Fenazaquin

306.4

306.40

410-580-0

DK5Q534WEE

DTXSID4040476

Colorless crystals

35

5.51 at 20 deg C

white or almost white power

1.16

78.5 °C

447.01°C (rough estimate)

165.1±15.6 °C

1.5700 (estimate)

In water, 0.102 mg/L (pH 5, 7) , 0.135 mg/L (pH 9); both at 20 deg C

3.4 x l0 -6 Pa (25 °C)

LD50 orally in rats, mice (mg/kg): 134, 1480; dermally in rabbits (mg/kg): >5000; LC50 (96 hr) in bluegill, trout (mg/l): 34.1, 3.8 (Longhurst)

Henry's Law constant = 1.0X10-7 atm-cu m/mol at 25 °C (est)

pKa = 2.44

6.1

UN28116.1/PG3

3

20-25-50/53

37-45-60-61

VA1382000

T,N

DT50 of aqueous solution exposed to sunlight is 15 days (pH7, 25 deg C)

P261

H301-H332-H410

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity 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 and plant life; and conformance with environmental and public health regulations.

USEPA Office of Prevention, Pesticides and Toxic Substances, Pesticide Fact Sheet for Fenazaquin (August 2007).[Available from, as of June 1, 2011: http://www.epa.gov/opprd001/factsheets/]

|Danger|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P271, P273, P301+P310, P304+P312, P304+P340, P312, P321, P330, P391, P405, and P501|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|Aggregated GHS information provided by 194 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Aggregated GHS information provided by 2 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

LC50 Rat inhalation 1.9 mg/L/ 4 hr|LD50 Rabbit dermal >5000 mg/kg|LD50 Mouse oral (female) 1480 mg/kg|LD50 Mouse oral (male) 2449 mg/kg|For more Non-Human Toxicity Values (Complete) data for Fenazaquin (7 total), please visit the HSDB record page.

/BIRDS and MAMMALS/ Reproduction studies conducted with bobwhite quail and rats indicate no frank reproductive effects in either birds or mammals. In the avian reproduction study, the only observed effect was on growth in males at the highest concentration tested /(953 ppm for 22 weeks)/ /98.0% AI/|/AQUATIC SPECIES/ Rainbow trout (Oncorhynchuys mykiss) /were studied in a/ 63-day early life stage /experiment under/ unaerated continuous flow /conditions/. 80 embryos/concentration level. 0, 0 (solvent), 0.20, 0.51, 0.96, 1.98 and 3.92 mg/L. NOAEC: 0.96 ug/L LOAEC 1.98 ug/L. At test termination, survival, body weight and body length were significantly reduced at 1.98 ug/L. No fish survived at 3.92 ug/L. Excessive analytical variation (> or =20% of the mean measured value) at the three lowest levels, which included the NOAEC level; solvent level not constant; test initiation was with eyed-embryos (e.g., the exposure period was too short) and no time to swim-up assessment. /98% a.i. technical fenazaquin/ /from table/|/AQUATIC SPECIES/ In a 96 hr acute toxicity study, rainbow trout (/Oncorhynchus mykiss/) were exposed to EL-436 (fenazaquin) at nominal concentrations of 0 (negative and solvent controls), 2.5, 5.0, 7.0, 8.5 and 10.0 ug/L under flow-through conditions. TWA concentrations (reviewer-calculated) were <1 ( or =3.0 ug ai/L exposure levels. The NOAEC for immobility and the other sublethal observations was 0.8 ug ai/L. Based on the results of this study, EL-436 (fenazaquin) would be classified as very highly toxic to Daphnia magna in accordance with the classification system of the USEPA.

Fenazaquin's production may result in its release to the environment through various waste streams; its use as an acaricide(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 18700 to 42100(2) indicate that fenazaquin is expected to be immobile in soil(SRC). Volatilization of fenazaquin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.0X10-7 atm-cu m/mole(SRC), based upon its vapor pressure, 2.55X10-8 mm Hg(3), and water solubility, 0.102 mg/L(3). Fenazaquin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). The half-life in soil is approximately 45 days(3).|AQUATIC FATE: Based on a classification scheme(1), a Koc range of 18700 to 42100(2) indicates that fenazaquin is 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 of 1.0X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 2.55X10-8 mm Hg(4), and water solubility, 0.102 mg/L(4). According to a classification scheme(5), a BCF of 500(2) suggests that bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). The half-life of an aqueous solution exposed to sunlight is 15 days at pH 7, 25 °C(4). Biodegradation data in water were not available(SRC, 2011).|AQUATIC FATE: Using an aquatic microcosm study simulation of 5% drift and 1% runoff from agricultural fields, fenezaquin was applied at rates of 225, 440, and 1125 g active ingredient/ha. After 2 hours, fenazaquin concentrations in a model pond were 0.58, 1.07, and 2.68 ug/L, respectively. Over 22 hours, concentrations dropped by 60-70%. No fenazaquin was detected in the water after 21 days(1).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fenazaquin, which has a vapor pressure of 2.55X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase fenazaquin may be removed from the air by wet or dry deposition(SRC). Fenazaquin contains chromophores that absorb at wavelengths >290 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

Fenazaquin is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Fenazaquin contains chromophores that absorb at wavelengths >290 nm(1), and therefore may be susceptible to direct photolysis by sunlight(SRC). The photolysis half-life in water is about 15 days(2).

