Glyoxylic acid (GA), the active ingredient of heat-activated hair straightening products (GHSPs) has been discussed in the context of acute kidney injury (AKI) via oxalic acid (OA) crystal formation and of heat-decomposition resulting in release of formaldehyde. Assessment of dermal absorption following realistic GHSP treatments with two marketed products resulted in maximally 7.73 μg/cm2 of bioavailable GA/application. Considering the scalp area of 580 cm2, the systemic GA exposure of consumers was 4.48 mg, equivalent to 1.1 mg OA taking into account that 25% GA is dermally metabolized to OA. Assessment of GA exposure to stylists' hands indicated systemic OA levels in the range of 0.026 mg/day (assuming 3 treatments in one day). Compared to typical dietary and endogenous sources of OA of 22-45 mg/day, GHSP-dependent OA exposures of consumers and stylists were 20-41-fold and > 860-fold lower, respectively. PBK prediction of GHSP-dependent renal OA excretion of consumers was <1.27 mg/day compared with normal excretion of ∼25 mg/day and the 40 mg/day threshold associated with AKI. Predicted kidney OA concentrations during GHSP exposure further indicated that OA crystal formation is unlikely to occur. Assessment of the release of the GA heat-decomposition byproduct formaldehyde in the ambient air during GHSP treatment was <25 μg/m3 and below regulatory exposure limits e.g., 100 μg/m3 (WHO indoor air quality limit). In conclusion, quantification of GA-dependent formaldehyde and OA exposure indicates no health concerns for consumers and stylists under the described realistic GHSP treatment conditions.

New in vivo data cannot be generated for cosmetics. New safety assessments for genotoxicity must rely on in vivo data from the in vivo Mammalian Erythrocyte Micronucleus (MN) Test generated before the ban. Many used intraperitoneal (i.p.) administration, which is no longer recommended without scientific justification. Therefore, we investigated whether these studies are still valid for evaluating genotoxicity of hair dyes. Small to medium size molecules, including hair dyes, are preferentially absorbed via the portal vein and undergo first-pass metabolism, whereas large molecules are taken up by the lymphatics directly into the systemic circulation. Plasma concentrations of small molecules are generally similar, if not higher, after i.p. than after p.o. administration. Importantly, outcomes from in vivo MN Test using the i.p. and p.o. routes were equivalent. Most genotoxic carcinogens with positive outcomes in the in vivo MN Test were administered by i.p. injection. Differences between in vivo genotoxicity assay results using administration routes are attributed to the Mode of Action and/or tissue-specific effects. In conclusion, the i.p. route achieves sufficiently high internal exposure i.e., in the plasma and bone marrow. Therefore, legacy OECD test guideline compliant studies using the i.p. route are valid for current safety assessments of hair dyes.

The potent sensitizer PPD is considered a key sensitizer in hair dye contact allergy. Modification of its molecular structure to 2-methoxymethyl-p-phenylenediamine (ME-PPD) reduces its skin sensitizing potency. We investigated the usage, behavior, and tolerance profile of ME-PPD-containing professional hair color products in a specifically tailored proactive market surveillance program in hairdresser salons across 5 countries. Hairdressers completed record cards for their clients, which were evaluated at the end of the program. 497 individuals received in total 2461 hair color treatments with ME-PPD-containing hair color. Feedback on compatibility was provided for 194 individuals: 6 individuals reported intolerance reactions, which were assessed as likely allergic contact dermatitis (2), likely irritation (2), or were unassessable (2); none of these reactions were severe or serious. Mild discomfort was reported by 46 individuals, while 142 individuals explicitly reported good tolerance to the ME-PPD-containing hair color. A total of 27 individuals applied ME-PPD-containing hair color more than 15 times (long-term tolerability). The study confirms good tolerability of ME-PPD-containing hair color. This is consistent with the primary prevention benefit of ME-PPD in terms of significantly reduced risk of skin sensitization induction and the reduced severity of elicitation reactions for all hair dye users.

