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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:
1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A published study that is reported in sufficient detail to judge it as sufficiently reliable to add to the overall understanding of the toxicokinetic assessment of this substance.

Data source

Reference
Reference Type:
publication
Title:
Inhalation toxicokinetics of butoxyethanol and its metabolite butoxyacetic acid in the male Sprague-Dawley rat.
Author:
Johanson G
Year:
1994
Bibliographic source:
Arch Toxicol, 68, -588-94

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Disposition of butoxyethanol and its metabolite butoxyacetic acid followed in rats following inhalation exposure over a period of days. Elimination in urine followed as well as disposition of the two substances in key tissues at interim sacrifice time points.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
2-butoxyethanol
EC Number:
203-905-0
EC Name:
2-butoxyethanol
Cas Number:
111-76-2
Molecular formula:
C6H14O2
IUPAC Name:
2-butoxyethanol
Details on test material:
- Analytical purity: 99%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
no data

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Details on exposure:
no data
Duration and frequency of treatment / exposure:
up to 12 days.
Doses / concentrationsopen allclose all
Dose / conc.:
20 ppm
Dose / conc.:
100 ppm
No. of animals per sex per dose / concentration:
8
Control animals:
no
Positive control reference chemical:
none
Details on study design:
no further data
Details on dosing and sampling:
no further data
Statistics:
no data

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
In all the tissues examined, the 2-butoxyethanol concentration rapidly increased during the first three days and continue to increase more slowly during the remaining days of exposure.
Type:
distribution
Results:
Following a 100 ppm exposure the tissues concentrations were approximately 5 times higher higher in blood, 3.5 and 3.6 in muscle and testis respectively and 7.5 in the liver.
Type:
excretion
Results:
The blood clearance rate 2.6 +/- 1.3 l/h/kg bw. The urinary excretion of BAA averaged 0.2 mmol/day in the 20 ppm group and 1.03 mmol/day in the 100 ppm group. (64 % of the calculated respiratory uptake. The renal clearance was 0.53 l/h/kg.

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
The table below shows the tissue concentrations reached in the 20 ppm exposure group.
Details on excretion:
The blood clearance of 2-butoxyethanol was estimated to 2.6 +/- 1.3 l/h/kg bw whichever the dose administered. The kinetic profile of butoxyacetic acid was approximately the same as 2-butoxyethanol. The 100ppm/20ppm concentration ratios were: 4.4 for blood, 4.7 for muscle, 2.3 for testis and 5.3 for liver. The urinary excretion of butoxyacetic acid averaged 0.2 mmol/day in the 20 ppm group and 1.03 mmol/day in the 100 ppm group. This corresponds to 64 % of the calculated respiratory uptake. The renal clearance was 0.53 l/h/kg.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
2-butoxyacetic acid

Any other information on results incl. tables

Average tissues concentrations of 2-BUTOXYETHANOL and butoxyacetic acid following 20 ppm exposure in mmol/l

Tissue concentration

Blood

Liver

Muscle

Testis

2-butoxyethanol

10 – 20

10

10

5

2-butoxyacetic acid

30 – 40

15 – 20

10

10

Following a 100 ppm exposure the tissues concentrations were approximately 5 times higher higher in blood, 3.5 and 3.6 in muscle and testis respectively and 7.5 in the liver.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
2-butoxethanol is readily absorbed following inhalation exposure and rapidly perfuses tissues. However, it is also readily excreted in urine, substantially in the form of the metabolite 2-butoxyacetic acid.
Executive summary:

A toxicokinetic study in male rats showed that 2-butoxethanol is readily absorbed following inhalation exposure and rapidly perfuses tissues to concentrations of 25-100% of those found in the bloodstream.  Absorbed levels are proportionate to exposure concentrations.The substance is readily eliminated in urine, substantially in the form of the metabolite 2-butoxyacetic acid.

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