1582-09-8

Basic information

• Product Name: Trifluralin
• Synonyms: Trifurex;TRIFLUREX;TRIFLURALIN;trilin 4ec;Trifiuralin;treflam;TREFLAN;TREFLAN(R)
• CAS NO: 1582-09-8
• Molecular Formula: C₁₃H₁₆F₃N₃O₄
• Molecular Weight: 335.28
• EINECS: 216-428-8
• Product Categories: Organics;HERBICIDE;DinitroanilineMethod Specific;Alpha sort;Endocrine Disruptors (Draft)Method Specific;EPA;Herbicides;Oeko-Tex Standard 100;Pesticides&Metabolites;PesticidesPesticides&Metabolites;Q-ZAlphabetic;TP - TZ;Agro-Products;Amines;Aromatics
• Mol File: 1582-09-8.mol
• Article Data: 22

Chemical Properties

• Melting Point: 48.5°C
• Boiling Point: 139°C
• Flash Point: 100 °C
• Appearance: Bright orange/Crystalline Solid
• Density: 1.294
• Vapor Pressure: 1.21E-05mmHg at 25°C
• Refractive Index: 1.527
• Storage Temp.: APPROX 4°C
• PKA: -1.45±0.50(Predicted)
• Water Solubility: <0.01 g/100 mL at 22.5℃
• Merck: 13,9757
• BRN: 1893555
• CAS DataBase Reference: Trifluralin(CAS DataBase Reference)
• NIST Chemistry Reference: Trifluralin(1582-09-8)
• EPA Substance Registry System: Trifluralin(1582-09-8)

Safety Data

• Hazard Codes: Xi;N,N,Xi,Xn,F
• Statements: 36-43-50/53-20/21/22-11-40
• Safety Statements: 2-24-37-60-61-36-26-16-46-36/37
• RIDADR: UN 2588
• WGK Germany: 2
• RTECS: XU9275000
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 1582-09-8(Hazardous Substances Data)

Usage

Uses

Used in Agricultural Industry:
Trifluralin is used as a pre-emergence herbicide for controlling many annual grasses and broadleaf weeds in a large variety of tree fruit, nut, vegetable, and grain crops, including soybeans, sunflowers, cotton, and alfalfa. It is also used on rights-of-way and set-aside land.
Used in Residential and Ornamental Plant Protection:
Trifluralin is registered for nonfood uses, including residential use, to protect residential ornamental plants such as trees, herbaceous plants, woody shrubs, and vines.
Used in Pre-Plant Soil Incorporation:
Trifluralin is used for pre-plant soil incorporation to control annual grasses and some broadleaf annual weeds in various crops, such as broccoli, cabbage, onions, leafy green vegetables, beans, tomatoes, potatoes, wheat, sugar beet, and sugar cane.
Used in the United States:
Trifluralin is registered for use in the U.S. and is a common commercially available herbicide. It is extensively used in the country for controlling weeds in various crops and plants.
Banned in Europe:
In the early 2000s, Trifluralin was banned in Europe due to reports of persistence in soil and groundwater, leading to concerns of increased risk for toxicity.
Toxicity:
Minimal to no toxicity has been reported in humans following either oral, dermal, or inhalation exposure. However, there is evidence that Trifluralin may have elevated toxicity in certain aquatic wildlife, as particular species of fish and tadpoles have displayed biomarkers of Trifluralin toxicity following exposure. Larger vertebrates such as canines have also demonstrated toxicological profiles suggesting an elevated toxicity compared to humans.

References

https://www.epa.gov http://www.toxipedia.org https://pubchem.ncbi.nlm.nih.gov http://www.who.int https://aggie-horticulture.tamu.edu

Reactivity Profile

Trifluralin is a trifluoromethyl dinitroaniline derivative. Dinitroaniline has a record of industrial explosions. Nothing has been reported implicating Trifluralin in any such accidents. This may be because of the trifluoromethyl substitution may mitigate the instability of the molecule. However, care should be taken in the extremes of heat, shock, and friction sources that may trigger an explosive release of energy.

