1,4-ビス(2,2,2-トリクロロ-1-ホルミルアミノエチル)ピペラジン

Acaricides, Fungicides

Active substance -> EU Pesticides database: Not approved

Pesticides -> Fungicides

Fungicides

Pesticide (Triforine) -> USDA PDB

log Kow = 2.20

2.2

Readily soluble in dimethylformamide (330 g/L), dimethyl sulfoxide and N-methylpyrrolidone (476 g/L). Soluble in tetrahydrofuran. Slightly soluble in acetone (11 g/L), dichloromethane (1 g/L), methanol (10 g/L), dioxane, and cyclohexanone. Insoluble in benzene, petroleum ether and cyclohexane.

Soluble in CMF, DMSO, N-methylpyrrolidine; moderately soluble in tetrahydrofuran; Insolubgle in acetone, benzene, carbon tetrachloride, chloroform, methylene chloride, and petroleum ether.

In water, 30 mg/L at 25 °C.

When heated to decomposition it emits toxic fumes of /nitrogen oxides and hydrogen chloride/

Decomposed to chloral and piperazine salts by concentrated /sulfuric acid/ and /hydrochloric acid/; slowly decomposed to chloroform and piperazine by concentrated alkali.

Decomposed in aqueous solution exposed to u.v. or daylight. Decomposed in strongly acidic media (to trichloroacetaldehyde and piperazine salts) and in strongly alkaline media (to chloroform and piperazine); DT50 (pH 5-7, 25 °C) 3.5 days.

0.0000002 [mmHg]

2.00X10-7 mm Hg at 25 °C.

Triforine appears as colorless crystals. Non corrosive. Used as a fungicide.

White solid; [Merck Index] Colorless solid; [CAMEO] White to light brown solid; [HSDB] White solid; Formulated as emulsifiable concentrate and ready-to-use aerosol; [Reference #2]

Warning

H302 (41.8%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P270, P271, P301+P317, P304+P340, P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 67 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard Traits - Developmental Toxicity

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

2002/2076

Triforine: 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.

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

Low acute toxicity in animals, and no cases of human poisoning reported; [EPA Pesticides] Allergic contact dermatitis reported in chrysanthemum growers; [Kanerva, p. 787; PMID 7821004] No evidence in rats of adverse effects to male or female fertility or teratogenicity; The metabolite dinitrosopiperazine is carcinogenic in mice exposed transplacentally and by lactation; [REPROTOX]

Tolerances are established for residues of the fungicide triforine (N,N-(1,4-piperazinediylbis(2,2,2-trichloroethylidene))bis(formamide)) in or on the following food commodities: almond, hulls; almond; apple; apricot; bell pepper; blueberry; cantaloupe; cherry; cranberry; cucumber; eggplant; hop, dried cone; hop, spent; nectarine; peach; plum; plum, prune, fresh; strawberry; and watermelon.

Tolerances with regional registration are established for residues of the fungicide triforine (N,N-(1,4-piperazinediylbis(2,2,2-trichloroethylidene))bis(formamide)) in or on the following food commodities: asparagus.

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. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Triforine is found on List B. Case No: 2720; Pesticide type: fungicide; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the RED document.; Active ingredient (AI): N,N'-(1,4-piperazinediyl-bis(2,2,2-trichloroethylidine))bis(formamide); Data Call-in (DCI) Date(s): 06/12/1991, 03/06/1995, 10/13/1995; AI Status: The producers of the pesticide have made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

Do not store below 32 °F

Store in a cool dry place, Avoid prolonged exposure to temperatures above 100 °F

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. 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 soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

The protective clothing should be kept in separate places where it cannot be contaminated with toxic chemicals. It should be forbidden to keep this clothing in living quarters. Protective clothing must be washed at least once a week and each time it is contaminated with pesticides. Before washing the clothing should be soaked for several hours in a calcium carbonate solution. /Pesticides/

Smoking, eating, and drinking before washing should be absolutely prohibited when any pesticide ... is being handled or used. /Pesticides/

Tolerances are established for residues of the fungicide triforine (N,N-(1,4-piperazinediylbis(2,2,2-trichloroethylidene))bis(formamide)) in or on the following food commodities: almond, hulls, 0.20 ppm; almond, 0.01 ppm; apple, 0.01 ppm; apricot, 8.0 ppm; bell pepper, 5.0 ppm; blueberry, 0.1 ppm; cantaloupe, 1.0 ppm; cherry, 3.0 ppm; cranberry, 0.1 ppm; cucumber, 0.5 ppm; eggplant, 1.0 ppm; hop, dried cone, 60 ppm; hop, spent, 60 ppm; nectarine, 8.0 ppm; peach, 8.0 ppm; plum, 3.0 ppm; plum, prune, fresh, 3.0 ppm; strawberry, 2.0 ppm; and watermelon, 1.0 ppm.

