2-(2-Aminoethoxy)ethanol

Classification/MAK value: see Section IIb of the

List of MAK and BAT Values
Synonyms: aminodiglycol
2-aminoethoxyethanol
diglycolamine
2-(2-hydroxyethoxy)ethylamine
2,2'-hydroxyethoxyethylamine
Trade names: 2-2'-Aminoethoxyethanol
DGA

Diglycolamine

Agent
Chemical name (CAS): 2-(2-aminoethoxy)ethanol
CAS number: 929-06-6
Structural formula: H
2
NCH
2
CH
2
OCH
2
CH
2
OH
Molecular formula: C
4
H
11
NO
2
Molecular weight: 105.14
Melting point: 11C
Boiling point: 223224C
Density at 20C: 1.06 g/cm
3
Vapour pressure at 120C: 2 hPa
Solubility: miscible in all proportions with water at
20C, miscible with almost all common
organic solvents
pH value at 20C: 13.3 (at 500 g/l water)
10.2 (at 10 g/l water)
Stability: in closed containers indefinitely stable
(BASF 1992b); thermal decomposition
yields only oxides of nitrogen and carbon
(Texaco Chemical Deutschland 1993)
2-(2-Aminoethoxy)ethanol Volume 9 216
Production: catalytic conversion of diethylene glycol
with ammonia followed by distillation
2 NH
3
+ 2 HO