Health Hazard

Dust may irritate eyes. No toxic symptoms have been observed during the manufacture and use of Trifluralin.

Fire Hazard

Special Hazards of Combustion Products: Toxic and irritating hydrogen fluoride gas may be formed in fires.

Trade name

AGREFLAN?; AGRIFLAN? 24; ASHLADE TRIMARAN?; AUTUMN KITE?; BROADSTRIKE?; BUCKLE?; CALLIFORT?; CAMPBELL'S TRIFLURON?; CHANDOR?; COMMENCE?; CRISALIN?; DEVRINOL T?; DIGERMIN?; ELANCOLAN?; FLINT?; FLORA?; FLURENE SE?; FLUTRIX?; FREEDOM?; GORDON’S WEEDER?; HERBIFLURIN?; IPERSAN?; JANUS?; L-36352?; LILLY 36,352?; LINNET?; MARKSMAN?; MARKSMAN 2, TRIGARD?; M. T. F?; NITRAN?; OLITREF?; ONSLAUGHT?; PREMERLIN 600 CE?; SINFLOWAN?; SOLO?; SU SEGURO CARPIDOR?; TEAM?; TREFANOCIDE?; TREFICON?; TREFLAN?; TREFLANOCIDE?; TRIFARMON?; TRIFLURALINA? 600; TRIFLUREX?; TRIFUREX?; TRIGARD?; TRIKEPIN?; TRILIN?; TRILIN? 10G; TRIM?; TRIMARAN?; TRIPART TRIFLURALIN 48 EC; TRISTAR?; TRUST?; TURFLAN?; URANUS? (trifluralin + linuron)

Safety Profile

Moderately toxic by ingestion and intraperitoneal routes. Experimental teratogenic and reproductive effects. Questionable carcinogen with experimental carcinogenic and tumorigenic data. Human mutation data reported. When heated to decomposition it emits very toxic fumes of Fand NOx. See also FLUORIDES.

Potential Exposure

A potential danger to those involved in the manufacture, formulation and application of this selective, preemergence herbicide.

Environmental Fate

Biological. Laanio et al. (1973) incubated 14CF3-tri?uralin with Paecilomyces, Fusar- ium oxysporum, or Aspergillus fumigatus and reported that <1% was converted to 14CO2. From the first-order biotic and abiotic rate constants of tri?uralin in estuarine water and sediment/water systems, the estimated biodegradation half-lives were 2.5–9.7 and 2.4–7.1 days, respectively (Walker et al., 1988).Soil. Anaerobic degradation in a Crowley silt loam yielded α,α,α-tri?uoro-N4,N4- dipropyl-5-nitrotoluene-3,4-diamine and α,α,α-tri?uoro-N4,N4-dipropyltoluene-3,4,5-tri- amine (Parr and Smith, 1973). Probst and Tepe (1969) reported that tri?urGolab et al. (1979) studied the degradation of tri?uralin in soil over a 3-year period. They found that the herbicide undergoes N-dealkylation, reduction of nitro substituents, followed by the formation cyclized products. Of the 28 transformation productsZayed et al. (1983) studied the degradation of tri?uralin by the microbes Aspergillus carneus, Fusarium oxysporum and Trichoderma viride. Following an inoculation and incubation period of 10 days in the dark at 25°C, the following metabolites were identified: α,α,α-trifluoro-2,6-dinitro-N-propyl-p-toluidine, α,α,α-trifluoro-2,6-dinitro-p-toluidine, 2-amino-6-nitro-α,α,α-tri?uoro-p-toluidine and 2,6-dinitro-4-tri?uoromethyl phenol. The reported half-life in soil is 132 days (Jury et al., 1987).The half-lives for tri?uralin in soil incubated in the laboratory under aerobic and anaerobic conditions ranged from 33 to 375 days (Probst et al., 1967; Parr and Smith, 1973; Kearney et al., 1976; Zimdahl and Gwynn, 1977) to 4 to 70 days, respectively (

