Suitability of the in vitro Caco-2 assay to predict the oral absorption of aromatic amine hair dyes

ABSTRACTOral absorption is a key element for safety assessments of cosmetic ingredients, including hair dye molecules. Reliable in vitro methods are needed since the European Union has banned the use of animals for the testing of cosmetic ingredients. Caco-2 cells were used to measure the intestinal permeability characteristics (Papp) of 14 aromatic amine hair dye molecules with varying chemical structures, and the data were compared with historical in vivo oral absorption rat data. The majority of the hair dyes exhibited Papp values that indicated good in vivo absorption. The moderate to high oral absorption findings, i.e. ≥60%, were confirmed in in vivo rat studies. Moreover, the compound with a very low Papp value (APB: 3-((9,10-dihydro-9,10-dioxo-4-(methylamino)-1-anthracenyl)amino)-N,N-dimethyl-N-propyl-1-propanaminium) was poorly absorbed in vivo as well (5% of the dose). This data set suggests that the Caco-2 cell model is a reliable in vitro tool for the determination of the intestinal absorption of aromatic amines with diverse chemical structures. When used in combination with other in vitro assays for metabolism and skin penetration, the Caco-2 model can contribute to the prediction and mechanistic interpretation of the absorption, metabolism and elimination properties of cosmetic ingredients without the use of animals

Assessing the safety of cosmetic chemicals: Consideration of a flux decision tree to predict dermally delivered systemic dose for comparison with oral TTC (Threshold of Toxicological Concern)

AbstractThreshold of Toxicological Concern (TTC) aids assessment of human health risks from exposure to low levels of chemicals when toxicity data are limited. The objective here was to explore the potential refinement of exposure for applying the oral TTC to chemicals found in cosmetic products, for which there are limited dermal absorption data. A decision tree was constructed to estimate the dermally absorbed amount of chemical, based on typical skin exposure scenarios. Dermal absorption was calculated using an established predictive algorithm to derive the maximum skin flux adjusted to the actual ‘dose’ applied. The predicted systemic availability (assuming no local metabolism), can then be ranked against the oral TTC for the relevant structural class. The predictive approach has been evaluated by deriving the experimental/prediction ratio for systemic availability for 22 cosmetic chemical exposure scenarios. These emphasise that estimation of skin penetration may be challenging for penetration enhancing formulations, short application times with incomplete rinse-off, or significant metabolism. While there were a few exceptions, the experiment-to-prediction ratios mostly fell within a factor of 10 of the ideal value of 1. It can be concluded therefore, that the approach is fit-for-purpose when used as a screening and prioritisation tool

Biographisierung, Dokumentation, Inskription - Gegenstandstheoretische und methodologische Reflexionen aus Perspektive der Kindheitsforschung

Kelle H. Biographisierung, Dokumentation, Inskription - Gegenstandstheoretische und methodologische Reflexionen aus Perspektive der Kindheitsforschung. In: Rothe D, Schwendowius D, Thoma N, Thon C, eds. Biographische Verknüpfungen. Zwischen biographiewissenschaftlicher Forschung, Theoriebildung und Praxisreflexion. Biographie- und Lebensweltforschung des Interuniversitären Netzwerkes Biographie- und Lebensweltforschung (INBL). Vol 15. 1st ed. Frankfurt: Campus Verlag; 2022: 317-337

A Third Dose of the COVID-19 Vaccine, CVnCoV, Increased the Neutralizing Activity against the SARS-CoV-2 Wild-Type and Delta Variant

A third dose of CVnCoV, a former candidate mRNA vaccine against SARS-CoV-2, was previously shown to boost neutralizing antibody responses against SARS-CoV-2 wild-type in adults aged 18–60 and >60 years in a phase 2a clinical study. In the present study, we report the neutralizing antibody responses to a wild-type and a variant of concern, Delta, after a third dose of the vaccine on day (D)57 and D180. Neutralization activity was assessed using a microneutralization assay. Comparable levels of neutralizing antibodies against the wild-type and Delta were induced. These were higher than those observed after the first two doses, irrespective of age or pre-SARS-CoV-2-exposure status, indicating that the first two doses induced immune memory. Four weeks after the third dose on D180, the neutralizing titers for wild-type and Delta were two-fold higher in younger participants than in older participants; seroconversion rates were 100% for wild-type and Delta in the younger group and for Delta in the older group. A third CVnCoV dose induced similar levels of neutralizing responses against wild-type virus and the Delta variant in both naïve and pre-exposed participants, aligning with current knowledge from licensed COVID-19 vaccines that a third dose is beneficial against SARS-CoV-2 variants