Methyl-5-(2,4-dichlorphenoxy)-2-nitrobenzoat

Agrochemicals -> Pesticide active substances

Active substance -> EU Pesticides database: Approved

Pesticides -> Herbicides, Protox-Inhibiting

Environmental transformation -> Pesticides (parent, predecessor)

Herbicides

Pesticide (Bifenox) -> USDA PDB

log Kow = 4.48

4.48

Solid

Yellow tan crystals

Solubility in xylene at 25 °C: 30%

Solublity in organic solvents g/ml @ 25 °C: acetone, 40; chlorobenzene, 35-40; ethanol, <5; kerosene, <1; xylene, 30.

In water, 0.398 mg/l @ 25 °C

0.0000001 [mmHg]

2.4X10-6 mm Hg @ 25 °C

Warning

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P273, P301+P317, P330, P391, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 4.2% (3 of 72) of reports.

Warning

H302 (38.9%): Harmful if swallowed [Warning Acute toxicity, oral]

Commission Regulation (EC) No 1490/2002

2008/66, Reg. (EU) 2018/1796, Reg. (EU) 2019/1589, Reg. (EU) 2020/1511, Reg. (EU) 2021/1449, Reg. (EU) 2023/2592, Reg. (EU) No 1124/2013, Reg. (EU) No 540/2011

The protox inhibitor herbicides (Fomesafen, Oxadiazon, Lactofen, Sulfentrazone, Carfentrazone-ethyl, Oxyfluorofen and Bifenox) can disrupt porphyrin metabolism; It has been speculated that a transient form of porphyria variegate may occur following a massive exposure or long-term exposure to lower doses. Effects in 4 week high-dose feeding study with rats include increase in liver weights; [HSDB] See Fluthiacet-methyl.

California Environmental Protection Agency/Department of Pesticide Regulation; Toxicology Data Review Summaries. Available from: http://www.cdpr.ca.gov/docs/toxsums/toxsumlist.htm on Bifenox as of March 13, 2003. Provides a summary of available toxicological information for pesticides currently or previously registered for use in California.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Bifenox is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA '88. Case No: 0013; Pesticide type: herbicide; Registration Standard Date: 08/12/81 PB83-138818; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.; Active ingredient (AI): bifenox; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled.".

Acute Tox. 4 (38.9%)

Aquatic Acute 1 (100%)

Acute Tox. 4

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 2,658 to 3,107(2), indicates that bifenox is expected to have slight to no mobility in soil(SRC). Volatilization of bifenox from moist soil surfaces is expected to be an environmental fate process(SRC) given an estimated Henry's Law constant of 2.7X10-6 atm-cu m/mole(SRC), based upon its vapor pressure, 2.4X10-6 mm Hg(3), and water solubility, 0.398 mg/l(4); however, adsorption to soil is expected to attenuate volatilization(SRC). Bifenox is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 2.4X10-6 mm Hg(3). Bifenox exhibited a half-life of 3 to 7 days following preemergence application to a greenhouse soil(5) and, therefore, biodegradation may be an important environmental fate process in soil.

AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 2,658 to 3,107(2) indicate that bifenox is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(5) based upon a estimated Henry's Law constant of 2.7X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 2.4X10-6 mm Hg(3), and water solubility, 0.398 mg/l(4). Using this Henry's Law constant and an estimation method(5), volatilization half-lives for a model river and model lake are 25 and 190 days, respectively(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 3 years if adsorption is considered(10). The major photoreaction pathways observed following solution-phase irradiation at 300 nm of bifenox at 0.25 to 1.0 g/l were decarbomethoxylation, reduction of the nitro substituent to the amino, and cleavage of the ether linkage(11). According to a classification scheme(6), an estimated BCF of 560(SRC), from its log Kow of 4.48(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Based on a half-life of 4 days from a field study involving flooded rice paddy soils(9), biodegradation may be an important fate process in anoxic aquatic environments.

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bifenox, which has a vapor pressure of 2.4X10-6 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase bifenox 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 15 days(SRC), calculated from its rate constant of 1.1X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase bifenox may be removed from the air by wet and dry deposition(SRC).

