2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine

Endpoint summary

Additional information

The absorption, distribution, metabolism and excretion of¹⁴C-FR-245 have been studied after a single oral application to rats at concentrations of 50mg/kg/day and 1000mg/kg/day.

Absorption and Excretion: The radioactivity was entirely excreted via the faeces (95.4-105%) with the majority excreted within the interval 0-48 hours. Only very low amounts of radioactivity were found in the urine (0.2%), expired air (<0.1%), carcass (<0.01% low dose; 0.03-1.27% high dose) and cage washes (0.01-0.26%). Total absorption was therefore, 0.2% of the administered dose. No biliary excretion was considered to have occurred since the majority of faecal radioactivity was recovered within a short time period (0-48 hours) and was mainly unmetabolised parent compound. Thus, there was no significant additional contribution from entero-hepatic recirculation via the bile to the overall absorption for this compound.

 

Distribution: The proportion of the absorbed dose in all tissues, carcasses and including blood at the time of the peak plasma concentration (4 hours) was only 0.3%. This reduced to 0.2-0.3% after 24 hours and to < 0.01-0.02% after 168 hours. The maximum proportion of the dose in whole blood was only 0.05-0.07% indicating there was minimal absorption into the blood stream and re-circulation back to the intestine via bile.

At 4 hour sampling the highest levels were detected in liver and kidney with all other tissues concentrations representing less than 151 ng equivalents/g. At 24 hour sampling the highest levels were detected in liver, kidney, epididymis, ovaries and uterus with all other tissue concentrations less than 86.1 ng equivalent/g.After 168 hours the highest concentrations were detected in epididymis, fat and kidney with all other tissue representing less than 14.5ng equivalent/g.

Metabolites: The majority (81.3-93.2%) of the excreted radioactivity over 0-48 hours was confirmed by analysis to be unmetabolised FR-245 parent test substance. Several unknown components were detected none of which represented greater than 2/6% of the dose. The minor components detected (total of <9.1%) are most likely formed as a results of the aggressive action of both gastric and intestinal secretions, including various enzymes, on FR-245 molecules during transit through the gastro-intestinal tract.

 

Based on the experimental results it can be concluded that FR-245 is not likely to accumulate in biological tissues.