Triforine

434.96

434.96

247-872-0

N1A4W8U0HH

263493

2588

DTXSID5032654

White to light brown crystals.

2933599019

64.7

2.20

1.554 g/cm³ @ Temp: 20 °C

155 °C (decomp)

561.5±50.0 °C at 760 mmHg

293.4±30.1 °C

1.571

In water, 30 mg/L at 25 deg C.

0-6°C

8 x 10 -2 Pa (25 °C)

Oral-Rat LD50: 6000 mg/kg; Oral-Mouse LD50: 6000 mg/kg

Combustion produces toxic chloride and nitrogen oxide gases

Henry's Law constant = 3.8X10-9 atm-cu m/mole @ 25 °C /Estimated/

pKa = 10.6

185.83 Ų [M+Cl]-

Stable at less than or equal to 180 °C. Decomposed in aqueous solution exposed to UV or daylight. Decomposed in strongly acidic media (to trichloroacetaldehyde and piperazine salts) and in strongly alkaline media (to chloroform and piperazine); half-life of 3.5 days at pH 5 to 7 , 25 °C.|Hydroxyl radical reaction rate constant = 6.6X10-11 cu cm/molecule-sec @ 25 °C /Estimated/

No rapid reaction with air. No rapid reaction with water.

Amides and Imides

A piperazine, trichloromethylformamide derivative. Decomposed in strong acid to trichloroacetaldehyde and piperazine salts, and in strongly alkaline media to chloroform and piperazine.

UN3077 (solid); UN3082 (liquid)

2

52/53-20

61

TK9200000

Xn

The warehouse is ventilated, low temperature and dry; stored and transported separately from food materials

Stable </=180 deg C.

P261, P264, P270, P271, P301+P312, P304+P312, P304+P340, P312, P330, P501

H332

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.

Should no be mixed with wetting agents, spreader-stickers, or other adjuvants.

|Warning|H302 (80.41%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P301+P312, P304+P312, P304+P340, P312, P330, and P501|Aggregated GHS information provided by 194 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Goggles, face shield and impervious clothing including gloves, apron and overshoes when handling.

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/

practically nontoxic

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.

LD50 Rabbit dermal >10 g/kg|LD50 Rat dermal >10 g/kg|LD50 Rat oral >16 g/kg|LD50 Dog oral >2 g/kg|For more Non-Human Toxicity Values (Complete) data for TRIFORINE (7 total), please visit the HSDB record page.

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).

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).

The rate constant for the vapor-phase reaction of triforine with photochemically-produced hydroxyl radicals has been estimated as 6.6X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 6 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). A hydrolysis half-life of 2 to 3 days was reported for triforine(2). The compound decomposes in strongly acidic media to trichloroacetaldehyde and piperazine salts and in strongly alkaline media to chloroform and piperazine(3). Triforine decomposes in aqueous solution exposed to UV or daylight(3).

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).

199.53 L/kg|A Koc of 200 has been reported for triforine(1). According to a classification scheme(2), this Koc value suggests that triforine is expected to have moderate mobility in soil.

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).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 644 workers (123 of these are female) are potentially exposed to triforine in the US(1). The NOES Survey does not include farm workers. Occupational exposure to triforine may occur through inhalation and dermal contact with this compound at workplaces where triforine is produced or used(SRC). Monitoring data indicate that the general population may be exposed to triforine via ingestion of food and dermal contact with consumer products containing triforine(SRC).

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.

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.

Skin decontamination. Dermal contamination should be washed off with soap and water. Flush contamination from the eyes with copious amounts of water. If irritation persists, specialized medical care should be obtained. /Miscellaneous organic fungicides/|Gastrointestinal decontamination. If a large amount of the fungicide has been ingested in the last few hours, and if copious vomiting has not already occurred, it may be reasonable to consider GI decontamination. Activated charcoal can be used along with the addition of the cathartic sorbitol to the charcoal slurry. If sorbitol is given separately, it should be diluted with an equal volume of water before administration. No more than one dose of sorbitol is recommended and it should be used with caution in children and the elderly. ...If contact with the toxicant has been minimal (for example, oral contamination only, promptly flushed out of the mouth), administration of charcoal without a cathartic, followed by careful observation of the patient, probably represents optimal management. /Miscellaneous organic fungicides/

/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.

N,N'-bis(1-formamido-2,2,2-trichloroethyl)piperazine

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).

Product analysis by thin layer chromatography. Residues determined by GLC

Agrochemicals -> Acaricides, Fungicides|Fungicides