C12-15 ALKYL BENZOATE

C12 alkyl benzoate is present in the commercial emollient cosmetic ingredient C12-15 alkyl benzoate (Finsolv TN). Finsolv TN is a mixture of linear and branched esters of benzoic acid and aliphatic alcohols where linear C12 alkyl benzoate is a representative homolog with the shortest alkyl C-chain and lowest molecular weight. A preliminary non-GLP in vitro skin penetration study which monitored dermal bioavailability of all C12-15 alkyl benzoate constituents using GC-MS was carried out which demonstrated C12 alkyl benzoate could be considered a worst-case representative constituent to determine dermal absorption of the overall substance. Subsequently, [14C]-C12 alkyl benzoate was mixed into Finsolv TN, and applied, neat (10 µl/cm2), to dermatomed human skin mounted in a flow-through diffusion cell system. Receptor fluid was collected up to 24 h postdose and the skin was decontaminated at 8 h postdose. The absorbed dose, dermal delivery, potentially absorbable dose and dermally absorbed value of [14C]-C12 alkyl benzoate were 0.41%, 0.97%, 2.20%, and 2.97%, respectively. Metabolism during absorption was assessed in skin from the same donors, with no C12 alkyl benzoate detected in the receptor fluid, although the primary metabolite, [14C]-benzoic acid (>93%), was detected. A phenyl acetate esterase assay confirmed the presence of esterase activity in the donor skins used. Therefore, this study confirmed that dermal exposure of C12-15 alkyl benzoate (Finsolv TN) results in an absorbed dose of 2.97% completely metabolized to benzoic acid and aliphatic alcohol(s) in human skin. These findings indicate that a more in-depth investigation and assessment of toxicokinetic behavior (specifically for occupational exposures via the skin) provide opportunities to develop exposure-led strategies to avoid unnecessary animal testing allowing registrants to fulfill obligations to adhere to the "last resort" principle under REACH.

The idea of increasing the performance of sunscreens without adding more UV-filters is very attractive. Early studies reported an influence of solvents on the absorbing properties of UV-absorbers which was shown to be connected to the solvent polarity. However, the polarity differed a lot between tested solvents and most were unsuitable UV-filter solubilizers. The aim of the present study was to focus exclusively on emollients pertinent for sunscreens and investigate their impact on the performance of UV-filter combinations. The UV absorbance of Bis-ethylhexyloxyphenol Methoxyphenyl Triazine, Ethylhexyl Triazone, Diethylamino Hydroxybenzoyl Hexyl Benzoate, and Ethylhexyl Methoxycinnamate was measured in suncare relevant emollients comprising C12-15 Alkyl Benzoate, Dibutyl Adipate, Caprylic/Capric Triglyceride, Coco-caprylate, Isopropyl Myristate, Dicaprylyl Carbonate. The wavelength of maximum absorbance (λmax) and specific extinction at λmax (E1,1 (λmax) ) were assessed for each UV-filter - emollient system. The performance of market relevant UV-filter combinations based on the studied UV-filters was simulated for each emollient with a computational method using the absorbance values measured for each UV-filter - emollient system. The difference in polarity of emollients led to a 2-3 nm bathochromic shift and a variation of the E1,1 (λmax) ranging from 4 to 20% for tested UV-filters. The emollient type showed nearly no influence on the sun protection factor (SPF) of market relevant UV-filter combinations probably due to a different influence an emollient shows on the UVB filters resulting in cancelling of the corresponding effect. Conversely, for all UV-filter combinations the UVA protection decreased with a decrease in the emollient polarity. Whilst the SPF was not impacted by standardly used cosmetic oils, the results advocate to use polar emollients to optimize the UVA protection. This is of advantage since polar emollients better dissolve crystalline UV-filters. From tested emollients, Dibutyl Adipate performed the best for both SPF and PPD factors.

The chemical stability of benzoyl peroxide (BPO) was studied in solutions and gels. The solutions (1% w/v) were prepared in single solvents (alcohol USP, isopropyl alcohol USP, ethyl benzoate, C12-15 alkyl benzoate, dimethyl isosorbide, propylene carbonate, and acetone) and in binary and tertiary combinations of these solvents, with and without the addition of antioxidant(s) (BHT, BHA, eugenol, tert-butyl hydroquinone, Tenox-2, vitamin E, and vitamin C). The solutions were stored at 37 degrees C for 5 weeks, and each week were analyzed for remaining BPO. Using first-order kinetics, the stability of BPO in solution was found to decrease in the order: ternary>binary>single solvent systems. Regardless of the number of solvents present, the highest stability of BPO (t1/2>7.5 weeks) was attained in the presence of ethyl benzoate and C12-15 alkyl benzoate. The stability of BPO in solution did not change significantly with the addition of most antioxidants. The solutions in which BPO remained most stable were one in alcohol USP-ethyl benzoate-C12-15 alkyl benzoate (60:20:20; t1/2=18.15 weeks) and another in alcohol USP-C12-15 alkyl benzoate-isopropanol plus 0.1% BHT (65:20:15; t1/2=12.44 weeks). In turn, these two solutions were converted to homogeneous gels by the addition of Cab-O-Sil. The chemical stability of BPO in these gels was evaluated at 37 degrees, 45 degrees, 50 degrees, and 55 degrees C for 5 weeks. Parallel experiments were conducted with two commercial BPO products, a 2.5% tinted gel and 5% vanishing lotion. BPO was less stable in commercial products (t1/2<or=13 weeks) than in the extemporaneously prepared gels (mean t1/2 approximately 23 weeks). The present results suggest that aromatic esters can enhance the chemical stability of BPO in solutions and gel formulations to a significant extent.