Quinoxyfen

308.13

308.13

1312995-182-4

PPC78J1VCW

DTXSID2034881

Crystals from heptane|Off-white solid

22.1

4.66

liquid

1.56

105-106°

423℃

>100 °C

1.648

In water, 116 ug/L at 20 deg C (pH 6.45)

0-6°C

1.50X10-7 mm Hg at 25 deg C

Henry's Law constant = 9.65X10-9 atm-cu m/mol at 25 °C (est)

pKa = 3.56, weak base

Hydroxyl radical reaction rate constant = 5.35X10-10 cu cm/molec-sec at 25 °C (est)

III

9

UN30779/PG3

43-50/53

24-37-46-60-61

VB4287500

Xi,N

In dark at 25 deg C, stable to hydrolysis at pH 7 and 9; DT50 75 days (pH 4). Degraded more rapidly in light.

P273-P280-P501

H317-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.|Wastes resulting from the sue of this product must be disposed of on site or at an approved waste disposal facility.|Do not dump into any sewers, on the ground, or into any body of water. For unused and uncontaminated product, the preferred options include sending to a licensed, permitted: reclaimer or incinerator or other thermal destruction device. If wastes and/or containers cannot be disposed of according to the product label directions, disposal of this material must be in accordance with your local or area regulatory authorities.|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

|Warning|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P273, P280, P302+P352, P321, P333+P313, P363, P391, and P501|H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]|Aggregated GHS information provided by 255 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Applicators and other handlers must wear: Long-sleeved shirt and long pants, chemical-resistant gloves, shoes plus socks. /Quintec Fungicide/|... Restricted-entry interval (REI) of 12 hours. Personal protective equipment (PPE) required for early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated, such as plants, soil, or water is: Coveralls, Chemical resistant gloves made of any waterproof material. Shoes plus socks. /Quintec Fungicide/

Wear positive-pressure self-contained breathing apparatus (SCBA) and protective fire fighting clothing (includes fire fighting helmet, coat, trousers, boots, and gloves). If protective equipment is not available or not used, fight fire from a protective location or safe distance. /Quintec Fungicide/|Keep people away. Isolate fire and deny unnecessary entry. Consider feasibility of a controlled burn to minimize environment damage. foam fire extinguishing system is preferred because uncontrolled water can spread possible contamination. Burning liquids may be moved by flushing with water to protect personnel and minimize property damage. /Quintec Fungicide/|Extinguishing media: Water fog or fine spray, carbon dioxide, dry chemical, or foam. General purpose synthetic foams (including AFFF type) or protein foams are preferred if available. Alcohol resistant foams (ATC type) may function. /Quintec Fungicide/

Prevent from entering into soil, ditches, sewers, waterways, and/or groundwater.|Large spills: Dike area to contain spill.|Do not contaminate water when cleaning equipment or disposing of equipment washwaters.

Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR Part 170. /Quintec Fungicide/|This product is toxic to fish and aquatic invertebrates. Do not apply directly to water, or to areas where surface water is present or to intertidal areas below the mean high water mark. Do not apply when weather conditions favor runoff or drift from the target areas. /Quintec Fungicide/|Follow manufacturer's instructions for cleaning/maintaining personal protective equipment (PPE). If not such instructions for wasables exist, use detergent and hot water. Keep and was PPE separately from other laundry. /Quintec Fungicide/|Users should: Wash hands before eating, drinking, chewing gum, using tobacco or using the toilet. Remove contaminated clothing immediately if pesticide gets inside. Then wash thoroughly and put on clean clothing. Remove personal protective equipment (PPE) immediately after handling this product. Wash the outside of gloves before removing. As soon as possible, wash thoroughly and change into clean clothing. /Quintec Fungicide/|For more Preventive Measures (Complete) data for Quinoxyfen (7 total), please visit the HSDB record page.

