Tolclofos-methyl

301.13

301.13

260-515-3

G42OQL6F5B

DTXSID0034776

White crystals from methanol|Colorless crystals|White cyrstalline solid

3808929029

59.8

4.03

1.4±0.1 g/cm3

79 °C

338.5±52.0 °C at 760 mmHg

>100 °C

1.563

1.10 mg l -1 (25 °C)

2-8°C

1.84 x 10 -3 (Pa 25 °C)

Oral-Rat  LD50: 5000 mg/kg; Oral-Mouse LD50: 3500 mg/kg

Combustible; burning produces toxic chloride; nitrogen oxides and phosphorus oxide fumes

149.82 Ų [M+H]+

Colorless to light brown solid (technical toclofos-methyl)|MP: 78-80 °C. VP: 57 mPa (20 °C)

UN 3077 9 / PGIII

3

43-50/53

22-24/25-61-60-37-24

TF0460000

Xi,N

Storehouse ventilated at low temperature and dry; stored separately from oxidants, alkalis, food additives

Stable under recommended storage conditions.

P273-P280-P501

H317-H410

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.

Incompatible materials: Strong oxidizing agents.

USEPA/Office of Pesticide Programs; Registration Decision for the New Active Ingredient, Tolclofos-methyl, for use as a seed treatment on a variety of vegetable crops and ornamental plants, Docket Number EPA-HQ-OPP-2011-0488 (January 2013)[Available from, as of July 11, 2018: https://iaspub.epa.gov/apex/pesticides/f?p=chemicalsearch:1]

|Warning|H317: May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P273, P280, P302+P352, P321, P333+P313, P363, P391, and P501|H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]|P273, P391, and P501|Danger|H301: Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P264, P270, P280, P281, P301+P310, P302+P352, P307+P311, P308+P313, P312, P314, P321, P322, P330, P361, P363, P405, and P501

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).

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.

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.

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.|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 Tolclofos-methyl (6 total), please visit the HSDB record page.

One male and two female New Zealand white rabbits received 0.1 mL of '50% flowable' tolclofos-methyl in one eye. Slight redness was observed in conjunctiva after application, which disappeared within 24 hr.|Groups of nine male New Zealand white rabbits received 100 mg of either a '50% wettable power' or '10% dust' in one eye; 30 sec after the application, the treated eyes of three animals per group were flushed with 300 mL lukewarm water for 1 min. Slight congestion of the iris was observed 24 hr after application. Slight to moderate hyperemia and slight chemosis and/or discharge in conjunctiva were also observed 1-48 hr after application of the '50% wettable powder' to unwashed eyes. These changes had disappeared by 72 hr after application in all animals. No ocular lesions were found in the washed eyes. The irritation potency of this formulation was judged to be mild. Slight conjunctival hyperemia and/or chemosis were observed in animals with unwashed eyes and in one with washed eyes 1-24 hr after application of the '10% dust'. There were no other signs of irritation at any time. The formulation was classified as minimally irritating to eyes.|Each of eight male albino Japanese rabbits received 50 mg of tolclofos-methyl (purity, 97%) in one eye. Five minutes after the application, the treated eyes of five animals were flushed with 300 mL saline for 2 min. The treated eyes of the remaining animals were similarly flushed 24 hr after treatment. There were no corneal, conjunctival or iridal effects up to seven days after treatment.|Two male and one female New Zealand white rabbits received 0.5 mL of '50% flowable' tolclofos-methyl on 1 sq inch (6.5 sq cm) of clipped dorsal intact or abraded skin for 4 hr under an occlusive dressing. No irritation was observed.|Groups of six male New Zealand white rabbits received 500 mg of either a '50% wettable powder' or '10% dust' moistened with saline on 1-sq inch (6.5-sq cm) sites on the clipped dorsal intact or abraded skin for 24 hr under an occlusive dressing. No irritation, such as erythema and edema, was observed.|Six male albino Japanese rabbits received 500 mg of tolclofos-methyl (purity, 97%) on clipped intact or abraded dorsal skin for 4 hr under an occlusive dressing. No signs of irritation were seen at any of the application sites seven days after treatment.