Tolerances with regional registration are established for residues of the fungicide triforine (N,N-(1,4-piperazinediylbis(2,2,2-trichloroethylidene))bis(formamide)) in or on the following food commodities: asparagus, 0.01 ppm.

Groups of 25 or 50 male and 25 or 50 female Swiss mice were given 0.05% sodium nitrate in drinking-water, triforine suspended in water at 300 mg/kg bw by gavage twice each week, or a combination of the two treatments for up to 180 days. Tumor incidences were compared with those in a control group of 184 males and 117 females. Triforine alone did not increase the number of tumors; however, the combination increased the frequencies of lymphomas (including thymoma) and of epithelial adenomas and carcinomas of the gastrointestinal tract, the lung, and, in males, the liver. Incubation of triforine with 4% acidified sodium nitrite solution for 24 hr formed dinitrosopiperazine, which is known to be carcinogenic and was suspected to be the substance that induced the tumors.

LC50 Oncorhynchus mykiss (Rainbow trout) >1,000 mg/L/96 hr; static

LC50 Lepomis macrochirus (Bluegill sunfish) >1,000 mg/L/96 hr; static

LD50 Colinus virginianus (Bobwhite quail, >/=16 weeks) oral >5,000 mg/kg

LC50 Daphnia magna (Water flea) 117 mg/L/48 hr /Conditions of bioassay not specified in source examined/

For more Ecotoxicity Values (Complete) data for TRIFORINE (12 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), a Koc value of 200(2), indicates that triforine is expected to have moderate mobility in soil(SRC). Volatilization of triforine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.8X10-9 atm-cu m/mole(SRC), based upon its vapor pressure, 2.0X10-7 mm Hg(3), and water solubility, 30 mg/L(3). Triforine is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). A half-life of 19 days was reported for triforine in soil(4).

AQUATIC FATE: Based on a classification scheme(1), a Koc value of 200(2), indicates that triforine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.8X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 2.0X10-7 mm Hg(4), and water solubility, 30 mg/L(4). According to a classification scheme(5), an estimated BCF of 10(SRC), from its log Kow of 2.20(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Triforine decomposes in aqueous solution exposed to UV or daylight(6). A hydrolysis half-life of 2 to 3 days was reported for triforine(8).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), triforine, which has a vapor pressure of 2.0X10-7 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase triforine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 6 hrs(SRC), calculated from its rate constant of 6.6X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase triforine may be removed from the air by wet and dry deposition(SRC).

/HUMAN EXPOSURE STUDIES/ Medical reports from three companies that synthesize triforine were available. Boehringer Ingelheim, Germany, examined 12 workers repeatedly between 1970 and 1983 and reported no hematological or blood chemical results considered to be related to exposure to triforine. The industrial medical service of E. Merck Co., Darmstadt, Germany, found no adverse systemic, dermal, or mucosal effects of exposure to triforine among production workers during routine examinations performed in conformity with the requirements of the German Chemical Trade Union. No adverse effects were observed during triforine production at Shell Agrar GmbH in Spain between 1987 and 1993.

/HUMAN EXPOSURE STUDIES/ ...In a mass examination of chrysanthemum growers among whom triforine was commonly used, the highest rate of positive patch test reaction was seen to triforine (17%) among the 7 pesticides and chrysanthemum extracts tested. A higher prevalence rate of work-related skin symptoms was seen in subjects with a positive patch test reaction to triforine (44%) than in those with negative reactions to all allergens tested (15%) (p<0.05). 12 subjects (67%) with positive patch test reactions to triforine were also positive to dichlorvos (DDVP), with a high kappa coefficient (0.65). The grading of guinea pig maximization test to triforine was grade IV (66%), defined as "strong". Cross-sensitization between triforine and dichlorvos was also shown. The present results confirm that triforine is capable of including delayed-type allergy among chrysanthemum growers and of showing cross-reactivity with dichlorvos.

Triforine's production may result in its release to the environment through various waste streams; it's use as a foliar and postharvest fungicide active against powdery mildew, rust and leaf spot diseases of fruit, ornamentals, vegetables, and cereals(1) will result in its direct release to the environment(SRC).

An estimated BCF of 10 was calculated for triforine(SRC), using a log Kow of 2.20(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC), provided the compound is not altered physically or chemically once released into the environment(SRP).

