Spirodiclofen

411.32

411.32

203-625-9

3X7G31F5MX

DTXSID6034928

White powder

52.6

5.8 (pH 4); 5.1 (pH 7)

white power

1.29

101-108°

550.2±50.0 °C(Predicted)

4 °C

1.571

In water, 50 (pH 4); 190 (pH 7); both in ug/L at 20 deg C

0-6°C

7X10-7 Pa /5.25X10-9 mm Hg/ at 25 deg C

LD50 in rats (mg/kg): >2500 orally; >2000 dermally (24 hr); LC50 (4 hr) in rats (mg/m3): >5000 by inhalation; LC50 (96 hr) in fish: >68 mg/l (Wachendorff)

No characteristic odor

Henry's Law constant = 5.68X10-8 atm-cu m/mol at 25 °C (est)

UN12943/PG2

2

43-67-65-63-48/20-38-11

36/37-62

Xi,Xn,F

Hydrolysis DT50 119.6 days (pH 4), 51.2 days (pH 7), 2.5 days (pH 9) (all 20 deg C).

P280

H317

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.|Improper disposal of excess pesticide, spray mixture, or rinsate is a violation of Federal Law. If these wastes cannot be disposed of by use according to label instructions, contact your State Pesticide or Environmental Control Agency, or the Hazardous Waste representative at the nearest EPA Regional Office for guidance. /Envidor 2 SC Miticide/|Container Disposal: Non-refillable container. Do not reuse or refill this container. Triple rinse container (or equivalent) promptly after emptying. Triple rinse as follows: Empty the remaining contents into application equipment or a mix tank and drain for 10 seconds after the flow begins to drip. Fill the container 1/4 full with water and recap. Shake for 10 seconds. Pour rinsate into application equipment or a mix tank or store rinsate for later use or disposal. Drain for 10 seconds after the flow begins to drip. Repeat this procedure two more times. Then offer for recycling, if available, or puncture and dispose of in a sanitary landfill, or by other procedures approved by State and local authorities. /Envidor 2 SC Miticide/|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.

USEPA Office of Prevention, Pesticides and Toxic Substances, Pesticide Fact Sheet for Spirodiclofen (2005).[Available from, as of June 1, 2011: http://www.epa.gov/opprd001/factsheets/]

|Danger|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P201, P202, P260, P261, P272, P273, P280, P281, P302+P352, P308+P313, P314, P321, P333+P313, P363, P391, P405, and P501|Warning|H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P201, P202, P261, P272, P273, P280, P281, P302+P352, P308+P313, P321, P333+P313, P363, P391, P405, and P501|Aggregated GHS information provided by 130 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H351: Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P260, P264, P270, P273, P281, P308+P313, P309+P311, P314, P391, P405, and P501

Personal Protective Equipment (PPE). Mixers, loaders, applicators and other handlers must wear: Long-sleeved shirt and long pants; Waterproof gloves; Shoes plus socks. /Envidor 2 SC Miticide/|Restricted entry interval (REI) of 12 hours. PPE required for early entry to treated areas that is permitted under the Worker Protection Standard that involves contact with anything that has been treated, such as plants, soil, or water, is: long-sleeved shirt and long pants, waterproof glovees, shoes plus socks. /Envidor 2 SC Miticide/|Eye/Face Protection: Safety glasses; Hand Protection: Chemical resistant nitrile rubber gloves. /Envidor 2 SC Miticide/

Suitable extinguishing media: water, dry chemical, foam. /Envidor 2 SC Miticide/|Fire Fighting Instructions: Keep out of smoke. Fight fire from upwind position. Cool closed containers/tanks exposed to fire with water spray. Do not allow run-off from fire fighting to enter drains or water courses. Wear self-contained breathing apparatus and protective suit.. /Envidor 2 SC Miticide/

In the event of fire the following can be released: hydrogen chloride, carbon monoxide. /Envidor 2 SC Miticide/

