Yanagisawa, Toshihiko published the artcileSubacute and chronic toxicity studies of triethylenetetramine dihydrochloride (TJA-250) by oral administration to F-344 rats, Safety of N1,N1′-(Ethane-1,2-diyl)bis(ethane-1,2-diamine) dihydrochloride, the publication is Journal of Toxicological Sciences (1998), 23(Suppl. 4), 619-642, database is CAplus and MEDLINE.
Triethylenetetramine dihydrochloride (trientine-2HCl, TJA-250), a copper chelating agent used to treat Wilson’s disease, was administered orally to male and female F-344 rats for 4 or 8 wk at dosages of 0, 100, 350 or 1200 mg/kg/day or for 26 wk at dosages of 50, 175 or 600 mg/kg/day. Two males receiving 1200 mg/kg/day died during week 8 of treatment. In males receiving 1200 mg/kg/day during weeks 5 to 8 of treatment, body weight gain and food consumption were decreased and hunched posture and thin build were observed During week 4 or 8 of treatment urinalysis revealed, for males receiving 100 mg/kg/day or animals receiving 350 mg/kg/day or more, increased electrolyte outputs possibly due to the hydrochloride nature of trientine-2HCl, with low plasma alk. phosphatase activities evident in animals receiving 350 or 1200 mg/kg/day. After 4 and 8 wk, and during 8 wk of treatment, high lung weights and bronchiolar epithelium hypertrophy and broncho-alveolar pneumonia were recorded for animals receiving 1200 mg/kg/day, and submucosal acute inflammation within the glandular region of the stomach was recorded for males receiving 350 or 1200 mg/kg/day and in all treated female groups. One male receiving 175 mg/kg/day and three males receiving 600 mg/kg/day died, showing lung changes in the 26 wk study. The body weight gain of animals receiving 600 mg/kg/day was slightly decreased. Blood chem. and urinalysis examinations showed changes similar to those indicated in the 4- or 8-wk study. The low plasma copper concentrations seen in males receiving 600 mg/kg/day, the slightly low liver copper concentrations found in animals receiving 600 or 175 mg/kg/day and the high urinary copper concentrations found in all treated groups, are attributed to the pharmacol. action of trientine-2HCl. Histopathol. revealed a dosage-related incidence and severity of focal chronic interstitial pneumonitis accompanied by fibrosis of the alveolar walls in females receiving 175 mg/kg/day or more and all treated male groups, but no significant pathol. changes in the stomach. Apart from the histol. changes found in the lung, all the above changes were reversible. In conclusion, the NOAEL of trientine-2HCl in this 26-wk study was considered to be 50 mg/kg/day for females and less than 50 mg/kg/day for males.
Journal of Toxicological Sciences 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 C4H3Cl2N3, Safety of N1,N1′-(Ethane-1,2-diyl)bis(ethane-1,2-diamine) dihydrochloride.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia