Tris(2-butoxyethyl) phosphate

リン酸トリス (2-ブトキシエチル) エステル


[CAS No. 78-51-3]

Tris (2-butoxyethanol) phosphate

トリス (2-ブトキシエチル) フォスフェート

Molecular formula: C18H39O7P　Molecular weight: 398.54

ABSTRACT

A 28-day repeat dose oral toxicity test of tris(2-butoxyethyl) phosphate was conducted in Sprague-Dawley rats of both sexes at dose levels of 0 (vehicle control), 100, 300, and 1000 mg/kg/day.

There were no mortalities in any group. Transient salivation was observed immediately after exposure to the test chemical in both sexes of all dosed groups and this was considered to be caused by the test chemical. Muscle weakness, adoption of a prone position and deep respiration were also noted in some females of the 1000 mg/kg group after the first exposure to the test chemical and continued for several hours.

On blood biochemical examination, the cholinesterase activity was found to be decreased with statistical significance in both sexes of the 1000 mg/kg group.

Absolute and relative liver weights increased in males and females of the 1000 mg/kg group and in females of the 300 mg/kg group. On histological examination, microgranulomas in the liver tended to be increased in females of the 300 and 1000 mg/kg groups.

The incidence or severity of vacuolation of hepatocytes in the periportal area tended to increase in males and females of the 300 and 1000 mg/kg groups. These findings for toxicity had vanished after the withdrawal of test chemical for 14 days.

The NOEL for repeat dose toxicity was 100 mg/kg/day.

Tris(2-butoxyethyl) phosphate was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogeneous metabolic activation system.

Genotoxicity of tris(2-butoxyethyl) phosphate was studied by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells.

Tris(2-butoxyethyl) phosphate did not induce structural chromosomal aberrations and/or polyploidy in the concentration range of 0.011 - 0.20 mg/ml with and without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Toxicity１）

Purity:98.2%
Test species/strain :Rats/Crj:CD (SD)
Test method:Guidelines for 28-Day Repeat Dose Toxicity Testing of Chemicals (Japan)
　Route:Oral (gavage)
　Doses:0 (vehicle), 100, 300, 1000 mg/kg/day
　Number of animals/group:Males,5; females,5
　Vehicle:Corn oil
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, days 29 or 43
GLP:Yes

　Test results:

Transient salivation, considered to be caused by the irritating effects of the test chemical, was observed in both sexes of all dosed groups. In the 1000 mg/kg group, a significant decrease of cholinesterase activity in the blood plasma was noted in both sexes and muscle weakness, adoption of a prone position and deep respiration were also observed in some females of this group. On pathological examination, vacuolation of the hepatic cells was found to be increased in males and females of the 300 and 1000 mg/kg groups and microgranulomas in the liver tended to be more common in females of those groups. These findings suggestive of toxicity had vanished 14 days after the withdrawal of the test chemical. Therefore, the NOEL for repeat dose toxicity is considered to be 100 mg/kg/day in both sexes.

2. Genetic Toxicity

2-1. Bacterial test１）

Purity:98.2 %
Test species/strains:Salmonella typhimurium, TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 471 and 472
　Procedures:Pre-incubation method
　Solvent:DMSO
　Positive controls:-S9 mix, 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (TA100, TA98, WP2), Sodium azide (TA1535) and 9-Aminoacridine (TA1537)
+S9 mix, 2-Aminoanthracene (five strains)
　Doses:-S9 mix;
0, 7.81, 15.6, 31.3, 62.5, 125, 250 μg/plate (TA100, TA1537)
0, 15.6 - 500 μg/plate (TA1535, TA98)
0, 156 - 5000 μg/plate (WP2)

+S9 mix;
0, 15.6 - 500 μg/plate (TA100, TA1535, TA1537)
0, 78.1 - 2500 μg/plate (TA98, WP2)

　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 apparent mutations in the S. typhimurium and E. coli strains. Toxicity was observed at 125 μg/plate (TA1537), 150 μg/plate (TA100), 250 μg/plate (TA1535, TA98), 5000 μg/plate (WP2) without S9 mix, and at 500 μg/plate (TA100, TA1535, TA1537), 1250 μg/plate (TA98), 1500 μg/plate (WP2) with S9 mix.

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

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

2-2. Non-bacterial in vitro test (chromosomal aberration test)１）

Purity:98.2%
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 473
　Solvent:Dimethylsulfoxide
　Positive controls:-S9 mix, Mitomycin C
+S9 mix, Cyclophosphamide
　Doses:-S9 mix (continuous treatment):0, 0.011, 0.023, 0.045, 0.090 mg/ml
-S9 mix (short-term treatment):0, 0.023, 0.045, 0.090 mg/ml
+S9 mix (short-term treatment):0, 0.050, 0.10, 0.20 mg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Cytogenetic effects were not seen under the conditions of this experiment.

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

1)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