Tembotrione

440.814

440.82

608-879-8

WA5UZ202KS

DTXSID5047037

Beige powder

103

-1.37 (pH 9.0, 23 deg C)

1.56 at 20 deg C

123 deg C

612.86ºC at 760 mmHg

324.446ºC

1.519

In water, 0.22 (pH 4), 28.3 (pH 7) (both in g/L, 20 deg C)

Safe Storage of Pesticides. Always store pesticides in their original containers, complete with labels that list ingredients, directions for use, and first aid steps in case of accidental poisoning. Never store pesticides in cabinets with or near food, animal feed, or medical supplies. Do not store pesticides in places where flooding is possible or in places where they might spill or leak into wells, drains, ground water, or surface water. /Residential users/

1.1X10-5 mPa (20 deg C) /SRC: 8.3X10-11mm Hg at 20 deg C/

Henry's Law constant = 1.7X10-15 atm-cu m/mol at 20 °C (est)

pKa = 3.2

UN 3077 9 / PGIII

3

43-50/53

36/37-60-61

Xn,N

P280

H317-H400

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.|Wastes resulting from the use of this product may be disposed of on site or at an approved waste disposal facility. Improper disposal of excess pesticide, spray mixture, or rinsate is a violation of Federal law. For questions about proper disposal, contact your state pesticide and environmental control agency. /Laudis Herbicide/|Safe Disposal of Pesticides. The best way to dispose of small amounts of excess pesticides is to use them - apply them - according to the directions on the label. If you cannot use them, ask your neighbors whether they have a similar pest control problem and can use them. If all of the remaining pesticide cannot be properly used, check with your local solid waste management authority, environmental agency, or health department to find out whether your community has a household hazardous waste collection program or a similar program for getting rid of unwanted, leftover pesticides. These authorities can also inform you of any local requirements for pesticide waste disposal. /Residential users/|Safe Disposal of Pesticides. An empty pesticide container can be as hazardous as a full one because of residues left inside. Never reuse such a container. When empty, a pesticide container should be rinsed carefully three times and the rinsewater thoroughly drained back onto the sprayer or the container previously used to mix the pesticide. Use the rinsewater as a pesticide, following label directions. Replace the cap or closure securely. Dispose of the container according to label instructions. Do not puncture or burn a pressurized container like an aerosol - it could explode. Many communities have programs to recycle household waste such as empty bottles and cans. Do not recycle any pesticide containers, however, unless the recycling program specifically accepts pesticide containers and you follow the program's instructions for preparing the empty containers for collection. /Residential users/

|Warning|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P201, P202, P260, P261, P272, P273, P280, P281, P302+P352, P308+P313, P314, P321, P333+P313, P363, P391, P405, and P501|H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P273, P280, P302+P352, P321, P333+P313, P363, P391, and P501|Aggregated GHS information provided by 211 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Applicators and other handlers must wear: Long-sleeved shirt and long pants, socks, shoes and chemical-resistant gloves made of any waterproof material such as natural rubber . 14 mils. Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for washables exist, use detergent and hot water. Keep and wash PPE separately from other laundry. /Laudis Herbicide/|Engineering control statement: When handlers use closed systems, such as enclosed cabs, in a manner that meets the requirements listed in the Worker Protection Standard (WPS) for agricultural pesticides [(40 CFR part 170.240(d)(4- 6)], the handler PPE requirements may be reduced or modified as specified in the WPS. /Laudis Herbicide/|PPE /personal protective equipment/ that is required for early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated such as plants, soil or water, is coveralls over long-sleeved shirt and long pants, socks and shoes and chemical-resistant gloves made of any waterproof material. /Laudis Herbicide/

Suitable Extinguishing Media: Water spray, foam, carbon dioxide (CO2), dry posder. /Laudis Herbicide/|Fire Fighting Instructions: Keep out of smoke. Fight fire from upwind position. Cool closed containers/ tanks exposed to fire with water spray. Do not allow run-off from fire fighting to enter drains or water courses. Firefighters should wear NIOSH approved self-contained breathing apparatus and full protective clothing. /Laudis Herbicide/

