シプロジニル

log Kow = 3.59

4.00

Fine beige powder

White crystalline solid

Powder with agglomerates at 20 °C

In water, 13 mg/L (pH 7.0); 20 mg/L (pH 5.0) at 25 °C

In ethanol 160, acetone 610, toluene 440, n-hexane 26, n-octanol 140 (all in g/L at 25 °C)

0.013 mg/mL at 25 °C

DT50 in pH range 4-9 (25 °C) >>1 yr. Photolysis DT50 in water 0.4-13.5 days.

In soil, the compound dissipated with DT50 @ 20-60 days at normal soil humidities & soil temperatures ... .

75.9 °C

76 °C

0.00000368 [mmHg]

3.68X10-6 mm Hg at 25 °C

White solid; [Merck Index]

Solid

Stable under recommended storage conditions.

Hydrolytically stable.

Stable in the presence of steel, tin & aluminum. Stable in the presence of zinc(II), copper(II), & aluminum(VI) ions. Unstable in the presence of iron(II) ions. Stable in sunlight & elevated temperatures.

Warning

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]；H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P261, P272, P273, P280, P302+P352, P321, P333+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

Warning

Regulation (EC) No 396/2005 (amended)

Cyprodinil is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

06/64/EC, Reg. (EU) 2018/524, Reg. (EU) 2019/168, Reg. (EU) 2020/421, Reg. (EU) 2021/566, Reg. (EU) 2022/378, Reg. (EU) 2023/689, Reg. (EU) 2025/99, Reg. (EU) No 540/2011, Reg. (EU) No 678/2014

Cyprodinil: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

USEPA/Office of Pesticide Programs; Joint FAO/WHO Meeting on Pesticide Residues - Pesticide residues in food, Cyprodinil (121552-61-2) (2003)[Available from, as of June 28, 2016: http://www.inchem.org/documents/jmpr/jmpmono/v2003pr03.htm]

USEPA; Office of Prevention, Pesticides and Toxic Substances, Pesticide Fact Sheet for Cyprodinil, Reason for Issuance: Registration (April 6, 1998).[Available from, as of June 24, 2016: https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-288202_06-Apr-98.pdf]

Tolerances are established for residues of the fungicide cyprodinil, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only cyprodinil 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine.[Table#6631]

Tolerances are established for residues of the fungicide cyprodinil, 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 only the sum of cyprodinil 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine and free and conjugated CGA-304075 4-(4-cyclopropyl-6-methyl-pyrimidin-2-ylamino)-phenol, calculated as the stoichiometric equivalent of cyprodinil.[Table#6632]

Pesticide Fact Sheet: Name of Chemical: Cyprodinil; Reason for Issuance: Registration; Date Issued: April 6, 1998.

Skin Irrit. 2 (25.2%)；Skin Sens. 1 (100%)；Eye Irrit. 2 (25.2%)；Aquatic Acute 1 (100%)；Aquatic Chronic 1 (100%)

Hazardous to the aquatic environment (Acute) - Category 1；Hazardous to the aquatic environment (Long-term) - Category 1

Skin sensitization - Category 1B；Specific target organ toxicity - Repeated exposure - Category 2 (liver)

Skin Sens. 1；Aquatic Acute 1；Aquatic Chronic 1

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical, or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Keep container tightly closed in a dry and well-ventilated place.

Store in a well-ventilated, secure area out of the reach of children and domestic animals. Do not store food, beverages, or tobacco in the storage area.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Control spill at its source and contain to prevent it from spreading, contaminating soil, or entering sewage and drainage systems or any body of water. Clean up immediately. Solid: Sweep up material and place into compatible disposal container. Liquid: Cover entire spill with absorbing material and place into compatible disposal container. Scrub area with hard water detergent. Pick up wash liquid with additional absorbent and place into container. Seal container and arrange for deposition.

