Dimethenamid

275.79

275.79

DTXSID4032376

Yellowish-brown, viscous liquid|Clear brown liquid

2934999026

57.8

2.97160

Yellow-brown viscous liquid

1.195 g/cm3

<25 °C

127 °C

185.4ºC

1.551

0.00 M|In water, 1174 mg/L at 25 °C|In water, 1.2X10+3 m g/L at 25 °C, pH 7|In heptane 282, iso-octane 200 (both in g/kg, 25 °C). In ether, kerosene, ethanol (all >50%, 25 °C)

0-6°C

2.75e-04 mmHg|VP: 36.7 mPa at 25 °C|2.75X10-4 mm Hg /36.7 mPa/ at 25 °C

LD50 in rats (mg/kg): 1570 orally; >2000 dermally; LC50 in bluegill sunfish, rainbow trout (mg/l): 6.4, 2.6 (Harr)

Combustible in case of open flame and high heat; volatile gas in case of acid; toxic chloride and nitrogen oxides, sulfur oxide fumes when heated

Odorless to weak tar-like odor|Moderate sweet odor

8.20e-08 atm-m3/mole|Henry's Law constant = 8.21X10-8 atm-cu m/mole (8.32X10-3 Pa-cu m/mol) at 25 °C

Mixture of 4 stereoisomers (1RS,aRS)|Hydroxyl radical reaction rate constant = 5.2X10-11 cu cm/molecule-sec at 25 °C (est)

UN 3082 9 / PGIII

2

22-51/53

AB5444200

Xn,N

The warehouse is ventilated at low temperature and dry; stored separately from oxidants, acids and food additives

Stable under recommended storage conditions.

P273

H302-H411

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents

Joint Meeting on Pesticide Residues (JMPR): DIMETHENAMID-P/RACEMIC DIMETHENAMID (2005); JMPR is an international expert scientific group administered jointly by the Food and Agriculture Organization of the United Nations (FAO) and WHO. JMPR meets regularly since 1963 to review residues and analytical aspects of the pesticides, estimate the maximum residue levels, review toxicological data and estimate acceptable daily intakes (ADIs) for humans of the pesticides under consideration.[Available from, as of July 24, 2018: http://www.inchem.org/documents/jmpr/jmpmono/v2005pr09.pdf]

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P272, P273, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P321, P330, P333+P313, P363, P391, and P501|Aggregated GHS information provided by 128 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P273, P301+P312, P330, P391, and P501|Danger|H351: Suspected of causing cancer [Warning Carcinogenicity]|P201, P202, P260, P264, P270, P281, P308+P313, P314, 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: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. 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.

Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), sulfur oxides, hydrogen chloride gas

ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. 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: Soak up with inert absorbent material and dispose of as hazardous waste. Keep in suitable, closed containers for disposal.

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.|Avoid contact with skin and eyes. Avoid inhalation of vapor or mist.|ACCIDENTAL RELEASE MEASURES; Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid breathing vapors, mist or gas. 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.|Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

