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Toxicological information

Dermal absorption

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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Early non-GLP study.

Data source

Reference
Reference Type:
publication
Title:
In vitro absorption of some o-phthalate diesters through human and rat skin.
Author:
Scott, RC, Dugard, PH, Ramsey, JD and Rhodes, C
Year:
1989
Bibliographic source:
Environ Hlth Perspect, 74, 223-227

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Principles of method if other than guideline:
The absorption of several phthalate diesters by rat or human skin was investigated in vitro using glass diffusion cells. Viability of the tissue preparations was determined pre-test using tritiated water.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):
Diethylhexyl phthalate, Aldrich Chemical Co. Ltd, 99% pure
[14C]-Diethylhexyl phthalate, Amersham International Plc, >99% pure
14C]-Diethylhexyl phthalate was added to unlabelled diethylhexyl phthalate to give a final specific activity of approx. 35 uCi/ml.
Radiolabelling:
yes
Remarks:
[14C]-diethylhexyl phthalate

Test animals

Species:
other: rat, human
Details on test animals and environmental conditions:
Human abdominal skin was obtained from cadavers (mostly female, age 55 yr and above).
Rat skin (from Wistar derived animals was taken from the dorsal region.
The epidermis was peeled away from the dermis, stored at 4 degrees C and used within 7 days.

Administration / exposure

Details on in vitro test system (if applicable):
Epidermal membranes (3 cm diameter) were placed over the receptor chamber of a glass diffusion cell. Membrane integrity was determined by exclusion of tritiated water by the samples before and after each experiment.Approx. 0.5 ml of [14C]-DEHP applied to epidermal surface of the membrane (up to 72 hr contact time; minimum of 9 replicate experiments). Radioactivity in the receptor fluid was determined using liquid scintillation counting. Steady state rate of absorption (ug/cm^2/hr) determined by linear regression.

Results and discussion

Absorption in different matrices:
Absorption of DEHP was slower for human skin (1.06 ug/cm2/hr) than for rat skin (2.24 ug/cm2/hr).
Data reported for other phthalate esters (dibutyl, diethyl, dimethy) confirmed that human skin was consistently less permeable to phthalate esters than rat skin.
Conversion factor human vs. animal skin:
The results demonstrated slower absorption of diethylhexyl phthalate by human skin (1.06 ug/cm2/hr) than by rat skin (2.24 ug/cm2/hr) i.e. permeability of human skin is approx. one half of that of rat skin.

Any other information on results incl. tables

Data reported for other phthalate esters (dibutyl, diethyl, dimethy) confirmed the observation that human skin was consistently less permeable to phthalate esters than rat skin.

Applicant's summary and conclusion

Conclusions:
Human skin is less permeable to phthalate esters than is rat skin.
Executive summary:

The uptake of [14C]-diethylhexyl phthalate by samples of human and rat skin was investigated in vitro using a glass diffusion cell. Only tissue samples exhibiting acceptable membrane integrity (determined from exclusion of tritiated water) were used. Approx. 0.5 ml of [14C]-DEHP was applied to epidermal surface of the membrane, and samples taken from the receptor fluid (50% aq. ethanol) at regular intervals (up to 53 hr (rat) or 72 hr (human)) with a minimum of at least 9 replicate experiments. Radioactivity in the receptor fluid was determined using liquid scintillation counting. The steady state rate of absorption (ug/cm^2/hr) was determined by linear regression. The results demonstrated slower absorption of diethylhexyl phthalate by human skin (1.06 ug/cm2/hr) than by rat skin (2.24 ug/cm2/hr). Data reported for other phthalate esters (dibutyl, diethyl, dimethy) confirmed the observation that human skin was consistently less permeable to phthalate esters than rat skin.