Handle and open container in a manner as to prevent spillage. If container is leaking, invert to prevent leakage. If the container is leaking or material is spilled for any reason or cause, carefully dam up spilled material to prevent runoff. Refer to Precautionary Statements on label for hazards associated with the handling of this material. Do not walk through spilled material. Absorb spilled material with absorbing type compounds ... In spill or leak incidents, keep unauthorized people away. /Envidor 2 SC Miticide/

Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR part 170. /Envidor 2 SC Miticide/|Do not apply this product in a way that will contact workers or other persons, either directly or through drift. Only protected handlers may be in the area during application. /Envidor 2 SC Miticide/|This pesticide is toxic to fish and aquatic invertebrates. Avoid contamination of surface water through spray drift. ... Do not apply directly to water, or to areas where surface water is present, or to intertidal areas below the mean high water mark. /Envidor 2 SC Miticide/|Users should: Wash hands before eating, drinking, chewing gum, using tobacco or using the toilet; Remove clothing immediately if pesticide gets inside. Then wash thoroughly and put on clean clothing; Remove Personal Protective Equipment immediately after handling this product; Wash the outside of gloves before removing; As soon as possible, wash thoroughly and change into clean clothing. /Envidor 2 SC Miticide/|For more Preventive Measures (Complete) data for Spirodiclofen (7 total), please visit the HSDB record page.

LC50 Rat inhalation >5000 mg/cu m/ 4 hr|LD50 Rat dermal >2000 mg/kg.|LD50 Rat oral >2500 mg/kg.

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

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc range of 31,037 to 238,000(2) indicates that spirodiclofen is expected to be immobile in soil(SRC). Volatilization of spirodiclofen from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.7X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 5.25X10-9 mm Hg(3), and water solubility, 0.05 mg/L(4). Spirodiclofen is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Metabolism studies conducted in soil incubated at 20 °C resulted in spirodiclofen half-lives ranging from 10.0 to 63.9 days(3) suggesting that biodegradation is an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), a Koc range of 31,037 to 238,000(2), indicates that spirodiclofen 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 5.7X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 5.25X10-9 mm Hg(4), and water solubility, 0.05 mg/L(5). According to a classification scheme(6), an estimated BCF of 3100(SRC), from its log Kow of 5.8(5) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Hydrolysis half-lives of 119.6 days (pH 4), 52.1 days (pH 7) and 2.5 days (pH 9) have also been reported(2). The aerobic aquatic half-life ranges form 1-7 days(4), suggesting that biodegradation is an important environmental fate process(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), spirodiclofen, which has a vapor pressure of 5.25X10-9 mm Hg at 20 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase spirodiclofen may be removed from the air by wet or dry deposition(SRC). Spirodiclofen adsorbs UV at a maximum wavelength of 201 nm(1), therefore it is not expected to be susceptible to direct photolysis by sunlight(SRC).

Spirodiclofen is hydrolyzed at pH 4, pH 7, and pH 9 with reported half-lives of 63, 31, and 5 days, respectively(1). Hydrolysis half-lives of 119.6 days (pH 4), 52.1 days (pH 7) and 2.5 days (pH 9) have also been reported(2). Spirodiclofen adsorbs UV at a maximum wavelengths of 201 nm(1), therefore it is not expected to be susceptible to direct photolysis by sunlight(SRC). The compound is stable to light on soil but aqueous photolysis half-lives of 13.7 days (artificial light), 43.8 days (estimated; Phoenix, AZ), and 61.6 days (estimated; Edmonton, Canada) have been reported(1).

An estimated BCF of 3100 was calculated in fish for spirodiclofen(SRC), using a log Kow of 5.8(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

Koc values ranging from 31,037 to 238,000 have been reported for spirodiclofen(1). According to a classification scheme(2), this estimated Koc value suggests that spirodiclofen is expected to be immobile in soil. The pKa is not determinable due to the instability of the compound in aqueous solutions at pH greater than 4(3).

