Yakuri to Chiryo published new progress about 38260-01-4. 38260-01-4 belongs to catalysis-chemistry, auxiliary class Chelating Agents, name is N1,N1′-(Ethane-1,2-diyl)bis(ethane-1,2-diamine) dihydrochloride, and the molecular formula is C6H20Cl2N4, Application In Synthesis of 38260-01-4.
Maemura, Shunichi published the artcileMaximum tolerated dose and repeated dose toxicity studies of triethylenetetramine dihydrochloride, a copper chelating agent, by oral administration to beagle dogs, Application In Synthesis of 38260-01-4, the publication is Yakuri to Chiryo (1998), 26(5), 745-767, database is CAplus.
Triethylenetetramine dihydrochloride (trientine-2HCl), a copper chelating agent used to treat Wilson’s disease, was tested for maximum tolerated dose and, subacute and chronic toxicity in beagle dogs. Maximum tolerated dose study. One male and one female beagle dogs received trientine-2HCl by oral administration of variable dosages (50 to 2000 mg/kg) or at constant dosages of 200 or 600 mg/kg/day for two weeks. After one administration at 2000 or 1000 mg/kg severe signs (abnormal gait, ataxia, emesis, diarrhea, body tremor) and marked bodyweight loss were evident. In the constant dosage phase similar effects of treatment were apparent in both animals receiving 600 mg/kg/day. The approx. LD was considered to be more than 2000 mg/kg. Four week study. Beagle dogs received trientine-2HCl orally at dosages of 50, 125 or 300 mg/kg/day for 4 wk followed by a 4-wk reversibility phase. There were no deaths. For some animals receiving 300 mg/kg/day, during the last week of treatment underactivity, abnormal gait, ataxia and body tremor were observed In the lungs, interstitial pneumonia was recorded for one control male and four animals that received 300 mg/kg/day with or without recovery. Toxicokinetic anal. revealed that exposure of the animals to trientine-2HCl was dosage-dependent and that no significant accumulation of trientine-2HCl occurred during the dosing period. Twenty-six week study. Beagle dogs were scheduled to receive trientine-2HCl orally at dosages of 50, 100 or 200 mg/kg/day for 26 wk followed by a 13-wk reversibility phase. However, in view of the severe signs which resulted in the sacrifice for humane reasons of two males and one female receiving 200 mg/kg/day during week 9 of treatment, surviving dogs of this group were only treated for 10 wk. Signs before despatch included marked underactivity, body tremors, abnormal gait, limited use of limb and prone posture. The ante mortem neurol. examination generally indicated depressed postural and flexor withdrawal reactions. The signs were rapidly reversible except in the one female which was killed humanely on day 2 of the reversibility period. Abnormal “stiff legged” gait and underactivity were evident, from week 23 of treatment, in two males and one female receiving 100 mg/kg/day. In the absence of any macroscopic or histopathol. findings, even after the examination of addnl. samples of muscle and nerve, the exact nature of this condition could not be elucidated. In all treated groups low copper and zinc concentrations in the livers and high urinary copper and zinc concentrations were found. The no-observed-adverse-effect level was considered to be 50 mg/kg/day.
Yakuri to Chiryo published new progress about 38260-01-4. 38260-01-4 belongs to catalysis-chemistry, auxiliary class Chelating Agents, name is N1,N1′-(Ethane-1,2-diyl)bis(ethane-1,2-diamine) dihydrochloride, and the molecular formula is C6H20Cl2N4, Application In Synthesis of 38260-01-4.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia