Difenoconazole

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

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.

Open dumping is prohibited. Wastes resulting from the use of this product may be disposed of on site or at an approved waste disposal facility.

Avoid contact with skin, eyes, or clothing. Avoid breathing vapor or spray mist. ... Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, using tobacco or using the toilet. Remove contaminated clothing and wash before reuse.

User should remove clothing/personal protective equipment (PPE) immediately if pesticide gets inside. Then wash thoroughly and put on clean clothing. User should remove PPE immediately after handling this product. Wash thoroughly and change into clean clothing as soon as possible. Wash outside of gloves before removing.

This pesticide is toxic to fish, mammals, and aquatic invertebrates. Drift and runoff may be hazardous to aquatic, estuarine, and marine organisms in water adjacent to treated areas. For terrestrial uses: Do not apply directly to water, or to areas where surface water is present or intertidal areas below the mean high water mark. Do not contaminate water when disposing of equipment washwater or rinsate. DO NOT discharge effluent containing this product into lakes, streams, ponds, estuaries, oceans, or other waters unless in accordance with the requirements of a National Pollutant Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing prior to discharge. DO NOT discharge effluent containing this product to sewer systems without previously notifying the local sewage treatment plant authority. For guidance contact your State Water Board or Regional Office of the EPA.

Avoid skin contact and vapor inhalation.

For more Preventive Measures (Complete) data for Difenoconazole (6 total), please visit the HSDB record page.

Tolerances are established for residues of difenoconazole, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified below is to be determined by measuring only difenoconazole, 1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, in or on the following raw agricultural commodities:[Table#8405]

Tolerances are established for residues of difenoconazole, including its metabolites and degradates, in the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring the sum of difenoconazole, 1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, and its metabolite, CGA-205375, 1-[2-chloro-4-(4-chloro-phenoxy)phenyl]-2-[1,2,4]triazol-1-yl-ethanol, calculated as the stoichiometric equivalent of difenoconazole, in the following commodities:[Table#8406]

Wear long-sleeved shirt and long pants, socks, shoes, protective eyewear and chemical resistant gloves when handling.

Long-sleeved shirt and long pants. Protective eyewear. Rubber gloves for undiluted formulation Score; boots.

LD50; Species: Serinus canaria (Island Canary) age 9.5 months; oral via capsule >2,000 mg/kg[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 1-[[2-

LC50; Species: Colinus virginianus (Northern Bobwhite Quail) age 14 days; dietary 4760 ppm for 9 days (95% confidence interval: 4103-5522 ppm)[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 1-[[2-

LC50; Species: Anas platyrhynchos (Mallard Duck) age 8 days; dietary >5000 ppm for 11 days[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 1-[[2-

LD50; Species: Anas platyrhynchos (Mallard Duck) age 30 weeks; oral via capsule >2150 mg/kg[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on 1-[[2-

For more Ecotoxicity Values (Complete) data for Difenoconazole (25 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), reported Koc values ranging from 3200 to 7734(2,3) indicate that difenoconazole is expected to be slightly mobile to immobile in soil(SRC). Volatilization of difenoconazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.9X10-12 atm-cu m/mole(SRC), based upon its vapor pressure, 2.5X10-10 mm Hg(4), and water solubility, 15 mg/L(4). Difenoconazole is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Slow biodegradation of difenoconazole may occur under certain conditions; however, may be limited by its bioavailability(4,5).

AQUATIC FATE: Based on a classification scheme(1), reported Koc values ranging from 3200 to 7734(2,3) indicate that difenoconazole is not 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 8.9X10-12 atm-cu m/mole(SRC) derived from its vapor pressure, 2.5X10-10 mm Hg(5), and water solubility, 15 mg/L(5). According to a classification scheme(6), a BCF of 330(7), suggests that bioconcentration in aquatic organisms is high(SRC). Slow biodegradation of difenoconazole may occur under certain conditions; however, may be limited by its bioavailability(5,8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), difenoconazole, which has a vapor pressure of 2.5X10-10 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase difenoconazole may be removed from the air by wet and dry deposition(SRC). Difenoconazole contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

In 2010 residues of difenoconazole in rice fields were examined in samples from Guangxi, Hubei and Zhejiang province; the half life for difenoconazole in rice plants ranged from 1.39 to 2.59 days; additional half-lives reported for difenoconazole in the study were as follows: in Chinese cabbage 6.6 to 7.8 days, in apples 26.2 to 81.7 days, and in chili fruit 4.68 to 8.09 days. Residues of difenoconazole were undetectable in rice hull and husked rice samples 30, 40, and 50 days after application of pesticide at 90 to 135 grams a.i./ha(1).