The Henry's Law constant for spirodiclofen is estimated as 5.7X10-8 atm-cu m/mole(SRC) derived from its vapor pressure, 5.25X10-9 mm Hg(1), and water solubility, 0.05 mg/L(2). This Henry's Law constant indicates that spirodiclofen is expected to be essentially nonvolatile from water and moist soil surfaces(3). Spirodiclofen is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

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

Rapidly absorbed, widely distributed and mostly excreted within 48 hr.|Groups of Wistar Hsd/Cpb: Wu rats (about 200 g at treatment) were dosed with labeled spirodiclofen (radiopurity > 98%) in 10 mL/kg of 0.5% CMC suspension as follows (showing group designations in brackets): [6] single high dose (100 mg/kg, 4 M); [7] single low dose (including CO2 measurement) (2 mg/kg, 4 M); [8] single low dose (EPA basic test) (2 mg/kg, 4 M); [9] single low dose (2 mg/kg, 4 F); [10] 14 daily doses with 2 mg/kg/day non-radioactive a.i., then 1 labeled low dose (2 mg/kg, 4 M); and [13] single low dose, bile cannulation study (2 mg/kg, 6 M). In low dose groups, about 70% of administered dose was absorbed, with most of the label found in the urine, and about 12% of administered dose found in the bile. In the high dose (100 mg/kg) group, 61% of label was found in feces, vs. 35% in urine, suggesting saturable absorption at high dose levels. Very little label (0.05% of administered dose) was found in exhaled CO2. Peak plasma concentrations were observed between 2.5 hr to 3.9 hr in low dose groups, vs. 5.6 hr in high dose rats.|This study employed 2 male monkeys, each dosed with about 0.2 mg/kg spirodiclofen in a single treatment. The iv treatment was prepared as a PEG 200 solution in water, and the dermal treatment was a suspension of fine spirodiclofen crystals in water. The patch for the dermal treatment was removed after 8 hr, after which the application area was washed with 1% Ivory detergent solution followed by tape stripping and alcohol swab wiping. Monkeys were maintained in metabolism cages after dosing (except that the first 8 hr after the iv treatment was spent in a primate chair). Following iv dosing, urinary excretion was rapid: 64% of administered dose was obtained in urine within the first 8 hr, with an additional 18% in the next 16 hr. A total of 87% of dose was obtained in urine, and an additional 15% in cage debris/rinse (attributed primarily to urine). About 5% of administered dose was found in feces in the iv test. Measured recovery was slightly more than theoretical. Following dermal treatment, 1.1% of administered dose was found in urine, 0.3% in cage wash, and 0.2% in feces. Most of the dermally administered dose was found in the detergent swab process. An additional 9% was found in the patch or containment dome, and 10% was obtained with the alcohol swab step. Thus the dermal response from this one subject suggested only about 1.6% total absorption.|This study employed 5 male monkeys, each dosed dermally with an average of 0.04 mg/kg spirodiclofen as the SC 240 formulation in a single treatment, considered to represent a plausible field exposure level. About 2.0% of administered dose was recovered in urine plus cage rinse and other collected label attributed to urine. About 0.1% of administered dose was found in feces. Most of the material balance was found in skin wash soap swabs or ethanol extracts of the swabs (>74% of administered dose), plus small additional amounts in the patch, patch securing materials, tape strips, and alcohol swabs. Thus absorption was determined to be about 2.1% of administered dose.