All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited. Based on the physicochemical properties of human nails and permeability data of topical onychomycosis drugs, the nail plate is considered a good barrier to chemicals. We examine factors impacting penetration of nail care ingredients through the nail plate, including properties of the nails of the ingredients and formulations. The molecular weight, vapor pressure, logP, water solubility, and keratin binding, as well as formulations properties e.g., polymerization of acrylate monomers are considered important factors affecting penetration. To estimate systemic exposure of nail care ingredients through the nail plate, a standardized framework is applied that quantifies the impacts of these properties on penetration with an adjustment factor for each of these influencing properties. All the adjustment factors are then consolidated to derive an integrated adjustment factor which can be used for calculation of the systemic exposure dose for the ingredient. Several case studies are presented to reflect how this framework can be used in the exposure assessment for nail cosmetic products.

Background: Allergic contact dermatitis involving the hands is a common occupational skin disease for hairdressers and the potent sensitizers p-phenylenediamine (PPD) and toluene-2,5-diamine (PTD) are associated with the development of occupational allergic contact dermatitis. Objective: The aim of the study was to analyze whether the use of the moderate sensitizer 2-methoxymethyl-PPD (ME-PPD) in professional hair dyes is a suitable tool to reduce the occupational contact allergy risk for hairdressers. Methods: Hand exposure of hairdressers (N =11) to ME-PPD was analyzed under routine hair coloring conditions in commercial salons. By accounting for wet work and uneven hand exposure, the daily hand exposure was derived and compared with the occupational acceptable exposure level (AEL), that is, the sensitization induction threshold of ME-PPD adjusted for interindividual variability among workers. Results: The daily hand exposure to ME-PPD was 1.6 mu g/cm(2), and the occupational AEL was 215 mu g/cm(2). The ratio of hand exposure to AEL was calculated as the margin of safety (MOS) against occupational sensitization. For ME-PPD, the MOS of 134 indicates a low likelihood of sensitization versus PPD and PTD with MOS values of 2.7 and 5.9, respectively. Conclusions: Our data predict that the use of ME-PPD in professional hair color products improves the protection of hairdressers against hair dye-related contact allergy versus the use of PPD and PTD.

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Am Beispiel von Resorcinol, einem weitverbreiteten Haarfarbstoff, stellt dieser Übersichtbeitrag dar, wie die Daten zur Hautsensibilisierung und Hautexposition aus der SCCS (Scientific Committee on Consumer Safety) opinion (Wissenschaftliches Berater-Gremium bei der Europäischen Union [EU]) und aus anderen Quellen verwendet werden, um eine quantitative Risikobewertung (QRA) durchzuführen. Hierbei wird bewertet, welche Konzentration in Haarfarbprodukten maximal eingesetzt werden kann, ohne dass die Neuentstehung einer Hautsensibilisierung zu erwarten ist. Hierbei liegt der Fokus darauf, die Entstehung (Induktion) einer Kontaktallergie zu vermeiden. Epidemiologische Daten zur Kontaktallergie gegen Resorcinol – wie sie z. B. in Deutschland vom IVDK (Informationsverbund Dermatologischer Kliniken) erarbeitet werden, sind dabei eine wichtige Informationsquelle, die hilft, die Qualität und Effektivität des QRA zu beurteilen.

