Skin Sensitization Potential Research Articles

Safety and efficacy of a feed additive consisting of Lactiplantibacillus plantarumDSM 11520 for horses, dogs, cats and pet rabbits (Animal Probiotics Sweden AB).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on Lactiplantibacillus plantarum DSM 11520 when used as a technological additive (acidity regulator) in feed for horses, dogs, cats and pet rabbits. The additive is intended to be incorporated into oat-derived products (ca. 55% moisture content), carrot root-derived products (≥ 90% moisture) and coconut flesh-derived products (≥ 90% moisture) at a minimum inclusion level of 8.0 × 1010 CFU/kg of the feed material under scope. The bacterial species L. plantarum is considered by EFSA to be suitable for the qualified presumption of safety (QPS) approach to safety assessment. The identity of the strain has been clearly established and it did not show acquired resistance to antibiotics of human and veterinary importance. The FEEDAP Panel concluded that the use of this strain in animal nutrition is safe for the target species, consumers of horse meat and the environment. Regarding the user safety, the additive Lactiplantibacillus plantarum DSM 11520 is not irritant to skin or eyes in the product tested containing maltodextrin and oat bran as carriers, but owing to its proteinaceous nature, it should be considered a respiratory sensitiser. No conclusions can be drawn on the skin sensitisation potential of the additive. The FEEDAP Panel concluded that incorporation of Lactiplantibacillus plantarum DSM 11520 at a minimum concentration of 8.0 × 1010 CFU/kg into oat-derived products (ca. 55% moisture content), carrot root-derived products (≥ 90% moisture) and coconut flesh-derived products (≥ 90% moisture) has the potential to reduce the pH of these feedingstuffs.

Safety and efficacy of a feed additive consisting of the bacteriophages PCM F/00069, PCM F/00070, PCM F/00071 and PCM F/00097 (Bafasal®) for all avian species (Proteon Pharmaceuticals S.A.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of a product consisting of four bacteriophages infecting Salmonella enterica ser. Gallinarum B/00111, intended to be used as a zootechnical additive (functional group: other zootechnical additives) for all avian species. The additive (tradename Bafasal®) is not currently authorised in the European Union. Bafasal® is intended to be used in water for drinking and liquid complementary feed to guarantee a minimum daily dose of 2× 106 PFU/bird, to reduce the Salmonella spp. contamination of poultry carcasses and load in the environment, and to improve the zootechnical performance of the treated animals. In a previous opinion, the FEEDAP Panel could not conclude on the additive's potential to be irritant or a dermal sensitiser, or on its efficacy for any avian species due to insufficient data. The applicant provided supplementary information to address these data gaps. The new data showed that Bafasal® is not a skin or eye irritant. No conclusions could be drawn on its skin sensitisation potential. The Panel was not in the position to conclude on the efficacy of Bafasal® to improve the zootechnical performance of the target species based on the available data. The additive showed the potential to decrease the counts of two strains of Salmonella Enteritidis in boots swabs and caecal digesta of chickens for fattening. No conclusions could be drawn on the capacity of Bafasal® to reduce the contamination of other Salmonella enterica strains, serovars or other species of Salmonella. The potential of Bafasal® to reduce the Salmonella spp. contamination poultry carcasses and/or the environment is limited. The FEEDAP Panel recommended a post-market monitoring plan to address the potential selection and spread of resistant variants of Salmonella to Bafasal®.

Assessment of the feed additive consisting of Pediococcus pentosaceusDSM 23376 for all animal species for the renewal of its authorisation (Agri-King, Inc.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Pediococcus pentosaceus DSM 23376, as a technological additive to improve ensiling of forage for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concludes that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the additive is not irritant to skin or eyes but owing to its proteinaceous nature, it should be considered a respiratory sensitiser. No conclusions can be drawn on the skin sensitisation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Safety and efficacy of a feed additive consisting of Lacticaseibacillus rhamnosusCNCM I-3698 and Companilactobacillus sp. CNCM I-3699 for all animal species (STI Biotechnologie).

Following a request from the European Commission, the Panelon Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety andefficacy of a feed additive consisting of Lacticaseibacillus rhamnosus CNCM I-3698 and Companilactobacillus sp. CNCM I-3699 intended to be used as a technological additive (functional group: silage additives) in forage for all species. In a previous opinion, the additive was described as containing viable but not cultivable cells of the two strains in a 1:1 ratio, with a minimum of total lactic acid bacteria counts of 5× 108 Viable Forming Units (VFU)/g additive. However, in that opinion the Panelcould not fully characterise the additive or conclude on its dermal/ocular irritancy or sensitisation potential. In the current assessment, the applicant provided supplementary information to address these gaps. The proposed methodology to discriminate and individually quantify the two strains composing the additive still presented limitations. Therefore, the Panelconcluded that the data available do not allow to fully characterise the additive. The Panelwas not in the position to conclude on the taxonomical identification of the strain CNCM I-3699, and consequently, on its eligibility for the application of the qualified presumption of safety (QPS) approach. Therefore, the previous conclusions on the safety of the additive based on the QPS approach could not be confirmed. The Panelwas not in the position to conclude on the safety of the additive for the target species, consumer and the environment. The additive is not irritant to skin. The Panelcould not conclude on the eye irritancy or skin sensitisation potential of the additive. The Panelreiterated its previous conclusions that no conclusions can be drawn on the efficacy of the additive to improve the ensiling process of forage.

Safety and efficacy of a feed additive consisting of Lacticaseibacillus rhamnosus CNCM I-3698 and Companilactobacillus sp. CNCM I-3699 for chickens for fattening (STI Biotechnologie).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Sorbiflore® ADVANCE, a feed additive consisting of Lacticaseibacillus rhamnosus CNCM I-3698 and Companilactobacillus sp.CNCM I-3699 intended to be used as a zootechnical additive (functional group: other zootechnical additives) in feed for chickens for fattening to improve their performance. In a previous opinion, the additive was described as containing viable but not cultivable cells of the two strains in a 1:1 ratio, with a minimum of total lactic acid bacteria counts of 5× 108 viable forming units (VFU)/g additive. However, in that opinion, the Panel could not fully characterise the additive or conclude on its dermal/ocular irritancy or sensitisation potential. In the current assessment, the applicant provided supplementary information to address the missing information for the characterisation of the additive. The proposed methodology to discriminate and individually quantify the two strains composing the additive still presented limitations. Therefore, the Panel concluded that the data available do not allow to fully characterise the additive. The Panel was not in the position to conclude on the taxonomical identification of the strain CNCM I-3699, and consequently, on its eligibility for the application of the qualified presumption of safety (QPS) approach. Therefore, the previous conclusions on the safety of the additive based on the QPS approach could not be confirmed. The Panel was not in the position to conclude on the safety of the additive for the target species, consumer and the environment. Sorbiflore® ADVANCE is not irritant to skin. The Panel could not conclude on the eye irritancy or skin sensitisation potential of the additive.

Safety and efficacy of a feed additive consisting of Bacillus paralicheniformisDSM 5749 and Bacillus subtilisDSM 5750 (BioPlus® 2B) for piglets, calves for fattening and other growing ruminants (Chr. Hansen A/S).

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of a feed additive consisting of two bacilli strains (tradename: BioPlus® 2B) when used in suckling piglets, calves for fattening and other growing ruminants. BioPlus® 2B is composed of viable cells of Bacillus subtilis DSM 5750 and Bacillus licheniformis DSM 5749. In the course of the current assessment, the latest strain was reclassified as Bacillus paralicheniformis. BioPlus® 2B is intended for use in feedingstuffs and water for drinking for the target species at the minimum inclusion level of 1.3× 109CFU/kg feed and 6.4× 108CFU/l water, respectively. B. paralicheniformis and B. subtilis are considered eligible for the qualified presumption of safety (QPS) approach. The identity of the active agents was established, and the qualifications regarding the lack of acquired antimicrobial resistance genes, toxigenic potential and bacitracin production ability were complied with. Following the QPS approach, B. paralicheniformis DSM 5749 and B. subtilis DSM 5750 are presumed safe for the target species, consumers and the environment. Since no concerns are expected from the other components of the additive, BioPlus® 2B was also considered safe for the target species, consumers and the environment. BioPlus® 2B is not irritant to the eyes or skin but should be considered a respiratory sensitiser. The Panel could not conclude on the skin sensitisation potential of the additive. BioPlus® 2B when supplemented at 1.3× 109CFU/kg complete feed and 6.4× 108CFU/l water for drinking has the potential to be efficacious in suckling piglets, calves for fattening and other growing ruminants (e.g. sheep, goat, buffalo) at the same developmental stage.

Bidirectional role of synthetic musk tonalide as photosensitizer and activator on amino acids: Formation of sensitizer imine at aqueous chemistry interface of skin

Personal care products (PCPs) inevitably come into contact with the skin in people’s daily life, potentially causing adverse effects on human health. The adverse effects can be exacerbated under UV irradiation but are rarely studied. In this study, to clearly understand the damage of representative PCPs to human skin and their photochemical transformation behaviors, fragrance tonalide (AHTN) was measured in the presence of amino acids as a basic building block of human tissue. The results showed that amino acids could decelerate the photochemical transformation rate of AHTN, increasing the likelihood of AHNT persisting on the skin surface and the health risk to the human being. Further, the interaction between amino acids and AHTN was investigated. AHTN could play bidirectional roles in damaging amino acids: the photosensitizer and reactive activator. As a photosensitizer, the 1O2 generated from the AHTN photosensitization was partly employed to oxidative damage amino acids. Furthermore, by combining experiments with quantum chemical computation, the carbonyl group of the activator AHTN was found to be the active site to activate the N-containing group of amino acids. The activation mechanism was the electron transfer between AHTN and amino acids. Imines formed during the photochemical transformation of AHTN with histidine/glycine were the molecular initiating event for potential skin sensitization. This study reported for the first time that skin photosensitizer formation threatens human health during the photochemical transformation of AHTN.

Retrospective quantitative risk assessment of skin sensitization caused by an antimicrobial agent used in a consumer product: 2,3,5,6-Tetrachloro-4-(methylsulfonyl) pyridine.

Serious cases of allergic contact dermatitis (ACD) caused by exposure to 3,5,6-tetrachloro-4-(methylsulfonyl)pyridine (TCMSP; CAS no. 13108-52-6) used as an antimicrobial agent for desk mats have been reported in Japan. A quantitative risk assessment (QRA) of TCMSP contained in desk mats was performed retrospectively. A local lymph node assay (LLNA): BrdU-ELISA was conducted to determine a reliable EC1.6 value for TCMSP. The acceptable exposure level (AEL) for TCMSP was derived from the EC1.6 value by applying sensitization assessment factors (SAFs). The exposure level was estimated based on the assumption referring to the use conditions of thiabendazole in the same purpose. Then, the estimated exposure level was compared with the AEL to evaluate the skin sensitization risk. The AEL was calculated as 0.00458 μg/cm2 based on the EC1.6 value (0.011%, 2.75 μg/cm2 ) by applying a composite SAF of 600. The estimated TCMSP exposure level from the desk mat was 500 times greater than the AEL, indicating a serious skin sensitization risk. Assessments of skin sensitization potencies of chemicals to be used in consumer products are strongly recommended, and QRAs should be performed at the pre-marketing stage to avoid the skin sensitization risk in consumers.