Metabolism in rats and ruminants involves cleavage of the ester, followed by hydroxylation of the cyclohexane ring. In rats, metabolism continues with cleavage of the enol ring, leading to formation of the cyclohexyl ester of 2,4-dichloromandelic acid, which is further metabolised. The residue definition comprises spirodiclofen enol.|The primary initial product of ester cleavage (removing a 2,2-dimethylbutyric acid moiety) is designated BAJ 2510 (or BAJ 2740 enol). Two major products of this enol are the 4-OH and 3-OH addition products to the cyclohexyl ring, i.e. "4-OH BAJ 2510" and "3-OH BAJ 2510."|Groups of Wistar Hsd/Cpb: Wu rats (about 200 g at treatment) were dosed with labeled spirodiclofen (radiopurity > 98%) in 10 mL/kg of 0.5% CMC suspension as follows (showing group designations in brackets): single high dose (100 mg/kg, 4 M); single low dose (including CO2 measurement) (2 mg/kg, 4 M); single low dose (EPA basic test) (2 mg/kg, 4 M); single low dose (2 mg/kg, 4 F); 14 daily doses with 2 mg/kg/day non-radioactive a.i., then 1 labeled low dose (2 mg/kg, 4 M); and single low dose, bile cannulation study (2 mg/kg, 6 M). ... There was a sex difference in urinary metabolites: low dose females excreted 53% of administered dose as the enol, whereas low dose males excreted low amounts of the enol (< 5%), but instead favored subsequent hydroxylation of the cyclohexyl moiety of the enol at carbon 3 or 4. Positions of the ring hydroxyls in the plain of the ring (designated "e" for equitorial) were most abundant: low dose males had 26% to 30% of administered label as the 3-hydroxy-enol (e) metabolite, and 13% to 15% of administered label as the 4-hydroxy-enol (e) metabolite. The associated axial "a" isomers with the hydroxyls perpendicular to the ring were comparatively minor metabolites. The combined 3- and 4-hydroxy-enol metabolites in females constituted only 17% of administered dose. There were no other common urinary metabolites. Pre-treatment with unlabeled low doses of spirodiclofen for 2 weeks had no obvious effect on metabolism. Fecal metabolism yielded 1 to 4% of parent spirodiclofen after low dose exposure, compared to 16% in high dose males (consistent with reduced absorption). The enol constituted 4 to 7% of administered dose in feces of low-dose non-cannulated rats (16% in high dose M), with 3- and 4-hydroxy-enol (e) metabolites as modest contributors (1% to 7% of administered dose for each of these isomers). Fecal metabolites included a few percent of mandelic acid-cyclohexyl-methyl esters (created by oxidatively opening the 5-membered ring at the location of the enol hydroxyl group), and subsequent metabolic products. Glucuronides were not observed in feces. The two most common bile residues were the OH-enol glucuronide and 3-hydroxy-enol (e) (3% and 4% of administered dose, respectively).|At week 20, blood samples were taken from 4 dogs per sex at the high dose (600 ppm) at 0, 2, 4, 7, and 24 hours after feeding. Plasma concentrations of BAJ 2740 and the metabolite BAJ 2510 were evaluated by high performance liquid chromatography (HPLC). BAJ 2740 was below the limit of quantification since it was rapidly cleaved by esterases in plasma and liver to the metabolite BAJ 2510. No other metabolites were identified. Week 20 high dose group mean concentrations of metabolite BAJ 2510 in plasma were 24.8, 17.6, 19.1, 26.7, and 32.4 nmol/mL for males and 26.8, 15.9, 15.8, 25.0, and 28.1 nmol/mL in females at 0, 2, 4, 7, and 24 hours after feeding respectively. BAJ 2510 was also quantified in urine samples taken from 3 female and 1 male high dose (600 ppm) dogs at week 28. One hour after receiving treated diet, dogs were placed in metabolism cages for 5 hours. Urine volumes were 74, 281, and 305 mL in females and 18.6 mL in the male. BAJ 2510 concentrations in urine were 0.46, 0.16, and 0.12 umol/mL in females and 0.05 umol/mL in the male respectively.

The half life of spirodiclofen was investigated using spiked rat plasma; it was estimated to be about 15 minutes.|Groups of Wistar Hsd/Cpb: Wu rats (about 200 g at treatment) were dosed with labeled spirodiclofen (radiopurity > 98%) in 10 mL/kg of 0.5% CMC suspension as follows (showing group designations in brackets): single high dose (100 mg/kg, 4 M); single low dose (including CO2 measurement) (2 mg/kg, 4 M); single low dose (EPA basic test) (2 mg/kg, 4 M); single low dose (2 mg/kg, 4 F); 14 daily doses with 2 mg/kg/day non-radioactive a.i., then 1 labeled low dose (2 mg/kg, 4 M); and single low dose, bile cannulation study (2 mg/kg, 6 M). ... Plasma radioactivity typically dropped about 10-fold in all groups between 8 hr and 24 hr after dosing (plasma phase 1 elimination t 1/2 values were 2.4 hr to 4.2 hr). This is consistent with swift clearance from organs and tissues as previously reported. ...

