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Diss Factsheets

Administrative data

additional toxicological information
Type of information:
Adequacy of study:
supporting study
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference Type:
other: Derek analysis
Report date:

Materials and methods

Test guideline
no guideline followed
Principles of method if other than guideline:
DEREK for Windows 13.0.0
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
N-butyl-2,2,6,6-tetramethylpiperidin-4-amine, oligomeric reaction products with N,N'-bis(3-aminopropyl)ethylenediamine and 2,4,6-trichloro-1,3,5-triazine
EC Number:
EC Name:
N-butyl-2,2,6,6-tetramethylpiperidin-4-amine, oligomeric reaction products with N,N'-bis(3-aminopropyl)ethylenediamine and 2,4,6-trichloro-1,3,5-triazine
Cas Number:
1,3-Propanediamine,N-N’’-1,2-ethanediylbis- reaction product with 1,3,5-triazine-2,4-diamine,N,N’-dibutyl-6-chloro-N,N’-bis(2,2,6,6-tetramethyl-4-piperidinyl), polymer with N-butyl-4,6-dichloro-N-(2,2,6,6-tetramethyl-4-piperidinyl)-1,3,5-triazin-2-amine

Results and discussion

Any other information on results incl. tables

This alert describes the hepatotoxicity of 2,4-diamino substituted 1,3,5-triazines and is based primarily on 28-day repeat-dose study data contributed by a Lhasa Limited member. These compounds have been reported to cause hepatocellular damage observed as hypertrophy, single cell necrosis and vacuolization of hepatocytes, increases in liver weight, elevation of hepatic enzymes and cholesterol levels and damage to the bile canaliculi in experimental animals. The mechanism of toxicity remains unknown but it could be associated with their

metabolism. The metabolic routes of these compounds in humans and rodents involve primarily N-dealkylation reactions of the nitrogen side chains and/or glutathione conjugation [1, 2]. In vitro hepatotoxicity studies on fresh isolated hepatocytes and primary cultured hepatocytes of ametryn and prometryn gave a positive response for cytotoxicity characterised by decreased levels of glutathione content in the cells and increased levels of lactate dehydrogenase [3].

Applicant's summary and conclusion

DEREK for Windows 13.0.0 predicts that hepatotoxicity is PLAUSIBLE in human and mammal due to Alert 651 – 2,4-Diamino-1,3,5-triazine. HA88 is a very large dimer derived from 2,4,6-triamino-1,3,5-triazine, more commonly known as melamine (CAS number 108-78-1). As indicated in the alert description in the DEREK for Windows 13.0.0 output report (attached), whether HA88 has any potential for hepatotoxicity is likely to depend on how the compound is metabolised.
A dendrimer based on melamine has been reported to produce hepatotoxicity in acute and subchronic studies in mice [4]. However, the same group of workers showed that such dendrimers can reduce the hepatotoxicity of solubilised cancer drugs administered by intraperitoneal injection [5].