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.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

Do not reuse product containers. Dispose of product containers, waste containers, and residues according to local, state, and federal health and environmental regulations.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

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

Tolerances are established for residues of the fungicide cyprodinil, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only cyprodinil 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine.[Table#6628]

Tolerances are established for residues of the fungicide cyprodinil, 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 only the sum of cyprodinil 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine and free and conjugated CGA-304075 4-(4-cyclopropyl-6-methyl-pyrimidin-2-ylamino)-phenol, calculated as the stoichiometric equivalent of cyprodinil.[Table#6629]

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Coveralls. Shoes plus socks. Waterproof gloves.

... A previous study identified the seven most common pesticide mixtures to which the French population was exposed through food consumption in 2006. The aim of this study was to investigate if the seven mixtures are potentially cytotoxic and genotoxic and if so, whether compounds in a same mixture have a combined effect. The cytotoxicity and genotoxicity of the seven mixtures were investigated with a new assay (gamma-H2AX) using four human cell lines (ACHN, SH-SY5Y, LS-174T, and HepG2). Mixtures were tested at equimolar concentrations and also at concentrations reflecting their actual proportion in the diet. Irrespective of the cell line tested, parallel cytotoxicity of the seven mixtures was observed. Only one mixture was genotoxic for the HepG2 cells at concentrations = 3 uM in equimolar proportion and at 30 uM in actual proportion. Caspase 3/7 activity, the comet assay, and reactive oxygen species production were also investigated using the same mixture and HepG2 cells. Our results suggest that pesticide metabolites from the mixture generated by HepG2 cells were responsible for the observed damage to DNA. Among the five compounds in the genotoxic mixture, only fludioxonil and cyprodinil were genotoxic for HepG2 cells alone at concentrations = 4 and 20 uM, respectively. Our data suggest a combined genotoxic effect of the mixture at low concentrations with a significantly higher effect of the mixture of pesticides than would be expected from the response to the individual compounds.

LD50; Species: /Colinus virginianus/ (Bobwhite) oral >2000 mg/kg bw

LD50; Species: /Anas platyrhynchos/ (Mallard) oral >500 mg/kg bw

LC50; Species: /Colinus virginianus/ (Bobwhite) diet >5200 ppm for 5 days

LC50; Species: Colinus virginianus (Bobwhite) age 9 days; diet >5180 ppm for 8 days

For more Ecotoxicity Values (Complete) data for CYPRODINIL (10 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 1679-3980(2-3), indicate that cyprodinil is expected to have low to slight mobility in soil(SRC). Volatilization of cyprodinil from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.4X10-8 atm-cu m/mole(SRC), based upon its vapor pressure, 3.68X10-6 mm Hg(4), and water solubility, 13 mg/L(4). Cyprodinil is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Mineralization of cyprodinil was reported as 6.3-24.7% in four soils, 54.1-63% was found bound to the same soils(5). These results indicate that the major route of dissipation for cyprodinil is adsorption(5). Cyprodinil had a half-life of 12.5 and 6.5 days in soil under open field and greenhouse conditions, respectively(6). The half-life of cyprodinil was 5.8-15.6 days on soil at two experimental stations in China(7).

AQUATIC FATE: Based on a classification scheme(1), Koc values of 1679-3980(2-3), indicate that cyprodinil 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 8.4X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 3.68X10-6 mm Hg(5), and water solubility, 13 mg/L(5). Cyprodinil is stable to hydrolysis under environmental conditions (pH 5 to 9)(5). According to a classification scheme(6), a BCF of 511 in bluegill sunfish(7), suggests the potential for bioconcentration in aquatic organisms is high(SRC). The half-life for photodegradation of cyprodinil in water was reported as 13.5 days(5). Biodegradation data in water were not available(SRC, 2016).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cyprodinil, which has a vapor pressure of 3.68X10-6 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase cyprodinil 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 1.9 hours(SRC), calculated from its rate constant of 2.0X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase cyprodinil may be removed from the air by wet and dry deposition(SRC). Cyprodinil does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Of 173 agricultural products analyzed in 2006 from Japan, four were reported to contain cyprodinil at 1.9-22.2 ng/g(1). Cyprodinil was not detected (detection limit 0.02 mg/kg) in 16 apricot, 19 peach, 7 plum, 23 sour cherry or 27 sweet cherry samples collected from 2012 to 2014 from production farms in Poland(2). Cyprodinil was detected in 7 of 50 ready-to-eat Italian meals (main course, side dish, fruit, bread, wine); samples were collected on Feb 8, May 26, Oct 24 and Dec 21, 2005(3). Cyprodinil was detected in 24 of 47 wine grape (Vitis vinifera L.) samples collected from the 2006 harvest in Slovenia at a concentration range of 0.03-0.40 mg/kg(4).