Isolate hazard area. Keep unauthorized people away. Use personal protective equipment. Avoid contact with spilled product or contaminated surfaces. /Laudis Herbicide/|Soak up with inert absorbent material (e.g. sand, silica gel, acid binder, universal binder). Keep in suitable, closed containers for disposal. Clean contaminated floors and objects thoroughly, observing environmental regulations. /Laudis Herbicide/|If a spill occurs, clean it up promptly. Don't wash it away. Instead, sprinkle the spill with sawdust, vermiculite, or kitty litter. Sweep it into a plastic garbage bag, and dispose of it as directed on the pesticide product label./Residential users/|After Applying a Pesticide, Indoors or Outdoors. To remove pesticide residues, use a bucket to rinse tools or equipment three times, including any containers or utensils that you used when mixing the pesticide. Then pour the rinsewater into the pesticide sprayer and reuse the solution by applying it according to the pesticide product label directions. After applying any pesticide wash your hands and any other parts of your body that may have come in contact with the pesticide..To prevent tracking pesticides inside, remove or rinse your boots or shoes before entering your home. Wash any clothes that have been exposed to a lot of pesticide separately from your regular wash. /Residential users/

Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR part 170. /Laudis Herbicide/|Do not apply this product in a way that will contact workers or other persons, either directly or through drift. Only protected handlers may be in the same area during application. For any requirements specific to your State or Tribe, consult the agency responsible for pesticides. /Laudis Herbicide/|Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of 12 hours. PPE that is required for early entry to treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated such as plants, soil or water, is coveralls over long-sleeved shirt and long pants, socks and shoes and chemical-resistant gloves made of any waterproof material. /Laudis Herbicide/|A level, well-maintained vegetative buffer strip between areas to which this product is applied and surface water features such as ponds, streams and springs will reduce the potential for contamination of water from runoff. Runoff of this product will be reduced by avoiding applications when rainfall is forecasted to occur within 48 hours. /Laudis Herbicide/|For more Preventive Measures (Complete) data for Tembotrione (16 total), please visit the HSDB record page.

