/ demyelinating process of spinal cord... Demyelination in man has been attributed only to mipafox, agent not used in United States.|/SIGNS AND SYMPTOMS/ See Parathion. Symptomatology: 1. Nausea...vomiting, abdominal cramps, diarrhea, excessive salivation... 2. Headache, giddiness, vertigo and weakness. 3. Rhinorrhea and sensation of tightness in chest are common in inhalation exposure. 4. Blurring or dimness of vision, miosis... Tearing, ciliary muscle spasm, loss of accommodation and ocular pain... Mydriasis...sometimes seen...probably due to sympatho-adrenal discharge. 5. Loss of muscle coordination, slurring of speech, fasciculations and twitching of muscles (particularly of tongue and eyelids), and generalized profound weakness. 6. Mental confusion, disorientation and drowsiness. 7. Difficulty in breathing, excessive secretion of saliva and of respiratory tract mucus, oronasal frothing, cyanosis, pulmonary rales and rhonchi and hypertension (presumably due to asphyxia). 8. Random jerky movements, incontinence, convulsions, and coma. 9. Death primarily due to respiratory arrest arising from failure of respiratory center, paralysis of respiratory muscles, intense bronchoconstriction or all three. /Parathion/

mipafox

For experimental use: anhydrous solution (50% active ingredient) with wetting agent. Usually applied as spray in concn 0.5-1.0% active ingredient.

Has been withdrawn from market being suspect as cause of paralysis of two operators...|/It is/ absorbed & translocated by plant which is rendered systemically insecticidal to sap-feeding insects & mites.

PRESUMABLY GENERAL METHOD...FOR ENZYMIC DETERMINATION OF ORG PHOSPHORUS INSECTICIDES COULD BE APPLIED TO MEASURE ISOPESTOX AIR CONTAMINATION. PA GIANG & SA HALL, ANAL CHEM, 23, 1830 (1951).