Methoxyacetic acid

Basic toxicokinetics

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

Guideline:

OECD Guideline 417 (Toxicokinetics)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methoxyacetic acid

EC Number:

210-894-6

EC Name:

Methoxyacetic acid

Cas Number:

625-45-6

Molecular formula:

C3H6O3

IUPAC Name:

2-methoxyacetic acid

Constituent 2

Reference substance name:

2-methoxyacetic acid

IUPAC Name:

2-methoxyacetic acid

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 / concentration:

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 %).