CH
2

CH
2

CH
2

CH
2

OH
diethylene glycol
H
2
N

CH
2

CH
2

CH
2

CH
2

OH +
O
N
H
morpholine
+ 3 H
2
O
2-(2-aminoethoxy)ethanol
Purity: the purity is given by a producer as at
least 98 % (BASF 1992a)
Impurities: maximum 0.4 % diethylene glycol and
maximum 0.2 % water (BASF 1992a)
Uses: as emulsifying agent for metal-working
fluids;
as a component in the production of
detergents;
in gas scrubbing to remove H
2
S and
CO
2
from natural and refinery gases
(Texaco Chemical Company 1989)
1 ml/m
3
(ppm) = 4.36 mg/m
3
1 mg/m
3
= 0.23 ml/m
3
(ppm)
Note
2-(2-Aminoethoxy)ethanol is a primary amine and does not form nitrosamines. When a
cutting oil to which 2-(2-aminoethoxy)ethanol (purity 93 %) and nitrite had been added
was heated to 100C for 48 hours, N-nitrosodiethanolamine (10 g/ml) and N-nitroso
morpholine (10 g/ml) were formed. However, this was ascribed to the presence of
impurities in the additive: 2.7 % diethanolamine and 0.7 % triethanolamine (Loeppky et
al. 1983).
Volume 9 2-(2-Aminoethoxy)ethanol 217
1 Toxic Effects and Modes of Action
2-(2-Aminoethoxy)ethanol is of low acute toxicity.
Undiluted 2-(2-aminoethoxy)ethanol has corrosive effects on the skin and eyes of
rabbits. It does not cause sensitization in guinea pigs.
In the Salmonella mutagenicity test and the DNA repair test in rat hepatocytes no
genotoxic effects were observed.
Studies of the toxicokinetics and metabolism of 2-(2-aminoethoxy)ethanol are not
available.
2 Mechanism of Action
The corrosive effects of 2-(2-aminoethoxy)ethanol are probably a result of its alkalinity.
3 Effects in Man
There are no reports of the effects of 2-(2-aminoethoxy)ethanol in man.
4 Effects on Animals
Studies of the subacute, subchronic and chronic toxicity of 2-(2-aminoethoxy)ethanol are
not available, nor have reproductive toxicity studies with the substance been carried out.
4.1 Acute toxicity
4.1.1 Inhalation
In two time-hazard tests (8 hours, 20C), 2-(2-aminoethoxy)ethanol was tolerated by rats
(6 and 12 animals, respectively) without symptoms (BASF 1969, Smyth et al. 1951).
2-(2-Aminoethoxy)ethanol Volume 9 218
4.1.2 Ingestion
The acute oral toxicity of 2-(2-aminoethoxy)ethanol in the rat is low, the LD
50
being
2560 mg/kg body weight. Females are more sensitive than males (Table 1).
Table 1. Acute oral toxicity of 2-(2-aminoethoxy)ethanol in the rat
Strain LD
50
(mg/kg
body weight)
Symptoms References
Sprague-
Dawley
3222
2270
+ 2558
reduced activity, unkempt fur, tremor, prostration,
discoloured urine, diarrhoea, dyspnoea;
autopsy of animals which died: distended
gastrointestinal tract filled with fluid, stomach
mucosa discoloured, sometimes necrotic, ascites,
discoloured spleen;
autopsy of survivors: kidneys mottled, adhesions
between liver and stomach/small intestine with
greenish-yellow mass at the adhesion sites
Texaco
Chemical
Company
1991a
n.s. 3400 dyspnoea, apathy, prostration;
autopsy: haemorrhage in the gastrointestinal tract,
snouts smeared with serous secretions, more
sensitive than
BASF 1969
Wistar 5600 n.s. Smyth et al.
1951
n.s. not specified
4.1.3 Dermal absorption
In an early study with rabbits (number of animals and sex not specified) a dermal LD
50
of
1261 mg/kg body weight was reported (no other details, Smyth et al. 1951). In contrast,
in a more recent study with 5 male and 5 female rabbits, even occlusive application of
doses of 3000 mg/kg body weight did not lead to deaths. The symptoms of toxicity
included reduced activity, abnormal gait and posture, diarrhoea, reduced preening, dysp-
noea and slimy faeces. At the application site, necrosis and yellow discoloration of the
fur were observed. Autopsy revealed severe irritation and yellow discoloration of the
muscle tissue at the application site, mottled lungs and pale kidneys (Texaco Chemical
Company 1991b).
4.1.4 Intraperitoneal injection
The approximate intraperitoneal LD
50
for the mouse was given as 350 mg/kg body
weight. The symptoms were dyspnoea and convulsive jerking. Autopsy revealed hyper-
aemia of the abdominal organs and intra-abdominal adhesions (BASF 1969).
Volume 9 2-(2-Aminoethoxy)ethanol 219
4.2 Effects on skin and mucous membranes
4.2.1 Skin
Applied to rabbit skin, undiluted 2-(2-aminoethoxy)ethanol caused marked erythema and
oedema with necrosis (Smyth et al. 1951). The irritation score according to Smyth et al.
(1949) was 6 on a scale with a maximum of 10 points.
In a preliminary study, 2-(2-aminoethoxy)ethanol applied to rabbit skin produced
marked erythema after as little as 15 minutes and, after 20 hours, marked erythema and
necrosis which were still evident after 8 days (no other details; BASF 1969).
2-(2-Aminoethoxy)ethanol (0.5 ml) was applied occlusively for 4 and 24 hours to
intact and abraded rabbit skin. After 0.5 to 1 hour, 24, 48 and 72 hours and also after 4 to
14 days, severe erythema and oedema were observed. In addition, necrosis, scab forma-
tion, skin fissures and exudation developed at the application site. The modified primary
irritation index after 4 hours exposure and the primary irritation index after 24 hours
exposure were both given the value 8.0, the highest value on the scale (Texaco Chemical
Company 1992).
4.2.2 Eyes
Tested on the rabbit eye by the method of Carpenter and Smyth (1946), 0.005 ml
undiluted 2-(2-aminoethoxy)ethanol was highly irritating (Smyth et al. 1951).
One hour after application of undiluted 2-(2-aminoethoxy)ethanol (0.05 ml) to the
rabbit eye, the substance was seen to cause corrosion (BASF 1969).
4.3 Allergenic effects
In three range-finding studies, 5 male and 5 female Hartley guinea pigs were each
