Registration Dossier

Administrative data

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Description of key information

Key value for chemical safety assessment

Additional information

Background

The UV-absorbing substance ethylhexyl methoxycinnamate is used in protective sun screen cream and has been on the market for many years. Available toxicokinetic information on ethylhexyl methoxycinnamate is therefore focussed on dermal absorption. Two in vitro studies were available in which the dermal absorption in naked rat skin and mini pig skin were determined. Furthermore, two studies with human volunteers are available, in which the dermal absorption and excretion was determined. Additional information from public literature and other toxicology studies is also discussed to describe the behaviour of ethylhexyl methoxycinnamate for the dermal and oral route. The inhalation route is not discussed as inhalation exposure is not expected.

 

Studies on toxicokinetics in the dossier

The in vitro dermal absorption of ethylhexyl methoxycinnamate in the mini pig skin is relatively low (Klecak et al., 1982). In this study, 14C-ethylhexyl methoxycinnamate was tested in two different creams and a lotion at a concentration of 7.5%, and absorption did not exceed 4% after 6 hours. With the availability of dermal absorption studies with minipig skin and from human volunteer studies (see below), known dermal absorption data for ethylhexyl methoxycinnamate in rat skin (DSM, 1979) is considered obsolete as rat skin is typically two to ten times more permeable than human (ECETOC 1993).

The in vivo dermal absorption and excretion was studied in healthy human volunteers (Davragh and Lambe, 1980). A solution of 14C-ethylhexyl methoxycinnamate in carbitol, at a concentration of 10%, was applied onto a piece of gauze taped onto the human skin without occlusion, and radioactivity was determined in the piece of gauze, on the skin, in the stratum corneum (by skin stripping), in blood plasma, urine, and faeces. Results show that a very high percentage of the dose was recovered from the application site, whereas radioactivity was not detectable in blood plasma and faeces. A very low percentage of the applied dose was recovered from the skin after stripping (0.16 -0.28%) and from urine (0.08 -0.68%). The total recovery of radioactivity was high in all subjects (94.1-101.1%). Based on these results, and the results obtained in the in vitro studies, it can be concluded that ethylhexyl methoxycinnamate has a low dermal absorption potential.

 

Information from public literature

From the use of ethylhexyl methoxycinnamate as uv-filter in sunscreen cream, it is obvious that the most likely route of exposure will be via the skin. In literature, several publications are available concerning dermal absorption of ethylhexyl methoxycinnamate, most of them focussing on the influence of different kinds of vehicle (sunscreen cream). Depending on the vehicle, ethylhexyl methoxycinnamate has a low dermal absorption potential. Information on other toxicokinetics properties were not found in literature.

 

Information from other studies

Physical/chemical parameters such as log Pow, water solubility, and molecular weight, as well as parameters like hydrolysis rate can provide useful information regarding the behaviour of a substance in the body. Ethylhexyl methoxycinnamate has a log Pow of >6, and is slightly soluble (0.22-0.75 mg/l). The molecular weight is 290.4. Furthermore, information from a hydrolysis study is available.

The combination of a high log Pow and low water solubility confirms the findings of the dermal penetration studies described above. Furthermore, in a dermal repeated dose toxicity study, no clear toxic effects were observed, indicating that ethylhexyl methoxycinnamate may not be taken up in the body via the dermal route.

Concerning the oral route, the highly lipophilic nature of ethylhexyl methoxycinnamate and its poor water solubility indicate poor absorption. However, according to the Guidance on information requirements, lipophilic compounds such as ethylhexyl methoxycinnamate may be taken up by micellular solubilisation, (of particular importance when log Pow>4 and water solubility<1 mg/l). More information on the toxicokinetics of ethylhexyl methoxycinnamate via the oral route may be obtained via the toxicity studies. In the dossier, studies are available concerning acute toxicity, skin and eye irritation, skin sensitization, mutagenicity, oral repeated dose toxicity, and developmental toxicity. None of the studies show a clear toxic effect of ethylhexyl methoxycinnamate, indicating poor absorption of the substance, or low toxicity of parent compound and metabolites.

In a hydrolysis study, a DT50 of more than one year was observed, which indicates that ethylhexyl methoxycinnamate is not expected to degrade in the GI-tract. Furthemore, from the structure of the compound ethylhexyl-methoxycinnamate it can be concluded that under normal to foreseen (physiological) conditions the compound is stable. The ester-bond is of a rigid type and will only tend to decompose under vigorous conditions. However, in the human body biotransformation of ethylhexyl methoxycinnamate may occur, as ester-bonds can be hydrolyzed by esterases.

 

Conclusions

In conclusion, ethylhexyl methoxycinnamate has a low absorption when applied to the skin. A very low amount is excreted in urine (<0.5%). The absence of effects in toxicological studies and the physical/chemical properties of ethylhexyl methoxycinnamate indicate low oral absorption, or low toxicity of the compound and its metabolites.

 

References

ECETOC (European Centre for Ecotoxicology and Toxicology of Chemicals), (1993). Percutaneous absorption. Monograph n° 20, ECETOC, Brussels, Belgium

 

European Chemicals Agency, (2008). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.