다이메텐아마이드

Herbicides

Active substance -> EU Pesticides database: Not approved

Environmental transformation -> Pesticides (parent, predecessor)

Pesticides -> Herbicides -> Amide herbicides

Pesticide (Dimethenamid) -> USDA PDB

Pesticide

log Kow = 2.15

2.15

Odorless to weak tar-like odor

Moderate sweet odor

Yellowish-brown, viscous liquid

Clear brown liquid

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)

VP: 36.7 mPa at 25 °C

2.75X10-4 mm Hg /36.7 mPa/ at 25 °C

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P333+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 146 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

Commission Regulation (EC) No 451/2000

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

2006/1009/EC

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

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]

Tolerances are established for residues of the herbicide dimethenamid, 1(R,S)-2-chloro-N-[(1-methyl-2-methoxy)ethyl]-N-(2,4-dimethylthien-3-yl)-acetamide, applied as either the 90:10 or 50:50 S:R isomers, in or on the following food commodities:[Table#8548]

Tolerances with regional registration are established for residues of dimethenamid, 1 (R,S)-2-chloro-N-[(1-methyl-2-methoxy) ethyl]-N-(2,4-dimethylthien-3-yl)-acetamide) in or on the following raw agricultural commodities:[Table#8549]

Acute Tox. 4 (100%)

Hazardous to the aquatic environment (Acute) - Category 1

Acute toxicity (Oral) - Category 4

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.

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.

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.

Tolerances are established for residues of the herbicide dimethenamid, 1(R,S)-2-chloro-N-[(1-methyl-2-methoxy)ethyl]-N-(2,4-dimethylthien-3-yl)-acetamide, applied as either the 90:10 or 50:50 S:R isomers, in or on the following food commodities:[Table#8546]

Tolerances with regional registration are established for residues of dimethenamid, 1 (R,S)-2-chloro-N-[(1-methyl-2-methoxy) ethyl]-N-(2,4-dimethylthien-3-yl)-acetamide) in or on the following raw agricultural commodities:[Table#8547]

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).

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.

LC50; Species: Colinus virginianus (Northern Bobwhite Quail) age 10 days; diet >5620 ppm for 8 days /94.1% purity/

LC50; Species: Anas platyrhynchos (Mallard Duck) age 10 days; diet >5620 ppm for 8 days /91.4% purity/

LD50; Species: Colinus virginianus (Northern Bobwhite Quail) age 21 weeks; oral via capsule 1908 mg/kg (95% confidence interval: 1486-3228 mg/kg) /91.4% purity/

LD50; Species: Apis mellifera (Honey Bee) worker; oral >1000 ug/bee /97% purity/

For more Ecotoxicity Values (Complete) data for Dimethenamid (18 total), please visit the HSDB record page.

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).

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,

/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.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of August 9, 2018: http://actor.epa.gov/dashboard/]

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).

/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.

AEROBIC: Dimethenamid has been shown to undergo aerobic soil metabolism(1). Oxalamide and carbon dioxide are major transformation products, and several other minor transformation products have been observed(1). In several studies, unextracted residues reached a maximum and then decreased slightly by the end of the study, suggesting the residues may be a transformation product(1). Dimethenamid, present at 1.6-2 ppm, exhibited a biodegradation rate of 0.0234/hr (half-life of 29.6 hrs) when incubated 7 days using sewage sludge from an anaerobic stabilizer of a sewage treatment plant (250 g/100 uL ethyl acetate) solution in shaker flasks at 25 °C. A degradation rate constant of 0.0890/day (half-life 7.8 days) was reported for dimethenamid present at 2-2.5 ppm and incubated in soil (sandy loam; 1.6% OM; pH 7.0; Wadenswil, Switzerland) with normal daylight for 64 days (2).

ANAEROBIC: In a study of dimethenamid dissipation under anaerobic redox conditions in soil(1), a disapperance time (DT50) of 14C-dimethenamid occurred in 13-14 days in soil-water biometers that had glucose pre-treatment, NO3- and ((SO4)2-) amendment, or were unamended. 14C-Metabolites accumulated up to 20% of applied 14C. At least two major metabolites were observed in nonautoclaved treatments, whereas only one was observed in autoclaved microcosms. More than 50% of the applied 14C was eventually incorporated into soil-bound residue. Another study(2) observed 16-25 day half-lives of dimethenamid in anaerobic soil slurries. Degradation in sediment was microbially-mediated. Under anaerobic aquatic conditions, dimethenamid half-life was 35 days, with major transformation products M3, M13 (sulfoxide of PL 3688), and M10 (sulfone of FL 3688) and several minor transformation products(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).

Tolerances are established for residues of the herbicide dimethenamid, 1(R,S)-2-chloro-N-[(1-methyl-2-methoxy)ethyl]-N-(2,4-dimethylthien-3-yl)-acetamide, applied as either the 90:10 or 50:50 S:R isomers, in or on the following food commodities:[Table#8548]

Tolerances with regional registration are established for residues of dimethenamid, 1 (R,S)-2-chloro-N-[(1-methyl-2-methoxy) ethyl]-N-(2,4-dimethylthien-3-yl)-acetamide) in or on the following raw agricultural commodities:[Table#8549]

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.

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.

For dimethenamid (USEPA/OPP Pesticide Code: 129051) ACTIVE products with label matches. /SRP: Registered for use in the USA but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Herbicide

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

Dimethenamid is produced by reaction of 2,4- dimethyl-3-aminothiene with 2-chloro-3-methoxypropane, followed by treatment with chloroacetyl chloride.

Preparation: K. Seckinger et al., United Kingdom patent 2114566; eidem, United States of America patent 4666502 (1983, 1987 both to Sandoz)

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%.

Pesticides -> Herbicides -> Amide herbicides

Environmental transformation -> Pesticides (parent, predecessor)

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.