Registration Dossier

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:
weight of evidence
Study period:
Received: 16 June 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test substance belongs to the homologue series of glymes. It can be assumed that each members exhibit comparable dermal penetration properties.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
yes
Remarks:
one concentration, skin not rinsed at termination
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
Supplier: Sigma Chemical Co., USA
Purity: 99%
Radiolabelling:
no

Test animals

Species:
human
Strain:
other: n.a.
Sex:
male
Details on test animals and environmental conditions:
The donors were men under 60 years of age.

Administration / exposure

Type of coverage:
other: in vitro study
Vehicle:
unchanged (no vehicle)
Duration of exposure:
30, 60, 90, 120, 150, 180 and 240 min.
Doses:
0.2 mL
No. of animals per group:
8 runs, one per determined time point
Control animals:
no
Remarks:
in vitro study
Details on study design:
Please refer to "Details on in vitro test system"
Details on in vitro test system (if applicable):
In vitro skin permeation using human skin was measured with the Franz method.

Results and discussion

Signs and symptoms of toxicity:
not examined
Remarks:
in vitro study
Dermal irritation:
not examined
Remarks:
in vitro study
Absorption in different matrices:


Lag time: 36 +/- 3 min for diglyme, 39 +/- 3 min for monoglyme

Flux at steady state permeation: 0.952 +/- 0.340 mg/cm2/h for diglyme, 3.434 +/- 1.897 mg/cm2/h for monoglyme

Permeation values of mixture (glycol ether 30% + acetone 70%)
Lag time: 49 +/- 28 min for diglyme, 35 +/- 27 min for monoglyme
Flux at steady state permeation: 0.674 +/- 0.305 mg/cm2/h for diglyme, 0.837 +/- 0.474 mg/cm2/h for monoglyme,
Total recovery:
not determined
Conversion factor human vs. animal skin:
n.a.

Any other information on results incl. tables

Analogue approach justification (target chemical: tetraglyme; source chemicals: di- and monoglyme)

The target and the source chemical belong to the homologues series of glymes, where there is an incremental increase in the number of CH2CH2O units. The dermal penetration property of the target chemical is expected to be comparable to those of the proposed source chemicals, because the relevant physico-data (water solubility, LogPow) on target and source chemicals do not deviate significantly from each other. The molecular size of target chemical, althogh significantly higher than those of source chemicals, is still in the range indicative of higher skin penetration and is not likely to influence the skin penetration property significantly.

Applicant's summary and conclusion

Conclusions:
Tetraglyme is readily bioavailable upon dermal exposure.

Executive summary:

Tetraglyme is expected to be readily bioavailable upon dermal application based on the read-across appraoch using di- and monoglyme as source chemicals.

An in vitro skin absorption study was performed applying diglyme to dermatomed human skin.

For diglyme, the lag time was reported to be 36 +/- 3 min and the flux at steady state permeation was 0.952 +/- 0.340 mg/cm2/h.

For monoglyme, the lag time was reported to be 39 +/- 3 min and the flux at steady state permeation was 3.434 +/- 1.897 mg/cm2/h.

Based on the obtained results, it can be concluded that diglyme and monoglyme are dermally readily bioavailable.