Poly(oxy-1,2-ethanediyl), α-butyl-ω-hydroxy-

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

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. Justification for read-across is given in the attached document; Chapter 13: Glycol ether E series Chemical Category

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Percutaneous penetration and metabolism of 2-butoxethanol

Author:

Lockley DJ, Howes D, Williams FH

Year:

2004

Bibliographic source:

Arch Toxicol, 78, 617-28

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The absorption of radiolabelled 2-butoxyethanol was followed after topical application using both in vitro and in vivo methods and the metabolism and elimination then followed. The in vivo results only are reported here.

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:

- Name of test material (as cited in study report): 2-butoxyethanol
- Analytical purity: >98%
- Radiochemical purity (if radiolabelling) :> 98% chemically pure
- Specific activity (if radiolabelling): 11uCi/mg
- Locations of the label (if radiolabelling): 2-butoxy [1-14C] ethanol
- Other: suppliers: SEAC Toxicology Laboratory, Unilever Research for labelled material. Sigma, Poole for unlabelled material

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 35 days
- Housing: individually in metabolism cages.
- Diet ad libitum
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- No data:

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

- Nominal doses 100ul (10.53uCi)

No. of animals per group:

3

Control animals:

no

Details on study design:

APPLICATION OF DOSE: Silicone O ring fixed with cyanoacrylate adhesive on clipped skin.

TEST SITE
- Area of exposure: 9.6cm2
- Type of wrap if used: Glass protective device containing a charcoal pad fixed over O ring then surgical tape wrapping to prevent evaporation and oral ingestion.

SITE PROTECTION? USE OF RESTRAINERS FOR PREVENTING INGESTION: yes see below

SAMPLE COLLECTION
- Collection of blood: yes, at 1, 3, 7, 24hrs from the heart.
- Collection of urine and faeces:
- Collection of expired air: yes
- Terminal procedure: Protective device and filter soaked in ethanol, dichloromethane and methanol respectively overnight. Skin site washed with 3% Teepol solution, dried and stratum corneum tape stripped. Remaining skink, liver, carcass solubilised for counting. Cage rinses analysed.
- Analysis of organs: yes, liver

SAMPLE PREPARATION
- Preparation details: Blood EDTA sequestered

ANALYSIS
- Method type(s) for identification HPLC for metabolites. Liquid scintillation counting for quantification.

Details on in vitro test system (if applicable):

The dermis from topical application sites of the rats killed at 4 and 24hrs was divided and placed on microscope slides coated in photographic emulsion and exposed for 120hr at -20C.  The slides were then photographically developed, stained with H&E then the silver grain distribution assessed to determine levels of radioactivity distribution.  Unexposed skin was used as a control.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

24 HOUR RESULTS (END OF STUDY)-
Non-occlusive cover (including charcoal filter and air + enclosure rinse:56.2%
- Skin wash: 0.3%
- Skin test site: 0.1%
- Blood: 0%
- Carcass+liver: 1.6%
- Urine: 18.8%
- Cage wash + cage wipe: 3%
- Faeces: 1.5%
- Expired air (if applicable): 5.7%

FATE OF ABSORBED DOSE (24hr)
- Skin test site: 4.3%
- Blood: 0%
- Carcass: 1.6%
- Liver: 4.7%
- Urine: 66%
- Cage wash + cage wipe: 0.9%
- Faeces: 0.4%
- Expired air (if applicable): 20%

Total recovery:

- Total recovery: 85-90% over all time points
- Recovery of applied dose acceptable: Yes

Any other information on results incl. tables

Absorbed dose over time:

1hr	4hrs	7hrs	24hrs
7.5%	14.5%	23.5%	28.5%

HPLC analysis of urine showed the following metabolites in the cumulative percentages of applied dose shown:
ethylene glycol (0.6%)
butoxyacetic acid (7.9%)
Glucoronide and conjugate (2.6%)
sulphate conjugate (0.7%)
2-butoxyethanol (0.6%)

The microautoradiographs showed a low density of silver grains on or slightly above the stratum corneum and on hair shafts with background levels in the remaining layers of skin.  There was no evidence of localization within skin appendages.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: no bioaccumulation potential

Executive summary:

In a study in rats, topical application of radiolabelled 2-butoxyethanol resulted in 28% of the applied dose being absorbed over a 24 hour period (24% in 7 hours). Nearly 90% of the absorbed material was excreted within this 24 hour period and only 1.4% remained in the carcass. The dominant metabolite was butoxyacetic acid eliminated in the urine.