IDENTIFICATION AND USE: Dimethenamid is a herbicide and a racemic mixture of the M (or R) and P (or S) stereoisomers. When this compound was originally registered in various countries, all studies of toxicity were conducted with the racemic mixture. Later, it was discovered that only the P (or S) enantiomer has useful herbicidal activity. HUMAN STUDIES: In 50 people handling racemic dimethenamid and its formulated products over 7 years there were no reported cases of skin irritation or other adverse health effects. Dimethenamid did not increase sister chromatid exchange frequency in cultured human lymphocytes. ANIMAL STUDIES: In short-term studies with racemic dimethenamid, the signs of toxicity observed in mice, rats and dogs were similar, with reduced body-weight gain and liver enlargement being common features. Histopathology confirmed the liver as a target organ with observation of hypertrophy of hepatocytes. In addition, however, vacuolization of hepatocytes and dilatation of liver sinusoids occurred in dogs. Long-term feeding studies with racemic dimethenamid in rats and mice demonstrated that the primary target organ was the liver. There was no evidence for a carcinogenic potential in these studies. Apart from an equivocal result in one of three assays for unscheduled DNA synthesis in vitro with racemic dimethenamid, none of the other genotoxicity assays gave any indication that racemic dimethenamid might be genotoxic. The reproductive toxicity of racemic dimethenamid was investigated in a two-generation study in rats and in a study of developmental toxicity in rabbits. Reproductive function was not affected in rats in the two-generation study of racemic dimethenamid. In a study of developmental toxicity, rats were given racemic dimethenamid at doses of up to 425 mg/kg bw per day. Signs of maternal toxicity that were recorded included excess salivation at 215 mg/kg bw per day and 425 mg/kg bw per day, and urine-stained abdominal fur at 425 mg/kg bw per day. Fetal body weights were reduced and the frequency of early deaths was increased at doses of 215 mg/kg bw per day and 425 mg/kg bw. In a study of developmental toxicity in rabbits given racemic dimethenamid at doses of up to 150 mg/kg bw per day, significant maternal toxicity (body-weight loss preceded by reduced food consumption and associated with dry feces) was observed at the highest dose and less severe effects were noted at 75 mg/kg bw per day. Abortions in two rabbits at 150 mg/kg bw per day were considered to be treatment-related, but secondary to the clear maternal toxicity. ECOTOXICITY STUDIES: In minnow larvae, exposure to river water containing a mixture of pesticides including dimethenamid, upregulated androgen receptor gene expression whereas exposure to the sediment downregulated estrogen receptor a expression. Adult males previously exposed to both water and sediment were feminized through the induction of an ovipositor structure whereas no impacts were observed in other reproductive or sex characteristic endpoints for either sex based on exposure history. Dimethenamid induced significant modifications of the phytoplankton populations,

The first elongation step to form very-long-chain fatty acids (VLCFAs) is catalyzed by the VLCFA-synthase. CoA-activated fatty acids react with malonyl-CoA to condense a C2-unit. As shown with recombinant enzyme this reaction is specifically inhibited by chloroacetamide herbicides. The inhibition is alleviated when the inhibitor (e.g. metazachlor) is incubated together with adequate concentrations of the substrate (e.g. oleoyl-CoA). Malonyl-CoA has no influence. However, once a chloroacetamide has been tightly bound to the synthase after an appropriate time it cannot be displaced anymore by the substrate. In contrast, oleoyl-CoA, is easily removed from the synthase by metazachlor. The irreversible binding of the chloroacetamides and their competition with the substrate explains the very low half-inhibition values of 10(-8) M and below. Chiral chloroacetamides like metolachlor or dimethenamid give identical results. However, only the (S)-enantiomers are active.

LD50 Rat dermal > 2000 mg/kg bw|LD50 Rat (female) oral 427 mg/kg bw|LD50 Rat (male) oral 371 mg/kg bw|LC50 Rat inhalation > 4990 ug/L/4 hr

/AQUATIC SPECIES/ Microcosms, each consisting of 2 L natural surface seawater maintained in 2.3-L glass bottles, were immersed at a depth of 6 m. The renewal of 10% of microcosm volumes was carried out every other day. Phytoplankton-containing seawater was used for renewal (previously filtered through 25-, 50- or 200-um cut-off). Phytoplankton community pigment analysis (by HPLC) and flow cytometry analysis were performed. After 13 days, data exhibited phytoplankton characteristics in microcosms in the same range as that of the natural surrounding sea water over the same period. Furthermore, in these microcosms, a negative correlation was observed between the filtration cut-off used for renewal water, and the total cell count. Herbicides were tested as commercial mixtures at 1, 10 and 100 ug/L active substance. Both Frontier (dimethenamid) and Basamais (bentazon) induced significant modifications of the phytoplankton populations at every concentration tested. Such results suggest a possible disturbance in polluted coastal areas.|/AQUATIC SPECIES/ Agricultural runoff is a non-point source of chemical contaminants that are seasonally detected in surface water and sediments. Agrichemicals found within seasonal runoff can elicit endocrine disrupting effects in organisms as adults, juveniles and larvae. The objectives of this study were (1) to determine if exposure to water, sediment or the water-sediment combination collected from an agricultural runoff event was responsible for changes in endocrine-responsive gene expression and development in fathead minnow larvae, and (2) whether such early life exposure leads to adverse effects as adults. Larvae were exposed during the first month post-hatch to water and sediment collected from the Elkhorn River and then allowed to depurate in filtered water until reaching sexual maturity, exemplifying a best-case recovery scenario. Gas chromatography mass spectrometry (GC/MS) analysis of the water and sediment samples detected 12 pesticides including atrazine, acetochlor, metolachlor and dimethenamid. In minnow larvae, exposure to river water upregulated androgen receptor gene expression whereas exposure to the sediment downregulated estrogen receptor a expression. Adult males previously exposed to both water and sediment were feminized through the induction of an ovipositor structure whereas no impacts were observed in other reproductive or sex characteristic endpoints for either sex based on exposure history. Results from this study indicate that both water and sediments found in agricultural runoff elicit responses from minnow larvae, and larvae can recover following early life exposure under a best-case scenario. /Mixture/|/PLANTS/ Chemicals called safeners protect cereal crops from herbicide toxicity. Proteomic methods (2-D PAGE and LC-MS/MS) were utilized to identify safener- and/or herbicide-regulated proteins in three tissues (root, leaf, and coleoptile) of Triticum tauschii seedlings to better understand a safener's mechanism of action. Growth experiments showed that the safener cloquintocet-mexyl protected seedlings from injury by the herbicide dimethenamid. In total, 29 safener-induced and 10 herbicide-regulated proteins were identified by LC-MS/MS. These proteins were classified into two major categories based on their expression patterns, and were further classified into several functional groups. Surprisingly, mutually exclusive sets of proteins were identified following herbicide or safener treatment, suggesting that different signaling pathways may be recruited. Safener-responsive proteins, mostly involved in xenobiotic detoxification, also included several new proteins that had not been previously identified as safener-responsive, whereas herbicide-regulated proteins belonged to several classes involved in general stress responses. Quantitative RT-PCR revealed that multidrug resistance-associated protein (MRP) transcripts were highly induced by safeners and two MRP genes were differentially expressed. Our results indicate that safeners protect T. tauschii seedlings from herbicide toxicity by coordinately inducing proteins involved in an entire herbicide detoxification pathway mainly in the coleoptile and root, thereby protecting new leaves from herbicide injury.

