Effects of Oral Tag 1-MeATN02 (TRIAMINOGUANIDINIUM-1-METHYL-5- NITRIMINOTETRAZOLATE-TAG-MNT/K-26) Exposure to Female Rats (RATTUS NORVEGICUS) TAG-MNT/K-26 Exposure to Female Rats (Rattus norvegicus)

摘要

The objective of this research is to determine the oral LD50 of Triaminoguanidinium- 1-methyl-5nitriminotetrazolate (TAG-MNT), and to determine if adverse effects occur fom a 14-day repetitive oral exposure regime of TAG- MNT in the female rat, i.e., derive the no-observable-effect-level (NOAEL) and lowest-observed-effect-level (LOAEL). TAG-MNT is not acutely toxic at the limit dose, but as early as 14-days of daily oral exposure caused liver toxicity and death. The primary target organ is the liver; TAG-MNT causes centrilobular hypertrophy, vacuolization and increased liver weight. In the higher dose groups liver pathology is correlated with decreased food consumption, body weight loss, and death. The LOAEL from oral exposure to TAG-MNT for 14-days, as determined from this study, is 50 mg/kg-day based on significant adverse event of increased kidney and liver weight ratios and adverse histological alterations in the liver. The NOAEL is therefore determined to be 250 mg/kg-d where only mild adaptive hepatic vacuolization was observed in a subset of exposed individuals.