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2-Ethoxyethanol
CASRN 110-80-5
Contents
0513
2-Ethoxyethanol; CASRN 110-80-5
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR 2-Ethoxyethanol
File On-Line 05/01/1991
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) on-line 05/01/1991
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- 2-Ethoxyethanol
CASRN -- 110-80-5
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- 2-Ethoxyethanol
CASRN -- 110-80-5
Last Revised -- 05/01/1991
The inhalation Reference Concentration (RfC) is analogous to the oral RfD and
is likewise based on the assumption that thresholds exist for certain toxic
effects such as cellular necrosis. The inhalation RfC considers toxic effects
for both the respiratory system (portal-of-entry) and for effects peripheral
to the respiratory system (extrarespiratory effects). It is expressed in
units of mg/cu.m. In general, the RfC is an estimate (with uncertainty
spanning perhaps an order of magnitude) of a daily inhalation exposure of the
human population (including sensitive subgroups) that is likely to be without
an appreciable risk of deleterious effects during a lifetime. Inhalation RfCs
were derived according to the Interim Methods for Development of Inhalation
Reference Doses (EPA/600/8-88/066F August 1989) and subsequently, according to
Methods for Derivation of Inhalation Reference Concentrations and Application
of Inhalation Dosimetry (EPA/600/8-90/066F October 1994). RfCs can also be
derived for the noncarcinogenic health effects of substances that are
carcinogens. Therefore, it is essential to refer to other sources of
information concerning the carcinogenicity of this substance. If the U.S. EPA
has evaluated this substance for potential human carcinogenicity, a summary of
that evaluation will be contained in Section II of this file.
___I.B.1. INHALATION RfC SUMMARY
Critical Effect Exposures* UF MF RfC
-------------------- --------------------------- ----- --- ---------
Decreased testis NOAEL: 380 mg/cu.m (103 ppm) 300 1 2E-1
weight, seminiferous NOAEL(ADJ): 68 mg/cu.m mg/cu.m
tubule degeneration NOAEL(HEC): 68 mg/cu.m
and decreased
hemoglobin LOAEL: 1485 mg/cu.m (403 ppm)
LOAEL(ADJ): 265 mg/cu.m
New Zealand White LOAEL(HEC): 265 mg/cu.m
Rabbit Subchronic
Toxicity Study
Barbee et al., 1984
*Conversion Factors: MW = 90.12. Assuming 25C and 760 mm Hg, NOAEL (mg/cu.m)
= 103 ppm x 90.12/24.45 = 380 mg/cu.m. NOAEL(ADJ) = 380 x 6 hours/24 hours, 5
days/7 days = 68 mg/cu.m. The NOAEL(HEC) was calculated for a
gas:extrarespiratory effect assuming periodicity was attained. Since the b:a
lambda values are unknown for the experimental animal species (a) and humans
(h), a default value of 1.0 is used for this ratio. NOAEL(HEC) = NOAEL(ADJ) x
(b:a lambda (a) / b:a lambda (h)) = 68 mg/cu.m.
___I.B.2. PRINCIPAL AND SUPPORTING STUDIES (INHALATION RfC)
Barbee, S.J., J.B. Terrill, D.J. DeSousa and C.C. Conaway. 1984. Subchronic
inhalation toxicology of ethylene glycol monoethyl ether in the rat and
rabbit. Environ. Health Perspect. 57: 157-163.
Barbee et al. (1984) exposed groups of Sprague-Dawley rats (15/sex/group)
to 0, 25, 103 or 403 ppm (0, 92, 380 or 1485 mg/cu.m, assuming 25C and 760 mm
Hg) ethylene glycol monoethyl ether, 6 hours/day, 5 days/week for 13 weeks.