Tolclofos-methyl was detected at 0.003 ug/L in catchment water from a paddy in 1992, monitoring data was collected May-Nov each year from 1990 to 1993(1). Less than 1% of tolclofos-methyl was found in leachate samples collected 3-37 days after standard application to a golf course in Japan(2).

SEDIMENT: Tolclofos-methyl was not detected (detection limit 3 ug/kg) in sediment samples collected May-Sep 1999 from the Shin River, Niigata, Japan(1).

URBAN/SUBURBAN: Tolclofos-methyl was detected at 0.05 ng/cu m in atmospheric samples collected Apr 23-24, 1992 from Kitakyushu City, Japan; it was not detected (detection limit 0.04 ng/cu m) in samples collected Jul 21-22, 1991 in the same city(1).

Tolclofos-methyl was not detected (detection limit 0.01 mg/kg) in raw wool samples from Uruguay(1).

moderately toxic

IDENTIFICATION AND USE: Tolclofos-methyl is agricultural fungicide. HUMAN STUDIES: Tolclofos-methyl induced weak responses in vitro in human estrogenicity assays. Negative results were reported for in vitro unscheduled DNA synthesis assay conducted in human carcinoma cells (HeLa). ANIMAL STUDIES: Tolclofos-methyl was minimally irritating to eyes and not irritating on skin when tested in rabbits. It was not a skin sensitizer when tested in guinea pigs. After acute exposure of rats, mice, and dogs to tolclofos-methyl, animals showed decreased spontaneous motor activity, dyspnea, piloerection, urinary incontinence and ataxia. Recovery was complete by day 10. Brain cholinesterase activity was lower 16 days after treatment in dogs given 1000 mg/kg bw than in animals given lower doses. In dogs at 2000 ppm, plasma cholinesterase activity was decreased by 19-26% in females throughout the study, but no significant decreases were seen in erythrocyte cholinesterase activity in animals of each sex or in plasma cholinesterase activity in males. Brain cholinesterase activity was unaffected by treatment. In rabbits treated dermally erythrocyte cholinesterase activity was lower than in controls in males, but there was no dose-effect relationship. Plasma cholinesterase activity was lower (by 22-29%) than in controls in animals of each sex at 300 and 1000 mg/kg bw per day. The relative weights of the kidneys were increased (by 20%) in females at 1000 mg/kg bw per day. Tolclofos-methyl was not teratogenic in rabbits at doses up to and including 3000 mg/kg bw per day, which was toxic to dams. Tolclofos-methyl was not embryotoxic, fetotoxic or teratogenic in rats at doses up to and including 50 mg/kg bw per day. An in vitro reverse mutation assay with Salmonella typhimurium TA98, 100, 1535, 1537, 1538 was negative with and without metabolic activation. In vivo genotoxicity studies in rats and mice were negative as well.

LD50 Rat (male) oral approximately 5000 mg/kg|LD50 Rat (male) dermal >5000 mg/kg|LD50 Rat (male) ip approximately 5000 mg/kg|LD50 Rat (male) sc >5000 mg/kg|For more Non-Human Toxicity Values (Complete) data for Tolclofos-methyl (18 total), please visit the HSDB record page.