The Henry's Law constant for triforine is estimated as 3.8X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 2.0X10-7 mm Hg(1), and water solubility, 30 mg/L(1). This Henry's Law constant indicates that triforine is expected to be essentially nonvolatile from water surfaces(2). Triforine's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may not occur(SRC). Triforine is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

/LABORATORY ANIMALS: Acute Exposure/ In a Maurer optimization test involving aggravation of testing conditions by additional injection of Freund's adjuvant in groups of 12 male and 12 female Dunkin-Hartley albino guinea-pigs, triforine (purity, 99.9%) showed no sensitizing potential after epidermal and intradermal challenge.

/LABORATORY ANIMALS: Acute Exposure/ Triforine, moistened with water and left on the shaven skin of Sprague-Dawley rats for 24 hr, was tolerated with no irritation up to a dose of 10,000 mg/kg bw. When 0.5 g of moistened triforine (purity, 98.1%) was applied to shaven skin areas of three male and three female New Zealand white rabbits and left on the skin for 4 hr under a semi-occlusive bandage, no erythema or edema occurred within the 72-hr follow-up.

/LABORATORY ANIMALS: Acute Exposure/ No reactions occurred in mucosa or eyes of New Zealand white rabbits after insertion of 0.1 g triforine into the conjunctival sac. When triforine (purity, 98.1%) was inserted into the conjunctival sac of three male and three female New Zealand white rabbits, all rabbits showed mild local reactions (reddening, chemosis, discharge) 1 hr after application. The reaction disappeared almost entirely within 24 hr, and only one female still had minor conjunctival reddening (mean cumulative score, 0.17). No changes were observed in the eyes with a slit-lamp ophthalmoscope 48 and 72 hr after application. No systemic clinical reactions occurred during the testing period, and body weight was not affected. The overall irritation score was 0.83 out of a maximum attainable score of 13.

/LABORATORY ANIMALS: Acute Exposure/ The acute toxicity of triforine has been tested by administration by various routes in mice, rats, and dogs. The only reported observations were reduced activity, swaying, or dyspnea. There were no deaths, and no substance-induced changes in organs were detected post mortem.

For more Non-Human Toxicity Excerpts (Complete) data for TRIFORINE (22 total), please visit the HSDB record page.

Tolerances are established for residues of the fungicide triforine (N,N-(1,4-piperazinediylbis(2,2,2-trichloroethylidene))bis(formamide)) in or on the following food commodities: almond, hulls; almond; apple; apricot; bell pepper; blueberry; cantaloupe; cherry; cranberry; cucumber; eggplant; hop, dried cone; hop, spent; nectarine; peach; plum; plum, prune, fresh; strawberry; and watermelon.

Tolerances with regional registration are established for residues of the fungicide triforine (N,N-(1,4-piperazinediylbis(2,2,2-trichloroethylidene))bis(formamide)) in or on the following food commodities: asparagus.

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. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern and List D pesticides of less concern. Triforine is found on List B. Case No: 2720; Pesticide type: fungicide; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the RED document.; Active ingredient (AI): N,N'-(1,4-piperazinediyl-bis(2,2,2-trichloroethylidine))bis(formamide); Data Call-in (DCI) Date(s): 06/12/1991, 03/06/1995, 10/13/1995; AI Status: The producers of the pesticide have made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

Triforine is rapidly metabolized and excreted in rats; unchanged compound accounts for only 0-5% of the dose. Substantial quantities of unchanged triforine were recovered only from feces. The first metabolite to be identified was N-[2,2,2-trichloro-1-(piperazin-1-yl)ethyl]-formamide, which is formed by the cleavage of an entire side chain. In later metabolic studies with 14C labelling in the piperazine ring and aliphatic side chain, triforine underwent virtually complete metabolism after administration as a single oral dose of 10 mg/kg bw. N-[2,2,2-Trichloro-1-(piperazin-1-yl)ethyl]formamide, the major radiolabelled urinary component in rats receiving [piperazine 14C]-triforine, accounted for 46-53% of the dose over 0-24 hr; however, in rats receiving side-chain-labelled 14C-triforine, the proportion was reduced to 24-27% after a single 10 mg/kg bw dose and 21-24% after repeated doses. It was excreted as the glucuronide. The side-chain metabolite trichloroethanol and its glucuronide represented 18-21% of the dose. Another side-chain metabolite occurring in the urine was the N-acetylcysteine conjugate of 2,2,2-trichloroethylamine, which represented 13-15% of the administered dose. In feces collected from female rats over 0-48 hr, 3.6% of the single 10 mg/kg bw dose and 3.4% of the repeated doses was present as N-[2,2,2-trichloro-1-(piperazin-1-yl)ethyl]formamide. This metabolite was not detected in the feces of rats receiving 1,000 mg/kg bw. Very little unchanged triforine (0-1%) was detected in the feces of rats given the low dose, whereas it represented 70-80% of the dose in rats given 1,000 mg/kg bw. This result suggests that absorption of triforine is a saturable process, unless there is extensive biliary excretion at the high dose.