Cyprodinil was detected in 5.6% of 250 fruit berries grown, collected and analyzed from 2009 to 2011 in south-eastern Poland(1).[Table#6633]

The half-life range of cyprodinil was 9.6-20.8 days on grapes at two experimental stations in China(1). Fourteen days after three low dosage applications the residual concentration was <1.0 mg/kg on grapes(1). The half-lives of cyprodinil on strawberries in China under open field and greenhouse conditions were 14.5 and 5.5 days, respectively(2). The half-lives of cyprodinil on emerald and jewel blueberries were 2.2 and 3.4 days, respectively; samples were collected in Concordia, Argentina(3).

Azoxystrobin, boscalid, cyprodinil, fenhexamid, and pyrimethanil are new generation fungicides extensively employed in order to combat diseases affecting vineyards worldwide. Owing to their physico-chemical characteristics, residues of these compounds on grapes are transferred to must and wine. In this study, a survey of the occurrence of these fungicides in international wines was carried out by using rapid antibody-based assays. Results are discussed as a function of wine type and sample geographical origin. 44.4% of the samples contained at least one of the targets (>10 ug/L). Fungicide residue occurrences were 22.4%, 19.2%, 18.8%, 6.8%, and 1.2% for pyrimethanil, boscalid, fenhexamid, cyprodinil, and azoxystrobin, respectively, while residue contents higher than 100 ug/L were found in 8.4% of the samples. This study shows that contamination of commercial wines with pesticides is an issue of worldwide relevance with potential implications for consumer health and international trade.

Greenhouse studies were conducted to evaluate the dissipation rate kinetics and estimate the behavior of selected pesticides after washing, peeling, simmering, and canning of tomato expressed as processing factor (PF). Two varieties (Marissa and Harzfeuer) were treated by six fungicides: azoxystrobin, boscalid, chlorothalonil, cyprodinil, fludioxonil, and pyraclostrobin at single and double dose and risk assessment defined as hazard quotient was performed. The QuEChERS method was used for sample preparation followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The dissipation of fungicides approximately fitted to a first-order kinetic model, with half-life values ranging from 2.49 and 2.67 days (cyprodinil) to 5.00 and 5.32 days (chlorothalonil) for Marissa and Harzfeuer variety, respectively. Results from processing studies showed that treatments have significant effects on the removal of the studied fungicides for both varieties. The PFs were generally less than 1 (between 0.01 and 0.90) and did not depend on variety. The dietary exposure assessed based on initial deposits of application at single and double dose on tomatoes and concentration after each process with PF correction showed no concern to consumer health. Our results would be a useful tool for monitoring of fungicides in tomatoes and provide more understanding of residue behavior and risk posed by these fungicides.