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

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 761-1540(2) indicate that tolclofos-methyl is expected to have low mobility in soil(SRC). Volatilization of tolclofos-methyl from moist soil surfaces is expected(SRC) given an estimated Henry's Law constant of 1.5X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, 4.3X10-4 mm Hg(2), and water solubility, 1.1 mg/L(3). Tolclofos-methyl is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). Tolclofos-methyl had field half-lives of 26-30 days(3). Tolclofos-methyl, applied to soil and exposed to sunlight outdoors from May-Jun had a degradation half-life of 1-2 days(4).|AQUATIC FATE: Based on a classification scheme(1), Koc values of 761-1540(2), indicate that tolclofos-methyl is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.5X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, 4.3X10-4 mm Hg(2), and water solubility, 1.1 mg/L(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 15 hours and 10 days, respectively(SRC). Tolclofos-methyl has a reported hydrolysis half-life of 90 days at pH 6.1(5). According to a classification scheme(6), BCFs of 281-1383 measured in fish(7), suggest bioconcentration in aquatic organisms is high to very high. Tolclofos-methyl is rapidly biodegraded(4).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tolclofos-methyl, which has a vapor pressure of 4.3X10-4 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase tolclofos-methyl 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 6 hours(SRC), calculated from its rate constant of 6.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Tolclofos-methyl 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).

The rate constant for the vapor-phase reaction of tolclofos-methyl with photochemically-produced hydroxyl radicals has been estimated as 6.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Tolclofos-methyl has a reported hydrolysis half-life of 90 days at pH 6.1(2). Tolclofos-methyl does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC). The compound shows high peristence to photolysis in water and on soil(4). Tolclofos-methyl, applied to soil and exposed to sunlight outdoors from May-June had a degradation half-life of 1-2 days, the degradation half-life was 2->15 days in the dark(5). Degradation of tolclofos-methyl in an aqueous/clay suspension exposed to light at >320 nm was believed to occur via hydroxyl radical reaction(5). Indirect photo-oxidation product of tolclofos-methyl on soil was 2,6-dichloro-4-methylphenol(5).

724.44|Tolclofos-methyl BCFs measured in guppy (Lebistes reticulatus), killifish (Oryzias latipes), goldfish (Carassius aurapus) and white cloud mountain fish (Tanichthys albonubes) were 828-1383, 714, 283 and 281, respectively(1). According to a classification scheme(2), these BCF values suggest bioconcentration in aquatic organisms is high to very high(SRC).

5.01e+03 L/kg|The Koc of tolclofos-methyl was reported to range from 761-1540(1). According to a classification scheme(2), this Koc range suggests that tolclofos-methyl is expected to have low mobility in soil(SRC). A Koc of 3620 was reported in sediment(3).|Measured sorption coefficient for tolclofos-methyl in five soils(1).[Table#8530]

The Henry's Law constant for tolclofos-methyl is estimated as 1.5X10-4 atm-cu m/mole(SRC) derived from its vapor pressure, 4.3X10-4 mm Hg(1), and water solubility, 1.1 mg/L(2). This Henry's Law constant indicates that tolclofos-methyl is expected to volatilize from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 15 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 10 days(SRC). Tolclofos-methyl's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Tolclofos-methyl is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

SURFACE WATER: Tolclofos-methyl was not detected (detection limit 0.01 ng/mL) in surface water samples collected Apr 1992-Mar 1993 from seven rivers flowing into Lake Biwa, Japan(1). Tolclofos-methyl was not detected (detection limit 0.01 ug/L) in surface water samples collected May-Sep 1996 from the Shinano River, Niigata Prefecture, Japan(2). Mean concentrations of tolclofos-methyl were reported as <0.01 ng/L in all surface water samples collected 2010-2013 from the Turia and Jucar Rivers in Spain(3).|RAIN: Tolclofos-methyl was detected at <0.010-0.012 ug/L in six of eight rainwater samples taken May-Jul 1997 in South Holland, Netherlands(1). Tolclofos-methyl was detected in 1, 20 and 4% of rainwater samples collected 1999, 2000 and 2001 at locations in Flanders, Belgium at respective annual average concentrations of 0.026, 3.8 and 1.0 ng/L(2).