A BCF range of 500 was measured in fish for radio-labeled fenazaquin, at a concentration of 0.02 and 0.01 ug/L, using rainbow trout (Oncorhynchus mykiss) exposed for 21 to 28 days. BCF values were 400-500 for days 1-2 and 400-600 on days 21-28, irrespective of initial test compound concentration. At the end of the depuration period (days 1 and 14) no radioactivity was detected in the water above the detection limit of 0.05 ug/L. Residues in fish fell rapidly with 80% of radioactivity eliminated within the first 24 hours, <7% remaining on day 7. The depuration half-life was 1.4 days over days 1-7(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of fenazaquin has been reported to range from 18700 to 42100(1). The compound is rapidly adsorbed onto soil particles with 88% and 96% of the adsorption from a sandy loam soil and a clay loam soil, respectively, occurring within 2 hours. Adsorption increases with the organic content and clay content(1). According to a classification scheme(2), this Koc range suggests that fenazaquin is expected to be immobile in soil.

The Henry's Law constant for fenazaquin is estimated as 1.0X10-7 atm-cu m/mole(SRC) derived from its vapor pressure, 2.55X10-8 mm Hg(1), and water solubility, 0.102 mg/L(1). This Henry's Law constant indicates that fenazaquin is expected to be essentially nonvolatile from water and moist soil surfaces(2). Fenazaquin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

Occupational exposure to fenazaquin may occur through inhalation and dermal contact with this compound at workplaces where fenazaquin is produced or used. (SRC)

EL-436 (Fenazaquin, 97.36-98.80% ai; EL-436 uniformly labeled on either the t-butyl-phenyl ring (phenyl; 97.33->99.9%, 4.23 and 5.44 uCi/mg) or the quinazoline-phenyl ring (quinazoline; 98.8-99.2%, 19.8 uCi/mg) was administered to groups of five male and five female Fischer 344 (F344/Crl) rats as a single 1 mg/kg or 30 mg/kg radiolabeled dose. A group of eight male and eight female rats received 14-daily doses of 1 mg/kg unlabeled test material followed by a single radiolabeled gavage dose. An additional group of three male and three female rats received a single 1 mg/kg radiolabel dose to determine elimination of the compound in expired air. Overall recovery of the radiolabel was excellent (89.5-107.7% of the administered dose). Within 48 hours of treatment, approximately 75% of the radiolabel was recovered in the excreta, and by 72 hours after treatment, >84% was recovered. No sex-related differences in elimination were noted. Approximately 20% of the radiolabel was recovered in the urine with the remainder in the feces. Less than 1.6% of the radiolabel was recovered in the residual carcass or tissues and essentially no significant amount of radiolabel was recovered in the expired air. There are no available excretion studies following bile cannulation or intravenous (i.v.) administration to determine test material bioavailability (gastrointestinal absorption). Therefore, while the nearly 20% of the administered dose was absorbed before it was excreted in urine, it is not clear if any or all of the remaining dose (nearly 80%) that was found in feces was actually absorbed prior to its fecal elimination.

Metabolism involved cleavage of the ether bond, with formation of the 4-hydroxyquinazoline and carboxylic acid derivatives. Other biotransformations included oxidation of one of the methyl groups on the alkyl side chain to produce either an alcohol, which was further metabolised by hydroxylation of the O-ether alkyl moiety, or a carboxylic acid, which was further metabolised by hydroxylation of the 2-position of the quinazoline ring.|EL-436 (Fenazaquin, 97.36-98.80% ai; EL-436 uniformly labeled on either the t-butyl-phenyl ring (phenyl; 97.33->99.9%, 4.23 and 5.44 uCi/mg) or the quinazoline-phenyl ring (quinazoline; 98.8-99.2%, 19.8 uCi/mg) was administered to groups of five male and five female Fischer 344 (F344/Crl) rats as a single 1 mg/kg or 30 mg/kg radiolabeled dose. A group of eight male and eight female rats received 14-daily doses of 1 mg/kg unlabeled test material followed by a single radiolabeled gavage dose. An additional group of three male and three female rats received a single 1 mg/kg radiolabel dose to determine elimination of the compound in expired air. ... In the urine, the primary metabolite was AN-1 (4-(2-hydroxy-1,1-dimethylethyl) phenylacetic acid) (24-29% of total urinary radioactivity) plus numerous minor metabolites. This metabolite was characterized by the absence of protons associated with the quinazoline portion of the molecule, indicating cleavage of the ether bridge. No significant differences between the sexes or dose groups were observed. Four primary metabolites and numerous minor metabolites were found in the feces. The parent compound, fenazaquin, represented 1.2-4.2% of the recovered radioactivity in the single or multiple low-dose groups and 11.5-20.6% of the recovered activity in single high-dose rats. Metabolite F1 (4.6-9.4% of the administered dose) had the phenyl and quinazoline rings and both sets of methylene protons intact, as well as the addition of a single oxygen atom to the phenyl-t-butyl portion of the parent molecule. Metabolite F-1A, a minor metabolite contributing 0.6-2.6% of the radioactivity, was characterized by intact phenyl and quinazoline rings and hydroxylation of the ethoxy bridge. Metabolite F-2 was the primary fecal metabolite identified (16.3-22.8% of the recovered radioactivity) and was similar to metabolite F1, but with the addition of two oxygen atoms and the loss of two hydrogen atoms to form a carboxylic acid on one of the methyl alky groups attached to the phenyl ring. Metabolite F3 contributed 6.5-12.6% of the recovered radioactivity and contained both the phenyl and quinazoline ring systems; however, the quinazoline ring had been hydroxylated and one of the methyl alkyl groups of the phenyl ring had been carboxylated. While the fecal metabolites were likely produced by the liver, it is not possible to exclude metabolism by intestinal microflora. These studies show that radiolabeled fenazaquin is rapidly metabolized and eliminated from male and female rats following treatment with either single or multiple low doses or following a single high dose of the compound. However, there is no information on biliary excretion or fecal/urinary elimination following iv administration.