Dimethenamid'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 140(SRC), determined from a structure estimation method(2), indicates that dimethenamid is expected to have high mobility in soil(SRC). Volatilization of dimethenamid from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 8.21X10-8 atm-cu m/mole(3). Dimethenamid is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 2.75X10-4 mm Hg at 25 °C(4). A biodegradation rate of 0.0890/day (half-life 7.8 days) when incubated in soil(5) suggests that biodegadation is an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a structure estimation method(2), indicates that dimethenamid is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon a Henry's Law constant of 8.21X10-8 atm-cu m/mole(4). According to a classification scheme(5), a measured BCF of 57(6) suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Limited data (35-day half-life in anaerobic conditions) for metabolism in aquatic environments(6) suggest that biodegadation may be 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), dimethenamid, which has a vapor pressure of 2.75X10-4 mm Hg at 25 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase dimethenamid 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 7.4 hours(SRC), calculated from its rate constant of 5.2X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Dimethenamid contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of dimethenamid with photochemically-produced hydroxyl radicals has been estimated as 5.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 7.4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Dimethenamid is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Dimethenamid contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, is susceptible to direct photolysis by sunlight(SRC). Photolysis half-lives have been reported as approximately 7.8 days on soil and 23-33 days in water(3).

Dimethenamid is not expected to bioconcentrate(1); in one study average steady state bioconcentration factors for dimethenamid residues were 20 for the edible tissues, 100 for the nonedible tissue and 57 for whole fish, with depuration half-life for whole body as 10.7 days with approximately 80% of the residues eliminated 14 days after exposure stopped(1). According to a classification scheme(2), this BCF suggests bioconcentration in aquatic organisms is moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of dimethenamid can be estimated to be 140(SRC). According to a classification scheme(2), this estimated Koc value suggests that dimethenamid is expected to have high mobility in soil(SRC).

The Henry's Law constant for dimethenamid is 8.21X10-8 atm-cu m/mole(1). This Henry's Law constant indicates that dimethenamid is expected to be essentially nonvolatile from water and moist soil surfaces(2). Dimethenamid is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 2.75X10-4 mm Hg(3).