Tolclofos-methyl was detected in 3 of 122 head lettuce and 1 of 82 potato samples collected Jan 1995 to Dec 1996 in a Danish national commodity survey, it was not detected in grapefruit, lemon, mandarin, clementine, orange, apple, pear, quince, apricot, cherries, peach, nectarine, plum, grape, strawberry, black berry, boysenberry, elderberry, raspberry, rowanberry, bilberry, red and black currant, gooseberry, banana, fig, kiwi, pomegranate, beetroot, carrot, celeriac, horseradish, parsnip, parsley root, radish, garlic, onion, tomato, pepper, eggplant, cucumber, melon, squash, corn, broccoli, cauliflower, Brussel sprout, cabbage, kale, spinach, chive, dill, marjoram, rosemary, thyme, bean, pea, celery, leek, rhubarb, mushroom or sunflower seed(1). Tolclofos-methyl was not detected in 1579 food samples (cabbage, grape leaf, lettuce, melokhia, spinach, watercress, artichoke, beans, cauliflower, cantaloupe, cucumber, eggplant, peas, okra, onion, pepper, squash, tomato, carrot, sweet potato, taro, apple, apricot, banana, dates, fig, grape, guava, lemon, lime, mango, orange, peach, pear, plum, pomegranate, strawberry) collected throughout 1996 from 8 Egyptian local markets located in 6 governorates(2). Tolclofos-methyl was detected at 0.08 and 0.32-2.26 mg/kg in 1 of 20 banana and 4 of 95 tangerine samples collected Sep 2000 to Jun 2001 from agricultural cooperatives located near Valencia, Spain(3). It was not detected (detection limit 0.01 mg/kg) in 15 chard, 20 onion, 15 pepper, 15 lemon and 20 orange samples(3). Tolclofos-methyl was detected at 2.0 ng/g in 1 of 173 agricultural product samples from a local market in Japan(4). Tolclofos-methyl was detected at 18.25-404.5, 13.14-119.4 and 23.15-3673 ug/kg in 102 of 118, 22 of 24 and 9 of 10 fresh, red and dried ginseng samples tested(5). Tolclofos-methyl was not detected (detection limit 0.002 mg/kg) in 20 milk, 17 egg and 17 fish samples collected from the market in China(6). Tolclofos-methyl was not detected (detection limit 0.3 ug/kg) in six commercial honey and five raw citrus honey samples collected directly from Spanish beekeepers(7).|In a total market basket survey conducted in Belgium from 1991 to 1993 tolclofos-methyl was not detected in many food commodities (potatoes, onions, cauliflower, beans, mushrooms, peas, spinach, cucumbers, peppers, leeks, tomato, Belgian endive, carrots currents, apples, oranges, banana, lemon, strawberry, pineapple, grapes, kiwi, melon, nectarines, pear, peach, wheat flour, rice, tea, water, wine and bran)(1). Tolclofos-methyl was detected in the following commodities(1):[Table#8529]

Tolclofos-methyl was not detected (detection limit 0.002 mg/kg) in 20 milk samples collected from the market in China(1).

Occupational exposure to tolclofos-methyl may occur through inhalation and dermal contact with this compound at workplaces where tolclofos-methyl is produced or used. Monitoring data indicate that the general population may be exposed to tolclofos-methyl via ingestion of food containing residual fungicide. (SRC)

