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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication with detailed describtion of the conducted methods

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:
Fundam. App.l Toxicol. 21, 486-491

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
inhalation toxicity
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity of used 2-Ethoxyethanol: 99+ %
purchased from: Aldrich Chemical Co. (Milwaukee, WI)
Radiolabeled test substance: 2-Ethoxy[U-14C]ethanol, specific activity 56 mCi/mmol
Radiolabelling:
yes
Remarks:
2-Ethoxy[U-14C]ethanol

Test animals

Species:
rat
Strain:
other: F344/N
Sex:
male
Details on test animals and environmental conditions:
Age at time of exposure: 11-13 weeks (purchased from Taconic, Germantown, NY at 9 weeks of age)
Animal rooms were maintained at approximately 21 °C with a relative humidity of 20-60 % and a 12-hr light-dark cycle with light starting at 0600.
Food (Certified Lab-Blox, Allied Mills, Chicago, IL) and water via an automatic watering system were provided ad libitum except during inhalation exposures.

Administration / exposure

Route of administration:
other: inhalation in nose only tubes
Details on exposure:
Rats were exposed to 2-Ethoxy[U-14C]ethanol by inhalation in nose-only tubes.
Duration and frequency of treatment / exposure:
Eight rats were exposed for 5 hr 40 min to a target concentration of 5 ppm 2-Ethoxyethanol; eight rats were exposed for 6 hr to a target concentration of 50 ppm 2-Ethoxyethanol;
Doses / concentrations
Remarks:
Doses / Concentrations:
5 ppm for 5 hr 40 min
50 ppm 6 hr
No. of animals per sex per dose:
males, 8
Control animals:
no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Excreta (urine, feces, and exhaled breath) were collected for 66 hr.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
By reverse-phase HPLC identified urinary metabolites of 14C-2-Ethoxyethanol: Ethylenglycol, Ethoxyacetic acid, N-ethoxyacetylglycine.

Any other information on results incl. tables

Exposure and respiratory parameters:

The actual exposure concentrations were 5.03 +/-0.23 ppm and 46.0 +/- 2.2 ppm; Although the values for respiratory rate and tidal volume were statistically different between the two exposure groups, the values for minute volume were not significantly different for the two exposures.

Absorption and retention of 2 -Ethoxyethanol:

There was no significant difference between the body burden determined at the end of the exposure and the amount of 14C-2 -Ethoxyethanol equivalents in the total excreta (plus carcass) for the two exposures. The amount of 14C retained was proportional to the exposure concentration of the test substance.

Excretion of 14C-2 -Ethoxyethanol:

The majority of 14C was excreted in the urine and exhaled as 14CO2 at both exposure concentrations. There was a significant difference in the amount of radiolabeled test substance equivalents excreted in the feces for the two exposure groups, although this amount represented less than 2 % of the total 14C absorbed.

Applicant's summary and conclusion

Conclusions:
Male rats were exposed to either 5 or 50 ppm of radiolabeled 2-ethoxyethanol by inhalation for approximately 6 hours. No significant difference between the body burden determined at the end of the exposure and the amount of 14C-2-ethoxyethanol equivalents in total excreta for the two exposures were observed. The majority of 14C was excreted in the urine and exhaled as 14CO2. The main identified urinary metabolites were ethylenglycol, ethoxyacetic acid, and N-ethoxyacetylglycine.