Reports of surface water or ground water monitoring studies that included dimethenamid were found in searches of the United States Geological Survey (USGS) online National Water Quality Assessment Data Warehouse (NAWQA) database, or the EPA publication, EPA Pesticides in Ground Water, A Compilation of Monitoring Studies 1971-1991 National Summary(1).|DRINKING WATER: Selected neutral chloroacetamide degradates were detected in treated drinking water from 12 water utilities in the midwestern United States collected during fall 2003 and spring 2004 at median concentrations of 2-60 ng/L. Fall concentrations were almost the same as those in the source water; of the treatments used by the facilities, activated carbon was the only treatment that produced significant removals (average of 40% for all compounds) in the spring samples(1). /Chloroacetamide herbicides/|SURFACE WATER: Dimethenamid was tested for but not detected in samples from the Pearl, Bow, East Bow Creeks, and a confluence site with the Missouri River, all located in the Bow Creek watershed, Nebraska, sampled in June 2008(1). Concentrations of dimethenamid in Swiss lakes sampled 1992-1994 where 12, 5; 12; <1 and 5 ng/L in samples from Lake Greifen (inlet, outlet); Lake Baldagg (outlet); and Lake murten (center, outlet), respectively(2). The compound was present at 2 ug/L in area drainage canal sampled July 1, 1994(2). Dimethenamid was reported at a maximum concentration of 2X10+3 ng/L in unspecified surface waters in Italy as reported by a literature survey on the occurrence of emerging organic chemicals in surface water published between 1997 and 2013(3).|RAIN: At an agricultural site in St. Damase, Quebec, Canada in 2004, dimethenamid was detected in precipitation at concentrations of 80 ng/L in May and 14 ng/L in June. Dimethanimid was detected in rainwater samples collected in 3 locations in the canton of Zurich, Switzerland between February and October 1996 at a median concentration of 24 ng/L, maximum concentration 78 ng/L and total load 300 ng/(sq m/year)(2). Dimethenamid was reported at a concentraiton of 6 ug/L in a single rain event in Switzerland, sampled July 18-20, 1994(3).

Occupational exposure to dimethenamid may occur through inhalation and dermal contact with this compound at workplaces where dimethenamid is produced or used. Limited monitoring data indicate that the general population is likely to be exposed to dimethenamid via ingestion of and dermal contact with water in localized areas where dimethenamid was being applied or recently applied as a herbicide. (SRC)

Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE. (See all compounds classified as Herbicides.)

Racemic dimethenamid was well absorbed after oral administration in rats, as demonstrated by addition of the amount of radioactivity excreted in the urine, via the bile duct and that remaining in the organs and carcass. Biliary excretion accounted for 75-82% of the radiolabelled carbon, with an additional 2-4% being found in the feces and 8-12% in the urine. The total excretion by bile and urine for males was 89.8% and for females was 87.5%. After adding the amount of radioactivity found in the carcass, the total absorption after oral administration was 94.5% in males and 92.8% in females; therefore, essentially 100%. Excretion was very rapid primarily in the bile. Within 7 hr, 45-64% of the orally administered dose was excreted in bile of the cannulated rats. By 168 hr after treatment, an average of 90% of the administered dose was eliminated by all routes. There were some dose-dependent differences in the pattern of excretion. At the lower dose (10 mg/kg bw), urinary radiocarbon accounted for 35-47% of the administered dose compared with 62-63% at the higher dose (1000 mg/kg bw). Radioactivity in feces was 48-58% for groups at the lower dose compared with 26-30% at the higher dose. These data indicated that biliary excretion might be saturated for the group at the higher dose, resulting in more radioactivity being eliminated via the kidney.|The concentration of radioactivity in the blood decreased slowly over the experimental period of 168 hr. Half-lives of elimination from blood were 255 +/-79 hr and 334 +/-192 hr for male and female rats, respectively. The radioactivity was mainly associated with erythrocytes (the concentration of radioactivity in the plasma being much lower). A similar binding phenomenon was not observed in human blood; this can be explained by differences between rat and human hemoglobins. After a single oral lower dose (10 mg/kg bw) the maximum concentration of blood radioactivity was reached at about 72 hr after administration (0.05 ug of test material/g blood in males and 0.1 ug of test material/g blood in females). Afterwards, radioactivity decreased slowly. For the oral high dose, the maximum blood radioactivity was also reached at 72 hr, but did not significantly decrease between 72 and 168 hr. In general, tissue concentrations of radioactivity were similar in both sexes, and the pattern of absorption, distribution and elimination after oral administration was similar. Radioactivity concentrations were higher at 1-4 hr in adrenals, pancreas, kidney, spleen, liver and blood. Residue concentrations decreased steadily over time, with the exception of blood. Overall, tissue concentrations were low by 168 hr after treatment. For the rats treated at the lower dose, the concentration was < 0.5 ppm in all organs and tissues. After oral administration, it appeared that there was no significant difference in the absorption, distribution, and elimination of racemic dimethenamid in males and females. There was only a slight difference in the rate of elimination of radiocarbon between single and multiple doses. Residue concentrations in tissues were similar for groups given single or multiple doses, indicating that racemic dimethenamid and its metabolites had no tendency to accumulate in rat tissues.|The rates of dermal penetration of racemic [(14)C]dimethenamid through human and rat skin were compared in vitro. After correcting for the difference in skin thickness, the rate of penetration through human skin is three to seven times less than that through rat skin. However, saturation has occurred at the highest dose in the rat skin, as the penetration rate no longer continues to increase linearly with dose. The predicted exposure of workers involved in the mixing, loading and application of racemic dimethenamid is at most 0.4 mg/sq cm. Therefore, the comparative values for rat/human skin at the lower doses is considered to be more appropriate for use in predicting human exposure. Overall the rate of dermal penetration of racemic dimethenamid in humans is predicted to be approximately 4%.|The pharmacokinetic studies indicated that dimethenamid may bind to blood components in rats. This was based on 3% of the radiolabeled material administered remaining in the blood fraction. Therefore, the nature of the interaction between dimethenamid and rat blood was investigated. The results of the study showed that dimethenamid did not produce methemoglobin in rat blood following a four day treatment. Dimethenamid was shown to bind to rat hemoglobin, primarily to the globin portion, but no binding was demonstrated using human blood. The difference in hemoglobin binding between humans and rats is explained by the difference in three dimensional structure between the 2 species. It is known from the literature that the cysteine residue beta-125 in rat hemoglobin is accessible for chemical substitution, but in human hemoglobin, the sequence does not contain a cysteine residue in position 125. In summary, it can be concluded that the interaction between dimethenamid and hemoglobin is a species-specific reaction. This binding is irrelevant for humans.