Summary:Background. Allergic contact dermatitis after exposure to p-phenylenediamine (PPD)-containing hair dye products is a common and important clinical problem. Because there is a high rate of cross-elicitation of allergic contact dermatitis to other important hair dye products (such as p-toluene diamine [PTD] and other aminophenol hair dyes) in PPD allergic patients, safer alternative dyes with excellent hair coloring options are needed. We studied 2-methoxy methyl-PPD (Me-PPD), a chemical derivative of PPD for tolerance versus cross-elicitation in a cohort of eight PPD-allergic volunteers. Objective. To study tolerance to Me-PPD in a PPD highly allergic Italian cohort. Methods. Eight volunteers with a history of contact dermatitis to hair dyes or other PPD-containing chemicals and positive patch tests to 1% PPD in petrolatum, were recruited to study their immediate and delayed skin reactivity to PPD, vehicle control and 2-methoxy-methyl-PPD (Me-PPD), using the allergy alert test (simulating hair dyeing conditions) on volar forearm skin. This is a short-contact open patch test. Results. All eight volunteers reacted to PPD allergy alert test (100%); none reacted to vehicle (0%), and seven of eight reacted to Me-PPD allergy alert test (88%). However, in those seven volunteers who exhibited cross-elicitation to Me-PPD, their aggregate skin test reactivity to Me-PPD was significantly less than that of PPD (figure 3, p minore 0.0062, highly significant, paired two-tailed, students t test). Conclusions. Me-PPD may offer a safer alternative for PPD-allergic patients with an absent or reduced elicitation response in the allergy alert test simulating hair dye use conditions. Even patients with strong patch test reactions, with appropriate selection by allergy alert test and counselling, may be able to tolerate hair dyeing with Me-PPD containing products.

Background: Allergic contact dermatitis caused by p-phenylenediamine (PPD) is a health concern for hair dye users. Because of its lower sensitization potency, the PPD derivative 2-methoxymethyl-p-phenylenediamine (ME-PPD) has been developed as an alternative hair dye for primary prevention. However, cross-elicitation responses can occur in PPD-allergic subjects. Objectives: To compare cross-elicitation responses to ME-PPD in open use and diagnostic patch testing of PPD-allergic subjects with hair dye-related allergic contact dermatitis. Methods: Reactions to ME-PPD were investigated in 25 PPD-allergic subjects by performing (1) 45-minute open use testing with a hair dye containing 2.0% of either ME-PPD or PPD, and (2) patch testing with increasing ME-PPD concentrations (0.1%-2.0% pet.). Results: Of the 25 PPD-allergic subjects, 21 (84%) reacted to open use testing with a hair dye containing 2.0% PPD, and testing with 2.0% ME-PPD led to cross-elicitation in 12 (48%). When patch tested with increasing ME-PPD concentrations, 13 (52%) cross-reacted at 0.1% (lowest dose) and 21 (84%) at 2.0% (highest dose), indicating decreased reactivity as compared with published PPD dose-response data. Conclusion: In line with the decreased cross-reactivity of ME-PPD in hair dye open use testing, PPD-allergic subjects show an attenuated cross-elicitation dose response to ME-PPD in patch testing.

Skin sensitization is a toxicity endpoint of widespread concern, for which the mechanistic understanding and concurrent necessity for non-animal testing approaches have evolved to a critical juncture, with many available options for predicting sensitization without using animals. Cosmetics Europe and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods collaborated to analyze the performance of multiple non-animal data integration approaches for the skin sensitization safety assessment of cosmetics ingredients. The Cosmetics Europe Skin Tolerance Task Force (STTF) collected and generated data on 128 substances in multiple in vitro and in chemico skin sensitization assays selected based on a systematic assessment by the STTF. These assays, together with certain in silico predictions, are key components of various non-animal testing strategies that have been submitted to the Organization for Economic Cooperation and Development as case studies for skin sensitization. Curated murine local lymph node assay (LLNA) and human skin sensitization data were used to evaluate the performance of six defined approaches, comprising eight non-animal testing strategies, for both hazard and potency characterization. Defined approaches examined included consensus methods, artificial neural networks, support vector machine models, Bayesian networks, and decision trees, most of which were reproduced using open source software tools. Multiple non-animal testing strategies incorporating in vitro, in chemico, and in silico inputs demonstrated equivalent or superior performance to the LLNA when compared to both animal and human data for skin sensitization.

