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Additional toxicological data

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Administrative data

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

Data source

Reference
Reference Type:
publication
Title:
Effect of dose on the disposition of 2-ethoxyethanol after inhalation by F344/N rats
Author:
Kennedy CH, Bechtold WE, Chang I-Y, Henderson RF.
Year:
1993
Bibliographic source:
Fundamen. Appl. Toxicol. 21(4), 486-491

Materials and methods

Type of study / information:
Type: inhalative absorption
Principles of method if other than guideline:
Method: other: metabolism analysis in rats
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: 2-ethoxyethanol
radiolabeled 2-ethoxyethanol: purchased from Amersham Laboratories (Buckinghamshire, UK);
unlabeled 2-ethoxyethanol: purchased from Aldrich Chemical Co. (Milwaukee, WI), purity 99+ %;

Results and discussion

Any other information on results incl. tables

The actual exposure concentrations were 5.03 +/-0.23 ppm and 46.0 +/-2.2 ppm.

Absorption and retention of [14C]-2 -ethoxyethanol:

   Exposure 5.0 ppm  Exposure 46.0 ppm
 Volume inhaled (L)  132 +/-3  138 +/-6
 2 -ethoxyethanol inhaled (µmol/ppm)  4.41 +/-0.10  4.61 +/-0.20
 Body burdon (total body burdon at end of exposure, µmol/ppm)  1.23 +/-0.08  1.46 +/-0.02
 Total excreta (µmol/ppm)  1.31 +/-0.06  1.39 +/-0.04
 Amount retained (µmol/ppm)  1.25 +/-0.04  1.33 +/-0.04
 Percentage retained  28 +/-1.1  29 +/-1.6

Excretion of [14C]-2 -ethoxyethanol equivalents:

            µmol [14C]-2 -ethoxyethanol equivalents
Route of excretion   5 ppm  %  46 ppm  %
 14CO2 during exposure  1.4  21  14  22
 14CO2 postexposure  1.1 +/-0.1  16  10 +/-1  16
 Urine  3.1 +/-0.1  46  29 +/-1  46
 Feces  0.04 +/-0.01  0.6  1.0 +/-0.2  1.6
 Exhaled 2 -ethoxyethanol postexposure  0.23 +/-0.09  4.2  2.4 +/-0.3  3.7
 Carcass  0.74 +/-0.06  11  6.6 +/-0.2  10
 Total  6.6 +/-0.3  100  64 +/-2  100

4 urinary metabolites were detected from which three were identified by means of reverse-phase HPLC. The identified metabolites were ethylene glycol, ethoxyacetic acid and the glycine conjugate of ethoxyacetic acid (comparison via HPLC of authentic standards and GC/MS analysis).

Applicant's summary and conclusion

Conclusions:
The major urinary metabolites identified in male F344/N rats inhalatively exposed to 5 or 46 ppm of radiolabeled 2-ethoxyethanol were ethylene glycol, ethoxyacetic acid and the glycine conjugate of ethoxyacetic acid. An other major excretion route of radiolabeled 2-ethoxyethanol equivalents was the exhalation of 14CO2.