Cosmetic Percutaneous Absorption And Toxicity

The potential toxicity of cosmetics has in the past been dismissed as an event unlikely to occur. The argument was put forth that cosmetics did not contain ingredients that could prove harmful to the body. The argument went further to say that, because cosmetics were applied to skin with its barrier properties, the likelihood that a chemical would become systemically available was remote. The argument was proven false when carcinogens were

Figure 9 Methylene bisphenyl isocyanate (MDI) skin decontamination. Water alone and soap and water were relatively ineffective in removing MDI compared with the polypropylene-based decontaminants and corn oil.

shown to be present in cosmetics, and subsequent studies showed that these carcinogenic chemicals could be percutaneously absorbed [12].

Table 2 shows the relationship between percutaneous absorption and erythema for several oils used in cosmetics. The investigators attempted to correlate absorbability with erythema. The most-absorbed oil, isopropyl myristate, produced the most erythema. The lowest-absorbing oil, 2-hexyldecanoxyoctane, produced the least erythema. Absorbability and erythema for the other oils did not correlate [13]. The lesson to remember with percutaneous toxicity is that a toxic response requires both an inherent toxicity in the chemical and percutaneous absorption of the chemical. The degree of toxicity will depend on the contributions of both criteria.

In the rhesus monkey, the percutaneous absorption of safrole, a hepatocarcinogen,

Table 2 Relationship of Percutaneous Absorption and Erythema for Several Oils Used in Cosmetics

Absorbability (greatest to least)

Erythema

Isopropyl myristrate Glycol tri(oleate) w-Octadecane Decanoxydecane 2-Hexyldecanoxyoctane

was 6.3% of applied dose. When the site of application was occluded, the percutaneous absorption doubled to 13.3%. Occlusion is a covering of the application site, either intentionally, as with a piece of plastic taped over the dosing site during experimentation, or unintentionally, as by putting on clothing after applying a cosmetic. The percutaneous absorption of cinnamic anthranilate was 26.1% of the applied dose, and this increased to 39.0% when the site of application was occluded. The percutaneous absorption of cinnamic alcohol with occlusion was 62.7%, and that of cinnamic acid with occlusion was 83.9% of the applied dose. Cinnamic acid and cinnamic aldehyde are agents that elicit contact urticaria [14], and cinnamic aldehyde is positive for both Draize and maximization methods [15,16].

In vivo human skin has the ability to metabolize chemicals. Figure 10 shows the metabolic profile of extracted human skin after pure hydroquinone had been dosed on the skin for 24 hours. The metabolic profile shows unchanged hydroquinone and its metabolite benzoquinone [3].

We have thus learned that common cosmetic ingredients can readily penetrate skin and become systemically available. If the cosmetic chemical has inherent toxicity, then that chemical will get into the body of a user and exert a toxic effect. Metabolically, the skin can also produce a more toxic compound.

The development of topical drug products requires testing for skin toxicology reactions. A variety of patch-test systems are available with which chemicals are applied to skin. A study was performed to determine the skin absorption of p-phenylenediamine (PPDA) from a variety of such systems. [14C]PPDA (1% petrolatum UDP) was placed in a variety of patch-test systems at a concentration normalized to equal surface area (2 mg/

Figure 10 Hydroquinone dosed on viable skin was metabolically converted into the potential carcinogen benzoquinone within the human skin. The fate of a chemical within skin is more important than what is on the surface of skin.
Table 3 Percutaneous Absorption of p-Phenylenediamine (PPDA) from Patch-Test Systems

Total load

Concentration

Absorption

in chamber

in chamber

(mg)

(mg/mm2)

Percent*

Total (mg)

Hill Top chamber

40

2

53.4 ± 20.6

21.4

Teflon (control)

16

2

48.6 ± 9.3

7.8

Small Finn chamber

16

2

29.8 ± 9.0

4.8

Large Finn chamber

24

2

23.1 ± 7.3

5.5

AL-test chamber

20

2

8.0 ± 0.8

1.6

Small Finn chamber

with paper disc insert

16

2

34.1 + 19.8

5.5

* Each value is the mean + standard deviation for three guinea pigs.

* Each value is the mean + standard deviation for three guinea pigs.

mm2). Skin absorption was determined in the guinea pig by urinary excretion of 14C. There was a sixfold difference in the range of skin absorption (p < 0.02). In decreasing order, the percentage skin absorption from the systems were 53.4 ± 20.6 (Hill Top chamber), 48.6 ± 9.3 (Teflon control patch), 23.1 + 7.3 (small Finn chamber), and 8.0 + 0.8 (AL-test chamber). Thus, the choice of patch system could produce a false-negative error if the system inhibits skin absorption, with a subsequent toxicology reaction (Table 3) [17].

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