Multi-organic risk assessment of estrogenic properties of octyl-methoxycinnamate in vivo - A 5-day sub-acute pharmacodynamic study with ovariectomized rats

Sun protection products contain a variety of UV-filters, among others, octyl-methoxycinnamate (OMC). Recently, an uterotrophic effect in immature rats has been reported, indicating that OMC might have estrogenic properties and thus is an endocrine active chemical (EAC). However, determination of an estrogenic activity in the uterus only is a restricted approach with the potential risk of missing undesirable actions in other organs regulated by estrogens. A pharmacodynamic experiment with 5 dosages of OMC in adult ovariectomized (ovx) rats was carried out to quantify the multi-organic estrogenic properties of OMC. As control compound, estradiol-valerate (E2) was included. Animals were treated per gavage for 5 days. The expression levels of markers of estrogenic action in several organs were measured by RT-PCR. Effects on metabolic parameters were assessed by determination of the serum concentrations of leptin, cholesterol, high and low density lipoproteins (HDL and LDL), glucose and triglycerides. Observed changes upon OMC treatment were analyzed using the NO(A)EL and the benchmark dose approach. From the obtained pharmacodynamic data of the most sensitive parameter (truncated estrogen receptor protein 1 gene expression in the pituitary) we obtained threshold values that are exceeded by the recommended use of OMC containing formulations for skin protection in humans, therefore we propose to reduce the use of OMC in cosmetic products. In addition to estrogenic actions of OMC, non-estrogenic effects have been found for this chemical supporting the need of a multi-organic risk assessment of putative EACs. (c) 2005 Elsevier Ireland Ltd. All rights reserved.