The Cover Feature shows a persulfate reaction occurring under the conditions of a cosmetic hair bleaching procedure, applied worldwide to lighten hair. 1,13‐diamino‐4,7,10‐trioxatridecane is an ingredient marketed to hair salons and consumers for a so‐called “plex” service. In a model bleach it partially reacts and forms an unexpected azanyl ester whose occurrence is considered relevant for the toxicological assessment. More information can be found in the Communication by E. M. Gargano et al. on page 319 in Issue 5, 2018 (DOI: https://doi.org/10.1002/open.201800013).

BACKGROUND:Contact dermatitis to hair dyes remains a health concern. Regulations in many countries require consumer self-testing for hair dyes, but no standardized procedure exists.OBJECTIVE:The aim of this study was to develop a self-test protocol for an allergy alert test (AAT) that can elicit a self-noticeable alert signal in p-phenylenediamine (PPD)-allergic consumers.METHODS:Simulating consumer use conditions (open application for 45 minutes after mixing with a developer), PPD-positive hair dye-allergic subjects and PPD-negative control subjects were tested on the forearm and behind the ear with experimental products containing 0.05%, 0.25%, 0.75%, and 2% PPD. Reactions were self-evaluated by subjects and independently assessed by dermatologists.CONCLUSIONS:The AAT caused a reaction self-noticeable on the forearm in 90.5% (38/42) and behind the ear in 93% (39/42) of the PPD-positive subjects. This was objectified by a dermatological evaluation. The strength of the AAT response and the number of responding subjects increased with increasing PPD concentrations. Allergy alert test responses were also dependent on the reaction strength of the diagnostic patch test to PPD before the study; in subjects with (+++) patch test reactions, 19 of 19 were positive. All 48 control subjects were negative to the AAT. Therefore, the AAT protocol provides a signal indicative of an allergic reaction in PPD-allergic hair dye consumers.

Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSensTM, h-CLAT (human cell line activation test), U-SENSTM, SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.

Occupational exposure of hairdressers to hair dyes has been associated with the development of allergic contact dermatitis (ACD) involving the hands. p-Phenylenediamine (PPD) and toluene-2,5-diamine (PTD) have been implicated as important occupational contact allergens. To conduct a quantitative risk assessment for the induction of contact sensitization to hair dyes in hairdressers, available data from hand rinsing studies following typical occupational exposure conditions to PPD, PTD and resorcinol were assessed. By accounting for wet work, uneven exposure and inter-individual variability for professionals, daily hand exposure concentrations were derived. Secondly, daily hand exposure was compared with the sensitization induction potency of the individual hair dye defined as the No Expected Sensitization Induction Levels (NESIL). For PPD and PTD hairdresser hand exposure levels were 2.7 and 5.9 fold below the individual NESIL. In contrast, hand exposure to resorcinol was 50 fold below the NESIL. Correspondingly, the risk assessment for PPD and PTD indicates that contact sensitization may occur, when skin protection and skin care are not rigorously applied. We conclude that awareness of health risks associated with occupational exposure to hair dyes, and of the importance of adequate protective measures, should be emphasized more fully during hairdresser education and training.

The stability and unconventional reactivity of 1,13-diamino-4,7,10-trioxatridecane in the presence of NH3, H2O2, and (NH4)2S2O8 are described. The ether-diamine is an ingredient marketed to hair salons and consumers for so-called "plex" services to compensate for hair damage during bleaching. The main reaction product identified is an unexpected azanyl ester derivative. This is considered relevant for the safety evaluation when used in cosmetic products. The mechanism of reaction was explored through DFT calculations. This study represents the first attempt to assess the stability of a plex active in an oxidative environment.