A variety of bananas used in several field studies of difenoconazole, at an application of 800 g a.i./ha, had residues of this chemical ranging from <0.02 ppm to 0.13 ppm in whole banana samples, less than 0.02 ppm in banana pulp, and less than 0.02 ppm to 0.25 ppm in banana peel. Field studies conducted in several US states examined residues in wheat grain resulting in residue concentrations less than 0.01 ppm(1).

In an FDA total diet study analyzing foods in 4 market basket studies from the fiscal year 2012, difenoconazole was detected in 20 of 159 food items considered to be infant and toddler foods at a range of 0.0001 to 0.0009 ppm and in 47 of 912 food items other than infant and toddler foods at a range of 0.0001 to 0.006 ppm(1). In an FDA total diet study analyzing foods in 4 market basket studies from the fiscal year 2013, difenoconazole was detected in 73 of 1,070 food items at a range of 0.0001 to 0.005 ppm(2).

IDENTIFICATION AND USE: Difenoconazole is a white crystalline solid. It is used as fungicide, insecticide, seed treatment/protectant. HUMAN EXPOSURE AND TOXICITY: Harmful if inhaled or absorbed through skin. Causes moderate eye irritation. It did not cause chromosomal aberrations in human lymphocytes. One case of allergic reaction to a formulated product was reported. ANIMAL STUDIES: Difenoconazole was moderately and transiently irritating to the eyes of rabbits. It was very slightly and transiently irritating to the skin of rabbits. Difenoconazole was considered to be essentially non-toxic when applied topically under occlusion to intact rabbit skin. In rats treated dermally for 28 days there was an increased incidence of minimal centrilobular hepatocellular hypertrophy in males and females at 1000 mg/kg bw. In the thyroid, the incidence of minimal to moderate severity grades of hypertrophy of the follicular epithelium was slightly increased in the group of rats at 1000 mg/kg bw. The liver appeared to be the target organ for toxicity. There was no evidence for carcinogenicity or oncogenicity in rats. There were no indications of embryotoxicity, fetotoxicity or teratogenicity at a dose up to 75 mg/kg bw per day in rabbits. There were no indications of embryotoxicity or teratogenicity at any dose up to 200 mg/kg bw in rats. Microscopic examination of the central and peripheral nervous system of rats showed no effects of treatment with difenoconazole at dietary concentrations of up to 1500 ppm in males or females. Difenoconazole did not induce gene mutations in either bacterial cells or cultured mammalian cells. ECOTOXICITY STUDIES: In zebrafish experiments, a large suite of symptoms was induced in embryonic development by different dosages of difenoconazole, including hatching inhibition, abnormal spontaneous movement, slow heart rate, growth regression and morphological deformities. Exposure to difenoconazole could alter thyroid hormone levels and gene transcription in zebrafish larvae, indicating endocrine disruption. Genes related to hatching, retinoic acid metabolism and lipid homeostasis were up-regulated by difenoconazole in zebrafish embryos. Difenoconazole exposure could also change lipid metabolism and profiles in marine medaka (Oryzias melastigma). Difenoconazole inhibited the respiration of mitochondria of the flight muscles of bumblebee.

/BIRDS and MAMMALS/ Pesticide coated seeds are commonly used in agriculture, and may be an important source of food for some birds in times of scarcity, as well as a route of pesticide ingestion. We tested the lethal and sub-lethal effects of treated seed ingestion by the red-legged partridge (Alectoris rufa), a game bird of high socio-economic value in Spain. One year-old partridges (n = 42 pairs) were fed for 10 days in spring (prior to breeding) with wheat treated with difenoconazole (fungicide), thiram (fungicide) or imidacloprid (insecticide), using two doses for each pesticide (the one recommended, and its double to represent potential cases of abuse of pesticides). We investigated the direct and indirect effects on the body condition, physiology, immunology, coloration and subsequent reproduction of exposed partridges. For the latter, eggs were collected, measured and incubated and the growth and survival of chicks were monitored. Thiram and imidacloprid at high exposure doses produced mortalities of 41.6 and 58.3 %, respectively. The first death was observed at day 3 for imidacloprid and at day 7 for thiram. Both doses of the three pesticides caused sublethal effects, such as altered biochemical parameters, oxidative stress and reduced carotenoid-based coloration. The high exposure doses of imidacloprid and thiram also produced a decrease in cellular immune response measured by the phytohemagglutinin test in males. Bearing in mind the limitation of the small number of surviving pairs in some treatments, we found that the three pesticides reduced the size of eggs and imidacloprid and difenoconazole also reduced the fertilization rate. In addition, both thiram and imidacloprid reduced chick survival. These experiments highlight that the toxicity of pesticide-treated seeds is a factor to consider in the decline of birds in agricultural environments.