The duration-adjusted exposure concentrations were 0, 16, 68 and 265 mg/cu.m,
respectively. New Zealand white rabbits (10/sex/group) were similarly exposed
to 0, 25, 103 or 403 ppm (0, 92, 380 or 1485 mg/cu.m.). Physical examination
and body weights measurements were conducted weekly on all animals throughout
the study. Hematology, chemical chemistry and histopathological changes
(including bone marrow of the sternum) were also assessed. No respiratory
effects (nasal turbinates, tracheas and lungs were examined) were observed in
either species.
In exposed rats, there was a significant decrease in absolute and relative
pituitary weights in males at 403 ppm, a decrease in absolute spleen weight in
females at all concentrations and decreased white blood cell count in females
at 403 ppm. The decrease in spleen weight was significant only at the low and
high concentrations. Histopathologic lesions supportive of organ weight
changes for the pituitary or spleen were not observed. No other significant
dose-related effects were observed in exposed rats. The NOAEL(HEC) in rats
was 265 mg/cu.m, the highest concentration tested.
In both male and female rabbits, body weight was significantly depressed at
403 ppm. The adrenal weight in male rabbits exposed to 25 ppm ethylene glycol
monoethyl ether was significantly depressed, but was not found to be related
to a concentration response. Significantly decreased testes weight was
observed in rabbits exposed to 403 ppm ethylene glycol monoethyl ether.
Pathological changes in the testes were characterized as minimal to slight
focal degeneration of the seminiferous tubules with loss of epithelium in 3 of
10 rabbits. Spermatogenic activity in the affected males was judged by
overall organ morphology and deemed normal. Additionally, both sexes
exhibited significantly decreased hemoglobin, hematocrit and erythrocyte count
at 403 ppm. Based on the observed testicular and hematopoietic effects at 403
ppm, the NOAEL(HEC) and LOAEL(HEC) in the rabbit are identified as 68 and 265
mg/cu.m, respectively.
Doe (1984) exposed pregnant Wistar rats (24/group) to 0, 9.9, 50.8 or 249.2
ppm ethylene glycol monoethyl ether (0, 36, 187 or 919 mg/cu.m) 6 hours/day
during gestational days 6-15. The dams were killed on day 21 of pregnancy.
Body weight, food consumption, hematological parameters, organ weights and
uterine examination were factors in assessing maternal toxicity. Parameters
used to assess fetal toxicity included body weight and external, visceral and
skeletal examinations.
There were decreased hemoglobin and hematocrit levels and mean corpuscular
volume in the 249.2 ppm exposure group; however, no other signs of maternal
toxicity were observed. There was a significantly elevated preimplantation
loss in the dams exposed to 9.9 or 50.8 ppm ethylene glycol monoethyl ether.
Since exposure began on gestational day 6, the increased preimplantation loss
is probably not treatment related. Increased late intrauterine death,
decreased fetal body weight and an increased incidence of delayed ossification
were observed in the offspring of rats exposed to 249.2 ppm. Partial
ossification of the lumbar vertebrae was observed in rats exposed to 9.9 ppm;
however, the incidence was within the historical range for this strain of
rats. Based on the qualitative hematological effects, the identified
NOAEL(HEC) and LOAEL(HEC) for this maternal study are 47 and 230 mg/cu.m,
respectively.
Groups of pregnant Sprague-Dawley rats (n=14-15) were exposed to 0 or 100
ppm ethylene glycol monoethyl ether (369 mg/cu.m., assuming 25C and 760 mm Hg)
for 7 hours/24 hours/day on gestational days 7-13 or 14-20. No effect on
maternal or fetal body weight was observed. There was a statistically
significant increase in gestation length in rats exposed on days 14-20. The
mean length of gestation was 22.6 days for exposed rats compared with 21.9
days in the controls. These investigatiors also used six neurobehavioral
tests to assess CNS functioning at various stages of development: ascent,
rotorod, open field, activity wheel, avoidance conditioning and operant
conditioning. In the pups exposed during gestational days 7-13, a decreased
rotorod speed and an increased latency period for leaving the central area of
an open field were observed. The activity of the offspring of rats exposed
during gestational days 14-20 decreased on the activity wheel, and avoidance
conditioning, begun on day 60 of age, revealed that these pups received an
increased number and duration of shocks. Neurochemical and neurobehavioral
changes occurred. Whole brain norepinephrine levels in the newborns of the
exposed dams from both exposure groups (7-13 and 14-20 days) decreased. At
age 21 days, norepinephrine was increased in the cerebrum, brain stem and
midbrian of 7- to 13-day exposed pups only. Increased dopamine levels were
found in the cerebrum only of pups from both exposure periods, while serotonin
was increased in the 14-20 day exposure group. The midbrains of pups exposed
on gestation days 7-13 had protein levels that exceeded the controls. Gross
teratogenic anomalies (terata) were not detected due to insufficient numbers
of animals or inadequate procedures. The LOAEL for developmental effects is
369 mg/cu.m (HEC=369 mg/cu.m) (Nelson et al., 1981).