Causes moderate eye irritation. /Laudis Herbicide/

In a subchronic toxicity study, two groups of 10 male and 10 female Wistar rats (Groups 1 and 3) were fed basal diet while two groups of 10 male and 10 female Wistar rats (Groups 2 and 4) were fed diets supplemented with 20,000 ppm (2%) L-tyrosine (Lot/batch No. 078H06822 and 123K0376; purity >99%) for 28 days. (Tyrosine supplementation was approximately three to five times the normal dietary intake.) Rats in Groups 3 and 4 received 10 ug/kg bw/day 2-(2-nitro-4-trifluoromethyl-benzoyl)-1,3- cyclohexanedione (NTBC), an inhibitor of 4-hydroxyphenylpyruvate dioxygenase, daily by gavage. The study was done to determine the effects of increased plasma tyrosine to the eye, kidney, liver, pancreas, and thyroid of rats. One Group 3 female rat died during the study, but its death was unrelated to treatment. No treatment-related effects were noted on body weight, body weight gain, or food consumption. Nine of ten male and 3/10 female rats in Group 4 (2% tyrosine + 10 ug/kg bw/day NTBC) developed white areas on the eye between Days 23-26 on one or more occasions. Following opthalmoscopic examination prior to sacrifice, 9/10 male rats in Group 4 had developed corneal edema and all male and 3/10 female rats had developed 'snow flake' corneal opacities. In addition, three Group 4 male rats had developed congestive iritis. None of the male and female rats in Group 2 (2% tyrosine) or Group 3 (10 ug/kg bw/day NTBC) developed ocular abnormalities. The average plasma tyrosine concentration of Group 3 and Group 4 male and female rats was markedly increased 18-23 fold on the day of sacrifice, while plasma tyrosine was unaffected by treatment in Group 2 rats. Although the liver to body weight ratio of male and female rats in Group 4 was statistically increased, no histological correlates were found. No other treatment-related effects were noted on organ weight. Microscopic treatment-related effects were found in the pancreas, thyroid, and eyes of Group 4 rats. The incidences of focal/multifocal acinar atrophy/ fibrosis and/or acinar degeneration/apoptosis, as well as the incidence of focal/multifocal or diffuse inflammation were increased in the pancreas of Group 4 male and female rats. In the thyroid, an increased incidence of colloid alteration was found in male, but not female rats of Group 4 rats. In the eye, the incidence of unilateral and bilateral keratitis was markedly increased in male rats while minimal keratitis was found in 1/10 Group 4 female rats. No treatment-related effects were noted in male or female Group 2 and Group 3 rats.|In a subchronic toxicity study, two groups of five male and five female Wistar rats (Groups 1 and 3) were fed basal diet while two groups of five male and five female Wistar rats (Groups 2 and 4) were fed diets supplemented with 20,000 ppm (2%) L-tyrosine (Lot No. 114K0375, purity 98.9%) for 28 days. (The tyrosine supplementation was approximately three to five times the normal dietary intake.) Rats in Groups 3 and 4 received 10 ug/kg bw/day 2-(2-nitro-4-trifluoromethyl-benzoyl)-1,3-cyclohexanedione (NTBC), an inhibitor of 4-hydroxyphenylpyruvate dioxygenase, daily by gavage. The study was done to determine the effects of increased plasma tyrosine concentration to the eye, kidney, liver, pancreas, and thyroid of rats No toxicologically significant effects on body weight or food intake were noted. All male and 1/5 female rats in Group 4 (2% dietary tyrosine + 10 ug/kg bw/day NTBC by gavage) developed white areas on the eye beginning on Day 24 through the end of the study. In addition, the eyes of 4/5 Group 4 male rats were half-closed beginning on Day 22 through the remainder of the study. The average plasma tyrosine concentration of Group 4 male and female rats increased with time from approximately three to five fold on Day 2 to a 24-fold increase in males and 18-fold increase in females by Day 21. Treatment with 10 ug/kg bw/day NTBC alone had little effect on plasma tyrosine in male and female rats until Day 29/30 when it was increased 3-fold and 5.8- fold in males and females, respectively. After an overnight fast, plasma tyrosine was increased in NTBC-treated rats 18-fold in males and 27-fold in females. Treatment with 2% dietary tyrosine alone induced a < 5-fold increase of plasma tyrosine in male and female rats that decreased with fasting. There were no effects on the absolute or relative liver, brain, kidney, or thyroid weights of tyrosine-, NTBC, or tyrosine/NTBC-treated rats. Macroscopically, minimal to slight bilateral ocular opacity was observed in all male and 1/5 female rats treated with tyrosine/NTBC and microscopically, treatment-related effects were found in the eye, pancreas, and thyroid. Bilateral keratitis was observed in the eyes of all males and one female and diffuse interstitial mixed cell inflammation was noted in the pancreas of two males and one female rat treated with tyrosine/ NTBC. The pancreatic changes were associated with an increased incidence of focal/multifocal acinar degeneration and apoptosis. Minimal to slight thyroid colloid alteration was noted in 3/5 Group 4 male rats. No treatment-related effects, to the eye, pancreas, or thyroid, were noted in rats treated only with tyrosine or NTBC. This study demonstrated a prolonged threshold tyrosine concentration exists in rats, above which macroscopic and/or microscopic effects occur to the eye, pancreas, and thyroid. These effects occurred when rats were fed diets containing three to five times the normal dietary intake of tyrosine while one of the tyrosine catabolizing enzymes was inhibited.

LC50 Rat inhalation > 5.03 mg/L/4 hr|LD50 Rat dermal >2,000 mg/kg|LD50 Rat oral >2,000 mg/kg

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

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 14(SRC), determined from a log Kow of -1.09(2) and a regression-derived equation(3), indicates that tembotrione is expected to have very high mobility in soil(SRC). Volatilization of tembotrione from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.7X10-15 atm-cu m/mole(SRC), based upon its vapor pressure, 8.3X10-11 mm Hg(4), and water solubility, 28,300 mg/L(4). Tembotrione is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(4). Reported biodegradation half-lives of 4 to 56 days in soil under aerobic conditions(4) suggests that biodegradation is an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 14(SRC), determined from a log Kow of -1.09(2) and a regression-derived equation(3), indicates that tembotrione 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 1.7X10-15 atm-cu m/mole(SRC), derived from its vapor pressure, 8.3X10-11 mm Hg(5), and water solubility, 28,300 mg/L(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Tembotrione is stable to hydrolysis at environmental pH(2). Reported biodegradation half-lives of 4 to 56 days in soil under aerobic conditions(5) suggests 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), tembotrione, which has a vapor pressure of 8.3X10-11 mm Hg at 20 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase tembotrione may be removed from the air by wet or dry deposition(SRC). Tembotrione contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

