Fenhexamid

302.19600

302.20

422-530-5|603-167-3

Q68C3C9P1U

DTXSID3032549

White powder|Solid

49.33000

4.68090

1.338g/cm3

141 °C

457.9ºC at 760mmHg

230.7ºC

1.604

In water, 20 mg/L at 20 °C|Solubility in: dichloromethane 31, isopropanol 91, acetonitrile 15, toluene 5.7, n-hexane <0.1 (all in g/L, 20 °C)

0-6ºC

5.26E-09mmHg at 25°C

Henry's Law constant = 4.93X10-11 atm-cu m/mol at pH 7, 20 °C (calculated)

pKa = 7.3

164.82 Ų [M+H]+ [CCS Type: TW]|173.21 Ų [M-H]-

Hydroxy radical reaction rate constant: 17X10-12 cu cm/molecule-sec at 25 °C /Estimated/

UN 3077 9/PG 3

GU7879550

Stable under recommended storage conditions.|Stable to hydrolysis for 30 days at pH 5, 7, 9 (25 °C).|Stable at room temperature for 52 weeks.

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. Contaminated packaging: Dispose of as unused product.

Health Canada, Pest Management Regulatory Agency; Proposed Regulatory Decision Document- Fenhexamid PRDD2003-04 (March 26, 2003).[Available from, as of October 20, 2004: http://www.pmra-arla.gc.ca/english/pdf/prdd/prdd2003-04-e.pdf]|USEPA; Office of Prevention, Pesticides and Toxic Substances, Pesticide Fact Sheet for Fenhexamid, Reason for Issuance: New Chemical Registration (May 20, 1999).[Available from, as of June 24, 2016: https://www3.epa.gov/pesticides/chem_search/reg_actions/registration/fs_PC-090209_20-May-99.pdf]

|H411: Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]|P273, P391, and P501|H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory.|Aggregated GHS information provided by 107 companies from 1 notifications to the ECHA C&L Inventory.|H401: Toxic to aquatic life [Hazardous to the aquatic environment, acute hazard]|Danger|H330: Fatal if inhaled [Danger Acute toxicity, inhalation]|P260, P271, P284, P304+P340, P310, P320, P403+P233, P405, and P501

Eye/face protection: 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: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

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. 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.

Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. 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: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. 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.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

It was slightly irritating when applied to the skin of New Zealand White rabbits, and was minimally irritating when instilled into the eyes of the same species. /Elevate 50 WDG Fungicide formulation (identical to Decree 50 WDG), containing 49.6% technical fenheximid/

Fenhexamid was detected at <0.02 and <0.004 ug/L in winemaking effluents from two wastewater treatment plants in the Bordeaux region of France, incorporating biological treatment and sand filtration and operated under low-flow conditions(1).

IDENTIFICATION AND USE: Fenhexamid is a solid. Fenhexamid is a specific fungicide for the control of Botrytis cinerea, Monilinia fructigena, Monilinia laxa, and Sclerotinia sclerotiorum. HUMAN EXPOSURE AND TOXICITY: Fenhexamid showed endocrine disruptor activity as antiandrogen in an androgen receptor reporter assay in engineered human breast cancer cells. Fenhexamid increase miR-21 expression with downstream antiestrogenic activity in MCF-7, T47D, and MDA-MB-231 human breast cancer cells. ANIMAL STUDIES: It was slightly irritating when applied to the skin of rabbits, and was minimally irritating when instilled into the eyes of the same species. Results of skin sensitization testing in guinea pigs, employing the Buehler method, were negative. A 1-yr chronic oral toxicity study in dogs was conducted, in which decreased red blood cell (RBC) counts, hemoglobin and hematocrit and increased Heinz bodies in RBC were seen at the LOAEL of 124/133 mg/kg/day in males/females; also, in females, increased absolute and relative adrenal weights correlated with histopathological observations of increases in the incidence and severity of intracytoplasmic vacuoles in the adrenal cortex. In a developmental toxicity study, fenhexamid was administered to 16 female rabbits by gavage at dose levels of 0, 100, 300 or 1000 mg/kg/day from days 6 through 18 of gestation. No treatment-related effects were seen on mortality, general appearance or behavior. Administration of the test compound did not induce any treatment-related fetal malformations or deviations at any of the doses tested under the conditions of this study. All effects on intrauterine development were correlated with maternal toxicity and, therefore, no primary developmental effect was evident. Fenhexamid was not teratogenic up to and including 1000 mg/kg/day, the limit dose. Fenhexamid was tested in the following assays: Reverse Gene Mutation -Salmonella, non-mutagenic with or without metabolic activation; Forward Gene Mutation -HGPRT locus, non-mutagenic with or without metabolic activation; Micronucleus Assay -Mice, non-mutagenic; Unscheduled DNA Synthesis -Rat hepatocytes, non-mutagenic; Chromosome Aberration -CHO cells, non-mutagenic with or without metabolic activation. ECOTOXICITY STUDIES: Fenhexamid is moderately toxic to rainbow trout and bluegill sunfish, and slightly toxic to sheepshead minnow. Studies on the toxicity of fenhexamid to beneficial insects were done with formulated fenhexamid (50% a.i.). The NOEC based on mortality of predacious mite and rove beetle was 2 kg formulated fenhexamid/ha. The NOEC for parasitic wasp was 4 kg formulated fenhexamid/ha.