exposed dermally to four different concentrations of 2-(2-aminoethoxy)ethanol (0.1 % to
100 % and 20 % to 50 %) in 80 % ethanol or acetone. The 10 % solution was shown to be
without irritative effects and was then used in the Buehler test with Hartley guinea pigs.
For induction, 10 male and 10 female animals were treated once weekly for 3 weeks with
0.3 ml of a 10 % solution of 2-(2-aminoethoxy)ethanol in 80 % ethanol applied occlu-
sively for 6 hours to the shaved skin of the left shoulder. As positive control group, 3
male and 2 female guinea pigs were treated in the same way with 0.3 % 1-chloro-
2,4-dinitrobenzene (DNCB) in 80 % ethanol. The negative control group consisted of 5
male and 5 female animals treated just with 80 % ethanol. Provocation was carried out 14
days after the last induction treatment by application of the same concentration of the
same substance in acetone to an untreated site on the shaved skin of the left flank. The
provocation of the negative control group was carried out with acetone on the left and
2-(2-aminoethoxy)ethanol on the right flank. All the animals were examined for dermal
and systemic effects, 24 and 48 hours after removal of the patches.
2-(2-Aminoethoxy)ethanol Volume 9 220
In all the animals of the positive control group, the expected positive reaction was
seen. A mild, mottled reddening of the skin was seen in 3 animals of the negative control
group after provocation with 2-(2-aminoethoxy)ethanol and in 6 animals of the test
group. In one animal in the test group, moderate erythema developed. No reactions to
acetone provocation were seen in the negative control group. The animals of the
2-(2-aminoethoxy)ethanol test group were subjected to a second provocation with 10 %
2-(2-aminoethoxy)ethanol on a previously unexposed site, 7 days after the first provoca-
tion; after 24 and 48 hours erythema was seen in 2 animals.
In all tests, the body weights of the animals were unaffected by the treatment. On the
basis of these results, 2-(2-aminoethoxy)ethanol was considered to be not sensitizing for
guinea pigs under the conditions of the Buehler test (Texaco Chemical Company 1991c).
4.4 Genotoxicity
In vitro
2-(2-Aminoethoxy)ethanol was tested in the Salmonella mutagenicity test in the S.
typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 both in the presence
and absence of a metabolic activation system. In the concentration range tested (100 to
10000 g/plate) no evidence for a mutagenic potential of 2-(2-aminoethoxy)ethanol was
found (Texaco Chemical Company 1982a).
In another Salmonella mutagenicity test, 2-(2-aminoethoxy)ethanol was tested in the
S. typhimurium strains TA98, TA100, TA1535 and TA1537 by the plate-incorporation
method and by the preincubation method in the presence and absence of a metabolic
activation system. The concentrations tested were in the range between 20 and
5000 g/plate. In this study too, no evidence for mutagenic effects of 2-(2-amino
ethoxy)ethanol was found (BASF 1990).
In the DNA repair test in primary rat hepatocytes, 2-(2-aminoethoxy)ethanol concen-
trations of 10
-5
% to 10
-2
% v/v (about 1 to 1000 M) did not cause an increase in DNA
repair synthesis (autoradiographic detection method). Concentrations of 0.1 % and 1 %
v/v (about 10 and 100 mM) proved to have cytotoxic effects (Texaco Chemical Company
1982c).
In vivo genotoxicity tests have not been carried out.
4.5 Carcinogenicity
Long-term studies with 2-(2-aminoethoxy)ethanol are not available.
In a cell transformation test with BALB/3T3 mouse cells, 2-(2-aminoethoxy)ethanol
in the concentration range between 0.31 and 1.56 l/ml induced no increase in the inci-
dence of morphologically transformed colonies (foci). This concentration range had been
shown in a previous cytotoxicity test to permit survival of 100 % to 4 % of the cells
(Texaco Chemical Company 1982b).
Volume 9 2-(2-Aminoethoxy)ethanol 221
5 Manifesto (MAK value, classification)
2-(2-Aminoethoxy)ethanol is corrosive to the skin and eyes of experimental animals;
therefore similar effects may be expected at the workplace during skin contact and espe-
cially on exposure to aerosols containing the substance. There are no studies of human
sensitization to 2-(2-aminoethoxy)ethanol. In a Buehler test no sensitizing effects were
detected. 2-(2-Aminoethoxy)ethanol is of low acute toxicity. There are no studies of
long-term effects. The few studies which have been carried out provide no evidence of
genotoxic properties of 2-(2-aminoethoxy)ethanol.
Since the available data are inadequate for the establishment of a MAK value,
2-(2-aminoethoxy)ethanol has been included in Section IIb of the List of MAK and
BAT Values.
6 References
BASF (1969) AminodiglykolErgebnis der gewerbetoxikologischen Vorprfung. unpublished
report, 24.04.1969
BASF (1990) Ames-test (Standard plate test and preincubation test with Salmonella
typhimurium). unpublished report, 27.11.1990
BASF (1992a) 2-2'-Aminoethoxyethanol. DIN-Sicherheitsdatenblatt, (safety data sheet) 11/92
BASF (1992b) 2-2'-Aminoethoxyethanol. Datenblatt, (data sheet) December 1992
Carpenter CP, Smyth jr HF (1946) Chemical burns of the rabbit cornea. Am J Ophthalmol 29:
13631372
Loeppky RN, Hansen TJ, Keefer LK (1983) Reducing nitrosamine contamination in cutting fluids.
Food Chem Toxicol 21: 607613
Smyth jr HF, Carpenter CP, Weil CS (1949) Range-finding toxicity data, list III. J Ind Hyg
Toxicol 31: 6062
Smyth jr HF, Carpenter CP, Weil CS (1951) Range-finding toxicity data: list IV. Arch Ind Hyg
Occup Med 4: 119122
Texaco Chemical Company (1982a) Ames Salmonella/microsome plate test. Diglycolamine

