Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication

Data source

Reference
Reference Type:
publication
Title:
Ethylene Glycol Monoethyl Ether and Ethylene Glycol Monoethyl Ether Acetate Teratology Studies
Author:
Doe JE
Year:
1984
Bibliographic source:
Environ. Health Perspect. 57: 33-41

Materials and methods

Principles of method if other than guideline:
Method: other: Inhalation teratology study
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of the test substance as stated in the publication: Ethylene glycol monoethyl ether (EGEE)
purchased from: Imperial Chemical Industries PLC, Wilton, Middlesbrough, UK.
purity: >99 %

Test animals

Species:
other: rat; rabbit
Strain:
other: rat Alpk/AP (Wistar-derived)

Administration / exposure

Route of administration:
inhalation
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Wilks-Miran infrared analyzer: wavelength 8.9 µm, slit width 1 mm;
Duration of treatment / exposure:
rats: days 6-15 inclusive of gestation
rabbits: days 6 to 18 inclusive of gestation
Frequency of treatment:
6 hours/day
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
10, 50, 250 ppm
Basis:
nominal conc.
for rats
Remarks:
Doses / Concentrations:
10, 50, 175 ppm
Basis:
nominal conc.
rabbits
No. of animals per sex per dose:
rats: 24
rabbits: 24
Control animals:
other: yes, concurrent exposure to air
Details on study design:
Rats: duration of test: section on day 21 of gestation;
Rabbits: duration of test: section on day 29 of gestation;

Results and discussion

Results (fetuses)

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEC
Effect level:
10 ppm
Based on:
test mat.
Basis for effect level:
other: fetotoxicity
Dose descriptor:
LOAEC
Effect level:
10 ppm
Based on:
test mat.
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Rats:

Maternal observations: In the rats exposed to 250 ppm 2 -ethoxyethanol there were reductions in hemoglobin, hematocrit and mean cell volume in the red blood cells, but there were no effects at either 50 or 10 ppm.

Litter data: There was a higher level of preimplantation loss in all exposed groups compared with controls, although this was statistically significant only in the 10 and 50 ppm groups. The mean number of live fetuses was reduced in the exposed groups compared with the controls, and this was statistically significant in the 10 and 50 ppm groups but not at 250 ppm. Total litter weight was statistically significantly reduced in the 10 and 250 ppm groups, the reduction being most marked at 250 ppm.

Rabbits:

Maternal observations: There were no effects due to compound on body weight gain or food consumption and no clinical abnormalities which could be attributed to exposure to 2 -ethoxyethanol.

Litter data: There was no evidence for any treatment-related effects on the litter data. There were two major defects in the 175 ppm group: one fetus had a cardiovascular defect (heart and aorta reduced in size and the right subclavian artery was missing), and another fetus had a ventral wall defect (umbilical hernia). The incidence of skeletal defects was statistically significantly greater in the 175 ppm than in the control group, largely as a result of retarded ossification of the skeleton and an increased incidence of 27 presacral vertebrae. The incidence of minor skeletal defects was also increased in the 10 ppm group in comparison with the control group but is not considered to be treatment-related, as it was not statistically significant and there was only a very slight increase observed in the 50 ppm group. Taken overall, the results of the two studies reported here for the effect of 2 -ethoxyethanol in rats and rabbits indicate that levels of 175 to 250 ppm may be around the threshold level for teratogenicity; 175 to 250 ppm has been shown to be fetotoxic in both rats and rabbits, and 50 ppm is mildly fetotoxic in rats, although there were no effects in rabbits. These studies overall indicate a marginal fetotoxic effect level of 50 ppm and a clear no-effect level of 10 ppm in both species.

Remark of the author of this IUCLID dossier: According to the results in rats the lowest administered dose (10 ppm) had effects on the litter (higher level of preimplantation loss, reduction of mean number of live fetuses, reduction of litter weight). Therefore this concentration is considered to be the LOAEC.

Applicant's summary and conclusion

Conclusions:
The toxic potential of test substance 2-ethoxyethanol according to embryotoxicity and teratology has been evaluated in female rats and rabbits via inhalation of the substance during gestation. At the lowest dose administered (10 ppm, 6 h/d) different effects on the rat litter were observed (higher level of preimplantation loss, reduction of mean number of live fetuses, reduction of litter weight). Therefor this concentration corresponds to the LOAEC.