Nelson et al. (1982a,b) exposed Sprague-Dawley rats to 0 or 200 ppm
ethylene glycol monoethyl ether (737 mg/cu.m) on gestational days 7-13.
Decreased neuromotor ability, assessed by an ascent test and rotorod, and less
activity in an open field and shuttle box, were observed in the pups of
treated dams, as well as extended pregnancy duration for the dams given 200
ppm ethylene glycol monoethyl ether (Nelson et al., 1982a). Increased
dopamine and norepinephrine levels were also observed, especially in the
cerebrum, in the 21-day-old pups (Nelson et al., 1982b).
In a range-finding study, Nelson et al. (1981) exposed groups of 3-4
pregnant rats to 300, 600, 900 or 1200 ppm (1106, 2212, 3317 or 4423 mg/cu.m,
assuming 25C and 760 mm Hg) 7 hours/day on gestational days 7-13 or 14-20.
The dams exposed on gestational days 14-20 were also exposed to 200 ppm
ethylene glycol monoethyl ether. These investigators observed increased fetal
and pup mortality and increased gestation length at exposure levels greater
than or equal to 200 ppm (737 mg/cu.m).
___I.B.3. UNCERTAINTY AND MODIFYING FACTORS (INHALATION RfC)
UF -- An uncertainty factor of 10 was used to account for intraspecies
extrapolation, 10 for use of a subchronic study and 3 to account for
interspecies extrapolation. The reproductive and developmental studies for
ethylene glycol monoethyl ether are considered to be of sufficient number and
quality in various species exposed both by oral and inhalation exposure.
Thus, an uncertainty factor for an incomplete data base is not needed.
MF -- None
___I.B.4. ADDITIONAL STUDIES / COMMENTS (INHALATION RfC)
The potential for testicular toxicitiy in a group of workers exposed to
ethylene glycol monoethyl ether vapors was assessed by Clapp et al. (1987) and
Ratcliffe et al. (1989). Exposure levels ranged from not detectable to 24 ppm
(88 mg/cu.m, assuming 25C and 760 mm Hg), with average levels under 6 ppm (22
mg/cu.m) in one building and 11 ppm (41 mg/cu.m) in a second building (Clapp
et al., 1987). Exposure occurred by inadvertent skin contact, inhalation or
by airborne vapor condensing on the skin. Ratcliffe et al. (1989) obtained
semen samples from 37 exposed and 39 unexposed workers. Mean sperm count per
ejaculate in exposed workers showed a marginal statistically significant
(p=0.047) decrease compared with controls (corrected for abstinence, sample
age, caffeine, alcohol and tobacco consumption, urogenital and other medical
disorders). No statistically significant differences in semen volume, sperm
concentration, semen pH, viability, motility, velocity and morphology were
observed. Sperm counts of both exposed workers and controls were
significantly different from historical values, suggesting that controls may
also have had some exposure to ethylene glycol monoethyl ether or that both
groups may have been exposed to another compound that affects spermatogenesis.