... In this study, the effects of two fungicides, fenhexamid and myclobutanil were investigated individually and in combination on two human cell lines, SH-SY5Y neuronal cells and U-251 MG glial cells. After 48 hr of incubation with increasing concentrations of pesticides ranging from 1 to 1000 uM, gene expression profiles were studied in addition to toxicity end points, including cell viability, mitochondrial depolarization as well as cellular glutathione maintenance. There were no significant differences between the susceptibility of the two cell lines in terms of cell viability assessment or mitochondrial membrane potential, when agents were administered either individually or in combination. By contrast, in the presence of the fungicides, the SH-SY5Y cells showed significantly greater susceptibility to oxidative stress in terms of total thiol depletion in comparison with the astrocytic cells. Treatment with the two pesticides led to significant changes in the cell lines' expression of several genes which regulate cell cycle control and growth (RB1, TIMP1) as well as responses to DNA attrition (ATM and CDA25A) and control of apoptosis (FAS). There was no evidence in this study that the combination of fenhexamid and myclobutanil was significantly more toxic than individual exposure, although gene expression changes suggested there may be differences in the sub-lethal response of both cell lines to both individual and combined exposure.

LD50 Rat oral >5000 mg/kg|LD50 Rat dermal >2000 mg/kg|LC50 Rat inhalation >5057 mg/cu m/4 hr|LD50 Rat oral >2000 mg/kg /Elevate 50% WDG/ /from table/|LD50 Rat dermal >2000 mg/kg /Elevate 50% WDG/ /from table/

/BIRDS and MAMMALS/ Fenhexamid is practically non-toxic to bobwhite quail and mallard duck on an acute dietary basis. ...No fenhexamid treatment-related effects were observed in any of the reproductive parameters (egg production, eggshell thickness, hatchling health and survival) of bobwhite quail. In the reproductive toxicity study on bobwhite quail, the no observed effect concentration was 2000 mg a.i./kg body weight (based on the effect on reproductive parameters).|/AQUATIC SPECIES/ Fenhexamid is moderately toxic to rainbow trout and bluegill sunfish, and slightly toxic to sheepshead minnow. ...The NOEC /of fenhexamid technical and formulated fenhexamid in rainbow trout/ based on the behavioral changes was 1 mg a.i./L. The sublethal effects observed were labored respiration, lying on the bottom of the aquarium, hyperactivity and loss of equilibrium (turned laterally more or less from the normal body position). ...The NOEC /of fenhexamid in bluegill sunfish/ based on the transient hyperactive swimming was 1.50 mg a.i./L. ...The NOEC /of fenhexamid in sheepshead minnow/ based on mortality was 3.7 mg a.i./L. In the early life cycle toxicity test with rainbow trout, the mean adverse toxic concentration was 144 ug a.i./L and the NOEC (based on swim up-the developmental stage at which the newly hatched fry begin swimming up from the bottom of the test chamber) was 101 ug a.i./L.|/AQUATIC SPECIES/ Laboratory studies were conducted to determine the effects of different concentrations of fenhexamid (0.1, 1, and 10 mg/L) on growth, oxidative stress, protein, glycogen, and metallothionein (MT) contents in Tubifex tubifex after an exposure of 2, 4, and 7 days. In addition, residues of the fungicide were followed in water and in the worms. In water, fenhexamid concentration decreased slowly (maximum -2 +/- 0.03% after 2 days for 1 mg/L). In the worms, it increased after 4 days and decreased thereafter, confirming that the worms were exposed to the fungicide and not to a degradation product. LC50 values were between 95.22 +/- 5.36 and 32.11 +/- 1.8 mg/L depending on exposure time. Exposure to fenhexamid had a negative effect on T. tubifex growth (maximum effect -12.2 +/- 0.8% after 7 days with 10 mg/L) demonstrating the toxic effect of the pesticide. This growth rate decrease was accompanied by a reduction in protein and glycogen contents. The activity of catalase (CAT), and glutathione reductase (GR) increased in response to the fungicide demonstrating an oxidative stress in the worms. In contrast glutathion-S-transferase activity (GST) decreased. Exposure to fenhexamid also induced synthesis of MT (maximum +78 +/- 8% after 2 days for 10 mg/L). The specificity of MT concentration increase in response to metals is discussed.|/AQUATIC SPECIES/ Laboratory studies were conducted to determine the effects of different concentrations of fenhexamid and atrazine (25, 50 and 100 ug/L) on growth and oxidative stress on Scenedesmus obliquus (microalgae) after exposure for 24, 48, and 96 hr. In addition, residues of fenhexamid and atrazine were determined in the culture medium after 96 hr; 52%, 44% and 43% of fenhexamid remained in the medium for the lowest, middle and highest concentrations, respectively. ... The antioxidative enzyme activities were used as biomarkers to evaluate the toxic effects of fenhexamid and atrazine on the microalgae. Enzymatic activities were measured in the presence of each compound alone after 24, 48 and 96 hr and also in mixture after 24 hr exposure. The results showed that fenhexamid and atrazine induced antioxidative enzyme activities (GST, CAT and GR) at different concentrations. Catalase activities (CAT) in both pesticides treated-algae were significantly increased. Additionally, an increase in glutathione-S-transferase (GST) was observed in algae after 24, 48 and 96 hr of exposure to both fenhexamid and atrazine. Antioxidative enzymes in fenhexamid and atrazine mixture treatment showed an antagonistic interaction after 24 hr of exposure in algae.|For more Ecotoxicity Excerpts (Complete) data for FENHEXAMID (10 total), please visit the HSDB record page.