Male and female ICR mice, eight weeks of age, were given an oral dose of 5 mg/kg bw of [(14)C-4-methyl]-tolclofos-methyl (radiochemical purity, 99%) dissolved in corn oil, and radiocarbon was monitored in urine, feces and expired air for seven days after administration. Within 24 hr, 69-76% of the administered radiolabel was excreted in the urine, 4-6% in the feces and less than 1% in the expired air. Total radiocarbon residues in the whole body represented less than 1% of the dose seven days after administration.|Six-week old Sprague-Dawley rats were given an oral dose of 5 mg/kg bw of [(14)C-4-methyl]-tolclofos-methyl (radiochemical purity, 99%) dissolved in corn oil, and radiocarbon was monitored in urine, feces and expired air for seven days after administration. Within 24 hr, 62-67% of the administered dose was excreted in the urine, 16-21% in the feces and less than 1% in the expired air. Total radiocarbon residues in the whole body represented less than 1% of the dose seven days after administration. Whole-body autoradiography performed 1 and 6 hr after treatment showed the highest accumulation of radiolabel in stomach and intestines, followed by kidney and liver|Male and female Sprague-Dawley rats received single oral doses of 5 or 200 mg/kg bw of tolclofos-methyl labelled uniformly with (14)C in the benzene ring (radiochemical purity, > 99%). Another group of animals was treated orally for 14 consecutive days with unlabelled tolclofos-methyl at 5 mg/kg bw per day and then with a single oral dose of [(14)C-phenyl]-tolclofos-methyl at 5 mg/kg bw. The administered radiocarbon was readily excreted, more than 95% of the dose being eliminated in the urine and feces within 48 hr. The amount excreted in urine after seven days was 85-91%; elimination in feces at that time was: consecutive dose group, 9.3% in males and 12% in females; low-dose group, 20% in males and 19% in females; and high-dose group, 20% in males and 12% in females. Excretion as (14)C-carbon dioxide accounted for < 0.1% of the dose in all groups. The concentration of (14)C reached a peak within 2r h in almost all tissues. After administration of the low dose, the highest concentrations were found in the kidney; expressed in tolclofos-methyl equivalents, the levels were 4700 ng/g tissue in males and 3450 ng/g tissue in females; the levels in plasma were 1140 ng/mL in males and 1270 ng/mL in females. Those in the liver were 1240 ng/g tissue in males and 1220 ng/g tissue in females, and those in blood were 736 ng/mL in males and 835 ng/mL in females. The concentrations of (14)C in various organs 72 hr after administration were

Male ICR mice were given 5 mg/kg bw [(14)C-4-methyl]-tolclofos- methyl orally; metabolites were isolated from the feces and urine by chromatography and identified by co-chromatography with authentic standards and/or spectroanalysis. The following major metabolites were detected in the excreta: 2,6-dichloro-4-methylphenol (9% of administered label), O,O-dimethyl- O-(2,6- dichloro-4-carboxyphenyl)phosphate (11%), O-methyl- O-hydrogen-O-(2,6-dichloro-4-carboxyphenyl)phosphate (12%), 3,5-dichloro-4- hydroxybenzoic acid (12%) and 3,5-O-dichloro-4-hydroxybenzyl glycine (13%). The major biotransformation reactions are oxidative desulfuration to oxon and related derivatives, oxidation of the 4-methyl group to alcohols and acids, cleavage of P-O-aryl and P-O-methyl linkages and conjugation of the resultant acid with glycine. The metabolites found in mice are similar to those seen in rats, except for 3,5-O-dichloro-4-hydroxybenzylglycine|Male and female Sprague-Dawley rats were given an oral dose of 5 or 200 mg/kg bw tolclofos-methyl labelled with (14)C either in the 4-methyl group or uniformly in the phenyl ring, with or without pretreatment with unlabelled tolclofos-methyl at 5 mg/kg bw per day for 14 consecutive days. Metabolites were isolated from the feces, urine, bile and major tissues by chromatography and identified by co-chromatography with authentic standards and/or spectroanalysis. More than 10 metabolites were detected in the excreta. No marked differences were seen in relation to sex or dose. The major metabolites detected in the excreta were O-methyl O-hydrogen-O-(2,6-dichloro-4-methylphenyl)phosphate (10-26% of urinary (14)C), O-methyl-O-hydrogen-O-(2,6-dichloro-4- hydroxymethylphenyl) phosphorothioate (12-25%), O-methyl O-hydrogen-O-(2,6-dichloro-4-carboxyphenyl)-phosphorothioate (11-35%) and O-methyl-O-hydrogen-O-(2,6-dichloro-4-methylphenyl)-phosphorothioate (12-44%). In rats with bile cannulas, most of the radiolabel excreted into the bile within 24 hr after administration was associated with polar metabolites; the major metabolites in the bile were O-methyl-O-hydrogen-O-(2,6- dichloro-4-hydroxymethylphenyl)-phosphorothioate and 2,6-dichloro-4- methylphenol glucuronides. Radiocarbon excreted into the feces within 24 hr after administration was associated only with the parent compound. Two hours after oral administration, the major metabolites in blood, liver and kidney were O,O-dimethyl-O-(2,6-dichloro-4- carboxyphenyl) phosphorothioate, 3,5-dichloro-4- hydroxybenzaldehyde, O-methyl-O-hydrogen O-(2,6-dichloro-4-methylphenyl)-phosphorothioate and O-methyl-O-hydrogen-O-(2,6-dichloro-4-hydroxymethylphenyl)-phosphorothioate. Only a small amount of the parent compound was detected in the liver. The major biotransformation reactions were oxidative desulfuration to oxon and related derivatives, oxidation of the 4-methyl group to alcohols and acids, cleavage of the P-O-aryl and P-O-methyl linkages and conjugation of the resultant acids and phenols with glucoronic acids.