Solubility in organics

Freely soluble in Stoddard solvent (Windholz et al., 1983), chloroform, methanol (Probst et al., 1967), acetone (400 g/L), xylene (580 g/L) (Worthing and Hance, 1991), ether, and ethanol (quoted, Bailey and White, 1965)

Toxicity evaluation

Technical trifluralin has low acute toxicity, whereas solvents often used for the emulsification of trifluralin have been shown to be irritating to the eyes and skin. An active component of trifluralin toxicity is the volatile nitrosamine, N-nitroso-din- propylamine, which may be the active compound in trifluralin toxicity.

Incompatibilities

Trifluralin is a trifluoromethyl dinitroaniline derivative. Dinitroaniline has a record of industrial explosions. Nothing has been reported implicating trifluralin in any such accidents. This may be because of the trifluoromethyl substitution may mitigate the instability of the molecule. However, care should be taken in the extremes of heat, shock, and friction sources that may trigger an explosive release of energy. Fluorocarbons can react violently with barium, potassium, sodium.

Waste Disposal

Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. All federal, state, and local environmental regulations must be observed. Trifluralin does contain fluorine, and therefore incineration presents the increased hazard of HF in the off-gases. Prior to incineration, fluorine-containing compounds should be mixed with slaked lime plus vermiculite, sodium carbonate or sand-soda ash mixture (90-10).

InChI:InChI=1/C13H16F3N3O4/c1-3-5-17(6-4-2)12-10(18(20)21)7-9(13(14,15)16)8-11(12)19(22)23/h7-8H,3-6H2,1-2H3

Synthetic route

C13H17F3N3O5(1-) (72283-22-8) → 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8)

Conditions	Yield
With potassium hydroxide In water; dimethyl sulfoxide at 25℃; Equilibrium constant; Rate constant; var. of solvent mixture, var. KOH concentrations;

C17H26F3N4O4(1-)*K(1+) (79871-51-5) → 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) + N-butylamine (109-73-9)

Conditions	Yield
With water In dimethyl sulfoxide Equilibrium constant;

C18H26F3N4O4(1-)*K(1+) (79816-19-6) → piperidine (110-89-4) + 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8)

Conditions	Yield
With water In dimethyl sulfoxide Equilibrium constant;

4-chloro-3,5-dinitrobenzotrifluoride (393-75-9) → 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8)

Conditions	Yield
In water

4-chloro-3,5-dinitrobenzotrifluoride (393-75-9) + di-n-propylamine (142-84-7) → 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8)

Conditions	Yield
Reflux;
With water; sodium hydroxide at 85 - 90℃; for 5h; Large scale;
With sodium hydroxide; ascorbic acid In water at 60℃; for 2h; pH=7.5 - 8.5; Temperature;	33.02 g

piperidine (110-89-4) + 2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → C18H26F3N4O4(1-)*K(1+) (79816-19-6)

Conditions	Yield
With potassium hydroxide In water; dimethyl sulfoxide Equilibrium constant;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → C13H17F3N3O5(1-) (72283-22-8)

Conditions	Yield
With potassium hydroxide In water; dimethyl sulfoxide at 25℃; Equilibrium constant; Rate constant; var.of solvent mixture, var. KOH concentrations;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) + N-butylamine (109-73-9) → C17H26F3N4O4(1-)*K(1+) (79871-51-5)

Conditions	Yield
With potassium hydroxide In water; dimethyl sulfoxide at 25℃; Rate constant; Equilibrium constant;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → 1-Dipropylamino-2,6-dinitro-4-tribrommethyl-benzol (16766-93-1)

Conditions	Yield
With aluminum tri-bromide

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → 3-nitro-5-trifluoromethyl-1,2-phenylenediamine (2078-01-5) + 2,6-dinitro-4-trifluoromethylaniline (445-66-9) + α,α,α-trifluoro-5-nitro-N4-propyltoluene-3,4-diamine (2078-02-6) + α,α,α-trifluoro-2,6-dinitro-N-propyl-p-toluidine (2077-99-8) + 2,6-dinitro-4-trifluoromethyl-2',6'-dinitro-4'-<(trifluoromethyl)azo>benzene (69145-34-2) + 2-ethyl-7-nitro-5-(trifluoromethyl)-1H-benzimidazole (51026-15-4)