/AQUATIC SPECIES/ Zebrafish, during embryo, larvae and adult stages were selected to investigate the potential environmental risk and aquatic toxicity of a widely used fungicide, difenoconazole. In addition to mortality, embryo development endpoints, teratogenic effects and behavior abnormity were measured. Finally, the developmental parameters of the adult fish were assessed after 14 days' exposure. This study concluded that the acute toxicity of difenoconazole to the three phases of zebrafish were larvae (1.17 mg/L) > adult fish (1.45 mg/L) > embryo (2.34 mg/L). A large suite of symptoms was induced in embryonic development by different dosages of difenoconazole, including hatching inhibition, abnormal spontaneous movement, slow heart rate, growth regression and morphological deformities. 0.50 mg/L of difenoconazole could cause significant body color blackening and decrease in the heart rate of zebrafish larvae over 24 hr. In addition, 0.25 mg/L of difenoconazole apparently inhibited the growth weight of adult zebrafish measured after 14 days' exposure.

/AQUATIC SPECIES/ ... To investigate the effect of difenoconazole on cholesterol content and related mechanism, adult zebrafish were exposed to environmental related dosage (0.1, 10 and 500 ug/L) difenoconazole. The body weight and hepatic total cholesterol (TCHO) level was tested at 7, 15 and 30 days post exposure (dpe). The expressions of eight cholesterol synthesis genes and one cholesterol metabolism gene were assessed via Quantitative PCR method. The significant decrease of TCHO level in male zebrafish liver was observed at 15 and 30 dpe, which was accompanied by apparent hepatic cholesterol-genesis genes expression decline. In comparison with males, female zebrafish showed different transcription modification of tested genes, and the cholesterol content maintain normal level during the whole exposure.

Metabolism studies conducted with tomoatos, wheat, potatoes, grapes, and oilseed rape indicated that difenoconazole was the major residue found on these plants (fruits, seeds, and foliage) 7 to 40 days after the final application of this chemical(1).

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of December 8, 2016: http://actor.epa.gov/dashboard/]

The mobility of difenoconazole was examined using soil thin layer chromatography with a silt loam containing 2% organic matter; results indicated that this chemical will be essentially immobile in soil(1). Difenoconazole has a reported log Koc = 3.5 (Koc = 3200)(2). Reported adsorption coefficients for difenoconazole in agricultural sand, sandy loam soil, silt loam soil, and silty clay loam soils, are 3866, 3470, 7734, and 7734, respectively(3). According to a classification scheme(4), these Koc values suggest that difenoconazole is expected to be slightly mobile to immobile in soil(SRC).

/SIGNS AND SYMPTOMS/ Harmful if inhaled or absorbed through skin. Causes moderate eye irritation.

/GENOTOXICITY/ /Two/ studies on chromosomal aberrations were conducted ... in human lymphocytes. ... The two studies ... gave unambiguous negative results

/ALTERNATIVE and IN VITRO TESTS/ Various pesticides known or suspected to interfere with steroid hormone function were screened in H295R cells for effects on catalytic activity and mRNA expression of aromatase. ... Various imidazole-like fungicides were aromatase inhibitors. Imazalil and prochloraz were potent mixed inhibitors (K(i)/K(i)(') = 0.04/0.3 and 0.02/0.3 uM, respectively), whereas propiconazole, difenoconazole, and penconazole were less potent competitive inhibitors (K(i) = 1.9, 4.5, and 4.7 uM, respectively. ...

/OTHER TOXICITY INFORMATION/ Monthey, Switzerland; reporting period, 1992 until December 2002. Difenoconazole had been handled since 1992 in three buildings, with an estimated 5300 tons being produced over the decade. In 2002, about two thirds of the product was handled and packed as powder. The remaining one third was used in two premixes, which were either formulated in Monthey or sent in bulk to Aigues Vives, France. The exact number of people potentially in contact with the material was unknown, but it was estimated that "several hundred" temporary workers had been involved with difenaconazole over the 10-year period. No adverse health effects had been recorded within the three buildings concerned or within the medical service based at Monthey.

