2-butoxyethanol

Basic toxicokinetics

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Dose / conc.:

20 ppm

Doses / concentrations 2

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 results

Main ADME results 1

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.

Main ADME results 2

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.

Main ADME results 3

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.