LD50 Rabbit dermal >2000 mg/kg|LC50 Rat inhalation > 3.38 mg/L (mass median aerodynamic diameter 3.6 um) /Duration not specified/|LD50 Rat oral >5000 mg/kg

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

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3600(SRC), determined from a log Kow of 4.66(2) and a regression-derived equation(3), indicates that quinoxyfen is expected to have slight mobility in soil(SRC). Volatilization of quinoxyfen from moist soil surfaces is expected to be a minor environmental fate process(SRC) given an estimated Henry's Law constant of 9.6X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Quinoxyfen is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.5X10-7 mm Hg at 25 °C(2). Quinoxyfen biodegradation half-lives in soils have been reported to range from 106-508 days(2), suggesting that biodegradation is not an important environmental fate process(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3600(SRC), determined from a log Kow of 4.66(2) and a regression-derived equation(3), indicates that quinoxyfen is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 9.6X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 550(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). Photolysis in water is an important environmental fate process with half-lives of 1.7 hours (June) and 22.8 hours (December) reported(2). Using a water/sediment inoculum, half-lives of 35 to 150 days have been reported(2), suggesting that biodegradation is an environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), quinoxyfen, which has a vapor pressure of 1.50X10-7 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase quinoxyfen 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 day(SRC), calculated from its rate constant of 5.3X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase quinoxyfen may be removed from the air by wet or dry deposition(SRC). Quinoxyfen contains chromophores that absorb at wavelengths >290 nm(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of quinoxyfen with photochemically-produced hydroxyl radicals has been estimated as 5.3X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1 day at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Quinoxyfen is stable to hydrolysis at pH 7 and pH 9; a hydrolysis half-life of 75 days has been reported at pH 4(2). Quinoxyfen contains chromophores that absorb at wavelengths >290 nm(3), and therefore may be susceptible to direct photolysis by sunlight(SRC). Photolysis on soil is slow with a half-life in the field of greater than 1 year reported(2). Photolysis in water is an important environmental fate process as indicated by half-lives of 1.7 hours (June) and 22.8 hours (December)(2).

An estimated BCF of 550 was calculated in fish for quinoxyfen(SRC), using a log Kow of 4.66(1) and a regression-derived equation(2). According to a classification scheme(3), 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 quinoxyfen is estimated as 3600(SRC), using a log Kow of 4.66(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that quinoxyfen is expected to have slight mobility in soil.

The Henry's Law constant for quinoxyfen is estimated as 9.6X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that quinoxyfen is expected to be essentially nonvolatile from water and moist soil surfaces(2). Quinoxyfen is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 1.5X10-7 mm Hg(3).

EXPERIMENTAL: (14)C-quinoxyfen, labeled either in the phenoxy ring or the quinoline ring, was investigated in lactating dairy goats (n = 5; 51-60 kg bw). Two goats were orally dosed with phenoxy (14)C-quinoxyfen (purity: > 98%), twice per day for five consecutive days, at a concentration of 10.7 mg/kg feed. Similarly, two goats were treated with quinoline (14)C-quinoxyfen, twice per day for five consecutive days, at a concentration of 11.7 mg/kg feed. The remaining goat was used as the untreated control animal. Urine and feces were collected at intervals of 24 hrs until sacrifice. Milk samples were collected before the first treatment with quinoxyfen, and then twice daily throughout the study period until animals were sacrificed. ... The major component present in fat was quinoxyfen (approximately 90% TRR /total radio-labeled residue/), while milk contained quinoxyfen (approximately 40% TRR) and some very polar material. ...