Tembotrioine is stable to hydrolysis in the environment at environmental pH of 5 to 9(1,2). Tembotrione does contains chromophores that absorb at wavelengths >290 nm(2), and therefore may be susceptible to direct photolysis by sunlight(SRC). The compound is susceptible to photolysis in soil and water(1).

An estimated BCF of 3 was calculated in fish for tembotrione(SRC), using a log Kow of -1.09(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of tembotrione is estimated as 14(SRC), using a log Kow of -1.09(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that tembotrione is expected to have very high mobility in soil. However, the relatively rapid rate of biodegradation may attenuate this process(1).

The Henry's Law constant for tembotrione is estimated as 1.7X10-15 atm-cu m/mole(SRC) derived from its vapor pressure, 8.3X10-11 mm Hg(1), and water solubility, 28,300 mg/L(1). This Henry's Law constant indicates that tembotrione is expected to be essentially nonvolatile from water surfaces(2). Tembotrione is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

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

In a series of metabolism studies, [phenyl-U-14C]-AE 0172747 (/tembotrione/ Batch # Z 31053-4; radiochemical purity 99.5%) or [cyclohexyl-UL-14C]-AE 0172747 (/tembotrione/ Batch #s BECH 1517 or BECH 1523; radiochemical purity >98%) in PEG 200 was administered by oral gavage to groups of four Wistar rats/sex/dose at doses of 5 or 1000 mg/kg. The concentration time-courses of radioactivity in blood and plasma were calculated, the concentrations of radioactivity in tissues and excreta were determined, and metabolites were identified and quantified in the urine and feces. The test compound was absorbed rapidly, as radioactivity was detected in the blood and plasma of all animals at the first time point measured (30 min post-dosing) for both radiolabeled forms. Males had higher mean blood and plasma maximum concentrations (Cmax) than females. Also, males displayed higher AUC values than females in both blood and plasma at both doses. In both sexes, the AUC for both blood and plasma indicated a disproportionally higher mean systemic exposure at 1000 mg/kg than at 5 mg/kg (>200-fold) that was apparently due to a saturation of the initial elimination/biotransformation processes, resulting in a slower initial elimination phase. Other blood and plasma parameters were generally similar across doses and radiolabeled forms. In the 5 mg/kg animals dosed with either radiolabeled form, the liver and kidneys contained the highest mean levels of radioactivity. No other tissue exceeded 0.12% of the administered dose. In the 1000 mg/kg animals dosed with [phenyl-U-14C]-AE 0172747, the skin/fur and carcass contained the highest mean levels of radioactivity. No other tissue exceeded 0.06% of the administered dose. In the 5 mg/kg [phenyl-U-14C] males, the highest concentrations of radioactivity were detected in the, liver, kidneys, skin, and carcass. In the 5 mg/kg [phenyl-U-14C] females and [cyclohexyl- UL-14C] males and females, the highest concentrations of radioactivity were detected in the liver, kidneys, skin, and carcass. In the 1000 mg/kg [phenyl-U-14C] males and females, the highest concentrations of radioactivity were detected in the skin, liver, kidneys, stomach (and contents), and carcass and there was no evidence of bioaccumulation. Total recoveries ranged from 96.3-102.7% of the administered doses, with no differences observed between dose levels or position of the radiolabel. Substantial sex differences were observed in the routes of excretion. At 5 mg/kg, the majority of the radioactivity was recovered in the feces of the males, while in the females, the majority of the radioactivity was recovered in the urine. At this dose, the majority of the radioactivity in the urine was recovered during the first 6 h, while the majority of radioactivity in the feces was recovered during the first 24 h. Tissues and cage wash each accounted for <5.1%. Sex differences in the routes of excretion were also observed in the 1000 mg/kg group. In the males, approximately equal proportions of radioactivity were recovered in the feces and urine, while in the females, the majority of the radioactivity was recovered in the urine. At this dose, the majority of the radioactivity in the urine was recovered during the first 24 h, while the majority of radioactivity in the feces was recovered during the first 48 h. Tissues and cage wash each accounted for <10.1%. The test