1,3,5-Tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanuric acid

1,3,5-トリス(3,5-ジ-tert-ブチル-4-ヒドロキシベンジル)イソシアヌル酸


[CAS No. 27676-62-6]

1,3,5-Tris(3,5-di-tert-butyl-4-hydroxybenzyl)-s-triazine-2,4,6 (1h,3h,5h)-trione

1,3,5-トリス(3,5-ジ-tert-ブチル-4-ヒドロキシベンジル)イソシアヌレイト

Molecular formula: C48H69N3O6　Molecular weight: 784.10

ABSTRACT

A single dose oral toxicity test of 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanuric acid was performed in rats and no deaths or toxic signs were observed with 2000 mg/kg of the test substance.

1,3,5-Tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanuric acid was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 100, 300 and 1000 mg/kg.

No effects due to administration of the test substance were observed regarding clinical signs, body weights, food consumption, urinalysis, water consumption, hematological examination, blood chemical examination or pathological examination.

The NOEL is considered to be 1000 mg/kg/day for both sexes.

Genotoxicity of 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanuric acid was studied by a reverse mutation test in bacteria. This substance was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 or Escherichia coli WP2 uvrA, with or without an exogenous metabolic activation system.

Genotoxicity of 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanuric acid was studied by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

1,3,5-Tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanuric acid did not induce structural chromosomal aberrations under the present test conditions, but induced polyploidy in the absence of S9 mix.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:100 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (Gavage)
　Dosage:0 (Vehicle), 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:0.5 % Hydroxypropyl methylcellulose solution
GLP:Yes

　Test results:

No deaths occurred with 2000 mg/kg of the test substance. No abnormalities were observed regarding clinical signs, body weights or necropsy findings.

2. Repeat Dose Oral Toxicity 2)

Purity:100 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral (Gavage)
　Dosage:0 (Vehicle), 100, 300, 1000 mg/kg/day
　Number of animals/group:Males, 6; females, 6
　Vehicle:0.5 % Hydroxypropyl methylcellulose solution
　Administration period:Males and females, 28 days
　Terminal killing:Days 29 or 43
GLP:Yes

　Test results:

No effects due to administration of the test substance were observed regarding clinical signs, body weights, food consumption, urinalysis, water consumption, hematological examination, blood chemical examination or pathological examination.

The NOEL is considered to be 1000 mg/kg/day for both sexes.

3. Genetic Toxicity

3-1. Bacterial test 3)

Purity:100 %
Test species/strains:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:Dimethyl sulfoxide
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98, WP2 uvrA), Sodium azide (TA1535) and 9-Amino-acridine (TA1537)
+S9 mix; 2-Aminoanthracene (five strains)
　Dosage:-S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
+S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavon
　Plates/test:3 (1 for the cytotoxicity test)
　Number of replicates:2 (plus 1 cytotoxicity test)
GLP:Yes

　Test results:

This chemical did not induce gene mutations in S. typhimurium TA100, TA98, TA1535, TA1537 or E. coli WP2 uvrA strains with or without S9 mix. Growth inhibition was not observed up to 5000 μg/plate in any strain, with or without S9 mix.

Genetic effects:
Salmonella typhimurium TA100, TA98, TA1535, TA1537
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

Escherichia coli WP2 uvrA
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

3-2. Non-bacterial in vitro test (chromosomal aberration test) 2)

Purity:100 %
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Vehicle:0.5 % Sodium carboxymethylcellulose solution
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Dosage:-S9 mix (short-term treatment); 0, 1.3, 2.5, 5.0 mg/mL
+S9 mix (short-term treatment); 0, 1.3, 2.5, 5.0 mg/mL
-S9 mix (continuous treatment); 0, 1.3, 2.5, 5.0 mg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

The incidence of the cells with structural chromosomal aberrations was not biologically significant at any dose for all test systems, but polyploidy was significantly increased with dose-dependence after short-term and continuous treatment without metabolic activation.

Lowest concentration producing cytogenetic effects in vitro:
Without metabolic activation (short-term treatment):2.5 mg/mL (polyploidy)
Without metabolic activation (continuous treatment):1.3 mg/mL (polyploidy)

Genotoxic effects:
clastogenicitypolyploidy
+?-+?-
Without metabolic activation:[ ][ ][*][*][ ][ ]
With metabolic activation:[ ][ ][*][ ][ ][*]

1)The tests were performed by Bozo Research Center Inc, 1284, Kamado, Gotemba-shi, Shizuoka, 412-0039, Japan. Tel +81-550-82-2000 Fax +81-550-82-2379
2)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627