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

The jugular-vein cannulated rats (five males and five females per group) were killed at 48 hr after dosing. The bile-duct cannulated rats (three males per group) were killed at 24 hr after dosing. Blood samples were taken from the jugular cannula at 0.25, 0.5, 0.75, 1, 1.5, 3, 6, 12, 24 and 48 hr. Urine, feces and bile were collected regularly throughout the study. Peak plasma radioactivity (Cmax) was detected at approximately 0.5 hr (2-3 ug equiv./g) at 10 mg/kg bw and approximately 1.5 hr (80-90 mg equiv./g) at 500 mg/kg bw. ... There were no significant differences between the repeat-dose and single-dose groups. The elimination of radioactivity from blood followed a similar pattern. The area-under-the-curve (AUC) of the plasma versus time graph for the elimination of radiolabel in plasma (0-48 hr) was 22.3, 27.3 and 922 ug equiv. hr/g in males and 30.4, 29.6 and 963 ug equiv. hr/g in females after treatments with a single radiolabelled dose, a single radiolabelled dose after repeated dosing and 500 mg/kg bw (14)C-quinoxyfen respectively.|By 24 hr after dosing, 68-85% of the administered radioactivity had been recovered in the feces and urine, indicating rapid elimination from the body. After 48 hr, 90-96% of the administered (14)C-quinoline ring-labelled quinoxyfen was recovered in the urine, feces, cage wash and tissues. The feces represented the major route of elimination as 68-78% of the administered dose was eliminated via this route in 48 hr, while 13-20% was eliminated in the urine. Urinary half-lives ranged from 6 to 10 hr. The tissues and carcass accounted for 1-7%, contents of the gastrointestinal tract for < 3% and final cage wash for < 1% of the administered dose. There were no sex differences in the distribution of radiolabel. Repeated administration of quinoxyfen did not affect the distribution of the radio-labelled dose.|The distribution of radiolabel in organs and tissues (percentage of administered dose/g tissue) 48 hr after treatment with a single dose of quinoline ring-labelled quinoxyfen at 10 mg/kg bw showed that the highest amounts of radiolabel were present in perirenal fat (0.12 in males and 0.35 females) > ovaries (0.07) > liver (0.027 in males and 0.045 in females) and kidneys (0.014 in males and 0.033 in females). Significant levels were found in the skin. Similar amounts were obtained after repeated dosing and a similar pattern after the higher dose of 500 mg/kg bw. There were no data on tissue levels at times approximating to the plasma Cmax.|Comparison of the relative concentrations in bile and urine of intact and bile-duct cannulated rats indicated that enterohepatic recirculation is extensive with quinoxyfen at a dose of 10 mg/kg bw. In bile-duct cannulated rats, there was a marked difference in the amount of radiolabel in the feces of rats at 10 mg/kg bw (14.3%) compared with those at 500 mg/kg bw (57.3%) and in the amount of radiolabel in the bile of rats at 10 mg/kg bw (54.4%) compared with those at 500 mg/kg bw (21.4%). These findings indicated that absorption of quinoxyfen at a dose of 500 mg/kg bw dose was saturated.|For more Absorption, Distribution and Excretion (Complete) data for Quinoxyfen (7 total), please visit the HSDB record page.