Fenhexamid's production may result in its release to the environment through various waste streams; it's use as a 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 4100(SRC), determined from a structure estimation method(2), indicates that fenhexamid is expected to have slight mobility in soil(SRC). The pKa of fenhexamid is 7.3(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species of fenhexamid from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 4.93X10-11 atm-cu m/mole(3). Fenhexamid is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 3.0X10-9 mm Hg at 20 °C(3). A biodegradation half-life of <1 day has been reported under laboratory aerobic conditions(5) suggesting that biodegradation is an important environmental fate process in soil(SRC).|ECOSYSTEM STUDY: A study was conducted to investigate fenhexamid (FEX) behavior in soil and in water. FEX proved to be rather stable at acid pH but showed slight degradation at neutral and alkaline pH. After 101 days of FEX spiking of a soil sample, 94% at pH 4, 12% at pH 7 and 23% at pH 9 of the active ingredient was still present. In natural water the rate of FEX disappearance appeared to be slow which may be due to abiotic rather than biotic processes. The soil degradation tests showed low persistence of the active ingredient if a good microflora activity is guaranteed (DT(50) about 1 day). Moreover, in absence of microorganisms, FEX proved to be stable. Humidities of 25 and 50% of Water Holding Capacity (WHC) influenced in equal measure the rate of degradation. From the same soil, a bacterium was isolated and identified as Bacillus megaterium, which was able to metabolize FEX with the hydroxylation of the cyclohexane ring. Moreover, FEX showed an elevated affinity for humic acid (73%), smectite (31%), and ferrihydrite(20%) and low affinity for vermiculite (11%) and kaolinite (7%).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 4100(SRC), determined from a structure estimation method(2), indicates that fenhexamid is expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(3) based upon a Henry's Law constant of 4.93X10-11 atm-cu m/mole(4). A pKa of 7.3(4) indicates fenhexamid will exist partially in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(56), an estimated BCF of 96(SRC), from its log Kow of 3.51(4) and a regression-derived equation(2), suggests that the potential for bioconcentration in aquatic organisms is moderate(SRC). Fenhexamid degraded rapidly in laboratory aqueous photolysis studies(6). The major photolytic degradation products were dechlorinated and hydroxylated forms of fenhexamid and CO2(6). Fenhexamid is stable to hydrolysis(6). Biodegradation half-lives of 14-24 days have been reported using laboratory aerobic aquatic systems(6) suggesting that biodegradation is an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fenhexamid, which has a vapor pressure of 3.0X10-9 mm Hg at 20 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase fenhexamid may be removed from the air by wet and dry deposition(SRC). Fenhexamid degraded rapidly in laboratory aqueous photolysis studies(3). The major photolytic degradation products were dechlorinated and hydroxylated forms of fenhexamid and CO2(3); therefore, fenhexamid may be susceptible to direct photolysis by sunlight(SRC).

Fenhexamid is stable to hydrolysis(1) for 30 days at pH 5, 7 and 9 at 25 °C(2). Fenhexamid degrades rapidly in laboratory aqueous photolysis studies(1). The major photolytic degradation products were dechlorinated and hydroxylated forms of fenhexamid and CO2(1). In natural water/sediment systems, fenhexamid degraded rapidly, ultimately forming carbon dioxide(2).

An estimated BCF of 96 was calculated in fish for fenhexamid(SRC), using a log Kow of 3.51(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of fenhexamid can be estimated to be 4100(SRC). According to a classification scheme(2), this estimated Koc value suggests that fenhexamid is expected to have slight mobility in soil. The pKa of fenhexamid is 7.3(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).|The adsorption of fenhexamid (FEN) ... on vineyard soil amended with wine lees (WL) produced by vinery was studied. The adsorption extent depends on WL fraction. The addition of the centrifuged solid lees (SWL) increases the FEN adsorption on soil. Most likely, the organic insoluble fraction formed mainly by dead fermentation yeasts is responsible for the observed increase. The adsorption measured on some deactivated yeasts of wine fermentation shows that Saccharomyces cerevisiae are the most active in FEN retention. On the other hand, the soil amendment with whole WL decreases considerably the fungicide adsorption. This opposite effect may be the result of FEN hydrophobic bonds with the dissolved organic matter of lees that keeps fungicide in solution. This hypothesis is substantiated by the increased FEN solubility in the supernatant of centrifuged wine lees (LWL). The results of soil column mobility confirm that the elution with LWL increases the mobility of FEN in soil.

The Henry's Law constant for the neutral species of fenhexamid is calculated as 4.93X10-11 atm-cu m/mole(1). This Henry's Law constant indicates that fenhexamid is expected to be essentially nonvolatile from water and moist soil surfaces(3). Fenhexamid is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure of 3.0X10-9 mm Hg(1).

SURFACE WATER: Fenhexamid was detected at 15.1 ng/L in one of 11 samples from the Guadalquivir River in the Jaen Province, southeast Spain, sampled from April 2009 through November 2010. The region is a main olive oil producer(1).