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.；Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

IDENTIFICATION AND USE: Cyprodinil is a fine beige powder. It is used as a foliar fungicide in cereals, grapes, pome fruits, stone fruits, strawberries, and vegetables and as a seed dressing on barley; it controls a wide range of pathogens, including Pseudocercosporella herpotrichoides, Erysiphe spp., Pyrenophora teres, Rhynchosporium secalis, and Septoria nodorum. HUMAN EXPOSURE AND TOXICITY: Cyprodinil acts as an aryl hydrocarbon receptor activator, a potential endocrine disrupter, and an extracellular signal-regulated kinase disrupter. Weak androgen receptor binding was shown for cyprodinil. Cyprodinil was genotoxic for HepG2 cells at concentrations 20 uM. ANIMAL STUDIES: In a 28 day gavage study in rats, the LOEL is 100 mg/kg bw/day for rats, based on increased liver weights and abnormalities in liver morphology. In a two-generation reproduction study in rats, the LOEL for maternal systemic toxicity is 4000 (about 326 mg/kg/day) based on lower body weights in the F0 females during the pre-mating period. The NOEL for maternal systemic toxicity is 1000 ppm (about 81 mg/kg/day). The LOEL for reproductive/developmental toxicity is 4000 ppm (about 326 mg/kg/day) based on decreased pup weights (F1 and F2). The NOEL for reproductive toxicity is 1000 ppm (about 81 mg/kg/day). In an 18-month carcinogenicity study in mice, the LOEL is 2000 ppm (males- 212.4 mg/kg/day) based on a dose-related increase in the incidence of focal and multifocal hyperplasia of the exocrine pancreas in males. The NOEL is 150 ppm (males- 16.1 mg/kg/day). This study was tested to adequate levels based on signs of toxicity in males at 2000 ppm and females at 5000 ppm. There was no indication of carcinogenic potential at any dose level. ECOTOXICITY STUDIES: In plants, cyprodinil promoted a copious increase in exudate secretion and caused the most severe collapse of stigmatic cells of all the fungicides evaluated.

/PLANTS/ Fungicides can be detrimental to flower development, pollen function and fruit set in a number of crops. Almond is a self-incompatible nut crop that has a fruit set of only approx. 30% of the total number of flowers. Thus, interference of pollination and fertilization by fungicide sprays is of concern, and identification of chemicals having the least detrimental effects would be desirable. The objective of this study was to evaluate the effect of fungicide sprays on stigma morphology in almond using a laboratory spray apparatus that simulated field applications. Four fungicides (azoxystrobin, myclobutanil, iprodione and cyprodinil) were applied, and fresh, unfixed stigmatic surfaces were observed using a scanning electron microscope at 4 and 24 hr after spraying. .... Cyprodinil promoted a copious increase in exudate secretion and caused the most severe collapse of stigmatic cells of all the fungicides evaluated. Damage was somewhat localized at 4 hr but more global at 24 hr. ...

/PLANTS/ The beneficial fungus Neozygites floridana kills the two-spotted spider mite Tetranychus urticae, which is a serious polyphagous plant pest worldwide. ... The aim of this study was to conduct a laboratory experiment to evaluate the effect of pesticides used in strawberry and soybean crops on N. floridana. Among the pesticides used in strawberry, the fungicides sulfur and cyprodinil + fludioxonil completely inhibited both the sporulation and conidia germination of N. floridana. ...

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 July 7, 2016: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page for Cyprodinil, which tabulates all of the "Short-Term Toxicity Studies" and "Toxicogenomics Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp.niehs.nih.gov/testing/status/agents/ts-12027.html]

Koc values of 1679 to 2613 have been reported in eight soils from four vineyards in Spain(1). The Koc of cyprodinil was also reported as 3980(2). According to a classification scheme(3), this Koc range suggests that cyprodinil has low to slight mobility in soil.

Radio-labeled cyprodinil was added to four soils to determine environmental fate processes, soil binding was reported as follows(1):[Table#6634]

/BIOMONITORING/ In the present work, a highly sensitive method based on solid phase microextraction and gas chromatography tandem (triple quadrupole) mass spectrometry was used to test hair samples for 50 pesticides including 39 molecules from different chemical families currently used in agriculture and 11 organochlorines. The population investigated was composed of 18 farm workers who provided hair samples repeatedly collected during the entire treatment period (from March to November 2009). Among the 62 hair samples that were collected, 33 different target molecules were detected. The most frequently detected agricultural pesticides were Diflufenican and Pyrimethanil, two herbicides which were detected in 13 subjects. The concentration in volunteers' hair matched with agricultural activity and the highest concentration was observed for Cyprodinil (1161 pg/mg), an anilinopyrimidine used as a fungicide. ...

/ENDOCRINE MODULATION/ Cyprodinil is a pyrimidinamine fungicide, used worldwide by agriculture. It is used to protect fruit plants and vegetables from a wide range of pathogens. Benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are toxic environmental pollutants and are prototypes of aryl hydrocarbon receptor (AHR) ligands. Although the structure of cyprodinil distinctly differs from those of BaP and TCDD, our results show that cyprodinil induced nuclear translocation of the AHR, and induced the transcriptional activity of aryl hydrocarbon response element (AHRE). Cyprodinil induced the expression of cytochrome P450 (CYP) 1A1, a well-known AHR-targeted gene, in ovarian granulosa cells, HO23, and hepatoma cells, Hepa-1c1c7. Its induction did not appear in AHR signal-deficient cells, and was blocked by the AHR antagonist, CH-223191.Cyprodinil decreased AHR expression in HO23 cells, resulting in CYP1A1 expression decreasing after it peaked at 9 hr of treatment in HO23 cells. Dexamethasone is a synthetic agonist of glucocorticoids. Cyprodinil enhanced dexamethasone-induced gene expression, and conversely, its induction of CYP1A1 expression was decreased by dexamethasone in HO23 cells, indicating its induction of crosstalk between the AHR and glucocorticoid receptor and its role as a potential endocrine disrupter. In addition to BaP, TCDD, and an AHR agonist, beta-NF, cyprodinil also phosphorylated extracellular signal-regulated kinase (ERK) in HO23 and Hepa-1c1c7 cells, indicating its deregulation of ERK activity. In summary, our results demonstrate that cyprodinil, similar to BaP, acts as an AHR activator, a potential endocrine disrupter, and an ERK disrupter.

/ENDOCRINE MODULATION/ ... The transactivation potential of the pesticides Acorit, Frupica, Steward, Reldan, Switch, Cantus, Teldor, and Scala and their active compounds (hexythiazox, mepanipyrim, indoxacarb, chlorpyrifos-methyl, cyprodinil, fludioxonil, boscalid, fenhexamid, and pyrimethanil) were tested on human estrogen receptor alpha (ERalpha), androgen receptor (AR) and arylhydrocarbon receptor (AhR) in vitro. Relative binding affinities of the pure pesticide constituents for AR and their effect on human breast cancer and prostate cancer cell lines were evaluated. Residue concentrations of Switch's ingredients were below maximum residue limits. Fludioxonil and fenhexamid were ERalpha agonists (EC50 -values of 3.7 and 9.0 uM, respectively) and had time-dependent effects on endogenous ERalpha-target gene expression (cyclin D1, progesterone receptor, and nuclear respiratory factor 1) in MCF-7 human breast cancer cells. Fludioxonil, mepanipyrim, cyprodinil, pyrimethanil, and chlorpyrifos-methyl were AhR-agonists (EC50s of 0.42, 0.77, 1.4, 4.6, and 5.1 uM, respectively). Weak AR binding was shown for chlorpyrifos-methyl, cyprodinil, fenhexamid, and fludioxonil. Assuming a total uptake which does not take metabolism and clearance rates into account, our in vitro evidence suggests that pesticides could activate pathways affecting hormonal balance, even within permitted limits, thus potentially acting as endocrine disruptors.

