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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
publication
Title:
2-Methoxyethanol Metabolism in Pregnant CD-1 Mice and Embryos
Author:
Mebus CA, Clarke DO, Stedman DB, Welsch F
Year:
1992
Bibliographic source:
TOXICOLOGY AND APPLIED PHARMACOLOGY, 112: 87-94.

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Methoxyacetic acid was obtained from Eastman Kodak Co. (Lot No. B10E). No purity is indicated. Isotope [1-14C]Methoxyacetic acid was obtained from Wizard Laboratories and was >98% radiochemically pure. [2-14C]Methoxyacetic acid and [methoxy-14C]Methoxyacetic acid were generated in vivo.

Radiolabelling:
yes

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses / concentrations
Remarks:
Doses / Concentrations:
Metabolism of Methoxyacetic acid in vivo:
Dosing solutions for gavage were prepared freshly by neutralizing 100 µL of Methoxyacetic acid with 900 µL of 10% sodiumcarbonate solution and diluting further with 1 ml of acidified water with a pH value of ~2.0. The pH value was checked with a pH indicator paper to assure that it was in the range of 7.0 to 7.4. Single oral dose (3.3 mmol/kg) was administered at 5.04 µL/g bw in combination with a tracer dose of 2 µCi of [1-14C]Methoxyacetic acid. Control animals received an equivalent volume of the vehicle.
No. of animals per sex per dose:
Three pregnant females.
Control animals:
yes, concurrent vehicle
Details on dosing and sampling:
Metabolism of Methoxyacetic acid in vivo:
Immediately after dosing, animals were placed into an individual glass metabolic cage. Exhaled air were passed through CO2 traps and urine was collected from each dam over 12-hr intervals up to 48 hr. Aliquots of the trapping solution and of the urine samples were analyzed to detect radio-labelled parent substance and metabolites.

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes

Any other information on results incl. tables

Present data obtained with [1-14C]Methoxyacetic acid revealed that metabolism beyond 2-Methoxyacetic acid occurs. Dams exhaled ~6% of the radioactivity administered as a single teratogenic oral dose (3.3 mmol/kg on gestation day 11) as14CO2. Examined urine contained ~70% of the dose within 24 hr after administration and ~11% in the next 24 hrs. Three labeled products were resolved using HPLC: an unidentified Peak A (12-18% of dose), Methoxyacetic acid (~50%), and the glycine conjugate of Methoxyacetic acid (~25%). Short-term (4 hr) whole embryo culture on gestation day 11 with 3 mM 2-Methoxyacetic acid and a tracer dose of [1-14C]Methoxyacetic acid, [2 -14C]Methoxyacetic acid, or [methoxy-14C]Methoxyacetic acid showed that14CO2 evolved from the former two substrates, while there was none detectable from the latter. The data indicate that dams metabolized [methoxy-14C]Methoxyacetic acid to14CO2, while embryos apparently did not.

Applicant's summary and conclusion

Executive summary:
Conclusions: Complete absorption following a single oral dose; eliminated as CO2 (11 % of dose) in expired air and rapidly via urine (> 81 %, ~ 70 % within 24 h) as parent compound (~50 %), the glycine conjugate (~25 %) and unidentified metabolite (12 - 18 %).