N,N',N'',N'''-tetrakis(4,6-bis(butyl-(N-methyl-2,2,6,6-tetramethylpiperidin-4-yl)amino)triazin-2-yl)-4,7-diazadecane-1,10-diamine

Endpoint summary

Description of key information

Albino rats were treated with the substance for 90-days, administered in the diet. 
Doses (male): 0, 9.7, 47.9, 201 and 826 mg/kg bw/day
Doses (female):   50.4, 210 and 817 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: oral

Remarks:

other: not available

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1987

Reliability:

1 (reliable without restriction)

Qualifier:

no guideline available

Principles of method if other than guideline:

Guideline not available

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: Albino rat

Sex:

male/female

Route of administration:

oral: unspecified

Details on oral exposure:

Method of administration: diet

Duration of treatment / exposure:

Test duration: 90 days

No. of animals per sex per dose:

Male: 10 animals at 0 mg/kg bw/day
Male: 10 animals at 9.7 mg/kg bw/day
Male: 10 animals at 47.9 mg/kg bw/day
Male: 10 animals at 201 mg/kg bw/day
Male: 10 animals at 826 mg/kg bw/day

Female: 10 animals at 0 mg/kg bw/day
Female: 10 animals at 9.92 mg/kg bw/day
Female: 10 animals at 50.4 mg/kg bw/day
Female: 10 animals at 210 mg/kg bw/day
Female: 10 animals at 817 mg/kg bw/day

Details on results:

Clinical observation:
Dose-related reduction of mean body weight and food consumption at 12000 and 3000 ppm.
Water cosumption decreases at 12000 ppm.

Laboratory findings:
At 12000 ppm hypocromic microcytic anemia. At 12000, 3000 and 800 ppm dose-related leucocytosis with neutrophilia and relative lymphopenia. At 12000 ppm decrease in plasma glucose, cholesterol and plasma protein; dose-related decrease in plasma albumin at 12000 and 3000 ppm.
At 12000 ppm increases in plasma electrolytes, ASAT and alcaline phosphatase; ASAT increased in females at 3000 and 800 ppm too. Bilirubinuria at 12000 ppm.

Effects in organs:
Increase of liver relative weight in females at 12000 ppm and of spleen relative weight in females at 3000 and 12000 ppm. Enlarges mesenteric lymphonodes at 800, 3000 and 12000 ppm. Two/20 rats at 12000 ppm had mottled liver.

Marked, widespread presence of foam macrophages, expecially in the mucosa of small intestine and in the mesenteric lymphnodes. The change was evident form 150 ppm exposure upwards, and its intesity was dose-related.
At 800, 3000 and 12000 ppm necrotizing, inflammatory and cystic changes in mesenteric lymph nodes, peritoneal inflammation, and inflammatory infiltrates in liver (1/20 at 800 ppm) were also present.

Dose descriptor:

NOEL

Effect level:

< 9.7 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day

Critical effects observed:

not specified

Conclusions:

The substance is not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

9.7 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The Repeated dose toxicity study (90-days in rat) was submitted more than 12 years ago. It is not known if it was performed under GLP conditions.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Dose at which no toxic effects were observed: 9.7 mg/kg/day in males and 9.92 mg/kg/day in females

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The study with longest duration (90-days) and lowest NOAEL was chosen as key study.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Study scientifically unjustified.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Study scientifically unjustified.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
Study scientifically unjustified.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Study scientifically unjustified.

Justification for classification or non-classification

The substance N,N',N'',N'''-tetrakis(4,6-bis(butyl-(N-methyl-2,2,6,6-tetramethylpiperidin-4-yl)amino)triazin-2-yl)-4,7-diazadecane-1,10-diamine does not required classification for repeated dose toxicity.