/BIRDS and MAMMALS/ ...American kestrel (Falco sparverius) nestlings were orally dosed for 10 days with 5 ul/g of corn oil (controls) or one of the diphenyl ether herbicides (nitrofen, bifenox, or oxyfluorofen). At 500 mg/kg ...bifenox /resulted/ in high (66%) mortality... . .../For/ bifenox at 250 mg/kg ...crown-rump, humerus, radius-ulna and femur lengths were significantly less than controls. ...Bifenox ingestion (> or =50 mg/kg) resulted in increased hepatic GSH peroxidase activity. ...

Kocs for bifenox have been reported ranging from 2,658 to 3,107(1). According to a classification scheme(2), these Koc values suggest that bifenox is expected to have slight to no mobility in soil. The sorption kinetics for bifenox were characterized by immediate rapid sorption with 30-70% of the added chemical adsorbed within the first 4 hrs, followed by a slow sorption over a longer time period(3). Slight desorption (10%) was noted after 24 hrs(3). In runoff experiments, it was shown that poorly soluble compounds like bifenox are only removed from fields as a result of heavy, erosive rainfalls on areas with a slope >10%; concn in soil before irrigation was 0.78 mg/kg in the 0-5 cm layer, after irrigation concns were in 0.77, 0.01, and 0.01 mg/kg at soil depths of 0-5, 5-10, and 10-15 cm, respectively(4).

AEROBIC: Decarboxylation and N-acylation has been identified as cleavage reaction pathways for bifenox in soil(1). Biodegradation of bifenox has been shown to be limited to simple transformations such as the reduction of the nitro group with the most prominent metabolites being the corresponding anthranilic acid and nitrofen(2). Also observed when using C14-labelled compound, >60% of applied bifenox was found bound to the soil after 300 days(2). Bifenox exhibited a half-life of 3 to 7 days following preemergence application to a greenhouse soil; metabolites identified included 5-(2,4-dichlorophenoxy)-2-nitrobenzoic acid, nitrofen, and 5-(2,4-dichlorophenoxy) anthranilic acid over a 313-day period with an increase in the proportion of bound material(3). In non-flooded paddy soils, bifenox was degraded rapidly with a half-life of 6 days; the free acid was the main degradation product(4).

ANAEROBIC: A rate constant of -0.26 hr-1 for bifenox, which has a redox potential of -1.20, was obtained in anaerobic reduction experiment using digestor sewage sludge(1). In a field study using rice paddy soils under flooded conditions, bifenox was degraded rapidly with a half-life of 4 days; metabolites included the free acid and the amino derivatives of the ester and free-acid forms, acetyl- and formyl-amino derivatives of the ester and free acid forms and the salicylic acid derivative(2).

An estimated BCF of 560 was calculated for bifenox(SRC), using a log Kow of 4.48(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC). However, hydrolysis may attenuate this process(4). Radiolabeled bifenox, introduced to a model 33-day rice paddy ecosystem sand at a 1.29 kg/ha dosage, exhibited a comparatively low ecological magnification value of 49 in mosquito fish (Gambusia) as compared with the other rice paddy herbicides examined in this study, for example 1,546 for nitrofen and 867 formethoxy-nitrofen(4).

The Henry's Law constant for bifenox is estimated as 2.7X10-6 atm-cu m/mole(SRC) derived from its vapor pressure, 2.4X10-6 mm Hg(1), and water solubility, 0.398 mg/l(2). This Henry's Law constant indicates that bifenox 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 25 days(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 190 days(SRC). However, volatilization from water surfaces is expected to be attenuated by adsorption to suspended solids and sediment in the water column. The estimated volatilization half-life from a model pond is 3 years if adsorption is considered(4). Bifenox has been shown to hydrolyze rapidly(5) which may negate volatilization as an important fate process. Bifenox did not volatilize from distilled water nor river water under experimental conditions(6). Bifenox's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Bifenox is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