The plant and soil oxalamide (M23) and sulfonate (M27) metabolites of racemic dimethenamid, which also occur as products of metabolism in rats, were tested in studies of acute oral toxicity, assays for mutagenicity in bacteria and for micronucleus formation in bone-marrow cells of mice. Both compounds had low acute oral toxicity with LD50 values of > 5000 mg/kg bw. Neither compound was mutagenic in bacteria or induced micronucleus formation in bone-marrow cells of mice.|Racemic dimethenamid is rapidly and extensively metabolized. Only 1-2% of unchanged racemic dimethenamid was detected in excreta. About 40 metabolites were found in organic extracts that were analyzed by TLC. About 20 metabolites were identified. Metabolism occurred primarily via the glutathione conjugation pathways. Racemic dimethenamid was rapidly conjugated with glutathione and then passed through several steps to form cysteine conjugate (M25) and mercapturate (M17). M25 was further oxidized to form additional metabolites (M1, M2, M10, M13, M14, M16, M18, M19, M21, M22, M26, M27, M30, and M31). Although the glutathione adduct was not found in the study in rats, it was identified in the study in vitro. Other metabolites qualitatively identified in the study in vitro included the cysteine conjugate (M25), the mercapturate (M17), the sulfonate (M27), the sulfoxide of thiolactic acid (M30), the sulfoxide of thioglycolic acid (M31), and the thioglycolic acid (M30). Racemic dimethenamid was also metabolized by reductive dechlorination (M3), oxidation (M4, M23), hydroxylation (M5, M11, M15), O-demethylation (M7, M12) and cyclization (M6, M8, M9, M15, M20). In another supplementary study, metabolites found on maize, the sulfonate (M27) (0.025-0.030%) and sulfoxide of thioglycolic acid (M31) (0.002-0.007%), were identified in rat urine. These metabolites have also been identified in mouse urine.|Metabolism /in rats/ was primarily via the glutathione conjugation pathway, but racemic dimethenamid was also metabolized by cytochrome P450 enzymes via reductive dechlorination, oxidation, hydroxylation, O-demethylation, and cyclization pathways, as well as conjugation with glucuronic acid. Unchanged dimethenamid in excreta accounted for only 1-2% of the administered dose, more than 40 metabolites having been detected. At least 20 of these metabolites were structurally identified by mass spectrometry and nuclear magnetic resonance, and confirmed by reference to synthesized standards. There was no significant difference in metabolism between the sexes.