/GENOTOXICITY/ ... A previous study identified the seven most common pesticide mixtures to which the French population was exposed through food consumption in 2006. The aim of this study was to investigate if the seven mixtures are potentially cytotoxic and genotoxic and if so, whether compounds in a same mixture have a combined effect. The cytotoxicity and genotoxicity of the seven mixtures were investigated with a new assay (gamma-H2AX) using four human cell lines (ACHN, SH-SY5Y, LS-174T, and HepG2). Mixtures were tested at equimolar concentrations and also at concentrations reflecting their actual proportion in the diet. Irrespective of the cell line tested, parallel cytotoxicity of the seven mixtures was observed. Only one mixture was genotoxic for the HepG2 cells at concentrations = 3 uM in equimolar proportion and at 30 uM in actual proportion. Caspase 3/7 activity, the comet assay, and reactive oxygen species production were also investigated using the same mixture and HepG2 cells. Our results suggest that pesticide metabolites from the mixture generated by HepG2 cells were responsible for the observed damage to DNA. Among the five compounds in the genotoxic mixture, only fludioxonil and cyprodinil were genotoxic for HepG2 cells alone at concentrations = 4 and 20 uM, respectively. Our data suggest a combined genotoxic effect of the mixture at low concentrations with a significantly higher effect of the mixture of pesticides than would be expected from the response to the individual compounds.

/ALTERNATIVE and IN VITRO TESTS/ Fenhexamid and cyprodinil are antifungal agents (pesticides) used for agriculture, and are present at measurable amounts in fruits and vegetables. In the current study, the effects of fenhexamid and cyprodinil on cancer cell proliferation and metastasis were examined. Additionally, the protein expression levels of cyclin D1 and cyclin E as well as cathepsin D were analyzed in BG-1 ovarian cancer cells that express estrogen receptors (ERs). The cells were cultured with 0.1% dimethyl sulfoxide (DMSO; control), 17beta-estradiol (E2; 10-9 M), and fenhexamid or cyprodinil (10-5 - 10-7 M). Results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that fenhexamid and cyprodinil increased BG-1 cell proliferation about 1.5 to 2 times similar to E2 (5 times) compared to the control. When the cells were co-treated with ICI 182,780 (10-8 M), an ER antagonist, the proliferation of pesticide-treated BG-1 cells was decreased to the level of the control. A wound healing assay revealed that the pesticides reduced the disrupted area in the BG-1 cell monolayer similar to E2. Protein levels of cyclin D1 and E as well as cathepsin D were increased by fenhexamid and cyprodinil. This effect was reversed by co-treatment with ICI 182,780. In a xenograft mouse model with transplanted BG-1 cells, cyprodinil significantly increased tumor mass formation about 2 times as did E2 (6 times) compared to the vehicle (0.1% DMSO) over an 80-day period. ... Cyprodinil also induced cell proliferation along with the expression of proliferating cell nuclear antigen (PCNA) and cathepsin D in tumor tissues similar to E2. Taken together, these results imply that fenhexamid and cyprodinil may have disruptive effects on ER-expressing cancer by altering the cell cycle- and metastasis-related gene expression via an ER-dependent pathway.

Regulation (EC) No 396/2005 (amended)

Cyprodinil is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

06/64/EC, Reg. (EU) 2018/524, Reg. (EU) 2019/168, Reg. (EU) 2020/421, Reg. (EU) 2021/566, Reg. (EU) 2022/378, Reg. (EU) 2023/689, Reg. (EU) 2025/99, Reg. (EU) No 540/2011, Reg. (EU) No 678/2014

Cyprodinil: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Tolerances are established for residues of the fungicide cyprodinil, including its metabolites and degradates, in or on the commodities in the table below. Compliance with the tolerance levels specified below is to be determined by measuring only cyprodinil 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine.[Table#6631]

Tolerances are established for residues of the fungicide cyprodinil, 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 only the sum of cyprodinil 4-cyclopropyl-6-methyl-N-phenyl-2-pyrimidinamine and free and conjugated CGA-304075 4-(4-cyclopropyl-6-methyl-pyrimidin-2-ylamino)-phenol, calculated as the stoichiometric equivalent of cyprodinil.[Table#6632]

Pesticide Fact Sheet: Name of Chemical: Cyprodinil; Reason for Issuance: Registration; Date Issued: April 6, 1998.