Conditions	Yield
In methanol; water Mechanism; Irradiation;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → di-n-propylamine (142-84-7) + C7H2N2O7(2-)*2K(1+) + potassium; 2,6-dinitro-4-trifluoromethyl-phenolate + C13H16(2)HF3N3O5(1-)*K(1+) + C19H30F3N4O4(1-)*K(1+)

Conditions	Yield
With potassium deuteroxide In dimethylsulfoxide-d6; water-d2 Mechanism; other dinitroaniline herbicides; other nucleophiles;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → trifluralin-d2

Conditions	Yield
With deuteriated sodium hydroxide In dimethylsulfoxide-d6; water-d2 for 24h;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → α,α,α-Trifluoro-2,6-dinitro-p-cresol (393-77-1)

Conditions	Yield
With sodium hydroxide; water In 1,4-dioxane for 18h; Heating;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → α,α,α-trifluoro-2,6-diamino-N,N-dipropyl-p-toluidine (2078-06-0)

Conditions	Yield
With iron In methanol
With zero-valent iron nanoparticles with palladium In methanol
With sodium tetrahydroborate In water for 0.333333h; Reagent/catalyst;
With sodium tetrahydroborate In ethanol; water at 30℃; for 0.416667h;

2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzeneamine (1582-09-8) → 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole (51026-15-4) + α,α,α-trifluoro-2,6-dinitro-N-propyl-p-toluidine (2077-99-8)

Conditions	Yield
With 2,3-Dimethyl-2-butene; ozone Kinetics;

Upstream product

• 393-75-9 4-chloro-3,5-dinitrobenzotrifluoride 
• 142-84-7 di-n-propylamine 
• 79816-19-6 C₁₈H₂₆F₃N₄O₄^(1-)*K⁽¹⁺⁾ 
• 79871-51-5 C₁₇H₂₆F₃N₄O₄^(1-)*K⁽¹⁺⁾ 
• 72283-22-8 C₁₃H₁₇F₃N₃O₅^(1-) 

Downstream Products

• 51026-15-4 2-ethyl-4-nitro-6-(trifluoromethyl)-1H-benzimidazole 
• 2077-99-8 α,α,α-trifluoro-2,6-dinitro-N-propyl-p-toluidine 
• 2078-06-0 α,α,α-trifluoro-2,6-diamino-N,N-dipropyl-p-toluidine 
• 393-77-1 α,α,α-Trifluoro-2,6-dinitro-p-cresol 
• 2078-01-5 3-nitro-5-trifluoromethyl-1,2-phenylenediamine 
• 445-66-9 2,6-dinitro-4-trifluoromethylaniline 
• 2078-02-6 α,α,α-trifluoro-5-nitro-N⁴-propyltoluene-3,4-diamine 
• 69145-34-2 2,6-dinitro-4-trifluoromethyl-2',6'-dinitro-4'-<(trifluoromethyl)azo>benzene 
• 51026-15-4 2-ethyl-7-nitro-5-(trifluoromethyl)-1H-benzimidazole 
• 72283-22-8 C₁₃H₁₇F₃N₃O₅^(1-) 
• 79816-19-6 C₁₈H₂₆F₃N₄O₄^(1-)*K⁽¹⁺⁾ 
• 142-84-7 di-n-propylamine 
• 16766-93-1 1-Dipropylamino-2,6-dinitro-4-tribrommethyl-benzol 
• 79871-51-5 C₁₇H₂₆F₃N₄O₄^(1-)*K⁽¹⁺⁾ 

Relevant articles and documents

Trifluralin bulk drug synthesis method

The invention discloses a trifluralin bulk drug synthesis method, which comprises: carrying out a reaction by using p-chlorodinitrobenzotrifluoride and di-n-propylamine as raw materials, using causticsoda as a catalyst and using water as a reaction medium, and carrying out water washing, re-crystallization, centrifugation and vacuum drying to obtain trifluralin (2,6-dinitro-N,N-di-n-propyl-4-trifluoromethylaniline) finished product. Compared with the method in the prior art, the method of the invention has the following advantages that the used raw materials, catalysts and solvents are wide in source and convenient to prepare; caustic soda effectively promotes the reaction, the raw material conversion rate is high, the product selectivity is good, the synthesis reaction conversion rate ishigher than 99%, and the product purity is 99 wt%; the preparation process has low requirements on equipment, and special equipment does not need to be added; the discharge of three wastes in the reaction process is low, and the method is environment-friendly; and ethanol re-crystallization and convenient post-treatment are realized, so that the method is an environment-friendly trifluralin synthesis method and is beneficial to large-scale industrial development.

Synthesis method of trifluralin

The invention discloses a synthesis method of trifluralin. The method uses 4-chloro-3,5-dinitrotrifluorotoluene and di-n-propylamine as raw materials, a base as an acid binding agent, and vitamin C asan auxiliary agent, and the target compound is prepared under heating. The advantages of the method are as follows: (1) the used raw materials and auxiliary materials are wide in source, and convenient in preparation; (2) the catalytic effect is good, a raw material conversion rate is high, and the product selectivity is good; and (3) the content of N-nitroso-di-n-propylamine in the product is low, the post-treatment is simple and convenient, the method is a new preparation process of trifluralin, and the large-scale industrial development is facilitated.

Synthesis and evaluation of oryzalin analogs against Toxoplasma gondii

The synthesis and evaluation of 20 dinitroanilines and related compounds against the obligate intracellular parasite Toxoplasma gondii is reported. Using in vitro cultures of parasites in human fibroblasts, we determined that most of these compounds selectively disrupted Toxoplasma microtubules, and several displayed sub-micromolar potency against the parasite. The most potent compound was N1,N1-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3- benzenediamine (18b), which displayed an IC50 value of 36 nM against intracellular T. gondii. Based on these data and another recent report [Ma, C.; Tran, J.; Gu, F.; Ochoa, R.; Li, C.; Sept, D.; Werbovetz, K.; Morrissette, N. Antimicrob. Agents Chemother. 2010, 54, 1453], an antimitotic structure-activity relationship for dinitroanilines versus Toxoplasma is presented.

Synergistic herbicidal mixtures

PCT No. PCT/EP96/04935 Sec. 371 Date May 1, 1998 Sec. 102(e) Date May 1, 1998 PCT Filed Nov. 12, 1996 PCT Pub. No. WO97/17852 PCT Pub. Date May 22, 1997A synergistically active herbicidal composition which comprises, as active components, a mixture of 1-(3-chloro-4,5,6,7-tetrahydropyrazolo-[1,5-a]-pyridin-2-yl)-5-(methylpropargylamino)-4-pyrazolylcarbonitrile [Component (A)] and a herbicide selected from the group consisting of bentazone, molinate, daimuron, thiobencarb, butachlor, pretilachlor, dimepiperate, fenoxaprop-ethyl, clomeprop, cinmethylin, bromobutide, quinclorac, mefenacet, pyrazosulfuron-ethyl, esprocarb, cinosulfuron, thenylchlor, cumyluron, MK 243, naproanilide, anilofos, benfuresate, bifenox, CH-900, MCPA, nitrofen, oxadiazon, pendimethalin, simetryn, sulcotrione (ICIA0051), trifluralin, piperophos, pyributicarb, ethoxysulfuron, bensulfuronmethyl, pyrazolate, pyrazoxyfen, benzofenap, cyclosulfamuron, cyhalofop-butyl, NBA-061, azimsulfuron, propanil or imazosulfuron [Component (B)] and which are suitable for controlling undesirable plants in rice cultivation.