compound was extensively metabolized. The majority of radioactivity in urine and fecal extract samples was present as parent and up to eleven metabolites. Metabolic profiles were qualitatively similar for both radiolabeled forms; however, profiles for the high and low doses were dissimilar, and major differences were noted between sexes. The major route of metabolism was found to be hydroxylation (oxidative pathway) of the cyclohexyl ring of the molecule. In excreta, parent and identified compounds accounted for 68.1-93.2% of the administered dose, while unidentified metabolites accounted for 2.5-13.8% of the administered dose. The total administered dose accounted for in the excreta was 82.3-104.9%. Parent compound accounted for 1.9-59.9% of the total radioactivity eliminated, and was found in greatest quantity in the urine of the females (44.1-59.4%). Low dose males eliminated small amounts of parent (1.9-3.0%), while high dose males eliminated moderate amounts (33.8%). The metabolite found in the greatest quantity at both doses was 4-hydroxy-AE 0172747, with low dose males eliminating more than low dose females. High dose males and females eliminated approximately equal amounts. The only other metabolite found at >5% of the administered dose was 5-hydroxy-AE 0172747. Males excreted greater quantities than females.|Rat metabolism data indicate that tembotrione is well absorbed. More than 96.3% of the administered dose was recovered in urine and feces in 24 hours. Sex differences were observed in the routes of excretion. The primary routes of elimination were the urine in females and the urine and feces in males. At the low dose, males excreted up to 24.4% and 70.4%; females up to 79.1% and 20% of the administered dose in the urine and feces, respectively. At the high dose, females excreted up to 63.7% and 28.5%; males up to 44.2 % and 49.1% of the dose in the urine and feces, respectively. The highest mean levels of radioactivity were extracted from the liver (1.7-3.5%) and kidneys (0.14-0.26%) at the low dose. At the high dose, the mean levels of radioactivity were extracted from the skin/fur (0.22-0.33%) and carcass. The highest concentrations of radioactivity were found in the skin followed by the liver, kidneys, stomach (and contents) and carcass. Males had higher mean blood plasma maximum concentrations (Cmax) and AUC values than females. In both sexes, the area under the AUC for both blood and plasma indicated a disproportionally higher mean systemic exposure at 1000 mg/kg than at 5 mg/kg (>200-fold) that was apparently due to a saturation of the initial elimination/biotransformation processes, resulting in a slower initial elimination phase.|In an in vivo dermal penetration study, [phenyl- UL-14C]-AE 0172747 (/tembotrione/ >98% radiochemical purity; batch # BECH 0857) in a suspension concentrate formulation containing 420 g/L AE 0172747 and 210 g/L Isoxadifen-ethyl was applied to four male Wistar (Rj:WI[IOPS HAN]) rats/group on 2 x 6 sq cm skin areas at dose levels of 0, 6.6, 66, or 660 ug/sq cm. Exposure times were 0.5, 1, 2, 4, 10, and 24 hr for each dose. At the end of each exposure period, the skin was swabbed, and urine, feces, treated skin, cardiac blood, kidneys, liver, brain, spleen, and residual carcass were collected and analyzed for radioactivity. Recovery of the applied dose was 90.8-98.7% of the administered dose. The distribution profile of radioactivity was qualitatively similar between the dose groups. The majority of the administered dose was recovered from the skin swabs, accounting for 76-93% of the administered doses. A total of 76-94% of the applied doses was not absorbed. A general trend of increasing dermal absorption with increasing time was observed, and the amount of radioactivity found in the treated skin generally increased with decreasing dose level. Estimates of dermal absorption were based on the sum of the treated skin + the total directly absorbed (urine + feces + cage wash + carcass + brain + spleen + liver + kidneys + blood + non-treated skin + surrounding skin). Dermal absorption was 8.3-14.9% (low), 4.8-12.8% (intermediate), and 1.7- 4.8% (high) of the applied doses. The amount of dermal absorption was not proportional to dose. All treatments (dose levels applied) were for exposure periods for up to 24 hr. The most conservative value for risk assessment is a dermal-absorption of 15% observed at the low dose (6.6 ug/sq cm) at 4 hr after application. This value should be considered to protect commercial applicators.

