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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
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A published study but one which contains sufficient experimental detail to be able to judge it reliable for risk and hazard assessment purposes

Data source

Reference
Reference Type:
publication
Title:
Metabolic studies with diethylene glycol monobutyl ether acetate (DGBA) in the rat
Author:
Deisinger PJ, Guest D
Year:
1989
Bibliographic source:
Xenobiotica, 19, 9, 981-9

Materials and methods

Objective of study:
excretion
metabolism
Principles of method if other than guideline:
An in vivo study was conducted to determine the metabolic fate and disposition of the substance following a single oral gavage administration.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diethylene glycol monobutyl ether acetate (DGBA)
- Physical state: liquid
- Analytical purity: 95%
- Supplier: Kodak Laboratory CHemicals (ROchester, NY)
- Impurities (identity and concentrations): 2-(2-ethoxyethoxy)ethyl acetate, diethyl phthalate, methyl substituted DGBA.
- Radiochemical purity (if radiolabelling): 97.1%
- Specific activity (if radiolabelling): 0.951uCi/mole
- Locations of the label (if radiolabelling): no data
- Supplier: Wizard Laboratories (Davis, CA)
Radiolabelling:
yes
Remarks:
labelled material diluted with unlabelled as appropriate.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Wilmington, MA
- Weight at study initiation: 200-250g
- Individual metabolism cages: yes/no
- Diet: Purina Chow 5002, ad libitum, except for first 4 hours after dosing.
- Water: ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: labelled and unlabelled material blended to ensure that each dose contained approximately 20uCi.
Duration and frequency of treatment / exposure:
Single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
200 and 2000mg/kg
No. of animals per sex per dose:
5
Control animals:
yes
Positive control:
No
Details on dosing and sampling:
METABOLITE CHARACTERISATION STUDIES using glassmetabolism cages.
- Tissues and body fluids sampled: urine, faeces, tissues, cage washes, exhaled air.
- Time and frequency of sampling: 8 (urine and CO2 only), 24, 48, 72hrs. Tissues from 72hrs when animals sacrificed.
- From how many animals: (samples pooled or not)
- Method type(s) for identification: Liquid scintillation counting. HPLC and GCMS for urine samples.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The substance was rapidly and completely absorbed from the gastrointestinal tract.
Details on excretion:
Radioactivity was eliminated rapidly in the urine. At the lower dose, 58% of applied dose was excreted by this route within 24 hours, whilst only 42% was similarly excreted from the high dose animals. In both cases, total accounted for dose in this period was 81-82%.. Only trace amounts of radioactivity were detected in the urine after 24hrs. See table below for distribution between excretion routes.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
5 radiolabelled peaks identified accounting for 54% and 22% of the 0-8hr and 8-24hr urine collections respectively of the low dose animals. Similar results were seen in the high dose animals (41% and 39% for the first and second collection periods). A second major peak was observed in the higher dose animals as well as the single main peak seen in the low dose animals. Metabolites are shown in the table below.

Any other information on results incl. tables

Elimination

Distribution betwen routes of elimination for 200mg/kg dose:

   0 -24 hours  24 -72 hours
 Urine  82.3%  1.2%

 Faeces

 1.5%  0.5%
 Expired air*  4.5%  0.6%
 Cage wash  2.5%  0.5%
 Carcass and tissue     4.2%

*negligible amount as VOC, all CO2.

Total radioactivity recovery 97.4%

Distribution betwen routes of elimination for 2000mg/kg dose:

   0 -24 hours  24 -72 hours
 Urine  81.3%  3.1%

 Faeces

 2.9%  3.6%
 Expired air*  4.1%  0.8%
 Cage wash  3.7%  0.7%
 Carcass and tissue     4.1%

*negligible amount as VOC, all CO2.

Total radioactivity recovery 100.6%

Metabolites

Low dose animals (200mg/kg)

 Metabolite identified  Percentage
 Acid labile  2.3%
 Conjugate  15.4%
 2 -(2 -3 or 4 -hydroxybutoxy)-ethoxy)ethanol  11.5%
 diethylene glycol  11.8%
 2 -butoxyethoxyacetic acid  58.9%

High dose animals (2000mg/kg)

 Metabolite identified  Percentage
 Acid labile  8.3%
 Conjugate  6.8%
 2 -(2 -3 or 4 -hydroxybutoxy)-ethoxy)ethanol  31.5%
 diethylene glycol, 2 -butoxyethoxyacetic acid   53.4%

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
2-(2-butoxyethoxy)ethyl acetate is eliminated almost entirely within 24 hours of even a very large dose. The main route of elimination is the urine. There is more than one potential metabolic route, although all involve the initial step of hydrolysis of the substance to its parent glycol ether.
Executive summary:

An in vivo study was conducted to determine the metabolic fate and disposition of the 2 -(2 -butoxyethoxy)ethyl acetate following a single oral gavage dose. Urinary metabolites were analysed and all other possible routes were also examined. The substance was rapidly and completely absorbed from the gastrointestinal tract and nearly all eliminated within 24hours, primarily in the urine. Dose had little effect on the pattern of metabolites or relative importance of the possible elimination routes. The main metabolite observed was 2 -(2 -butoxyethoxy)acetic acid. No butoxyacetic acid was detected nor any unchanged parent compound.