0.78 Days

/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 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 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 ... . /Poisons A and B/

/EPIDEMIOLOGY STUDIES/ The medical records of 20 workers in Japan were reviewed. All workers had been engaged continuously in packaging operations since manufacture of technical-grade tolclofos-methyl began in 1988, for an average of 4 hr/day. No occupation-related problems were observed or reported. Plasma and erythrocyte cholinesterase activities were not measured.|/ENDOCRINE MODULATION/ The estrogenic potential of four pesticides (endosulfan, prochloraz, tolchlofos-methyl and propamocarb) was compared in parallel with 17beta-estradiol (E2) by reporter constructs in transient transfected MCF-7BUS and in stable transfected MVLN cells. Similar detection limit and half maximum effect concentration was determined for E2, whereas the maximum effect concentration of E2 was much higher in MCF-7BUS (10 nM) than in MVLN (150 pM), with the induced response being approximately six times the level in MVLN cells. Alone the four pesticides elicited the same relative response in the two bioassays, and similar data was obtained upon co-exposure with E2 for endosulfan and propamocarb. In contrast to the transient MCF-7BUS system, endosulfan further increased the E2 induced response in MVLN cells, whereas propamocarb did not induce the E2 response in MVLN cells as observed in MCF-7BUS cells. In conclusion, high agreement between the two reporter assays was observed, although some performance characteristics have to be considered.|/ENDOCRINE MODULATION/ A number of pesticides are used in agricultural production with some having estrogenic activities, such as endocrine-disrupting chemicals that may affect wildlife and humans. This study aimed to detect the estrogenic effects of some mixed agricultural chemicals in agricultural production. The assay to measure estrogenic activity was evaluated by the cell proliferative activity of MtT/Se cells, which respond well to estrogen. To evaluate MtT/Se cells we went down to the molecular level of estrogen receptor (ER)-alpha and ER-beta expression. The proportion of ER-alpha to ER-beta was 3.55:1, as determined by semi-quantitative real-time polymerase chain reaction (PCR). These results showed that ER-alpha was dominant in MtT/Se cells on the transcriptional level, therefore implying that the estrogenic activity detected by these cells may be mainly mediated by ER-alpha. It was found that diazinon, tolclofos-methyl, pyriproxyfen, prothiofos and thiabendazole had estrogenic activity. Several pesticides are often present in agricultural products. Therefore, we evaluated the estrogenic activity of a mixture of two pesticides. The REC(10) levels of prothiofos/pyriproxyfen and thiabendazole/orthophenylphenol were increased up to 10-fold. We concluded that those two pesticide combinations showed a significantly higher estrogenic effect in comparison to the results of the respective pesticides when tested individually.|/ENDOCRINE MODULATION/ Twenty-four pesticides were tested for interactions with the estrogen receptor (ER) and the androgen receptor (AR) in transactivation assays. Estrogen-like effects on MCF-7 cell proliferation and effects on CYP19 aromatase activity in human placental microsomes were also investigated. Pesticides (endosulfan, methiocarb, methomyl, pirimicarb, propamocarb, deltamethrin, fenpropathrin, dimethoate, chlorpyriphos, dichlorvos, tolchlofos-methyl, vinclozolin, iprodion, fenarimol, prochloraz, fosetyl-aluminum, chlorothalonil, daminozid, paclobutrazol, chlormequat chlorid, and ethephon) were selected according to their frequent use in Danish greenhouses. In addition, the metabolite mercaptodimethur sulfoxide, the herbicide tribenuron-methyl, and the organochlorine dieldrin, were included. Several of the pesticides, dieldrin, endosulfan, methiocarb, and fenarimol, acted both as estrogen agonists and androgen antagonists. Prochloraz reacted as both an estrogen and an androgen antagonist. Furthermore, fenarimol and prochloraz were potent aromatase inhibitors while endosulfan was a weak inhibitor. Hence, these three pesticides possess at least three different ways to potentially disturb sex hormone actions. In addition, chlorpyrifos, deltamethrin, tolclofos-methyl, and tribenuron-methyl induced weak responses in one or both estrogenicity assays. Upon cotreatment with 17beta-estradiol, the response was potentiated by endosulfan in the proliferation assay and by pirimicarb, propamocarb, and daminozid in the ER transactivation assay. Vinclozolin reacted as a potent AR antagonist and dichlorvos as a very weak one. Methomyl, pirimicarb, propamocarb, and iprodion weakly stimulated aromatase activity. Although the potencies of the pesticides to react as hormone agonists or antagonists are low compared to the natural ligands, the integrated response in the organism might be amplified by the ability of the pesticides to act via several mechanism and the frequent simultaneous exposure to several pesticides.|For more Human Toxicity Excerpts (Complete) data for Tolclofos-methyl (6 total), please visit the HSDB record page.

