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Diss Factsheets

Administrative data

dermal absorption in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is not following any offical validated methodology. It is a well described and scientifically valid study, well demonstrating metabolic pattern of dermal absorbtion

Data source

Reference Type:
Metabolism of topically applied fatty acid methyl esters in BALB/C mouse epidermis
Wertz.W, Downing D.T.
Bibliographic source:
Journal of dermatological science, 1 (1990) 33-38 - Elsevier

Materials and methods

Principles of method if other than guideline:
After a patch application in two subsequent days of the substance on neonatal BALB/C rats, they will sacrificed, the lipidic part of the skin separated and analysed by CG, to determine the nature of the coupled sphingolypids
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl oleate
EC Number:
EC Name:
Methyl oleate
Cas Number:
Molecular formula:
Methyl (Z)-octadec-9-enoate
Constituent 2
Reference substance name:
Methyl Palmitoleate
Methyl Palmitoleate
Details on test material:
No data

Test animals

not specified
Details on test animals or test system and environmental conditions:
Mice were provided a standard diet (5008 pellets, Ralston Purina) and water ad libitum. Pups were removed to separate cages at three days of age

Administration / exposure

Type of coverage:
not specified
100 microliters
Duration of exposure:
24 hours + 24 hours
50 mg
No. of animals per group:
Control animals:

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified

Any other information on results incl. tables

Table I shows the fatty acid compositions for acylceramide, acylglucosylceramide and phosphatidylethanolamine from each treatment group. The compositions of the acylceramide and acylglucosylceramide from the control animals were very similar to one another. The most outstanding feature of their fatty acid compositions was the presence of 70-80% linoleate. In contrast, the fatty acids from the control phosphatidylethanolamine fraction contained only 17.3% linoleate but included 14.7% arachidonate, which was not found in the sphingolipids, and 41.7% oleate. As can be seen, treatment with methyl oleate or methyl palmitoleate resulted in several small, but statistically significant, alterations in the fatty acid composition of the acylceramide. Larger effects were seen with the acylglucosylceramide and phosphatidylethanolamine. In the methyl oleate-treated group, the linoleate content of the acylglucosylceramide was reduced from 70.9 to 54.2% while the oleate content increased from 9.3 to 17.5 %. A small, but significant, increase in 16: 1 was also found. In the phosphatidylethanolamine fraction from this group, there was also a significant increase in oleate content mainly at the expense of linoleate.

TABLE I The effects of topically applied methyl oleate and methyl palmitoleate on the fatty acid composition of epidermal lipids Control Oleate Palmitoleate mean (sd) mean (sd) mean (sd) Acylceramide 14:o 16:O 16: 1 18:O 18: lA9 18: IA11 IS:2 Acylglucosylceramide 14:o 16:O 16: 1 18:O 18: IA9 18: lAl1 18:2 Phosphatidylethanolamine 14:o 16:O 16: 1 18:O 18: lA9 18: lAl1 IS:2 20 : 4 0.8” (0.5)b 7.0 (3.1) 2.6 (1.3) 4.4 (1.4) 5.6 (1.4) 0.7 (0.3) 79.0 (7.3) 0.8 (0.1) 5.0 ( 1.9) 3.9 (0.6) 3.0 (1.2) 9.3 (1.3) 7.1 (3.1) 70.9 (6.3) 1.4 (1.1) 5.7 (0.4) 4.7 (1.7) 12.5 (3.2) 41.7 (1.4) 2.2 (0.3) 17.3 (1.0) 14.7 (3.9) 0.5 (0.3) 1.0 (0.8) 3.8 (2.6)*’ 7.3 (4.6) 1.6 (0.3) 5.2 (1.2)* 2.9 (0.7)* 4.7 (2.3) 9.7 (3.9) 3.6 (1.7) 2.8 (3.8) 1.8 (1.7) 78.7 (4.8) 76.4 (10.6) 0.8 (0.4) 1.4 (0.8) 5.3 (4.5) 9.3 (2.2)* 5.2 (1.2)* 9.5 (2.6)* 7.7 (4.4) 5.1 (1.3)* t7.5 (4.8)* 10.5 (3.3) 9.5 (5.5) 11.6 (3.4)* 54.2 (5.8)* 52.7 (11.5)* 1.2 (0.8) 1.4 (1.1) 5.8 (1.2) 6.4 (0.4) 2.9 (0.8)* 20.7 (2.1)* 11.2 (1.4) 12.6 (2.1) 48.7 (3.1)* 31.7 (3.2)* 5.4 (6.8) 4.0 (0.6)* 12.9 (2.0)* 13.5 (1.2)* 12.1 (4.4) 12.9 (1.9) ’ Each value represents the mean weight percent from four experiments. b Standard deviations are given in parentheses. c Sets ofdata were compared using Students t-test for paired data, and cases where P

Applicant's summary and conclusion

Topically applied fatty acid methyl esters can penetrate to the living cells of normal epidermis,
enter into metabolism and significantly modify endogenous epidermal lipids.
Executive summary:

The present results demonstrate that topically applied fatty acid methyl esters are not metabolically inert but are capable of penetrating normal mouse stratum corneum and becoming incorporated into epidermal phosphatidylethanolamine and acylglucosylceramide. The observed substitution patterns suggest that oleate can directly compete with linoleate for incorporation into both phosphatidylethanolamine and acylglucosylceramide. Also, a portion of the oleate may be shortened to produce 16 : 1, which also replaces linoleate. Methyl palmitoleate appears to undergo chain extension to produce 18 : 1 Al 1 which, along with palmitoleate itself, displaces linoleate from acylglucosylceramide and replaces both linoleate and oleate in phosphatidylethanolamine. Acylceramide was not much affected in the present short-term experiments, probably because it is mainly confined to the cornified epidermal layers produced prior to the start of the experiment. The present results may be relevant to the mechanisms underlying the development of acne. It has been proposed that fatty acids derived from sebum penetrate into living cells of the pilosebaceous epithelium and there dilute the linoleate derived from circulating lipids, producing a localized essential fatty acid deficiency [ 191. As linoleate is replaced by sebaceous fatty acids, cell shedding becomes aberrant, leading to the formation of a comedo, and the barrier function of the follicular epithelium decreases so that water to support bacterial growth leaks into the follicular lumen, The present experiments support the feasibility of this proposal. Although cosmetic formulations are routinely screened for irritancy or toxic effects, review of the literature does not reveal screening for more subtle effects on epidermal biochemistry. Fatty acid substitutions of the magnitude found in the present study may not noticeably affect the health or function of the epidermis, but longer-term exposure could potentially lead to barrier impairment and other undesirable consequences. While methyl esters are not generally found in such preparations, other fatty acid esters and fatty alcohols, which may be oxidized to fatty acids, are commonly used.