Incorporating integrated testing strategy (ITSv1) defined approach into read-across (RAx) in predicting skin sensitization potency: ITSv1-based RAx

Recently, due to regulatory and ethical demands, new approach methodologies (NAMs), defined approaches (DAs), and read-across (RAx) have been used in the risk assessment of skin sensitization. Integrated testing strategy (ITS)v1 DA, adopted in OECD Guideline No. 497, can be used for skin sensitization potency categorization. However, ITSv1 DA alone is not used for further refinement of the potency prediction based on EC3 (the estimated concentration that produces a stimulation index of 3 in murine local lymph node assay) values. Moreover, there is no explicit approach to incorporating NAM/DA data into RAx to fill the data gap of EC3 values with high confidence. This study developed a strategy incorporating ITSv1 DA into RAx to predict skin sensitization potency: ITSv1-based RAx. To examine the reliability of this novel strategy, a case study with lilial, a fragrance material, was performed. Based on ITSv1-based RAx, the skin sensitization potency of lilial was determined by extrapolating the EC3 value of 9.5% for the suitable analogue bourgeonal, which was close to the historical EC3 value of 8.6%. The result suggested that the strategy can refine the prediction of EC3 values with high confidence and be useful for the risk assessment of skin sensitization.

Assessment of eight feed additives consisting of Lactiplantibacillus plantarumCNCM I-3235, L. plantarumCNCM I-3736/DSM 11672, Pediococcus acidilacticiCNCMI-3237, P. acidilacticiCNCM I-4622/DSM 11673, Pediococcus pentosaceusNCIMB 12455, Acidipropionibacterium acidipropioniciCNCM I-4661, Lentilactobacillus buchneriNCIMB 40788/CNCM I-4323 and L. buchneriNCIMB 40788/CNCM I-4323 plus Lentilactobacillus hilgardiiCNCM I-4785 for all animal species for the renewal of their authorisation (Danstar Ferment AG).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of eight technological additives, including two Lactiplantibacillus plantarum (formerly Lactobacillus plantarum) [CNCM I-3235 and CNCM I-3736/ DSM 11672], two Pediococcus acidilactici [CNCM I-3237 and CNCM I-4622/DSM 11673], one Pediococcus pentosaceus [NCIMB 12455], one Acidipropionibacterium acidipropionici (formerly Propionibacterium acidipropionici) [CNCM I-4661], one Lentilactobacillus buchneri (formerly Lactobacillus buchneri) [NCIMB 40788/ CNCM I-4323], and the additive composed by the two active agents L. buchneri NCIMB 40788/ CNCM I-4323 and Lentilactobacillus hilgardii (formerly Lactobacillus hilgardii) CNCM I-4785, as silage additives for use in forage for all animal species. The applicant has provided evidence that the additives currently on the market comply with the existing conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concluded that the additives remain safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the additives should be considered as respiratory sensitisers. In the absence of data, no conclusions could be drawn on the skin sensitisation, and skin and eye irritancy potential of the additives, with the exception for Pediococcus acidilactici CNCM I-4622/DSM 11673 (for which the Panel concluded that is non-irritant to skin and eyes). There is no need for assessing the efficacy of the additives in the context of the renewal of the authorisation.

Comparison of the acceptable surface limits derived from the skin sensitization potency for workers and swab residue limits determined from the permitted daily exposure derived from the systemic effects.

Allergic contact dermatitis is a common occupational and environmental health problem and setting of health-based exposure limits (HBELs) to prevent induction of skin sensitization is strongly desired. When manufacturing pharmaceuticals in a shared facility, cleaning validation using surface residue levels (SRLs) derived from permitted daily exposures (PDEs) is conducted to avoid cross-contamination from the perspective of protecting patients; however, it is unclear whether the SRLs are sufficient to prevent induction of skin sensitization for workers as well. In this study, we compared acceptable surface limits (ASLs) derived from acceptable exposure levels (AELs) based on EC1.6 obtained from local lymph node assay (LLNA): BrdU-ELISA for occupational risk management of skin sensitizers with PDE-based SRLs. ASLs for 1,4-phenylenediamine (GHS skin sensitization sub-category 1A), isoeugenol (sub-category 1A), and methyl methacrylate (sub-category 1B) were compared with SRLs based on the PDEs derived from their systemic effects. The results yielded an SRL for 1,4-phenylenediamine (PDE: 0.8 mg/day) of 30 mg/100 cm2, almost 1,000 times higher than ASL (0.031 mg/100 cm2) derived from its skin sensitization potency. SRL for isoeugenol (PDE: 3.1 mg/day) was 130 mg/100 cm2, over 500 times higher than ASL (0.18 mg/100 cm2). For methyl methacrylate (PDE: 5 mg/day) as well, SRL (200 mg/100 cm2) was higher, but it was within 20 times the ASL (10 mg/100 cm2). These results showed that ASL-based risk management is extremely important especially for strong sensitizers classified as GHS sub-category 1A for occupational skin sensitization risk management.