For more Human Toxicity Excerpts (Complete) data for Difenoconazole (8 total), please visit the HSDB record page.

Slow biodegradation of difenoconazole may occur under certain conditions; however, biodegradation may be limited by its bioavailability. Pure culture degradation of structurally similar diaryl ether pesticides and halogenated diphenyl ethers has been reported, although several dead-end metabolites may inhibit complete mineralization(1). In addition, it has been postulated that the bioavailability of diaryl ether pesticides, such as difenoconazole, decreases under the influence of sunlight as the production of polymeric material and formation of bound residues from activated derivatives occurs(1). In addition, structurally similar pyrethroids undergo photodecarboxylation which limits bioavailability for this class of pesticides(1). In water-sediment systems, rapid dissipation from water was reported for difenoconazole, half-life = 1 to 3 days, while slow degradation from the system was reported, half-life = 8 months(2). Aerobic soil metabolism half-lives ranging from 175 to 1600 days have been reported(3).

SOIL: In 2010 residues of difenoconazole in rice fields were examined in samples from Guangxi, Hubei and Zhejiang province; residues of difenoconazole were undetectable in paddy soil samples 30, 40, and 50 days after application of pesticide at 90 to 135 grams a.i./ha(1).

Tolerances are established for residues of difenoconazole, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified below is to be determined by measuring only difenoconazole, 1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, in or on the following raw agricultural commodities:[Table#8407]

Tolerances are established for residues of difenoconazole, including its metabolites and degradates, in the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring the sum of difenoconazole, 1-[2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triazole, and its metabolite, CGA-205375, 1-[2-chloro-4-(4-chloro-phenoxy)phenyl]-2-[1,2,4]triazol-1-yl-ethanol, calculated as the stoichiometric equivalent of difenoconazole, in the following commodities:[Table#8408]

New Active Ingredients ... includes chemicals not previously registered as pesticides, as well as pesticide active ingredients initially registered after November 1, 1984 and that currently have active product registrations. By law, these pesticides must meet new safety standards, such as those described in the Food Quality Protection Act of 1996 and, if new safety standards are met, will be reviewed again on a 15-year cycle. Difenoconazole is designated by EPA as a New Pesticide Active Ingredient. Active Ingredient Number: 128847; Type of Pesticide: conventional - fungicide; Use Site: food use/wheat grain; Year: 1994.

For difenoconazole (USEPA/OPP Pesticide Code: 128847) ACTIVE products with label matches. /SRP: Registered for use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./[

Difenoconazole... is a systemic triazole fungicide that controls a broad spectrum of foliar, seed and soil-borne diseases caused by Ascomycetes, Basidiomycetes and Deuteromycetes in cereals, soya, rice, grapes, pome fruit, stone fruit, potatoes, sugar beet and several vegetable and ornamental crops.

Fungicide, insecticide, seed treatment/protectant.

This is a man-made compound that is used as a pesticide.

Difenconazole is produced by ketalization of 2-bromo-2'-chloro-4'-(4-chlorophenyl)acetophenone with 1,2-propanediol, followed by nucleophilic substitution with sodium 1,2,4-triazolide in dimethylformamide under reflux.

Preparation: A. Hubele, P. Riebli, United Kingdom patent 2098607 (1982 to Ciba-Geigy).

The National Pesticide Information Retrieval System (NPIRS) identifies 4 companies with active labels for products containing the chemical difenoconazole. To view the complete list of companies, product names and percent difenoconazole in formulated products click the following url and enter the CAS Registry number in the Active Ingredient field.

Difenoconazole Technical (Syngenta Crop Protection, LLC): Active ingredient: Difenoconazole 95.0%.

Dividend Fungicide (Syngenta Crop Protection, LLC): Active ingredient: Difenoconazole 32.8%.

Dividend XL RTA (Syngenta Crop Protection, LLC): Active ingredient: Metalaxyl-M 0.27%; Difenoconazole 3.21%.

For more Formulations/Preparations (Complete) data for Difenoconazole (31 total), please visit the HSDB record page.

Fungicides

Environmental transformation -> Pesticides (parent, predecessor)

Pesticides -> Fungicides