Fenazaquin is a miticide that exhibits both contact and ovicidal activity against a broad spectrum of mite and certain insects by inhibiting mitochondrial electron transport at the Complex I site (NADH-ubiquinone reductase).|... In this study, ...the in vitro toxicity and mechanism of action of several putative complex I inhibitors that are commonly used as pesticides. The rank order of toxicity of pesticides to neuroblastoma cells was pyridaben > rotenone > fenpyroximate > fenazaquin > tebunfenpyrad. A similar order of potency was observed for reduction of ATP levels and competition for (3)H-dihydrorotenone (DHR) binding to complex I, with the exception of pyridaben (PYR). Neuroblastoma cells stably expressing the /rotenone/ (ROT)-insensitive NADH dehydrogenase of Saccharomyces cerevisiae (NDI1) were resistant to these pesticides, demonstrating the requirement of complex I inhibition for toxicity. ... PYR was a more potent inhibitor of mitochondrial respiration and caused more oxidative damage than ROT. The oxidative damage could be attenuated by NDI1 or by the antioxidants alpha-tocopherol and coenzyme Q(10). PYR was also highly toxic to midbrain organotypic slices. These data demonstrate that, in addition to ROT, several commercially used pesticides directly inhibit complex I, cause oxidative damage, and suggest that further study is warranted into environmental agents that inhibit complex I for their potential role in Parkinson's Disease.|Parkinson's disease (PD) brains show evidence of mitochondrial respiratory Complex I deficiency, oxidative stress, and neuronal death. Complex I-inhibiting neurotoxins, such as the pesticide rotenone, cause neuronal death and parkinsonism in animal models. We have previously shown that DJ-1 over-expression in astrocytes augments their capacity to protect neurons against rotenone, that DJ-1 knock-down impairs astrocyte-mediated neuroprotection against rotenone, and that each process involves astrocyte-released factors. To further investigate the mechanism behind these findings, we developed a high-throughput, plate-based bioassay that can be used to assess how genetic manipulations in astrocytes affect their ability to protect co-cultured neurons. We used this bioassay to show that DJ-1 deficiency-induced impairments in astrocyte-mediated neuroprotection occur solely in the presence of pesticides that inhibit Complex I (rotenone, pyridaben, fenazaquin, and fenpyroximate); not with agents that inhibit Complexes II-V, that primarily induce oxidative stress, or that inhibit the proteasome. This is a potentially PD-relevant finding because pesticide exposure is epidemiologically-linked with an increased risk for PD. Further investigations into our model suggested that astrocytic GSH and heme oxygenase-1 antioxidant systems are not central to the neuroprotective mechanism.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

fenazaquin

Emulsifiable concentrate; suspension concentrate.|Fenazaquin Technical (Gowan Company, LLC) Fenazaquin 99.4%|GWN-1708 Miticide/Insecticide (Gowan Company, LLC) Fenazaquin 18.79%

The majority of usage is in Europe (>80%)|The WHO Recommended Classification of Pesticides by Hazard identifies fenazaquin (technical grade) as Class II: moderately hazardous; Main Use: acaracide.

Adequate enforcement methodology (gas chromatography) is available to enforce the tolerance expression.

Agrochemicals -> Acaricides|Acaricides, Insecticides|Environmental transformation -> Pesticides (parent, predecessor)

Fenazaquin has known environmental transformation products that include 4-Hydroxyquinazoline, Fenazaquin metabolite NN1, Fenazaquin metabolite NN2, Fenazaquin metabolite NN3, Fenazaquin metabolite NN4, Fenazaquin metabolite NN5, Fenazaquin metabolite NN6, Fenazaquin metabolite NN7, M1 2-Oxy-fenazaquin, M2 4-(2-(4-(1,1-Dimethyl ethanoic acid)phenyl)ethoxy)quinazoline, M3 Phenyl-1-ethanoic acid-4-(1,1-dimethyl ethanoic acid), and M4 2-(Formylamino)-2-(4-(1,1-dimethylethyl)phenyl) ethyl benzoate.