Challenges integrating skin sensitization data for assessment of difficult to test substances.

Difficult to test substances, including poorly soluble, mildly irritating, or UVCBs (unknown or variable composition complex reaction products or biological materials), producing weak or borderline in vivo results, face additional challenges in in vitro assays that often necessitate data integration in a weight of evidence (WOE) approach to inform skin sensitization potential. Here we present several case studies on difficult to test substances and highlight the utility of the toxicological priority index (ToxPi) as a data visualization tool to compare skin sensitization biological activity. The case study test substances represent two poorly soluble substances, tetrakis (2-ethylbutyl) orthosilicate and decyl palmitate, and two UVCB substances, alkylated anisole and hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2 undecanone. Data from key events within the skin sensitization adverse outcome pathway were gathered from publicly available sources or specifically generated. Incorporating the data for these case study test substances as well as data on chemicals of a known sensitization class (sensitizer, irritating non-sensitizer, and non-sensitizer) into ToxPi produced biological activity profiles which were grouped using unsupervised hierarchical clustering. Three of the case study test substances concluded to lack skin sensitization potential by traditional WOE produced biological activity profiles most consistent with non-sensi­tizing substances, whereas the prediction was less definitive for a substance considered positive by traditional WOE. Visualizing the data using bioactivity profiles can provide further support for WOE conclusions in certain circumstances but is unlikely to replace WOE as a stand-alone prediction due to limitations of the method including the impact of missing data points.

Applying a next generation risk assessment framework for skin sensitisation to inconsistent new approach methodology information.

Cosmetic products must be safe for their intended use. Regulatory bans on animal testing for new ingredients has resulted in a shift towards the use of new approach methodologies (NAM), such as in silico predictions and in chemico/in vitro data. Defined Approaches (DA) have been developed to interpret combinations of NAM to provide information on skin sensitisation hazard and potency, three having been adopted within OECD Guideline 497. However, the challenge remains as to how DA can be used to derive a quantitative point of departure for use in next generation risk assessments (NGRA). Here we provide an update to our previously published NGRA framework and present two hypothetical consumer risk assessment scenarios (rinse-off and leave-on) on one case study ingredient. Diethanolamine (DEA) was selected as the case study ingredient based upon the existing NAM information demonstrating differences with respect to the outcomes from in silico predictions and in chemico / in vitro data. Seven DA were applied, and these differences resulted in divergent DA outcomes and reduced confidence with respect to the hazard potential and potency predictions. Risk assessment conclusion for the rinse-off exposure led to an overall decision of safe for all DA applied. Risk assessment conclusion for the higher leave-on exposure was safe when based upon some DA but unsafe for others. The reasons for this were evaluated, as well as the inherent uncertainty from the use of each NAM and DA in the risk assessment, enabling further refinement of our NGRA framework.

Assessment of the feed additive consisting of Lactiplantibacillus plantarum (previously Lactobacillus plantarum) DSM 19457 for all animal species for the renewal of its authorisation (Biomin GmbH).