Fenhexamid was tested for but not detected in red and white wines obtained from a US market basket survey; limit of detection is 13 ug/L(l). Fenhexamid exhibited dissipation half-lives of 6.5 and 4.5 days in 2012 and 2013, respectively, during the fermentation process to produce red wine from an experimental vineyard in Aldeanueva de Ebron, La Rioja (northern Spain)(2).|... A recent survey of pesticide residues in wines on the Swiss market ... fenhexamid was present in 61% of the samples at a maximum concentration of 0.59 mg/L and a Swiss maximum residue level of 1.5 mg/L. ... currently one of the most frequently used in /Swiss/ vineyard protection.|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.|The influence of six fungicides (famoxadone, fenhexamid, fluquinconazole, kresoxim-methyl, quinoxyfen and trifloxystrobin) on the volatile composition of red wines obtained from inoculated fermentation was studied. Although treatments were carried out under critical agricultural practices (CAP), the residues in the wines were below their maximum residue limit (MRL). Ethyl decanoate was the compound most influenced by these fungicides, while diethyl succinate, decanoic acid, beta-ionone, and citronellol concentration were not changed with any of the treatments. The treatment of grapes with trifloxystrobin induced changes in only one volatile compound, and the variation in volatile composition of wines from grapes treated with fenhexamid, fluquinconazole and quinoxyfen compared to control wines was almost negligible /in value/. The treatment with famoxadone influenced more volatile compounds than the other ones, except for wine from grapes treated with kresoxim-methyl, which was the only wine that showed a big change in its aromatic composition.|For more Food Survey Values (Complete) data for FENHEXAMID (8 total), please visit the HSDB record page.

Occupational exposure to fenhexamid may occur through inhalation and dermal contact with this compound at workplaces where fenhexamid is produced or used. Use and limited monitoring data indicate that the general population may be exposed to fenhexamid via dermal contact with consumer products containing fenhexamid and ingestion of contaminated produce or wine. (SRC)

Rapidly and completely absorbed/excreted (<48 hours) /in rats/; pronounced enterohepatic circulation. Metabolite in bile- glucuronide; major route of excretion/feces (mostly parent); lesser amounts in urine (mostly glucuronide).|At 10 hours, mean dermal absorption /in rats/ was 20% (low dose group). /From table/|The absorption, distribution, metabolism and excretion of [Phenyl-UL-(14)C] KBR 2738 /(pure Fenhexamid)/ in male and female Wistar rats was determined after a single oral low dose of 1 mg/kg, a single oral high dose of 100 mg/kg and 15 repeated low doses of 1 mg/kg/day. (14)C-KBR 2738 was rapidly absorbed from the gastrointestinal (GI) tract in all dose groups. After single and repeated administration of the low dose, the plasma concentration peaked within 5 to 10 minutes. After administration of the high dose, the maximum was detected 40 to 90 minutes post-dosing. The absorption of the test compound was shown to be almost complete in a bile-cannulation experiment, as more than 97% of the administered dose was absorbed from the GI tract 48 hours after intraduodenal administration. These results are indicative of a pronounced first pass effect and enterohepatic circulation. Tissue residues declined rapidly and after 48 hours the total radioactivity residue in the body, excluding the GI tract, was <0.3% of the administered dose in all dose groups. Liver and kidney were the organs with the highest concentrations of radioactivity in all dose groups. There was no evidence of bioaccumulation. Excretion was rapid and almost complete with feces as the major route of excretion. Approximately 62-81% of the recovered radioactivity was found in feces, and 15-36% in urine within 48 hours post-dosing. More than 90% of the recovered radioactivity was eliminated with bile in the bile cannulation experiment. Only 0.02% of the administered radioactivity was recovered in exhaled air. Radioactive residues in rat bodies (excluding GI tract) were significantly lower in females after a single high dose. There was significantly higher renal excretion for females in comparison with males after 15 repeated low doses. In both sexes renal excretion was significantly higher after a single low dose when compared with a single high dose.|In a 56-day bioavailability study, KBR 2738 (95.4% purity) was administered to 10/sex/dose SPF-bred Wistar rats in their diet (1% peanut oil excipient) at dose levels of 0, 1000, 5000, 10,000, 15,000 or 20,000 ppm (57.5, 284.7, 575.7, 943.8, and 1217.1 mg/kg/day for males and 78.0, 407.1, 896.5, 1492.5 and 1896.7 mg/kg for females) for 56 days. The purpose of this study was to determine whether or not there was saturation of intestinal absorption of KBR 2738 when given in the diet at concentrations of 10,000 to 20,000 ppm. Therefore, KBR 2738 levels were determined in plasma and urine samples after a treatment period of 3 or 4 weeks, when steady state conditions were expected. Results showed that plasma samples taken from 20,000 ppm rats had KBR 2738 levels below the limit of detection. Urine samples showed measurable excretion of conjugated KBR 2738 indicating intestinal absorption in the dose range examined. Males had a maximum excretion rate at 15,000 ppm indicating a saturation of intestinal absorption between 15,000 and 20,000 ppm. Urine excretion in females was somewhat lower than in males, at concentrations of 10,000 ppm and above. The highest value was determined at 20,000 ppm suggesting that saturation in intestinal absorption was not achieved with this dose level in females.

