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Toxicological information

Dermal absorption

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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

Reference
Name:
Unnamed
Type:
Constituent
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 %).