Following a request from the European Commission, the Panelon Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of Lactiplantibacillus plantarum (previously Lactobacillus plantarum) DSM 19457 as a technological additive for use in forage for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no evidence to lead the FEEDAP Panelto reconsider its previous conclusions. Thus, the Panelconcluded that the additive remains safe for all animal species, consumers and the environment under the authorised conditions of use. Regarding user safety, the additive is not irritant to skin or eyes but owing to its proteinaceous nature, it should be considered a respiratory sensitiser. In the absence of data, no conclusions could be drawn on the skin sensitisation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Development of an <i>in silico</i> consensus model for predicting the chemical reactivity to cysteine measured by the DPRA and its application to predict the skin sensitization potential of chemicals

Development of an <i>in silico</i> consensus model for predicting the chemical reactivity to cysteine measured by the DPRA and its application to predict the skin sensitization potential of chemicals

Read-across-based intelligent learning: development of a global q-RASAR model for the efficient quantitative predictions of skin sensitization potential of diverse organic chemicals.

Environmental chemicals and contaminants cause a wide array of harmful implications to terrestrial and aquatic life which ranges from skin sensitization to acute oral toxicity. The current study aims to assess the quantitative skin sensitization potential of a large set of industrial and environmental chemicals acting through different mechanisms using the novel quantitative Read-Across Structure-Activity Relationship (q-RASAR) approach. Based on the identified important set of structural and physicochemical features, Read-Across-based hyperparameters were optimized using the training set compounds followed by the calculation of similarity and error-based RASAR descriptors. Data fusion, further feature selection, and removal of prediction confidence outliers were performed to generate a partial least squares (PLS) q-RASAR model, followed by the application of various Machine Learning (ML) tools to check the quality of predictions. The PLS model was found to be the best among different models. A simple user-friendly Java-based software tool was developed based on the PLS model, which efficiently predicts the toxicity value(s) of query compound(s) along with their status of Applicability Domain (AD) in terms of leverage values. This model has been developed using structurally diverse compounds and is expected to predict efficiently and quantitatively the skin sensitization potential of environmental chemicals to estimate their occupational and health hazards.

Application of Defined Approaches to Assess Skin Sensitization Potency of Isothiazolinone Compounds.

Isothiazolinones (ITs) are widely used as antimicrobial preservatives in cosmetics and as additives for preservation of consumer and industrial products to control bacteria, fungi, and algae. Although they are effective biocides, they have the potential to produce skin irritation and sensitization, which poses a human health hazard. In this project, we evaluated nonanimal defined approaches (DAs) for skin sensitization that can provide point-of-departure estimates for use in quantitative risk assessment for ITs. The skin sensitization potential of six ITs was evaluated using three internationally harmonized nonanimal test methods: the direct peptide reactivity assay, KeratinoSens™, and the human cell line activation test. Results from these test methods were then applied to two versions of the Shiseido Artificial Neural Network DA. Sensitization hazard or potency predictions were compared with those of the in vivo murine local lymph node assay (LLNA). The nonanimal methods produced skin sensitization hazard and potency classifications concordant with those of the LLNA. EC3 values (the estimated concentration needed to produce a stimulation index of three, the threshold positive response) generated by the DAs had less variability than LLNA EC3 values, and confidence limits from the DAs overlapped those of the LLNA EC3 for most substances. The application of in silico models to in chemico and in vitro skin sensitization data is a promising data integration procedure for DAs to support hazard and potency classification and quantitative risk assessment.

Safety and efficacy of a feed additive consisting of endo-1,4-beta xylanase, endo-1,4-beta-glucanase and xyloglucan-specific-endo-beta-1,4-glucanase produced by Trichoderma citrinovirideDSM 33578 (Huvezym® neXo 100 G/L) for all poultry species, ornamental birds and piglets (weaned and suckling) (Huvepharma EOOD).