The parent molecule and 11 metabolites were identified & isolated from urine and feces /of the rat/. Metabolic profiles were qualitatively similar for both radiolabeled forms; however, profiles for the high and low doses were not the same and differences were noted between sexes. Females excreted the greatest quantity of the parent molecule in urine (44.1-59.4%). While low and high dose males eliminated 1.9-3.0% and 33.8%, respectively, in the urine. The metabolites found in the greatest quantities were 4-hydroxy-tembotrione and 5-hydroxy-tembotrione. Other identified metabolites found at <5% were the 4,5-dihydroxy, benzylic alcohol, dihydroxybezophenone, 4-hydroxy-benzylic alcohol, and ketohydroxy-hexanoic acid ([cyclohexyl-UL-14C] only). Males excreted greater quantities of both major metabolites than females; except, at the high dose where 4-hydroxy-tembotrione was eliminated in approximately equal amounts in both sexes. The primary step in the metabolism of tembotrione is the hydroxylation (oxidative pathway) of the cyclohexyl ring of the molecule.|In a series of metabolism studies (MRIDs 46695726, 46695727, 46695728, and 46695729), [phenyl-U-14C]-AE 0172747 (Batch # Z 31053-4; radiochemical purity 99.5%) or [cyclohexyl-UL-14C]-AE 0172747 (Batch #s BECH 1517 or BECH 1523; radiochemical purity >98%) in PEG 200 was administered by oral gavage to groups of four Wistar rats/sex/dose at doses of 5 or 1000 mg/kg. The concentration time-courses of radioactivity in blood and plasma were calculated, the concentrations of radioactivity in tissues and excreta were determined, and metabolites were identified and quantified in the urine and feces. The test compound was absorbed rapidly, as radioactivity was detected in the blood and plasma of all animals at the first time point measured (30 min post-dosing) for both radiolabeled forms. Males had higher mean blood and plasma maximum concentrations (Cmax) than females. Also, males displayed higher AUC values than females in both blood and plasma at both doses. In both sexes, the AUC for both blood and plasma indicated a disproportionally higher mean systemic exposure at 1000 mg/kg than at 5 mg/kg (>200-fold) that was apparently due to a saturation of the initial elimination/biotransformation processes, resulting in a slower initial elimination phase. Other blood and plasma parameters were generally similar across doses and radiolabeled forms. In the 5 mg/kg animals dosed with either radiolabeled form, the liver and kidneys contained the highest mean levels of radioactivity. No other tissue exceeded 0.12% of the administered dose. In the 1000 mg/kg animals dosed with [phenyl-U-14C]-AE 0172747, the skin/fur and carcass contained the highest mean levels of radioactivity. No other tissue exceeded 0.06% of the administered dose. In the 5 mg/kg [phenyl-U-14C] males, the highest concentrations of radioactivity were detected in the, liver, kidneys, skin, and carcass. In the 5 mg/kg [phenyl-U-14C] females and [cyclohexyl- UL-14C] males and females, the highest concentrations of radioactivity were detected in the liver, kidneys, skin, and carcass. In the 1000 mg/kg [phenyl-U-14C] males and females, the highest concentrations of radioactivity were detected in the skin, liver, kidneys, stomach (and contents), and carcass and there was no evidence of bioaccumulation. Total recoveries ranged from 96.3-102.7% of the administered doses, with no differences observed between dose levels or position of the radiolabel. Substantial sex differences were observed in the routes of excretion. At 5 mg/kg, the majority of the radioactivity was recovered in the feces of the males, while in the females, the majority of the radioactivity was recovered in the urine. At this dose, the majority of the radioactivity in the urine was recovered during the first 6 h, while the majority of radioactivity in the feces was recovered during the first 24 h. Tissues and cage wash each accounted for <5.1%. Sex differences in the routes of excretion were also observed in the 1000 mg/kg group. In the males, approximately equal proportions of radioactivity were recovered in the feces and urine, while in the females, the majority of the radioactivity was recovered in the urine. At this dose, the majority of the radioactivity in the urine was recovered during the first 24 h, while the majority of radioactivity in the feces was recovered during the first 48 h. Tissues and cage wash each accounted for <10.1%. The test compound was extensively metabolized. The majority of radioactivity in urine and fecal extract samples was present as parent and up to eleven metabolites. Metabolic profiles were qualitatively similar for both radiolabeled forms; however, profiles for the high and low doses were dissimilar, and major differences were noted between sexes. The major route of metabolism was found to be hydroxylation (oxidative pathway) of the cyclohexyl ring of the molecule. In excreta, parent and identified compounds accounted for 68.1-93.2% of the administered dose, while unidentified metabolites accounted for 2.5-13.8% of the administered dose. The total administered dose accounted for in the excreta was 82.3-104.9%. Parent compound accounted for 1.9-59.9% of the total radioactivity eliminated, and was found in greatest quantity in the urine of the females (44.1-59.4%). Low dose males eliminated small amounts of parent (1.9-3.0%), while high dose males eliminated moderate amounts (33.8%). The metabolite found in the greatest quantity at both doses was 4-hydroxy-AE 0172747, with low dose males eliminating more than low dose females. High dose males and females eliminated approximately equal amounts. The only other metabolite found at >5% of the administered dose was 5-hydroxy-AE 0172747. Males excreted greater quantities than females.|Rat metabolism data indicate that tembotrione is well absorbed. More than 96% of the administered dose was recovered in urine and feces in 24 hours. Minor sex differences were observed in the routes of excretion. The primary routes of elimination were the urine in females and the urine and feces in males. The highest concentrations of radioactivity were found in the skin followed by the liver, kidneys, stomach (and contents) and carcass. Males had higher mean blood, plasma maximum concentrations (Cmax) and area under the concentration-time curves (AUC) values than females. The primary step in the metabolism of tembotrione is the hydroxylation (oxidative pathway) of the cyclohexyl ring of the molecule.