(O,O-dimethyl O-(2,6-dichloro-4-methylphenyl)phosphorothioate)

ST Pre-mix #2 (Albaugh, LLC): Active ingredient: fludioxonil 1.79%; metalaxyl 11.23%; and tolclofos-methyl 6.95%.|Tolclofos-methyl Technical Fungicide (Valent USA, LLC): Active ingredient: tolclofos-methyl 97.0%.|Rizolex Flowable Fungicide (Valent USA, LLC): Active ingredient: tolclofos-methyl 42.0%.|Premix Partners: Thiram|For more Formulations/Preparations (Complete) data for Tolclofos-methyl (6 total), please visit the HSDB record page.

A method to determine five postharvest fungicides (dichloran, flutriafol, o-phenylphenol, prochloraz, tolclofos methyl) in fruits (cherries, lemons, oranges, peaches) has been developed using solid-phase microextraction (SPME) coupled to liquid chromatography (LC) with photodiode array (DAD), mass spectrometry (MS), or tandem mass spectrometry (MS/MS) with ion trap detection. Extraction involved sample homogenization with an acetone/water solution (5:1), filtration, and acetone evaporation prior to fiber extraction. The pesticides were isolated with a fused-silica fiber coated with 50-um Carbowax/template resin. The effects of pH, ion strength, sample volume, and extraction time were investigated, and their impact on the SPME-LC/MS was studied. Dynamic and static modes of desorption were compared and the variables affecting desorption processes in SPME-LC optimized. Static desorption provided the best recoveries and peak shapes. Recoveries at the limit of quantification (LOQ) levels were between 10% for prochloraz and 60% for o-phenylphenol, with relative standard deviations from 13.6% for prochloraz to 3.1% for o-phenylphenol. The versatility of the method was also exhibited by its excellent linearity in the concentration intervals between 0.0005 and 5 mg/kg for dichloran and 0.01-10 mg/kg for tolclofos methyl and prochloraz. LOQs ranged from 0.25 to 1 ug/g using DAD, from 0.002 to 0.01 ug/g using LC/MS, and from 0.0005 to 0.01 to ug/g using LC/MS/MS. LOQs obtained in the present study using LC/MS and LC/MS/MS are lower than maximum residue limits established for all the fungicides in any matrix studied. The method enables to determine polar pesticides at low-microgram per gram levels in fruits.|The organophosphorus pesticides including phorate, diazinon, tolclofos-methyl, fenitrothin, malathion, fenthion, isocarbophos, quinalphos and phenamiphos, in peanut oils were determined by liquid-liquid extraction coupled with dispersive solid phase extraction and gas chromatography-mass spectrometry (GC-MS). The mixture of multi-walled carbon nanotubes and alumina was used as adsorbent in dispersive solid phase extraction. The effects of some experimental conditions, such as types of multi-walled carbon nanotubes, amount of adsorbents and extraction time were examined. The limits of detection for the analytes were between 0.7 and 1.6 ug/kg. The obtained recoveries of the analytes in the samples were between 85.9 and 114.3% and relative standard deviations were lower than 8.48%.