Rapidly and completely absorbed/excreted (<48 hours) /in rats/; pronounced enterohepatic circulation. Metabolite in bile- glucuronide; major route of excretion/feces (mostly parent); lesser amounts in urine (mostly glucuronide).|Metabolite characterization studies /in rats/ showed that the main component detected in excreta was the unchanged parent compound which accounted for 62-75% of the dose independent of the dosing regime and sex. Metabolite 1, the glucuronic acid conjugate of the parent compound, ranged from 4 to 23% of the dose. Metabolite fractions 2 and 3 accounted for up to 3 and 7% of the dose, respectively. The proposed major pathway for biotransformation is via conjugation of the aromatic hydroxyl group with glucuronic acid. Prior to fecal excretion, hydrolysis in the intestine converts the conjugate back to the parent compound giving rise to enterohepatic circulation. This demonstrates that, although the main residues in the feces are due to unchanged parent compound, the absorption rate is close to 100% of the given dose. Furthermore, hydroxylation took place in the positions 2, 3 and 4 of the cyclohexyl ring followed by formation of glucuronic acid and sulfate conjugates of these hydroxylated metabolites. Identification of radioactive residues ranged from 88 to 99% and was independent of dose and sex.

Fenhexamid, a recently developed botryticide, is shown here to inhibit sterol biosynthesis. When the fungus Botryotinia fuckeliana was grown in the presence of fenhexamid, the ergosterol content was reduced, and three 3-keto compounds, 4 alpha-methylfecosterone, fecosterone and episterone, accumulated, suggesting an inhibition of the 3-keto reductase involved in C-4 demethylation. Thus, fenhexamid belongs to a new, promising class of sterol biosynthesis inhibitors not previously used in agriculture or in medicine.

