TRIFORINE JMPR 1977 IDENTITY Chemical name 1,4-bis(2,2,2-trichloro-1-formamidoethyl)piperazine 1,1'-piperazine-1,4-diyldi-(N-(2,2,2-trichloroethyl)formamide) Synonyms Cela W 524, W 524, Saprol(R), Flanginex Structural formulaOther information on identity and properties State: colorless and odorless, crystalline Melting point: 155°C Triforine is hydrolysed rapidly in aqueous solutions at 21°C, about 50% being degraded in the first two clays with the formation of chloride ions and, through several intermediates, 1-(dihydroxyacetyl)piperazine and piperazine. On exposure to sunlight, about half of the triforine was degraded in 150 hours. Photolysis by ultraviolet light in the absence of water leads preferentially to the removal of one side chain, the second side chain being attacked more slowly. In aqueous solution, triforine is rapidly decomposed by ultraviolet light. N-(2,2dichlorovinyl)formamide was isolated as an intermediate photodecomposition product (Darda et al., 1977), After 3 hours irradiation with u.v. light or 30 hours exposure to sunlight, 50% of triforine in aqueous solution was inactivated (Buchenanery 1975). EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, metabolism and excretion Male Wistar rats, weighing approximately 200 g, were dosed orally with 2.3 3H)-triforine (ring labelled) or 3.75 mg 14C-triforine (side chains labelled. After oral administration to 9 animals the blood level curve passed its maximum (1.3% of the administered dose) 4 hours after dosage, followed by a more rapid decrease in the 4-10 hours interval and a subsequent slower fall. At the end of this blood level experiment (96 hours), an average of 0.3% of the administered radioactivity was present in the total blood compartment of the rat. The main portion of the total radioactivity, 74.3% of the (3H)-triforine and 52.5% of the (14C)-labelled triforine, was excreted reneally within the first 24 hours. In this period the faecal excretion amounted to 16.5% of the (3H)-labelled and 39.5% of the (14C)-labelled triforine. The average total triforine eliminated by the rat within one day of dosing was 90.8% (3H) and 92.0% (14C). During a period of 30 hours after dosing, 19% of the orally administered (3H) dose was 15% of the (14C) dose was excreted via the bile. The elimination in the urine following increased dose of triforine (25, 50, 100 and 200 mg/kg for 8 animals) followed the same metabolic pattern: 70% of the (3H)-labelled and 50% of the (14C)-labelled substance was excreted after 24 hr. The main metabolite in the urine was identified as N-(2,2,2-trichloro-1-(piperazin-1-yl)ethyl)formaide (Darda, 1977). COMMENTS In rats, the compound was rapidly absorbed and excreted, mainly in the urine. The main metabolite was N-(2,2,2-trichloro-1-(piperazin-1-yl)ethyl)formaide. Full toxicological data are required before a recommendation of the ADI for humans can be made. RESIDUES IN FOOD AND THEIR EVALUATION No data were available for consideration. FURTHER WORK OR INFORMATION REQUIRED by 30 June 1978 and before an acceptable daily intake for humans (ADI) can be established and maximum residue limits (MRL) can be recommended. 1. Submission of full data relating to toxicological and residue studies. REFERENCES Buchanauer, H. (1975) Inactivation of triforine by u.v. and sunlight on glass and on leaves of bean plant. Pestic. Sci. 6, 553-559. Darda, S. (1977) Absorption, metabolism and excretion of the fungicide triforine in the rat. Pestic. Sci. 8, 193-202. Darda, S., Darskus, R.L., Eichler, D. Ost, W. and Wotschokowsky, M. (1977) Hyrdolysis and photolysis of the fungicide triforine. Pestic. Sci 8, 183-192.
See Also: Toxicological Abbreviations