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

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference Type:

other: Derek analysis

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

DEREK for Windows 13.0.0

GLP compliance:

no

Test material

Test material information

Constituent 1

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:

500-311-6

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:

120498-03-5

IUPAC Name:

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

Conclusions:

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].