Synergistic herbicidal compositions comprising 4-benzoylisoxazole and dinitroaniline herbicides

The invention relates to synergistic compositions comprising: (a) a 4-benzoylisoxazole of formula (I) STR1 wherein R, R1, R2 and n are as defined in the specification; and (b) a dinitroaniline herbicide; and to the use of these compounds as herbicides.

Substituted pyridinesulfonamide compounds or their salts, process for preparing the same, and herbicides containing the same

A substituted pyridinesulfonamide compound or its salt represented by the following general formula (I): wherein R1 is an unsubstituted or substituted alkyl group; R2 is an unsubstituted or substituted alkyl group, or an unsubstituted or substituted alkoxy group; and X and Y are each independently a member selected from the group consisting of alkyl groups and alkoxy groups, is disclosed. This compound is useful as the effective ingredient of a herbicide showing a wide weed-control spectrum even if used in a small amount.

Plant-protective pesticidal composition

The invention relates to a plant-protective solution containing 2.5 to 40 % by weight of one or more water-insoluble plant-protective ingredient(s) 20 to 71.5 % by weight of dimethylformamide and/or dimethylsulfoxide and/or acetone as water-miscible solvent, 10 to 71.5 % by weight of furfurol and/or furfuryl alcohol as partially water-miscible solvent, 1 to 15 % by weight of commonly used additives such as anionic and/or nonionic surface active agents and macromolecules. The invention also relates to the ready-for-use plant-protective suspension containing 0.2 to 10 % by weight of one or more water-insoluble plant-protective ingredient(s) with a particle size of 0.1 to 50 μm, 0 to 60 % by weight of a fertilizer, 0.2 to 10 % by weight of dimethylformamide and/or dimethylsulfoxide and/or acetone as water-miscible solvent, 0.2 to 10 % by weight of furfurol and/or furfuryl alcohol as partially water-miscible solvent, 0.05 to 2.5 by weight of a commonly used additive such as anionic and/or nonionic surface active agents macromolecules and water in an amount supplementing up to 100 % by weight.

Agricultural sulfonamides

N-(heterocyclicaminocarbonyl)arylsulfonamides in which the aryl radical is substituted in the 2-position by a carboxy radical, ester, thioester, or amide thereof; e.g. N-[(4,6-dimethylpyrimidin-2-yl)-aminocarbonyl]-2-methoxycarbonylbenzenesulfonamide or N-[(4,6-dimethoxy-1,3,5-triazin-2-yl)aminocarbonyl]-2-methoxycarbonylbenzenesulfonamide; are useful for the regulation of plant growth and as pre-emergence and post-emergence herbicides.

Process for removing nitrosating agents from 1-chloro-2,6-dinitro-4-(trifluoromethyl) benzene

To obtain technical TRIFLURALIN with a nitrosoamine content not exceeding 1 ppm, for use as a herbicide, 1-chloro-2,6-dinitro-4-(trifluoromethyl) benzene (DINITRO-PCBT) is freed from nitrosating agents by a process in which DINITRO-PCBT is treated with an aqueous bisulphite solution having an SO2 concentration of between 1% and 5% at a pH of between 1 and 3, at a temperature of between 50° and 100° C. for a time of between 1 and 3 hours. The organic layer is then separated from the aqueous layer, and the acidity and last traces of the bisulphite solution are eliminated from the organic layer by means of an aqueous alkaline solution.

Method for removing nitrosation agent(s) from a nitrated aromatic compound

Nitrosation agent(s), contained as by-products in nitrated aromatic compounds after nitration with nitric acid or nitration acid, are removed by a water treatment, wherein the water is distilled off at least partially in vapor form, advantageously under reduced pressure. In the further reaction of the nitrocompounds treated in this manner undesired nitrosamines are practically not formed. The process is especially suitable for the manufacture of 4-di-n-propylamino-3,5-dinitrobenzotrifluoride (Trifluralin), a valuable herbicide, substantially free from nitrosamine(s).