Most of the workers in the control and some in the exposed group may have been
exposed to metal fumes and dusts, solvents (tetrachloroethylene) or heat and
vibration. Analysis of sperm parameters by duration and potential intensity
of exposure did not reveal an exposure-related effect. Ethylene glycol
monoethyl ether was not identified in the blood of exposed or control workers,
although ethoxyacetic acid (primary metabolite of ethylene glycol monoethyl
ether) was found in the urine of exposed but not control workers. Ratcliffe
et al. (1989) concluded that the results suggest a possible effect of ethylene
glycol monoethyl ether exposure on sperm quality in the workers, but noted
that the study is limited by the small sample sizes and the large
interpersonal variation in the examined parameters.
Doe (1984) exposed groups of pregnant Dutch rabbits (n=24) to 0, 10.1, 51
or 175 ppm ethylene glycol monoethyl ether (0, 37, 188 or 645 mg/cu.m,
assuming 25C and 760 mm Hg) 6 hours/day on gestational days 6-18. Maternal
toxicity was not observed; hematological parameters were not measured. The
offspring of does exposed to 645 mg/cu.m had an increased incidence of
skeletal defects and skeletal variants. The NOAEL(HEC) for this study is 188
mg/cu.m.
Andrew et al. (1981) exposed pregnant Wistar rats (n=37) to 0, 202 or 767
ppm (0, 743 or 2821 mg/cu.m, assuming 25C and 760 mm Hg) ethylene glycol
monoethyl ether 7 hours/day on gestational days 0-19. In the same study, New
Zealand white rabbits (n=29) were exposed to 0, 160 or 617 ppm (0, 588 or 2269
mg/cu.m) ethylene glycol monoethyl ether 4 hours/day on gestational days 0-19.
Decreased maternal weight gain was observed in rats exposed to 2827 mg/cu.m;
and no fetuses survived (100% litter resorption). In the offspring of rats
exposed to 202 ppm, decreased fetal body weight and crown-rump length,
increased incidence of cardiovascular defects (transposed and retrotracheal
pulmonary artery) and minor skeletal anomalies and common skeletal variants
were observed. The LOAEL(HEC) for developmental effects in rats is 743
mg/cu.m. Decreased maternal body weight and food intake were observed in the
does; however, no histopathological alterations in the lungs, liver or kidneys
were apparent. An increased incidence of resorptions at 160 ppm and in the
617 ppm group (100 resorptions) was observed. An increased incidence of major
malformations (ventral wall defects and fusion of aorta with pulmonary
artery), minor anomalies (renal changes) and common skeletal variants
(supernumerary ribs with associated variations and sternebral defects) were
observed in the offspring of the rabbits exposed to 160 ppm. The LOAEL(HEC)
is determined to be 588 mg/cu.m.
Female Wistar rats (37/group) were exposed to 1, 150 or 649 ppm ethylene
glycol monoethyl ether (36, 552 or 2387 mg/cu.m, assuming 25C and 760 mm Hg) 7
hours/day, 5 days/week for 3 weeks prior to mating with naive males. No
reproductive effects were observed (Andrew et al., 1981).
___I.B.5. CONFIDENCE IN THE INHALATION RfC
Study -- Medium
Data Base -- Medium
RfC -- Medium
Medium confidence is placed in the critical study because of its short
duration. Several other studies of rats and rabbits have corroborated the
reproductive effects observed in the principal study. Moreover, a subchronic
inhalation study in rats and rabbits suggests that reproductive toxicity is
the most sensitive endpoint. However, no chronic inhalation studies were
located in the available literature. Thus, medium confidence in the data base
is selected. Reflecting medium confidence in the key study and the data base,
confidence in the inhalation RfC is medium.