Following a request from the European Commission, the EFSA Panelon Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of the product Huvezym® neXo 100G/L containing an endo-1,4-beta xylanase, an endo-1,4-beta-glucanase and a xyloglucan-specific-endo-beta-1,4-glucanase produced by a non-genetically modified strain of Trichoderma citrinoviride (DSM 33578) as a zootechnical additive for feed in all poultry species, ornamental birds and piglets (weaned and suckling). The information regarding the production strain did not allow to confirm its taxonomic identification. The batches used for the characterisation of the final formulations showed compliance with the minimum specifications of the additive in terms of enzyme activities but showed ratios between the enzymes lower than the ones specified for the additive. The FEEDAP Panelconsidered that the below-described conclusions would apply to the final formulations of the additive as per specifications with xylanase:glucanase, xylanase:xyloglucanase and glucanase:xyloglucanase ratios of 15, 15 and 1, respectively. Based on the data available, the Panelconcluded that the additive is safe for the target species, consumers and the environment. Huvezym® neXo 100 G (granulated form) is neither skin corrosive nor eye irritant but should be considered a potential skin sensitiser. Huvezym® neXo 100 L (liquid) is neither skin corrosive nor sensitising and it is not an eye irritant. Due to lack of data, no conclusions can be drawn on the skin irritation of the final formulations of the additive. Due to the proteinaceous nature of the active substances, the additive is considered a respiratory sensitiser. The FEEDAP Panelconcluded that the additive has the potential to be efficacious in chickens for fattening, chickens reared for laying and breeding, and all growing poultry and ornamental birds at the minimum intended level of 1,500 EPU, 100 CU and 100 XGU/kg complete feed. Owing to the lack of sufficient data, the Panelcould not conclude on the efficacy of the additive for laying hens and weaned piglets.

Alternative Methods for Skin-Sensitization Assessment.

Skin sensitization is a term used to refer to the regulatory hazard known as allergic contact dermatitis (ACD) in humans or contact hypersensitivity in rodents, an important health endpoint considered in chemical hazard and risk assessments. Information on skin sensitization potential is required in various regulatory frameworks, such as the Directive of the European Parliament and the Council on Registration, Evaluation and Authorization of Chemicals (REACH). The identification of skin-sensitizing chemicals previously required the use of animal testing, which is now being replaced by alternative methods. Alternative methods in the field of skin sensitization are based on the measurement or prediction of key events (KE), i.e., (i) the molecular triggering event, i.e., the covalent binding of electrophilic substances to nucleophilic centers in skin proteins; (ii) the activation of keratinocytes; (iii) the activation of dendritic cells; (iv) the proliferation of T cells. This review article focuses on the current state of knowledge regarding the methods corresponding to each of the key events in skin sensitization and considers the latest trends in the development and modification of these methods.

Wound Healing Potential of an Oleoresin Essential Oil Chemotype from Canarium schweinfurthii Engl.

This study was conducted to investigate the chemical composition of essential oil (EO) extracted from an oleoresin of Canarium schweinfurthii widespread in the Gabonese tropical forest. A great variability in the chemical composition of EO was observed, among which a chemical profile rich in terpinolene and α-phellandrene (31.2 and 21.8%, respectively), was found and tested as a natural active ingredient for topical applications. After the evaluation of eye and skin irritancy and sensitization potentials of EO on in vitro and in chemico models, the in vitro modulating potential on a model of wound re-epithelialization was assessed. The terpinolene and α-phellandrene-rich chemotype have been proven to accelerate wound healing in a dose-dependent manner (concentration range from 1.8 to 9.0 μg/mL). In addition, the ability of this EO to modulate the pro-inflammatory response in human keratinocytes stimulated by UVB was observed in vitro by the reduction in levels of interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-α), suggesting a possible implication during the inflammation phase of wound healing. Despite the high variability in EO composition, a method of solid-phase microextraction (SPME) of the oleoresin headspace is proposed for the in situ identification of the terpinolene and α-phellandrene-rich chemotype instead of conducting hydrodistillation. These results offer interesting perspectives for the development of innovative natural ingredients for the topical route, ingredients obtained in an eco-responsible and non-destructive way.