Testicular mitochondrial preparations were evaluated for side chain cleavage of 25-OH cholesterol to pregnenolone (by assaying for progesterone after a subsequent oxidation step). In a mitochondrial preparation supplemented with NADP and in an environment of low malate levels (0.5 mM); 100 uM and 300 uM BAJ 2510 reduced progesterone synthesis to 68% and 24% of control groups, respectively. In contrast, spirodiclofen, 4-OH BAJ 2510, and 3-OH BAJ 2510 at concentrations up to 100 uM or (in the case of spirodiclofen, at the limits of solubility) had little or no effect on progesterone synthesis. When 0.5 mM citrate (and no malate) was present as a substrate (citrate also being capable of reducing NAD), even 300 uM BAJ 2510 had no remarkable effect on progesterone synthesis. This suggested an interference of BAJ 2510 with the Krebs cycle related to malate dehydrogenase activity. This was confirmed when investigators evaluated the oxidation of NADH due to malate dehydrogenase activity (assessing activity from both mitochondrial and cytoplasmic fractions): there was a clear dose-responsive inhibition of such activity due to BAJ 2510 concentrations in the 1 to 100 uM range (mitochondrial) or the 10 to 300 uM range (cytoplasmic). In contrast, BAJ 2510 had no effect on malic enzyme activity (assessed by NADP reduction with malate as substrate). In a dynamic organ culture of testicular tissue (6 hr incubation with steroidogenesis stimulated by 1 IU/mL hCG), BAJ 2510 concentrations of 10 to 300 uM caused marked, dose-related decrements in testosterone in both the tissue pieces and in the medium. An early step in progesterone synthesis from 25-OH cholesterol was markedly inhibited by BAJ 2510 in mitochondrial preparations. In contrast, progesterone levels were not statistically significantly reduced at any level with BAJ 2510 in the dynamic organ culture system with testicular tissue. As a positive control, ketoconazole profoundly reduced testosterone in tissues and medium, also without significantly reducing the quantity of progesterone in the tissue pieces. Thus it appears that BAJ 2510 toxicity is related to interference with cellular energy metabolism. /BAJ 2510, metabolite/

/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/

/ENDOCRINE MODULATION/ This study evaluated the effects of spirodiclofen, BAJ 2510, and one of the hydroxy BAJ 2510 metabolites, primarily on hormone response elements in human cell lines (MCF 7 breast cancer cell line or prostate PC-3 cell line for estrogen and androgen receptor, respectively). Hormone response was quantified via luciferase reporter genes using a chemiluminescence reader. In some cases, binding studies for alpha and beta estrogen receptors followed, using a fluorescence polarization technique which could be performed in microtiter wells. At pH's of 6 to 6.5, BAJ 2510 displayed estrogenic and anti-estrogenic activities. BAJ 2510 bound to alpha and beta estrogen receptors in this pH range. BAJ 2510 had no effects in the reporter or receptor binding assays at physiological pH (7 or higher). Spirodiclofen and hydroxy BAJ 2510 were uniformly negative in all assays.

spirodiclofen

Suspension concentrate; water dispersible granule; wettable powder.|Spirodiclofen Technical (Bayer Cropscience LP) Spirodiclofen 98.22%|Envidor 2 SC (Bayer Cropscience LP) Spirodiclofen 22.3%

Adequate enforcement methodology (a liquid chromatography (LC)/mass spectrometry (MS)/(MS) method) is available to enforce the tolerance expression.|Technical grade by RP HPLC; product by GC. Residues in soil and water by HPLC/MS/MS; in plants by GC/ECD and GC/MS.

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

Spirodiclofen has known environmental transformation products that include 2,4-dichlorobenzoic acid, BAJ 2740-dihydroxy, BAJ 2740-enol, BAJ 2740-ketohydroxy, and BAJ 2740-lactide.