Grouping of chemicals for safety assessment: the importance of toxicokinetic properties of salicylate esters.

Grouping of chemicals has been proposed as a strategy to speed up the screening and identification of potential substances of concern among the broad chemical universe under REACH. Such grouping is usually based on shared structural features and should only be used for the prioritization objectives. However, additional considerations (as well as structural similarity) are needed, e.

In vitro to in vivo extrapolation to derive a metabolism factor for estimating the aggregate exposure to salicylic acid after dermal exposure of its esters.

As part of the safety assessment of salicylate esters in cosmetics, we developed a metabolism factor based on in vitro to in vivo extrapolation (IVIVE) to provide a better estimation of the aggregate internal exposure to the common metabolite, salicylic acid. Optimal incubation conditions using human liver S9 were identified before measuring salicylic acid formation from 31 substances. Four control substances, not defined as salicylic esters but which could be mistaken as such due to their nomenclature, did not form salicylic acid.

Toxicokinetics of homosalate in humans after dermal application: applicability of oral-route data for exposure assessment by human biomonitoring.

Homosalate (HMS) is a UV filter used in sunscreens and personal care products as a mixture of cis- and trans-isomers. Systemic absorption after sunscreen use has been demonstrated in humans, and concerns have been raised about possible endocrine activity of HMS, making a general population exposure assessment desirable. In a previous study, it was shown that the oral bioavailability of cis-HMS (cHMS) is lower than that of trans-HMS (tHMS) by a factor of 10, calling for a separate evaluation of both isomers in exposure and risk assessment.

Diastereoselective metabolism of homomenthyl salicylate (homosalate): Identification of relevant human exposure biomarkers.

Homosalate (HMS) is a salicylate UV filter broadly used in sunscreens and personal care products. The aim of this study was the collection of human toxicokinetic data on HMS as a tool for risk assessment. For this purpose, metabolism and urinary excretion after a single oral HMS dose (98.

Reference Chemical Potency List (RCPL): A new tool for evaluating the accuracy of skin sensitisation potency measurements by New Approach Methodologies (NAMs).

Considerable progress has been made in the design of New Approach Methodologies (NAMs) for the hazard identification of skin sensitising chemicals. However, effective risk assessment requires accurate measurement of sensitising potency, and this has proven more difficult to achieve without recourse to animal tests. One important requirement for the development and adoption of novel approaches for this purpose is the availability of reliable databases for determining the accuracy with which sensitising potency can be predicted.

The BlueScreen HC assay to predict the genotoxic potential of fragrance materials.

BlueScreen HC is a mammalian cell-based assay for measuring the genotoxicity and cytotoxicity of chemical compounds and mixtures. The BlueScreen HC assay has been utilized at the Research Institute for Fragrance Materials in a safety assessment program as a screening tool to prioritize fragrance materials for higher-tier testing, as supporting evidence when using a read-across approach, and as evidence to adjust the threshold of toxicological concern. Predictive values for the BlueScreen HC assay were evaluated based on the ability of the assay to predict the outcome of in vitro and in vivo mutagenicity and chromosomal damage genotoxicity assays.

Identifying a reference list of respiratory sensitizers for the evaluation of novel approaches to study respiratory sensitization.

The induction of immunological responses that trigger bio-physiological symptoms in the respiratory tract following repeated exposure to a substance, is known as respiratory sensitization. The inducing compound is known as a respiratory sensitizer. While respiratory sensitization by high molecular weight (HMW) materials is recognized and extensively studied, much less information is available regarding low molecular weight (LMW) materials as respiratory sensitizers.

Updating exposure assessment for skin sensitization quantitative risk assessment for fragrance materials.

In 2008, a proposal for assessing the risk of induction of skin sensitization to fragrance materials Quantitative Risk Assessment 1 (QRA1) was published. This was implemented for setting maximum limits for fragrance materials in consumer products. However, there was no formal validation or empirical verification after implementation.

Applying non-animal strategies for assessing skin sensitisation report from an EPAA/cefic-LRI/IFRA Europe cross sector workshop, ECHA helsinki, February 7th and 8th 2019.

Four years on since the last cross sector workshop, experience of the practical application and interpretation of several non-animal assays that contribute to the predictive identification of skin sensitisers has begun to accumulate. Non-animal methods used for hazard assessments increasingly are contributing to the potency sub-categorisation for regulatory purposes. However, workshop participants generally supported the view that there remained a pressing need to build confidence in how information from multiple methods can be combined for classification, sub-categorisation and potency assessment.

Urinary metabolites of the UV filter 2-Ethylhexyl salicylate as biomarkers of exposure in humans.

The UV filter 2-ethylhexyl salicylate (EHS) is used in sunscreens and other personal care products worldwide and has been found in a variety of environmental media. We aimed to provide human toxicokinetic data on EHS as a tool for risk assessment. For that purpose, we investigated metabolism and urinary metabolite excretion after a single oral EHS dose (57.

Skin sensitisation--moving forward with non-animal testing strategies for regulatory purposes in the EU.

In a previous EPAA-Cefic LRI workshop in 2011, issues surrounding the use and interpretation of results from the local lymph node assay were addressed. At the beginning of 2013 a second joint workshop focused greater attention on the opportunities to make use of non-animal test data, not least since a number of in vitro assays have progressed to an advanced position in terms of their formal validation. It is already recognised that information produced from non-animal assays can be used in regulatory decision-making, notably in terms of classifying a substance as a skin sensitiser.

Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients.

Based on chemical, cellular, and molecular understanding of dermal sensitization, an exposure-based quantitative risk assessment (QRA) can be conducted to determine safe use levels of fragrance ingredients in different consumer product types. The key steps are: (1) determination of benchmarks (no expected sensitization induction level (NESIL)); (2) application of sensitization assessment factors (SAF); and (3) consumer exposure (CEL) calculation through product use. Using these parameters, an acceptable exposure level (AEL) can be calculated and compared with the CEL.

Characterization of the sensitizing potential of chemicals by in vitro analysis of dendritic cell activation and skin penetration.

Development of in vitro models to identify sensitizing chemicals receives public interest since animal testing should be avoided whenever possible. In this article we analyze two essential properties of sensitizing chemicals: skin penetration and dendritic cell (DC) activation. Activation of immature DC derived from peripheral blood monocytes was evaluated by flow cytometric analysis of CD86 positive cells and quantitative measurement of interleukin-1beta and aquaporin P3 gene expression.

Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data.

In this paper, we propose a quantitative risk assessment methodology for skin sensitization aiming at the derivation of 'safe' exposure levels for sensitizing chemicals, used e.g., as ingredients in consumer products.