Half-lives of elimination from blood were 255 +/-79 hr and 334 +/-192 hr for male and female rats, respectively.

/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/

/HUMAN EXPOSURE STUDIES/ The Sandoz Agro manufacturing facility at Beaumont, Texas, USA, produced three batches of Frontier herbicide in 1991 and one batch in 1992. Between five and ten people were involved in the process, which included charging raw materials, process sampling and manually filling containers with the final formulated material. In 1991, approximately 750 containers with a volume of 1 L and 475 containers with a volume of 0.5 L were filled, and in 1992 800 containers of 4 L in volume were filled. Employees wore protective gloves and clothing. Approximately five to seven people in the Research and Development Formulations group handled racemic dimethenamid and its formulations between 1986 and 1992. Activities included material transfer, drying and packaging. Employees wore protective gloves and clothing and were often working under protective hoods. During product development field trials, 20 people worked with racemic dimethenamid products between 1984 and 1991. Activities including mixing, loading and application of the formulation product for application and spraying of the product diluted in water. Most applications were made with a backpack hand sprayer and some applications were with a tractormounted sprayer. These activities were conducted 7-15 times per year. Personnel wore protective gloves and clothing during handling of the product. In none of the three groups surveyed were there any cases of skin irritation, skin rash or other signs of allergic response. In addition, no general signs of adverse health effects were reported. In addition, the sponsor states that: (1) no poisoning incidents are known; (2) no observations regarding health effects after exposure of the general public are known; (3) methods for determination of active substance or metabolites in biological fluids are not established; (4) specific signs of poisoning or clinical tests are not known; (5) no specific antidote is known and (6) expected effects of poisoning (irritation of exposed eyes and skin, dermatitis and eczema) were derived from studies in animals.|/GENOTOXICITY/ ... Isolated and cultured peripheral lymphocytes (mostly T cells) were used from two human donors to study the effects of the chloroacetanilides and their metabolites on primary human cells. In tests at 10 uM, the SCE frequency was increased by alachlor and possibly acetochlor but not by butachlor, metolachlor, dimethachlor (a 2,6-dimethyl analog) and dimethenamid (an analog based on 2,4-dimethyl-3-thienylamine). At 0.3 microM in cultured human lymphocytes, alachlor, the corresponding chloroacetanilide (N-dealkyl-alachlor) and aniline metabolites (and their 4-hydroxy derivatives), and diethylbenzoquinone were inactive or active in only one of the two donors whereas at 0.1-0.3 uM the SCE ratio for treated cells divided by the controls was always higher for diethylbenzoquinoneimine than for ethylmethyl- and dimethylbenzoquinoneimines. All the tested compounds were toxic to lymphocytes, but the depression of the mitotic index and increased duration of the cell cycle were not directly linked with SCE induction. Previous investigations have suggested that chloroacetanilide herbicides such as alachlor derived from 2,6-dialkylanilines are metabolized to 2,6-dialkylbenzoquinoneimines and the present study provides the first direct evidence that these metabolites are genotoxic in human lymphocytes.

2-chloro-N-(2,4-dimethyl-3-thienyl)-N-(1-methoxy-2-propanyl)acetamide

Frontier Herbicide (BASF Corporation): Active ingredient: dimethenamid 79.4%.|Dimethenamid Technical (BASF Corporation): Active ingredient: dimethenamid 96.9%.|Frontier 6.0 Herbicide (BASF Corporation): Active ingredient: dimethenamid 63.14%.|DPX-MX670 MT (E. I. Du Pont De Nemours and Company): Active ingredient: atrazine 28.4% and dimethenamid 24.8%.

Dimethenamid is a racemic mixture of the M (or R) and P (or S) stereoisomers. When this compound was originally registered in various countries, all studies of toxicity were conducted with the racemic mixture. Later, it was discovered that only the P (or S) enantiomer has useful herbicidal activity.|Dimethenamid was originally registered as a mixture of R and S-isomers (50:50, S:R), and tolerances for the 50:50 mixture were established for dry beans, field corn, sweet corn, peanuts, sorghum, and soybean. Manufacture of the 50:50 mixture has ceased and has been replaced by a mixture (dimethenamid-P) that is enriched in the biologically active S-isomer (90:10, S:R). Registration of the original 50:50 mixture will be cancelled when existing stock is depleted.|Registration Notes: Outside USA: Registered in many countries.