In studies of metabolism in rats, ... cyprodinil was primarily metabolized by hydroxylation of the phenyl and pyrimidine rings and methyl group, and excreted mainly as glucuronide or sulfate conjugates in urine, feces and bile. Approximately 3-8% of the parent compound was detected in the feces. Excretion, distribution and metabolite profiles were essentially independent of dose, pretreatment and site of radiolabel, although there were some quantitative sex-dependent differences in urinary metabolites.

The metabolic pathways are independent of sex, pre-treatment or dose level administered.

In tomatoes, the metabolism of CGA 219417 proceeded mainly via hydroxylation of the 6-methyl group of the pyrimidine ring as well as hydroxylation of the phenyl & pyrimidine ring.

... In rats, radiolabelled cyprodinil administered by gavage as a single dose of 0.5 or 100 mg/kg bw, or as repeated doses of 0.5 mg/kg bw per day for 14 days, was rapidly absorbed from the gastrointestinal tract and excreted. Approximately 75% (range, 71-85%) of an orally administered dose was absorbed over 48 hr. At a dose of 0.5 and 100 mg/kg bw, two plasma level maxima of radioactivity were observed at approximately 0.5-1 hr and 8-12 hr, probably caused by reabsorption of material excreted in the bile. Approximately 92-97% of the administered dose was eliminated within 48 hr in the urine (48-68%), feces (29-47%), and bile (accounting for up to 35.4% of the dose in cannulated rats), with elimination being almost complete by day 7. Seven days after single or repeated oral administration at the lower dose, total tissue residues accounted for 0.15-0.60% of the administered dose. ... Excretion, distribution and metabolite profiles were essentially independent of dose, pretreatment and site of radiolabel, although there were some quantitative sex-dependent differences in urinary metabolites.

After oral administration, CGA 219417 is rapidly absorbed and also rapidly and almost completely eliminated with urine and feces. ... Residues in tissues were generally low and there was no evidence for accumulation or retention of radioactivity.

Used as agricultural fungicide; [Merck Index] Used as a fungicide applied to the foliage of almonds, grapes, stone fruit crops, and pome fruit crops; [Reference #1] A fungicide in the anilinopyrimidine class; Also applied to cereal grains and ornamentals and as a seed dressing on barley; [Krieger, p. 1903-4]

Farming (Pesticides) [Category: Industry]

For cyprodinil (USEPA/OPP Pesticide Code: 288202) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Fungicide

It is used as a foliar fungicide in cereals, grapes, pome fruits, stone fruits, strawberries, and vegetables and as a seed dressing on barley; it controls a wide range of pathogens, including Pseudocercosporella herpotrichoides, Erysiphe spp., Pyrenophora teres, Rhynchosporium secalis, and Septoria nodorum.

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

Cyprodinil is produced by cyclocondensation of phenylguanidinium carbonate with 1-cyclopropyl-1,3-butenedione.

Preparation: A. Huberle, European Patent Office patent 310550; idem, United States of America patent 5153200 (1989, 1992 both to Ciba-Geigy).

Cyprodinil Technical (Syngenta Crop Protection, LLC): Active ingredient: Cyprodinil 99.0%.

Vangard WG Fungicide (Syngenta Crop Protection, LLC): Active ingredient: Cyprodinil 75.0%.

Switch 62.5WG (Syngenta Crop Protection, LLC): Active ingredient: Fludioxonil 25.0%; Cyprodinil 37.5%.

Inspire Super (Syngenta Crop Protection, LLC): Active ingredient: Difenoconazole 8.4%;Cyprodinil 99.0%.

For more Formulations/Preparations (Complete) data for CYPRODINIL (8 total), please visit the HSDB record page.

Environmental transformation -> Pesticides (parent, predecessor)

Fungicides