Agent. Pharmakon Research International, Inc, Study No PH 301-TX-010-81, unpublished

report
Texaco Chemical Company (1982b) Evaluation of Diglycolamine

Agent in the in vitro trans-

formation of BALB/3T3 cells assay. Litton Bionetics, Inc, LBI Project No 20992, unpublished
report
Texaco Chemical Company (1982c) The hepatocyte primary culture/ DNA repair assay on
Diglycolamine

Agent using rat hepatocytes in culture. Naylor Dana Institute, NDI/In vitro
Facility, Experimental No 030882, unpublished report
Texaco Chemical Company (1989) Diglycolamine

Agent. Product brochure

Texaco Chemical Company (1991a) Acute exposure oral toxicity. Diglycolamine

Agent.
Pharmakon Research International, Inc, Study No PH 402-TX-012-90, Project No 90-013,
unpublished report
Texaco Chemical Company (1991b) Acute exposure dermal toxicity. Diglycolamine

Agent.
Pharmakon Research International, Inc, Study No PH 422-TX-012-90, Project No 90-013,
unpublished report
2-(2-Aminoethoxy)ethanol Volume 9 222
Texaco Chemical Company (1991c) Delayed contact hypersensitivity in guinea pigs.
Diglycolamine

Agent. Pharmakon Research International, Inc, Study No PH 424-TX-006-90,

Project No 90-013, unpublished report
Texaco Chemical Company (1992) Primary dermal irritation study. Diglycolamine

Agent.
Pharmakon Research International, Inc, Study No PH 420-TX-011-90, Project No 90-013,
unpublished report
Texaco Chemical Deutschland (1993) DIN-Sicherheitsdatenblatt. Diglycolamine

Agent (DGA

),
(safety data sheet) 25.06.1993
completed 20.12.1994