An adequate enforcement method is available for determining residues of dimethenamid in plant commodities. The Gas Chromatography/NitrogenPhosphorus Detector (GC/NPD) method (AM-0884-0193-1) has been validated by the Agency and submitted for publication in the Food and Drug Administration (FDA) Pesticide Analytical Manual (PAM), Volume II. The limit of quantitation (LOQ; determined as the lowest level of method validation, LLMV) is 0.01 ppm. This method is not enantiomer specific.|A Good Laboratory Practices (GLP) validated, multiresidue analytical method is presented for the determination of the chloroacetanilide herbicides metolachlor, acetochlor, and alachlor, the chloroacetamide herbicide dimethenamid, and their respective ethanesulfonic (ESA) and oxanillic (OA) acid degradates in ground and surface water. A 50-mL water sample is subjected to purification using a C-18 SPE column. The four parent components and their eight ESA and OA degradates are isolated using 80/20 methanol/water (v/v) for elution. The eluate is reduced to < 1.0 mL and reconstituted in 10/90 acetonitrile/water (v/v) to the desired final fraction volume. Final analysis is accomplished using liquid chromatography/electrospray ionization-mass spectrometry/mass spectrometry in the + (parent compounds) and - (ESA and OA degradates) ion modes by monitoring appropriate precursor/product ion pairs for each of the 12 analytes. The method limit of quantification is 0.10 ppb and the limit of detection is 0.125 ng injected for each analyte. Average procedural recovery data range from 95 to 105% for fortification levels of 0.10-100 ppb. The method validation study was performed following GLP guidelines.|Dimethenamid [2-chloro-N-(2,4-dimethyl-3-thienyl)-N-(2-methoxy-1-methylethyl)acetamide] and flufenacet [N-(4-fluorophenyl)-N-(1-methylethyl)-2-(5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)oxy] were isolated by C-18 solid-phase extraction and separated from their ethanesulfonic acid (ESA) and oxanilic acid (OXA) degradates during their elution using ethyl acetate for the parent compound, followed by methanol for the polar degradates. The parent compounds were detected using gas chromatography-mass spectrometry in selected-ion mode. The ESA and OXA degradates were detected using high-performance liquid chromatography-electrospray mass spectrometry (HPLC-ESPMS) in negative-ion mode. The method detection limits for a 123-mL sample ranged from 0.01 to 0.07 ug/L. These methods are compatible with existing methods and thus allow for analysis of 17 commonly used herbicides and 18 of their degradation compounds with one extraction. In a study of herbicide transport near the mouth of the Mississippi River during 1999 and 2000, dimethenamid and its ESA and OXA degradates were detected in surface water samples during the annual spring flushes. For flufenacet, the only detections at the study site were for the ESA degradates in samples collected at the peak of the herbicide spring flush in 2000. The low frequency of detections in surface water likely is due to dimethenamid and flufenacet being relatively new herbicides. In addition, detectable amounts of the stable degradates have not been detected in ground water.|In this study, a gas chromatography-mass spectrometry method is successfully developed for the determination of 11 herbicide residues (alachlor, acetochlor, butachlor, pretilachlor, metolachlor, dimethenamid, propachlor, napropamid, propanil, atrazine, and metribuzin) in rice and soybeans. The sample is extracted with acetone-water, degreased by liquid-liquid partition, and purified through solid-phase extraction with Florisil. Experiments on 5 fortification concentrations are carried out, and the limit of determination is 0.02 mg/kg. The average recoveries of soybean samples range from 63.3% to 96.0%, and the relative standard deviations are from 2.14% to 11.2%. The average recoveries of rice samples range from 76.8% to 102% and the relative standard deviations are from 2.2% to 9.08%. The results indicate that the method developed is fast, accurate, and easy to operate. It also demonstrates that the method can meet the requirements of simultaneous determination of 11 herbicides in rice and soybeans.|For more Analytic Laboratory Methods (Complete) data for Dimethenamid (6 total), please visit the HSDB record page.

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

Dimethenamid has known environmental transformation products that include Dimethenamid ESA and Dimethenamid OXA.|Dimethenamid has known environmental transformation products that include Dimethenamid M11, Dimethenamid M23, Dimethenamid M26, Dimethenamid M27, Dimethenamid M30, Dimethenamid M31, and Dimethenamid M32.