2-(2-ethoxyethoxy)ethyl acetate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Urinary excretion of ethoxyacetic acid afterexperimental human exposure to ethylene glycolmonoethyl ether

Author:

D GROESENEKEN, H VEULEMANS, R MASSCHELEIN.

Year:

1986

Bibliographic source:

British Journal of Industrial Medicine ;43:615-619.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Not available

Principles of method if other than guideline:

Urinary excretion of ethoxyacetic acid after experimental human exposure to ethylene glycolmonoethyl ether.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-ethoxyethoxy)ethanol

EC Number:

203-919-7

EC Name:

2-(2-ethoxyethoxy)ethanol

Cas Number:

111-90-0

Molecular formula:

C6H14O3

IUPAC Name:

2-(2-ethoxyethoxy)ethanol

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report):Diethylene Glycol Ethyl Ether
- Molecular formula (if other than submission substance):CH3CH2–O–CH2CH2–O–CH2CH2–OH
- Molecular weight (if other than submission substance):134.2 g/mol
- Substance type:Organic
- Physical state:Liquid
- Impurities (identity and concentrations):NA

Radiolabelling:

not specified

Test animals

Species:

human

Sex:

male

Administration / exposure

Route of administration:

inhalation

Vehicle:

other: Air

Details on exposure:

10 healthy male subjects (aged 19-28)who were exposed for four hours to various concentrationsof EGEE in inspired air, both at rest andduring physical exercise.

Duration and frequency of treatment / exposure:

4 hrs

Doses / concentrations

Remarks:

Doses / Concentrations:
Group 1 (at rest): 10mg/m3, 20mg/m3, and 40mg/m3
Group 2 (at rest):20mg/m3
(during physical exercice):30W (20mg/m3) and 60 W (20mg/m3).

No. of animals per sex per dose / concentration:

10 healthy male

Control animals:

not specified

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Not available

Main ADME results 2

Type:

distribution

Results:

Not available

Main ADME results 3

Type:

metabolism

Results:

Not available

Main ADME results 4

Type:

excretion

Results:

During exposure, a noticable increase in the rate of excretion of ethoxyacetic acid was observed from first hour of the experiment. The rate continued to increase when exposure was interrupted and reached a maximal level 3 to 4 hrs after end of exposure

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not Applicable,since the use is not as a drug but use in cosmetics and skin care products.

Details on distribution in tissues:

Not Applicable

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Ethoxyacetic acid was the main metabolite obtained after urinary excretion.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

Not available

Any other information on results incl. tables

Before exposure to EGEE, ethoxyacetic acid waseither not present in the urine or present only atconcentrations near the detection limit (approx 0.07 mg/l).During exposure, both at rest and during physicalexercise, a noticable increase in the rate of excretionof ethoxyacetic acid was observed from the first hourof the experiment. The rate continued toincrease when the exposure was interrupted andreached a maximal level three to four hours after theend of the exposure period. Thereafter a slowexponential decrease was observed with a biologicalhalf life between 21 and 24 hours. Even after 42hours, the excretion rate had not returned to baselinevalues.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
The urinary excretion study of the test substance EGEE showed that ethoxyaceticacid was excreted in the urine. On average, 23% of inhaled EGEE was recoveredas ethoxyacetic acid within 42 hours,showing low bioaccumulation potential.

Executive summary:

As soon as exposure to EGEE was started, ethoxyaceticacid was excreted in the urine. These resultssuggest that the metabolism of EGEE in man proceedsprimarily by oxidation and are consistent withthe biotransformation pathways reported for ethyleneglycol monoalkyl ethers in animals. After an initial rise during exposure, the rate of excretionof ethoxyacetic acid continued to increase afterthe exposure was interrupted and maximal levels werereached three to four hours after the end of the fourhour exposure period. Afterwards, the excretion ratedeclined slowly with a biological half life of 21-24 hrs. On average, 23% of inhaled EGEE was recovered as ethoxyacetic acid within 42 hours. No difference was found between experiments at rest and during physical work.