Groups of 5 Fischer 344 rats/sex were given a single 10 or 500 mg/kg oral dose of quinoline ring-labeled (14)C- quinoxyfen (XDE-795, >99% radiochemically pure, specific active 28.5 mCi/mmole), or 14 daily oral doses of 10 mg/kg of non-radiolabelled quinoxyfen (XDE-795, 99% pure) followed by a single 10 mg/kg oral dose of (14)C- quinoxyfen. Additional groups of 3 male bile duct cannulated rats received a single dose of 10 or 500 mg/kg quinoline ring-labelled (14)C- quinoxyfen and were sacrificed 24 hrs later. One rat/sex/group received 10 mg/kg of either phenyl ring (98.5% radiochemically pure, specific active 27.8 mCi/mmole) or quinoline ring-labelled (14)C- quinoxyfen for metabolite analysis. ... Major metabolites identified in the urine were derived from cleavage of the diaryl-ether linkage quinoxyfen resulting in the formation of acid-labile conjugates of 4-fluorophenol (4-FP) and 5, 7-dichloro-4-hydroxyquinoline (DCHQ), and lesser quantities of free DCHQ and 4-FP. Glucuronide and/or sulfate conjugates of two isomers of fluorophenyl ring-hydroxy- quinoxyfen were detected in the bile. Parent quinoxyfen and free forms of the same two isomers of fluorophenyl ring-hydroxy- quinoxyfen as seen in the bile were detected in feces. No substantive differences in the metabolism and disposition of quinoxyfen between sexes or single and repeated administration.|HPLC separation of pooled 0-12 hr urine samples from the preliminary study in rats given phenyl-ring-labelled (14)C-quinoxyfen produced eight peaks that were designated P1-P7 and P10. Peak P5 was the major urinary fraction in the unhydrolyzed urine sample (80% and 77.4% in the male and female respectively) followed by P3 (7.9% and 9.5%), P1 (4.2% and 4.7%) and P6 (3.1% and 3.0%). The remaining peaks contained less than 3% of the urinary radiolabel. Acid hydrolysis of the urine produced a significant change in the HPLC profile. The major fraction in unhydrolyzed urine was reduced to only 2.4% of the urine fraction; instead, P8 (not detectable in the unhydrolyzed sample) was the major fraction (73.6%). This suggested that P5 might be a conjugate of P8. The P8 fraction was found to co-elute with the standard for 4-fluorophenol. The remaining minor peaks after acid hydrolysis were P3 (11.7%), P9 (7.1%) and P1 (5.2%), but these metabolites were not identified. The standards used were 4-fluorophenol, 2-hydroxy-quinoxyfen and parent quinoxyfen. Parent quinoxyfen and 2-hydroxy-quinoxyfen retention times did not correspond to that of any of the HPLC urinary fractions. Fecal metabolites from phenyl-(14)C quinoxyfen showed a similar pattern to those from quinoline-(14)C quinoxyfen.|HPLC separation of pooled urine samples from groups receiving quinoline-(14)C quinoxyfen ... before and after acid hydrolysis produced up to 16 radiolabelled peaks that were designated Q1-Q16. In male rats receiving a single dose at 10 mg/kg bw, eight peaks were identified in unhydrolyzed urine: Q3, Q4, Q7, Q8, Q9, Q11, Q12 and Q13. In females rats receiving a single dose at 10 mg/kg bw, four additional peaks were detected: Q2, Q5, Q10 and Q15 (repeated-dose only). For the males and females at 500 mg/kg bw, the peaks in the radiochromatogram of pooled 0-12 hr urine samples were Q7, Q8, Q9, Q10 (female only), Q11, Q12 and Q13. The major peaks were Q11 (13-33%), Q8 (13-24%), Q9 (9-24%), Q12 (10-18%), Q13 (6-15%), Q7 (4-11%) and Q4 (< 13%). The only clearly identified urinary metabolite was 5,7 dichloro-4-hydroxyquinoline (DCHQ), which was found to co-elute with peak Q13. Acid hydrolysis resulted in a two- to four-times increase in Q13 (24-65%). In the males rats receiving a single dose at 10 mg/kg bw, increases were observed in peaks Q3, Q6 and Q14, while peaks Q1 and Q2 were increased after acid hydrolysis. In rats receiving a single dose at 500 mg/kg bw, peak Q14 was increased in males. Concomitantly, peaks Q4, Q5, Q7, Q8 and Q10 were observed to disappear from the respective radiochromatograms, while Q3 and Q9 were markedly reduced. Enzyme hydrolysis did not affect the metabolite profile.|HPLC separation of bile samples (taken at various time-points, 0-24 hr) from male rats receiving quinoline ring-labelled quinoxyfen at 10 mg/kg bw or 500 mg/kg bw produced six peaks (B2-B7). Peaks B6 and B7 constituted 20-66% and 26-59% of biliary excretion at various time-points. For the 10 mg/kg bw rats, the amount of radiolabel in the peaks at various time-points were B2 6-15%; B5 4-15%; B3 and B4 < 5%. Only peaks B6 and B7 were detected in the samples from rats at 500 mg/kg bw, but this was attributed to the higher detection limits required by the investigating laboratory. Additional peaks B1, B8, B9 and B10 were detected after enzyme hydrolysis. Peak B7 was noted to disappear with the appearance of peak B10 (approximately 25%) suggesting that B7 is the glucuronide or sulfatase of B10. Acid hydrolysis of the bile samples from rats at 10 or 500 mg/kg bw resulted in an increase in B6 by 20% of the biliary radioactivity compared with the control. Peaks B1, B8 and B9 appeared in the sample from rats at 10 mg/kg bw, but were not detected at 500 mg/kg bw. B10 eluted with quinoxyfen, but MS showed that the key ions were 16 mass units greater than the corresponding fragment ions from quinoxyfen. It was concluded that two metabolites associated with peak B10 were isomers of fluorophenyl-ring hydroxylated quinoxyfen.|For more Metabolism/Metabolites (Complete) data for Quinoxyfen (7 total), please visit the HSDB record page.

