2-hexyloxyethanol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted with compliance to Good Laboratory Practices TSCA Standards; Federal Register 48(230): 5397-53944, November 29, 1983.

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:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 85-3 (Dermal Penetration)

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hexyloxyethanol

EC Number:

203-951-1

EC Name:

2-hexyloxyethanol

Cas Number:

112-25-4

Molecular formula:

C6H13OCH2CH2OH

IUPAC Name:

2-hexyloxyethanol

Details on test material:

- Name of test material (as cited in study report): Ethylene Glycol Monohexyl Ether (EGHE)
- Physical state: clear liquid
- Analytical purity: 98.5% by gas chromatography
- Impurities (identity and concentrations): not specified
- Composition of test material, percentage of components: not specified
- Isomers composition: not specified
- Purity test date: not specified
- Lot/batch No.: S-020773/BRRC No. 50-383
- Expiration date of the lot/batch: not specified
- Radiochemical purity (if radiolabelling): 97.2% by thin layer chromatography and 99% by gas chromatography
- Specific activity (if radiolabelling): 2.1 mCi/mmole, which is equivalent to 31.88 x 10(6) DPM/mg.
- Locations of the label (if radiolabelling): 14C-labelled EGHE was synthesized by DuPont/New England Nuclear Products, Boston, MA
- Expiration date of radiochemical substance (if radiolabelling): not specified
- Stability under test conditions: stated to be stable in the Material Safety Data Sheet; stability studies at BRRC showed EGHE to be stable in physiological saline solution
- Storage condition of test material: The chemical was stored at ambient temperatures throughout the course of the study

Radiolabelling:

yes

Remarks:

C14- Labeled EGHE

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland, denver ,PA
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 2 - 3 kgs
- Housing: Open rack-type metabolism cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum):Ad libitum
- Acclimation period:5 days


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light):12 hour photoperiod

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

48 hour experimental period

Doses:

Percutaneous Male-10mg/kg
Percutaneous Female-10mg/kg

No. of animals per group:

5 animals per group

Control animals:

no

Details on study design:

APPLICATION OF DOSE: 10mg/kg EGHE to male and female rabbits.

TEST SITE
- Preparation of test site: The dose material was applied to the skin using a syringe and needle
- Area of exposure: Occluded with polyethylene sheeting held in place woth waterproof surgical tape and covered with stretch adhesive bandage tape.

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes:

SAMPLE COLLECTION
- Collection of blood: 1,2,4,8,12,24,30,36 and 48 hours
- Collection of urine and faeces: Done

Details on in vitro test system (if applicable):

not applicable

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

no effects

Absorption in different matrices:

Refer to attachment

Total recovery:

Refer to attachment

Conversion factor human vs. animal skin:

not applicable

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:

The results in rabbits indicates that EGHE (Ethylene glycol hexyl ether) has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.

Executive summary:

New Zealand White rabbits were used to access Skin Penetration and Pharmacokinetics of Ethylene Glycol Monohexyl Ether (EGHE). Intravenous doses of 10 and 1 mg/kg EGHE given to male rabbits were metabolized rapidly, so that EGHE levels were less than 1% of the total plasma radioactivity by 1 hour post-dosing. About 80% of the radioactivity was recovered in the urine, with less than 2% in the feces. Because the rabbits were housed in open metabolism cages, the recoveries of radioactivity in C02and organic volatile fractions could not be assessed; however, over 90% of the dose was recovered in the intravenous studies. After cutaneous dosing of 10 mg/kg EGHE to male and female rabbits, about 75% of the dose was recovered; the remainder of the dose may have been lost because the organic volatile fraction could not be collected. No sex differences in the disposition of EGHE were observed. EGHE penetrated the skin rapidly, and the radioactivity was widely distributed. Most of the radioactivity was eliminated in the urine (55-65%) with minimal recovery in feces. The cutaneous bioavailability, based on total radioactivity, was greater than 65%; however, EGHE was extensively metabolized so that it accounted for less than 10% of the total radioactivity by 1 hour post-dosing. In nearly all urine fractions no EGHE was detected, but up to nine metabolite peaks were found.

No marked accumulation of EGHE was observed in a variety of tissues and organs that were analyzed.

The results in and rabbits indicate that, while EGHE has a large potential for systemic absorption, it is rapidly and extensively eliminated from the plasma by metabolic conversion to multiple metabolite species.