___I.B.6. EPA DOCUMENTATION AND REVIEW OF THE INHALATION RfC
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- U.S. EPA, 1985
Agency Work Group Review -- 09/19/1990, 12/19/1990
Verification Date -- 12/19/1990
___I.B.7. EPA CONTACTS (INHALATION RfC)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- 2-Ethoxyethanol
CASRN -- 110-80-5
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- 2-Ethoxyethanol
CASRN -- 110-80-5
Last Revised -- 05/01/1991
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
Andrew, F.D., R.L. Buschbom, W.C. Cannon, et al. 1981. Teratologic
assessment of ethylbenzene and 2-ethoxyethanol. Prepared for the National
Institute for Occupational Safety and Health under Contract 210-79-0037,
Battelle Pacific Northwest Laboratories, Richland, WA 99352. Microfiche
#OTS0513150.
Barbee, S.J., J.B. Terrill, D.J. DeSousa and C.C. Conaway. 1984. Subchronic
inhalation toxicology of ethylene glycol monoethyl ether in the rat and
rabbit. Environ. Health Perspect. 57: 157-163.
Clapp, D.E., A.W. Smallwood, C. Moseley and K.E. DeBord. 1987. Workplace
assessment of exposure to 2-ethoxyethanol. Appl. Ind. Hyg. 2(5): 183-187.
Doe, J.E. 1984. Ethylene glycol monoethyl ether and ethylene glycol
monoethyl ether acetate teratology studies. Environ. Health Perspect. 57:
33-41.
Nelson, B.K., W.S. Brightwell, J.V. Setzer, B.J. Taylor, R.W. Hornung and T.L.
O'Donohue. 1981. Ethoxyethanol behavioral teratology in rats.
Neurotoxicology. 2: 231-249.
Nelson, B.K., W.S. Brightwell and J.V. Setzer. 1982a. Prenatal interactions
between ethanol and the industrial solvent 2-ethoxyethanol in rats: Maternal
and behavioral teratogenic effects. Neurobehav. Toxicol. Teratol. 4(3):
387-394.
Nelson, B.K., W.S. Brightwell, J.V. Setzer and T.L. O'Donohue. 1982b.
Prenatal interactions between ethanol and the industrial solvent 2-
ethoxyethanol in rats: Neurochemical effects in the offspring. Neurobehav.
Toxicol. Teratol. 4(3): 395-401.
Ratcliffe, J.M., S.M. Schrader, D.E. Clapp, W.E. Halperin, T.W. Turner and
R.W. Hornung. 1989. Semen quality in workers exposed to 2-ethoxyethanol. Br.
J. Ind. Med. 46(6): 399-406.
U.S. EPA. 1985. Health and Environmental Effects Profile for
2-Ethoxyethanol. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Solid Waste and Emergency Response, Washington, DC.
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- 2-Ethoxyethanol
CASRN -- 110-80-5
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
05/01/1991 I.B. Inhalation RfC summary on-line
05/01/1991 VI. Bibliography on-line
01/01/1992 IV. Regulatory Action section on-line
VIII. SYNONYMS
Substance Name -- 2-Ethoxyethanol
CASRN -- 110-80-5
Last Revised -- 05/01/1991
110-80-5
Ethanol, 2-ethoxy-
ATHYLENGLYKOL-MONOATHYLATHER [German]
BETA-ETHOXYETHANOL
Cellosolve
CELLOSOLVE SOLVENT
Celosolv [Czech]
Dowanol EE
Ektasolve EE
Emkanol
Eter monoetilico del etilenglicol [Spanish]
Ethanol, 2-Ethoxy-
ETHER MONOETHYLIQUE DE L'ETHYLENE-GLYCOL [French]
Ether monoethylique de l'ethyleneglycol [French]
Ethoxyethanol
ETHYL CELLOSOLVE
ETHYL GLYCOL
ETHYLENE GLYCOL ETHYL ETHER
Ethylene Glycol Monoethyl Ether
ETOKSYETYLOWY ALKOHOL [Polish]
GLYCOL ETHER EE
GLYCOL MONOETHYL ETHER
HSDB 54
Hydroxy ether
Jeffersol EE
NCI-C54853
NSC 8837
Oxitol
POLY-SOLV EE
UN 1171
2-ethoxyethanol
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0513.HTM
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