/LABORATORY ANIMALS: Acute Exposure/ ...The cytotoxic and porphyrinogenic effects of four diphenyl ethers (DPEs) /were studied/... in rat hepatocytes cultured on Matrigel. Cytotoxicity was determined as a decr in viability measured by the release of lactate dehydrogenase. ...No concn-dependent decr in viability was observed in the ...bifenox-treated hepatocytes at the concns up to 1.0 mM. ...The max porphyrin accumulation was observed at ...0.25 mM for ...bifenox (...21-fold).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Bifenox technical (purity not stated) was administered in diet for 4 weeks to Sprague-Dawley CD rats at 0, 1,000, 2,000, 3,500, 5,000 and 10,000 ppm (5/sex/group). NOEL= 2,000 ppm (body weight gain was significantly decreased in males at 10,000 ppm; liver weights were significantly increased in females at >3,500 ppm and in males at 10,000 ppm; livers appeared enlarged in males at >3,500 ppm; centrilobular hepatocyte enlargement was observed in males at 10,000 ppm).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Bifenox technical (98.3% pure) was administered in the diet to B6C3F1 mice at 0, 50, 200, and 1,000 ppm (60/sex/group) for 24 months. NOEL= 200 ppm (males showed increased liver weights and females showed increased kidney weights at 1,000 ppm with no accompanying histopathology; focal hypertrophy of convoluted kidney tubules was observed in males in a dose related manner but was viewed as focal enzyme induction). Adverse effects: (significant incr in hepatic adenomas and carcinomas in males at 1,000 ppm).

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Bifenox technical (purity= 98%) was administered by gavage to mated Crl:COBS CD(SD)BR rats at 0 (vehicle= 1% aq methylcellulose), 225, 900 and 3,600 mg/kg/day (25/group) from day 6-15 of gestation (presence of sperm or vaginal plug= day 0 of gestation). No adverse effect. Maternal NOEL= 900 mg/kg/day (increased deaths; decreased food consumption; salivation, staining of mouth and patchy hair loss). Developmental NOEL= 3,600 mg/kg/day (no significant effects observed at any dose).

For more Non-Human Toxicity Excerpts (Complete) data for BIFENOX (9 total), please visit the HSDB record page.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their future use. Under this pesticide reregistration program, EPA examines health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether they are eligible for reregistration. In addition, all pesticides must meet the new safety standard of the Food Quality Protection Act of 1996. Bifenox is found on List A, which contains most food use pesticides and consists of the 194 chemical cases (or 350 individual active ingredients) for which EPA issued registration standards prior to FIFRA '88. Case No: 0013; Pesticide type: herbicide; Registration Standard Date: 08/12/81 PB83-138818; Case Status: No products containing the pesticide are actively registered. Therefore, we are characterizing the case as "cancelled." Under FIFRA, pesticide producers may voluntarily cancel their registered products. EPA also may cancel pesticide registrations if registrants fail to pay required fees or make/meet certain reregistration commitments, or if EPA reaches findings of unreasonable adverse effects.; Active ingredient (AI): bifenox; AI Status: The active ingredient is no longer contained in any registered products ... "cancelled.".

Bifenox is relatively rapidly absorbed and eliminated from the body; 5-(2,4-dichlorophenyl)-2-nitrobenzoic acid was the major urinary metabolite, with no bifenox detected. Bifenox together with 5-(2,4-dichlorophenyl)anthranilate were detected in feces.

...Bifenox technical grade (98% purity) was administered orally after suspending in 1% carboxymethyl cellulose at 2 g/kg to 6 young adult goats of both sexes for oral kinetics. Blood samples were collected at different time intervals from each goat and concn of bifenox in blood were estimated by GLC. Bifenox in blood was detected at 2 hr (1.32 + or - 0.07 ug/ml) which attained max at 12 hr (6.76 + or - 0.17 ug/ml) followed by gradual decr in concn and reaching at min blood concn at 24 hr. The kinetic behavior of bifenox followed "two compartment open model". The .../volume of distribution/ area and /blood clearance/ values were ...2.73 + or - 0.28 l/kg and 0.88 + or - 0.07 l/kg/hr respectively, indicating wide distribution and shorter persistence in the body.

Used as a herbicide for control of annual broad leaved weeds and grasses in cereals, maize, soy beans, rice, and other crops; [HSDB]

Cancelled--no longer registered as a pesticide for use in the US; [HSDB]

Farming (Pesticides) [Category: Industry]

The active ingredient is no longer contained in any registered products ... "cancelled.".

For bifenox (USEPA/OPP Pesticide Code: 104301) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

EPA is initiating this action for those pesticides which have no food use registrations. The applicable registrations for these pesticides have been canceled because of nonpayment of maintenance fees or by registrant request. Effective date: This regulation becomes effective September 27, 1995.

Environmental transformation -> Pesticides (parent, predecessor)

Herbicides

The WHO Recommended Classification of Pesticides by Hazard identifies Bifenox (technical grade) as unlikely to present an acute hazard in normal use; Main Use: herbicide.

Based on 1987 usage data, 125,224 lbs active ingredient were applied to 3% of the rice crop in Louisiana.