Tris(2-ethylhexyl)
1,2,4-benzenetricarboxylate

1,2,4-ベンゼントリカルボン酸トリス(2-エチルヘキシル)エステル


[CAS No. 3319-31-1]

Tris(2-ethylhexyl) trimellitate

トリ-2-エチルヘキシルトリメリタート

Molecular formula: C33H54O6 Molecular weight: 546.87

ABSTRACT

The single dose oral toxicity test revealed an LD50 value of more than 2000 mg/kg for both sexes.

With regard to repeat dose toxicity, there were no abnormal changes attributable to the treatment in males or females of any group throughout the dosing period.

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

Tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate was not mutagenic to Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA, with or without an exogeneous metabolic activation system.

Tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate induced neither structural chromosomal aberrations nor polyploidsy in CHL/IU cells up to the limit concentration of 5.0 mg/ml, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity １）

Purity:99.0%
Test species/strain:Rats/Crj:CD (SD)
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Dosage:0 (vehicle), 2000 mg/kg
　Number of animals/group:Male 5; female, 5
　Vehicle:Corn oil
GLP:Yes

　Test results:

Loosening erring of the stool attributable to the treatment with corn oil was observed for 3 hours from the administration for both sexes in the groups given 0 and 2000 mg/kg. However, no deaths occurred of either male or female animals. The test substance did not cause any changes in body weight. No macroscopic abnormalities that could be attributed to treatment with the test substance were seen on pathological examination.
LD50: Male, > 2000 mg/kg; female, > 2000 mg/kg

2. Repeat Dose Toxicity １）

Purity:99.0%
Test species/strain:Rats/Crj:CD (SD)
Test method:Guidelines for 28-day Repeated Dose Toxicity Testing of Chemicals (Japan)
　Route:Oral
　Doses:0 (vehicle), 100, 300, 1000 mg/kg/day
　Vehicle:Corn oil
　Number of animals/group:Males, 5; females, 5
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, days 29 to 43
GLP:Yes

　Test results:

No test substance related changes were noted in terms of clinical signs, body weights, food consumption, and hematology, blood chemical examination, urinalysis, and pathological findings.
The NOEL for repeat dose toxicity is considered to be 1000 mg/kg/day for both sexes.

3. Genetic Toxicity

3-1. Bacterial test ２）

Purity:above 99.0%
Test species/strain:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD (471 and 472)
　Procedures:Plate incorporation method
　Solvent:Acetone
　Positive controls:-S9 mix, 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, WP2, TA98), Sodium azide (TA1535) and 9-Aminoacridine (TA1537)
+S9 mix, 2-Aminoanthracene (five strains)
　Doses:0, 313, 625, 1250, 2500 and 5000 μg/plate in five strains with -S9 mix and +S9 mix.
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3
　Number of replicates:2
GLP:Yes

　Test results:
This chemical did not induce gene mutations in the S. typhimurium and E. coli strains. Toxicity was not observed at 5000 μg/plate in the five strains in either the without S9 mix or the with S9 mix cases.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, 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:more than 99.0 %
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Solvent:Acetone
　Positive controls:-S9 mix, Mitomycin C
+S9 mix, Cyclophosphamide
　Doses:-S9 mix (continuous 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 (short-term treatment): 0, 1.3, 2.5, 5.0 mg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:
This chemical did not induce structural chromosomal aberrations or polyploidy under the conditions of this experiment.

Genotoxic effects:

clastogenicitypolyploidy

+?-+?-
without metabolic activation:[ ][ ][*][ ][ ][*]
with metabolic activation:[ ][ ][*][ ][ ][*]

1)The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides (An-pyo Center), Japan, 582-2 Shioshinden Arahama, Fukude-cho, Iwata-gun, Shizuoka, 437-12, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393
2)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627

Tris(2-ethylhexyl)1,2,4-benzenetricarboxylate

1,2,4-ベンゼントリカルボン酸トリス
(2-エチルヘキシル)エステル


[CAS No. 3319-31-1]

Tris(2-ethylhexyl)trimellitate

トリス(2-エチルヘキシル)トリメリタート

Molecular formula: C33H54O6　　　　　Molecular weight: 546.87

ABSTRACT

Tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate was studied for oral toxicity in rats in an OECD preliminary reproduction toxicity screening test at doses of 0, 100, 300 and 1000 mg/kg/day.

Histopathological examination of the testes revealed decreases in spermatocytes and spermatids in males of the 300 and 1000 mg/kg groups. No effects of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate were detected on general appearance, body weight, food consumption, autopsy findings, and weights of the reproductive organs of both sexes, or on histopathological examination of the ovary. On the basis of these findings, the NOELs of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate for repeat dose toxicity are considered to be 100 mg/kg/day for males, and 1000 mg/ kg/day for females.

Except for the effects in males observed on histopathological examination, no influence of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate was detected regarding reproductive ability, organ weights or histopathological appearance of the ovaries, delivery or maternal behavior of dams. No effects of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate were detected on viability, general appearance, body weight or autopsy findings of offspring. On the basis of these findings, the NOELs of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate for reproductive/developmental toxicity were considered to be 100 mg/kg/day for males, 1000 mg/kg/day for females, and 1000 mg/kg/day for offspring.

SUMMARIZED DATA FROM THE STUDIES

1. Preliminary reproduction toxicity screening test１）

Purity:99.0 %
Test species/strain:Rat/Crj:CD(SD)
Test method:OECD Preliminary reproductive toxicity screening test
　Route:Oral(gavage)
　Doses:0(vehicle), 100, 300, 1000 mg/kg/day
　Number of animals/group:Males, 12; females, 12
　Vehicle:Corn oil
　Administration period:Males, 46 days
Females, from 14 days before mating to day 3 of lactation
　Terminal kill:Males, day 47
Females, day 4 of lactation
GLP:Yes

　Test results:

<Repeat dose toxicity>

Histopathological examination of the testes, demonstrated decrease of spermatocytes and spermatids in males of the 300 and 1000 mg/kg groups. No effects of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate on general appearance, body weight, food consumption, autopsy findings, weights of the reproductive organs of both sexes, or histopathological features of the ovary were detected.

On the basis of these findings, the NOELs of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate for repeat dose toxicity are considered to be 100 mg/kg/day for males, and 1000 mg/kg/day for females.

<Reproductive and developmental toxicity>

Except for the effects in males observed on histopathological examination, no influence of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate was detected regarding reproductive ability, organ weights or histopathological features of the ovary, delivery or maternal behavior of dams. No effects of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate were detected on viability, general appearance, body weights or autopsy findings for offspring.

On the basis of these findings, the NOELs of tris(2-ethylhexyl) 1,2,4-benzenetricarboxylate for reproductive/developmental toxicity are considered to be 100 mg/kg/day for males, 1000 mg/kg/day for females, and 1000 mg/kg/day for offspring.

1)The tests were performed by the Safety Research Institute for Chemical Compounds Co., Ltd., 363-24, Shin-ei, Kiyota-ku, Sapporo, Hokkaido, 004-0839, Japan. Tel +81-11-885-5031 Fax +81-11-885-5313