|A liquid chromatography (LC) method for the quantitative determination of five fungicide residues (dichloran, flutriafol, o-phenylphenol, prochloraz and tolclofos methyl) in oranges, lemons, bananas, peppers, chards and onions is described. The residues were extracted by matrix solid-phase dispersion (MSPD) using C8. Quantitative analysis was performed by isocratic LC coupled to quadrupole mass spectrometer using atmospheric pressure chemical ionization in the negative ionization mode. The limit of quantification was 0.01 mg/kg for flutriafol, o-phenylphenol and dichloran, and 0.1 mg/kg for prochloraz and tolclofos methyl. The MSPD method is also suitable for LC-UV analysis but higher limits of quantification (between 1 and 5 mg/kg) were obtained. Validation of the method was performed between 0.01 and 25 mg/kg. Recoveries for fungicides ranged from 52.5 to 91.1% with relative standard deviations between 6.1 and 11.9%. The method was applied to the determination of residues in samples taken from agricultural cooperatives. The fungicides most often detected were o-phenylphenol and prochloraz.|In this study, a new analytical method was developed based on gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS) and used to determine 32 multiclass pesticides in ginseng products. The analytical method was validated, yielding recovery rates in the range of 55.2-108.3%, with precision values expressed as relative standard deviation (RSD) lower or equal to 12% at the spiking levels of 30, 100, and 1000 ug/kg. Correlation coefficients and LOQs (limit of quantification) were in the range 0.9801-0.9989 and 0.15-70 g/kg, respectively. With these validation data and this method, multiresidue pesticides of ginseng samples (fresh ginseng (n=118), red ginseng (n=24), dried ginseng (n=10)) were analyzed. Among them, the most frequently detected pesticide was tolclofos-methyl. Tolclofos-methyl was detected in 86.4% of fresh ginseng (18.25-404.5 ug/kg), 91.7% of red ginseng (13.14-119.4 ug/kg), and 87.5% of dried ginseng (23.15-3673 ug/kg).|A method was developed for monitoring dichloran, flutriafol, o-phenylphenol, prochloraz, and tolclofos-methyl in fruits and vegetables, using matrix solid-phase dispersion and liquid chromatography with mass spectrometry detection. The method was used to determine fungicide content in 200 samples of chards, onions, peppers, bananas, lemons, and oranges. Of the samples examined, 54% contained o-phenylphenol with concentrations ranging from 0.005 to 3.34 mg/kg and 35% showed prochloraz in the range of 0.06-1.95 mg/kg. Dichloran, flutriafol, and tolclofos-methyl were detected only occasionally. Only 4% of the samples exceeded the European Union maximum residue limits. The pesticides involved were tolclofos-methyl in 3 samples, o-phenylphenol and flutriafol in 2, and dichloran in one. The calculation of estimated daily intake from these monitoring data showed that dietary intakes were much lower than the acceptable daily intakes established by international agencies.

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

Tolclofos-methyl has known environmental transformation products that include O-(2,6-dichloro-4-methylphenyl) O-methyl O-hydrogen phosphorothioate.|Tolclofos-methyl has known environmental transformation products that include DM-TM, DM-TMO, TM-CH2OH, TM-COOH, TMO, ph-CH2OH, ph-CH3, and ph-COOH.