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/|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 ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in 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 an IV with D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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 (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/ENDOCRINE MODULATION/ Fenhexamid and fludioxonil are antifungal agents used in agricultural applications, which are present at measurable amounts in fruits and vegetables. Fenhexamid and fludioxonil showed endocrine disruptor activity as antiandrogens in an androgen receptor reporter assay in engineered human breast cancer cells. Little is known about how environmental chemicals regulate microRNA (miRNA) expression. This study examined the effect of fenhexamid and fludioxonil on the expression of the oncomiR miR-21 in MCF-7, T47D, and MDA-MB-231 human breast cancer cells and downstream targets of miR-21 in MCF-7 cells. Fenhexamid and fludioxonil stimulated miR-21 expression in a concentration-dependent manner and reduced the expression of miR-21 target Pdcd4 protein. Antisense to miR-21 blocked the increase in Pdcd4 protein by fenhexamid and fludioxonil. Fenhexamid and fludioxonil reduced miR-125b and miR-181a, demonstrating specificity of miRNA regulation. Induction of miR-21 was inhibited by the estrogen receptor antagonist fulvestrant, by androgen receptor antagonist bicalutamide, by actinomycin D and cycloheximide, and by inhibitors of the mitogen-activated protein kinases and phosphoinositide 3-kinase pathways. Fenhexamid activation was inhibited by the arylhydrocarbon receptor antagonist alpha-napthoflavone. Fenhexamid and fludioxonil did not affect dihydrotestosterone-induced miR-21 expression. Fludioxonil, but not fenhexamid, inhibited MCF-7 cell viability, and both inhibited estradiol-induced cell proliferation and reduced cell motility. Together these data indicate that fenhexamid and fludioxonil use similar and distinct mechanisms to increase miR-21 expression with downstream antiestrogenic activity.|/ALTERNATIVE and IN VITRO TESTS/ ... We used estimated human exposure data to select pesticides to test for antiandrogenic activity, focusing on highest use pesticides. We used European databases to select 134 candidate pesticides based on highest exposure, followed by a filtering step according to known or predicted receptor-mediated antiandrogenic potency, based on a previously published quantitative structure-activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists ("active"), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists ("inactive"), and 13 had unknown activity, which were "out of domain" and therefore could not be classified with the QSAR ("unknown"). All 14 pesticides with previous evidence of AR antagonism were confirmed as antiandrogenic in our assay, and 9 previously untested pesticides were identified as antiandrogenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, lambda-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds as androgenic ...|/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. In contrast, fenhexamid did not promote ovarian tumor formation in this mouse model. 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.|/ALTERNATIVE and IN VITRO TESTS/ ... In this study, the effects of two fungicides, fenhexamid and myclobutanil were investigated individually and in combination on two human cell lines, SH-SY5Y neuronal cells and U-251 MG glial cells. After 48 hr of incubation with increasing concentrations of pesticides ranging from 1 to 1000 uM, gene expression profiles were studied in addition to toxicity end points, including cell viability, mitochondrial depolarization as well as cellular glutathione maintenance. There were no significant differences between the susceptibility of the two cell lines in terms of cell viability assessment or mitochondrial membrane potential, when agents were administered either individually or in combination. By contrast, in the presence of the fungicides, the SH-SY5Y cells showed significantly greater susceptibility to oxidative stress in terms of total thiol depletion in comparison with the astrocytic cells. Treatment with the two pesticides led to significant changes in the cell lines' expression of several genes which regulate cell cycle control and growth (RB1, TIMP1) as well as responses to DNA attrition (ATM and CDA25A) and control of apoptosis (FAS). There was no evidence in this study that the combination of fenhexamid and myclobutanil was significantly more toxic than individual exposure, although gene expression changes suggested there may be differences in the sub-lethal response of both cell lines to both individual and combined exposure.|/ALTERNATIVE and IN VITRO TESTS/ ... The pesticide Switch was applied to grape vines, and the maximum residue concentration of its active ingredients was quantified. 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 (EC50 s 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.

fenhexamid

Fenhexamid Technical (Arysta Lifescience North America, LLC): Active ingredient: Fenhexamid 98.6%.|Captevate 68 WDG Fungicide (Arysta Lifescience North America, LLC): Active ingredient: Captan 53.6%; Fenhexamid 14.3%.|Elevate 50 WDG Fungicide (Arysta Lifescience North America, LLC): Active ingredient: Fenhexamid 50.0%.|Suspension concentrate, water dispersible granule, wettable powder.|For more Formulations/Preparations (Complete) data for FENHEXAMID (6 total), please visit the HSDB record page.

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

An analytic procedure was developed for the determination of the fungicides ametoctradin, boscalid, cyazofamid, dimethomorph, fenhexamid, kresoxim-methyl, mepanipyrim, metrafenone, and pyraclostrobin in grape and wine. A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) procedure was used for the extraction. Analysis of the extract was performed by LC/triple quadrupole-MS/MS. A Poroshell 120 EC-C18 column was used with a programmed gradient mobile phase consisting of (A) acetonitrile containing 0.1% formic acid and (B) water containing 0.1% formic acid and 2 mM ammonium formate. The acceptance criteria for the method were those proposed in the SANCO guide. The method was linear for the range of concentration studied (5-100 ug/L), and R2 values were higher than 0.998 and RSD values below 18%. Recovery was over 73.2% in grape and 76.7% in wines, and there was no case of more than 100% recovery. The recovery RSDs in reproducibility conditions were below 17.13% in grape and 15.6% in wines.

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

Fenhexamid has known environmental transformation products that include Fenhexamid M20, [C-O-C] dimer and Fenhexamid M24.