1,3,5-Tris(2-hydroxyethyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione

1,3,5-トリス(2-ヒドロキシエチル)-1,3,5-トリアジン-2,4,6-(1H,3H,5H)-トリオン


[CAS No. 839-90-7]

1,3,5-Tris(2-hydroxyethyl) isocyanurate

1,3,5-トリス(2-ヒドロキシエチル)イソシアヌラート

Molecular formula: C9H15N3O6 Molecular weight: 261.23

ABSTRACT

1,3,5-Tris(2-hydroxyethyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione was studied for oral toxicity in rats of both sexes in a single dose toxicity test at doses of 0, 500, 1000 and 2000 mg/kg. The LD50 value was estimated to be higher than 2000 mg/kg for both sexes.

1,3,5-Tris(2-hydroxyethyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione was studied for oral toxicity in rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 30, 100, 300 and 1000 mg/kg/day (12 animals of each sex per group).

Regarding the males, no changes caused by the substance were noted for general signs, body weight, food consumption, urinalysis, hematological examination, blood chemical analysis, necropsy, organ weights, or histopathological examination.

Regarding the females, no changes caused by the substance were noted for general signs, body weight, food consumption, necropsy, or organ weights. On histopathological examination, extramedullary hematopoiesis in the liver was noted in the 1000 mg/kg group.

The NOELs for repeat dose toxicity are considered to be 1000 mg/kg/day for males, and 300 mg/kg/day for females.

Regarding reproductive/developmental toxicity, no changes caused by the substance were noted in the copulation index, gestation length, delivery conditions, nursing conditions, fertility index, number of corpora lutea, implantation rate, or gestation index.

The NOELs for reproductive performance are considered to be 1000 mg/kg/day for both sexes. Regarding the pups, no changes caused by the substance were noted in terms of the numbers of pups, stillbirths, and live pups born, sex ratio, delivery index, birth index, live birth index, viability index, or body weight.

The NOEL for pup development is considered to be 1000 mg/kg/day.

Reverse mutation assays using microorganisms (Salmonella typhimurium, Escherichia coli) were conducted to assess the potential of 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione to induce gene mutations.

1,3,5-Tris(2-hydroxyethyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione did not induce gene mutations in bacteria under the conditions of this study.

In vitro chromosomal aberration tests using cultured cells (CHL/IU) were conducted to assess the potential of 1,3,5-tris(2-hydroxyethyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione to induce chromosomal aberrations.

1,3,5-Tris(2-hydroxyethyl)-1,3,5-triazine-2,4,6-(1H,3H,5H)-trione did not induce chromosomal aberrations in cultured cells under the conditions of this study.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Toxicity 1)

Purity:99.0 %
Test species/strains:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
 Route:Oral (gavage)
 Doses:0(vehicle), 500, 1000, 2000 mg/kg
 Number of animals/group:Males, 5; females, 5
 Vehicle:Water for injection
GLP:Yes

 Test results:

No deaths occurred in either sex in the treated groups.
The LD50 value was estimated to be higher than 2000 mg/kg for both sexes.

2. Repeat Dose and Reproductive/developmental Toxicity 1)

Purity:99.0 %
Test species/strains:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 422
 Route:Oral (gavage)
 Doses:0(vehicle), 30, 100, 300, 1000 mg/kg/day
 Number of animals/group:Males, 12; females, 12
 Vehicle:Water for injection
 Administration period:Males, 49 days
Females, from 14 days before mating to day 3 of lactation
 Terminal kill:Males, day 50
Females, day 4 of lactation
GLP:Yes

 Test results:

<Repeat dose toxicity>

In the males, no changes caused by the substance were noted regarding general signs, body weight, food consumption, urinalysis, hematological examination, blood chemical analysis, necropsy, organ weights, or histopathological examination.

In the females, no changes caused by the substance were noted regarding general signs, body weight, food consumption, necropsy, or organ weights. On histopathological examination, extramedullary hematopoiesis in the liver was noted in the 1000 mg/kg group.

The NOELs for repeat dose toxicity are considered to be 1000 mg/kg/day for males, and 300 mg/kg/day for females.

<Reproductive and Developmental Toxicity>

No changes caused by the substance were noted in the copulation index, gestation length, delivery conditions, nursing conditions, fertility index, number of corpora lutea, implantation rate, or gestation index.

The NOELs for reproductive performance are considered to be 1000 mg/kg/day for both sexes.

Regarding the pups, no changes caused by the substance were noted in terms of the numbers of pups, stillbirths, and live pups born, sex ratio, delivery index, birth index, live birth index, viability index, or body weight.

The NOEL for pup development is considered to be 1000 mg/kg/day.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:99.0 %
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:Water for injection
 Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98 and WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine hydrochloride (TA1537)
+S9 mix; 2-Aminoanthracene (all strains)
 Doses:-S9 mix; 156, 313, 625, 1250, 2500, 5000 μg/plate(all strains)
+S9 mix; 156, 313, 625, 1250, 2500, 5000 μg/plate(all strains)
 S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plates/test:3
 Number of replicates:2
GLP:Yes

 Test results:

No increases in revertant colonies were observed in the test with either the non-activation method (-S9) or activation (+S9).

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98 and 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:99.0 %
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
 Solvent:Physiological saline
 Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
 Doses:-S9 mix(short-term treatment); 0, 653, 1306, 2612 μg/mL
+S9 mix(short-term treatment); 0, 653, 1306, 2612 μg/mL
-S9 mix(continuous treatment 24 hr); 0, 653, 1306, 2612 μg/mL
S9 : Rat liver, induced with phenobarbital and 5,6-benzoflavone
 S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
 Plates/test:2
GLP:Yes

 Test results:

No increases in chromosomal aberrations were observed in the test with either the short-term treatment (-S9 and +S9) or continuous treatment.

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

1)The test was performed by Nihon Bioresearch Inc., 6-104 Majima, Fukuju-cho, Hashima, Gifu, 501-6251, Japan. Tel +81-58-392-6222 Fax +81-58-392-1284
2)The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides(An-pyo Center), 582-2 Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, 437-1213, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393