The jugular-vein cannulated rats (five males and five females per group) were killed at 48 hr after dosing. The bile-duct cannulated rats (three males per group) were killed at 24 hr after dosing. Blood samples were taken from the jugular cannula at 0.25, 0.5, 0.75, 1, 1.5, 3, 6, 12, 24 and 48 hr. Urine, feces and bile were collected regularly throughout the study. ... The elimination of plasma radioactivity followed a biphasic pattern with half-lives for the rapid and slow phases for the dose at 10 mg/kg bw of < 1 hr and 15-19 hr respectively, and 2-3 hr and 18-22 hr for the dose at 500 mg/kg bw. There were no significant differences between the repeat-dose and single-dose groups. ...

/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/

/HUMAN EXPOSURE STUDIES/ A formulation chemist ... was shown to be sensitized to aqueous solutions containing 10% or more quinoxyfen. No other cases had been found after checking all employees who have worked with the material. In addition, 20 control individuals were patch-tested specifically with quinoxyfen and this produced an entirely negative reaction. The data from the formulation laboratory were suggested by the applicant to indicate that there is a small possibility for idiosyncratic skin sensitization. Since the formulation chemist may have been sufficiently exposed to be sensitized compared with other workers and given the additional evidence from animal experiments, this finding is consistent with quinoxyfen being a skin sensitizer.|/CASE REPORTS/ ... Two operators and a supervisor were exposed to quinoxyfen while decanting a returned batch of a 50% w/w soluble concentrate formulation. All three developed rashes of the wrist/forearm. The supervisor and one operator were tested for sensitization to quinoxyfen, with positive results. The other operator had left the company before the follow-up testing was performed.|/SURVEILLANCE/ None of 28 individuals in a health surveillance program reported or presented for health concerns related to quinoxyfen between June 1992 and March 1995. Audits of clinical records of all individuals involved in the investigations were performed and no health-related problems relating to quinoxyfen were noted.

5,7-dichloro-4-(4-fluorophenoxy)quinoline

Soluble concentrate|Quinoxyfen Technical (Dow Agrosciences, LLC) Quinoxyfen 99.1%|Quinoxyfen Manufacturing Use Concentrate (Dow Agrosciences, LLC) Quinoxyfen 53.5%|Quintec (Dow Agrosciences, LLC) Quinoxyfen 22.58%

The WHO Recommended Classification of Pesticides by Hazard identifies quinoxyfen as unlikely to present an acute hazard in normal use; Main Use: fungicide, other than for seed treatment.

Adequate enforcement methodology (gas chromatography with mass-selective detection (GC-MSD)) is available to enforce the tolerance expression.|Residue analysis in plant, animal and soil matrices by GC with mass selective detection. Analysis in drinking water by HPLC with UV detection.

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

Quinoxyfen has known environmental transformation products that include 3-hydroxy-quinoxyfen.