2-ethoxyethanol

Dermal absorption

Administrative data

Endpoint:

dermal absorption

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication

Data source

Reference

Reference Type:

publication

Title:

Percutaneous penetration and metabolism of 2-ethoxyethanol

Author:

Lockley DJ, Howes D, Williams FM

Year:

2002

Bibliographic source:

Toxicol. Appl. Pharmacol. 180, 74 – 82

Materials and methods

Principles of method if other than guideline:

Method: other: in vivo and in vitro absorption through skin

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

2-ethoxyethanol

EC Number:

203-804-1

EC Name:

2-ethoxyethanol

Cas Number:

110-80-5

Molecular formula:

C4H10O2

IUPAC Name:

2-ethoxyethan-1-ol

Details on test material:

Name of the test substance as stated in the publication: 2-ethoxyethanol;
purity of radiolabeld 2-ethoxyethanol (2-ethoxy[1-14C]ethanol, specific activity 19.7 µCi/mg): > 99 %;
obtained from: SEAC Toxicology laboratory, Unilever Research, Colworth House, Bedfordshire;

Radiolabelling:

yes

Remarks:

2-ethoxy[1-14C]ethanol, specific activity 19.7 µCi/mg

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Administration / exposure

Type of coverage:

other: occlusive and open

Duration of exposure:

24 hours

Control animals:

no

Results and discussion

Any other information on results incl. tables

Results of in vitro absorption:

Absorption of the test substance to the receptor fluid when applied unoccluded in methanol or as neat solution was greater through dermatomed rat skin (29 or 19 % applied dose in 24 h) compared to whole rat skin (11 or 11 %), while absorption through dermatomed human skin (8 or 8 %) was lower than the rat. By occluding rat dermatomed skin in vitro, the absorption of neat 2 -ethoxyethanol was increased to 22 %. The test substance diffused through the skin with little retention in the stratum corneum, epidermis, or dermis.

Results of in vivo absorption:

The total absorbed dose of 14C at 1, 4, 7, and 24 h after dosing was 11, 18, 23, and 25 %, respectively.

Sample	Distribution of radiolabeled species 24h after application [%]
CO2	5.83 +/-0.74
Urine	15.36 +/-4.30
Feces	1.19 +/-0.77
Cage wash	1.24 +/-0.12
Blood	0.01 +/-0.00
Liver	0.05 +/-0.05
Carcass	1.44 +/-0.20
Treatment site	0.39 +/-0.04
Absorbed dose	25.11 +/-6.09
Air	24.24 +/-3.67
Skin rinse	0.17 +/-0.04
Skin swab	0.15 +/-0.01
Tape strip	0.26 +/-0.07
Charcoal	27.00 +/-8.22
Protective device	5.91 +/-1.16
Nonabsorbed dose	57.96 +/-10.59
Total recovery	83.08 +/-5.42

There was no evidence of metabolism during percutaneous absorption of 2 -ethoxyethanol through human or rat skin (in vitro for both species).

Cumulative recovery of metabolites from radiolabeled 2 -ethoxyethanol in rat urine by 24 h:

Metabolite	recovery of radioactivity (% of applied dose)
Ethoxyethanol	16.64 +/-2.42
Ethoxyacetic acid	12.93 +/-2.31
Ethoxyacetic glycine	0.75 +/-0.01
Ethylene glycol	0.80 +/-0.02

Applicant's summary and conclusion

Conclusions:

Percutaneous absorption and cutaneous metabolism of the test substance 2 -ethoxyethanol were assessed in vivo (rat skin) and in vitro (rat and human skin). The results showed that 25 % of the topically applied amount of radio labelled 2-ethoxyethanol was absorbed by the rat skin in vivo after 24 hours. There was no evidence of metabolism during the percutaneous absorption of the test substance through human or rat skin (in vitro for both species). The analysis of the rat urine showed that the parent compound was excreated in a high amount (16.6 % of applied dose) together with three metabolites (ethoxyacetic acid 12.9 %, ethoxyacetyl glycine 0.75 %, ethylene glycol 0.80 %).