The absorption and disposition of 14C-triforine suspended in 5% aqueous sodium carboxymethylcellulose was studied in male and female CD Sprague-Dawley-derived rats at doses of 10 mg/kg bw, /orally/ as a single dose and after treatment with unlabelled triforine for 14 days, and 1,000 mg/kg bw as a single radiolabelled dose. Both side-chain and ring-labelled 14C-triforine were available, but piperazine ring-labelled 14C-triforine was used only in a pilot experiment in which a single dose of 10 mg/kg bw was administered to two male and two female rats. In this experiment, the mean proportions of the administered dose excreted during 120 hr were: urine, 77% in males and 82% in females; feces, 18% in males and 19% in females; expired air, 3.3% in males and 1.5% in females; <3% remained in the carcass. Most of the radiolabel (73% in males and 76% in females) was excreted in the urine within 0-24 hr. In the main study with side-chain-labelled 14C-triforine, in which single doses of 10 mg/kg bw were given to five male and five female rats, the mean proportions of the administered dose excreted during 120 hr were: urine, 78% in males and 79% in females; feces, 12% in males and 14% in females; expired air, 5.2% in males and 6.0% in females. Less than 3% remained in the carcass. Most of the radiolabel (75% in males and females) was excreted in the urine within 0-24 hr.

...Side-chain-labelled 14C-triforine was administered /orally/ as a single dose of 1,000 mg/kg bw. The mean proportions of the administered dose excreted during 120 hr were: urine, 11% in males and 19% in females; feces, 85% in males and 77% in females; expired air, 0.9% in males and 1.6% in females. Only about 0.5% remained in the carcass. Most of the urinary radiolabel (7.7% in males and 12% in females) was excreted within 6-48 hr. The delayed urinary excretion (in comparison with /other/ experiments) probably reflects absorption limited by the dissolution rate. More than 90% of the radiolabel recovered from the feces over 0-72 hr was associated with side-chain-labelled 14C-triforine and presumably represented unabsorbed material.

Used as a fungicide on almonds, apples, asparagus, blueberries, cherries, hops, ornamentals, peaches, and roses; [EXTOXNET] Used as food additive, fungicide, and agricultural chemical; [Hawley] Registered in the US as fungicide for use on ornamental bushes, trees, and vines; [Reference #2]

All food uses voluntarily cancelled in the US in 1996; [Reference #2]

Farming (Pesticides) [Category: Industry]

For triforine (USEPA/OPP Pesticide Code: 107901) ACTIVE products with label matches. /SRP: Registered for 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./

For use against powdery mildew, scab, rust, and other diseases of fruits, vegetables, cereals, and ornamentals. Scab, powdery mildew, and rust on apples; postharvest for brown rot blossom blight on peaches, nectarines, almonds, apricots; mummyberry disease on high bush blueberries; powdery mildew, black spot, and rust on roses; powdery mildew, rust on various other ornamentals.

Control of powdery mildews on cereals, fruit, vines, hops, ornamentals, cucurbits, and some vegetables; rusts on cereals, fruit, ornamentals, and beans; Monilia spp. on stone fruit; Ascochyta blight on chrysanthemums; black spot on roses; scab on apples; and fairy rings on turf. Also suppresses tetranychid mite activity.

Chloral + formamide + piperazine (reductive amination/oxidative coupling)

Triforine is produced by reaction of piperazine with (1,2,2,2-tetrachloroethyl)formamide in the presence of triethylamine.

Dispersible concentrate, wettable powder.

Emulsifiable concentrate, wettable powder.

Tradenames: Saprol (BASF); Denarin (BASF); Funginex DC (BASF); Funginex (BASF); Tarsol (Aventis).

Phytotoxic to certain varieties of pear.

The following crops were treated with triforine in the United States during the 1989 to 1991 crop years (from federal and state pesticide surveys of fungicide use patterns), percent treated: almonds, 1%; apples, 2%; apricots, 7%; asparagus, 6%; blueberries, 42%; cherries, 11%; cranberries, 7%; nectarines, 25%; peaches, 31%; and plums, 3%(1).