N-(Aminoethyl)ethanolamine

N-(アミノエチル)エタノールアミン


[CAS No. 111-41-1]

Molecular formula: C4H12N2O　Molecular weight: 104.15

ABSTRACT

N-(Aminoethyl)ethanolamine was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 60, 250 and 1000 mg/kg/day.

In the repeat dose test, laboratory examinations revealed an increase in urinary protein in females given 250 mg/kg and in both sexes given 1000 mg/kg, an increase in the specific gravity of the urine in females given 250 or 1000 mg/kg, a decrease in urinary volume in females given 1000 mg/kg, a decrease in hemoglobin in both sexes given 1000 mg/kg, an increase in GOT in males given 250 and 1000 mg/kg, a decrease in total cholesterol in females given 1000 mg/kg and a decrease in chloride in males given 1000 mg/kg. The kidney weights were increased in both sexes given 1000 mg/kg and histopathologically, deposition of amphophilic bodies and swelling were noted in the renal proximal tubules in males given 250 mg/kg and in both sexes given 1000 mg/kg. In the stomach, mucosal thickening at the limiting ridge was noted in both sexes given 250 and 1000 mg/kg. Compound-related changes disappeared except for those in the kidney and stomach after a 14-day recovery period. The NOEL is considered to be 60 mg/kg/day for both sexes.

N-(Aminoethyl)ethanolamine induced polyploidy (0.88-4.00%) without an exogenous metabolic activation system. Structural chromosomal aberrations were not induce under the present experimental conditions.

N-(Aminoethyl)ethanolamine did not induce micronuclei in bone marrow cells of male and female mice.

SUMMARIZED DATA OF THE STUDIES

1. Repeat Dose Toxicity １）

Purity:99.9 %
Test species/strain:Rat/Crj:CD (SD)
Test method:Guidelines for 28-Day Repeat Dose Toxicity Test of Chemicals (Japan)
　Route:Oral (gavage)
　Doses:0 (vehicle), 60, 250, 1000 mg/kg/day
　Number of animals/group:Male, 6; female, 6
　Vehicle:Water for injection
　Administration period:Male and female, 28 days
　Terminal kill:Days 29 or 43
GLP:Yes

　 Test results:

A temporary decrease in the food consumption was noted in females given 250 mg/kg and in both sexes given 1000 mg/kg during the early administration period. Urinalysis revealed an increase in protein in females given 250 mg/kg and in both sexes given 1000 mg/kg, an increase in the specific gravity in females given 250 and 1000 mg/kg, and a decrease in urinary volume in females given 1000 mg/kg. Hematology revealed a decrease in hemoglobin in both sexes given 1000 mg/kg. Blood chemistry revealed an increase in GOT activity in males given 250 and 1000 mg/kg, a decrease in total cholesterol in females given 1000 mg/kg and a decrease in chloride in males given 1000 mg/kg. Increased kidney weights were noted in both sexes given 1000 mg/kg and histopathologically, deposition of amphophilic bodies and swelling in the renal proximal tubules in the cortico-medullary junction were noted in males given 250 mg/kg and in both sexes given 1000 mg/kg. In the stomach, mucosal thickening at the limiting ridge was noted in both sexes given 250 and 1000 mg/kg. The adrenal weights were decreased in males given 1000 mg/kg but no associated histopathological lesions were found.

Compound-related changes disappeared except for those in the kidney and stomach after a 14-day recovery period. The NOEL is considered to be 60 mg/kg/day for both males and females under the conditions of the present study.

2. Genetic Toxicity

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

Purity:more than 99.9%
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Solvent:Water for injection
　Positive controls:-S9 mix, Mitomycin C
+S9 mix, Cyclophosphamide
　Doses:-S9 mix (continuous treatment): 0, 0.25, 0.50, 1.0 mg/ml
-S9 mix (short-term treatment): 0, 0.25, 0.50, 1.0 mg/ml
+S9 mix (short-term treatment): 0, 0.25, 0.50, 1.0 mg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:
Structural chromosomal aberrations did not induce under the present experimental conditions.

With the mid (0.50 mg/ml) and high (0.10 mg/ml) concentrations after 48 h continuous treatment, polyploidy was significantly increased (0.88 - 4.00%) with dose-dependency.

Lowest concentration producing cytogenetic effects in vitro:
without metabolic activation (continuous treatment ): 0.50 mg/ml (polyploidy)

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

2-2. Non-bacterial in vivo test (Micronucleus test) ２）

Purity:above 99.9%
Test species/strains:Mice/Crj:BDF1, male and female
Test methods:Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD (474)
　Procedure:Bone marrow/acridine orange staining
　Solvent:Water
　Positive control:Cyclophosphamide 50 mg/kg
　Doses:0, 500, 1000 and 2000 mg/kg
　Mice/group:5 males and females
GLP:Yes
　Test results:
The frequency of micronucleated immature erythrocytes was not significantly increased in males or females up to the dose of 2000 mg/kg by oral gavage and animals were killed 24 h after treatment. Inhibition of bone marrow cell proliferation was not observed under the test conditions.

Lowest dose producing toxicity:
Maximum tolerated dose: above 2000 mg/kg in male and female

Genetoxic effect:
+?-
Micronucleus test:[ ][ ][*]

1)The tests were performed by Bozo Research Center Inc, 1284, Kamado, Gotemba-shi, Shizuoka, 412, 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, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627