Tembotrione is a broad-spectrum early and mid-postemergence herbicide that belongs to the triketone class of herbicides. It acts by inhibiting 4-hydroxyphenylpyruvate dioxygenase (HPPD), which leads to chlorophyll destruction by photooxidation and causes bleaching of emerging foliar tissue. In mammals, HPPD is a key enzyme in the catabolism of tyrosine. It catalyzes the conversion of 4-hydroxyphenylpyruvate (HPP) to homogentisate. Inhibition of HPPD leads to a reconversion of HPP to tyrosine and a consequent increase in blood tyrosine concentrations (tyrosinemia).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/GENOTOXICITY/ In vitro Mammalian Cytogenetics Chromosomal Aberration Assay in Human Lymphocytes: In the first assay, 0, 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5 and 10 mM (equivalent to 0, 35.26, 70.53, 136.65, 278, 551, 1102, 2204 and 4408 ug/mL) with and without metabolic activation (S9). In a second assay, 0, 1.25, 2.5, 5, 7.5 and 10 mM (equivalent to 0, 551, 1102, 2204, 3306 and 4408 ug/mL) with and without metabolic activation. Equivocal because structural aberrations and polyploidy were observed in the absence of excessive cytotoxicity at 3306 ug/mL with metabolic activation. In the first test, up to the limit concentration (4408 ug/mL); no increases were seen; therefore, clastogenicity and polyploidy were not confirmed.

tembotrione

Oil dispersion|Composition: Technical is greater than or equal to 94%.|PREMIX PARTNERS: Terbuthylazine; Thiencarbazone-methyl|AE 0172747 Herbicide (Bayer Cropscience LP.) 34.5% Tembotrione|For more Formulations/Preparations (Complete) data for Tembotrione (6 total), please visit the HSDB record page.

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

Tembotrione has known environmental transformation products that include M1 AE0968400, M2 AE1392936, M3 AE0941989, M6 AE0456148, M7 AE1124336, and Trifluoracetat.