Contact DermatitisVolume 80, Issue 3 p. 177-178 CONTACT POINT Immediate hypersensitivity to p-phenylenediamine Mark Wilkinson, Corresponding Author Mark Wilkinson s.m.wilkinson@btinternet.com orcid.org/0000-0001-7253-3461 Department of Dermatology, Leeds Teaching Hospitals NHS Trust, Leeds, UK Correspondence Mark Wilkinson, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA UK. Email: s.m.wilkinson@btinternet.comSearch for more papers by this authorLea Solman, Lea Solman orcid.org/0000-0002-6183-6608 Department of Dermatology, Leeds Teaching Hospitals NHS Trust, Leeds, UKSearch for more papers by this authorPieter-Jan Coenraads, Pieter-Jan Coenraads Department of Dermatology, University of Groningen, University Medical Centre Groningen, Groningen, The NetherlandsSearch for more papers by this authorCarsten Goebel, Carsten Goebel Coty Inc., Department of Toxicology, Darmstadt, GermanySearch for more papers by this author Mark Wilkinson, Corresponding Author Mark Wilkinson s.m.wilkinson@btinternet.com orcid.org/0000-0001-7253-3461 Department of Dermatology, Leeds Teaching Hospitals NHS Trust, Leeds, UK Correspondence Mark Wilkinson, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA UK. Email: s.m.wilkinson@btinternet.comSearch for more papers by this authorLea Solman, Lea Solman orcid.org/0000-0002-6183-6608 Department of Dermatology, Leeds Teaching Hospitals NHS Trust, Leeds, UKSearch for more papers by this authorPieter-Jan Coenraads, Pieter-Jan Coenraads Department of Dermatology, University of Groningen, University Medical Centre Groningen, Groningen, The NetherlandsSearch for more papers by this authorCarsten Goebel, Carsten Goebel Coty Inc., Department of Toxicology, Darmstadt, GermanySearch for more papers by this author First published: 13 November 2018 https://doi.org/10.1111/cod.13156Citations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume80, Issue3March 2019Pages 177-178 RelatedInformation

Various synthetic compounds are frequently discharged into the environment via human activities. Among them, certain contaminants may disrupt normal physiological functions of wildlife and humans via interactions with nuclear receptors. To protect human health and the environment, it is important to detect environmental ligands for human nuclear receptors. In this study, yeast-based reporter gene assays were used to investigate the occurrence of xenobiotic ligands for retinoid X receptors (RXR) and thyroid hormone receptors (TR) in the aquatic environment of Taiwan. Experimental results revealed that RXR agonist/antagonist activity was detected in river water and sediment samples. In particular, high RXR agonist/antagonist activity was found in the samples collected near river mouths. Additionally, few samples also elicited significant TR antagonist activity. Our findings show that the aquatic environment of Taiwan was contaminated with RXR and TR ligands. Further study is necessary to identify these xenobiotic RXR and TR agonists and antagonists.

With the government planning a congestion charging (CC) scheme for Jakarta, public support is regarded as a prerequisite for its implementation. Politicians typically see CC reform as a controversial policy if there is no public support. Yet a CC plan is currently under active development and remains under consideration as a way to mitigate the acute traffic congestion in Jakarta. The CC theme has been recognized as a powerful instrument in both delivering efficient road use and raising revenues. Studies indicate that revenue redistribution is one of the most important determinants of public support for such scheme. Given the absence of studies from the Asian megacity context, this paper presents a systematic study of how public perceptions relate to revenue spending choice behavior. A stated preference (SP) questionnaire is developed to investigate citizen’s perceptions of CC reform, their preferences for revenue redistribution and their current travel behavior. Using data collected using this SP questionnaire in 2013, a hybrid revenue allocation (HRA) model is formulated that captures the impact of tangible factors (i.e. charges, socio-demographic characteristics, travel behavior) and intangible factors (perceptions) during process of deciding among revenue spending alternatives. The proposed model is drawn from traditional utilitarian resource (time) allocation theory, with an extension consisting of latent constructs representing subjective individual psychological perceptions. We find that there is a strong correlation between revenue allocation preferences and an individual’s subjective psychological perceptions. The most preferred revenue allocations are for public transport improvements and traffic safety improvements, with 54% and 29% agreement, respectively. We find there is little support for spending revenues on other issues such as for stimulating local business (13%) and for parks/green spaces, driving education/enforcement and improving the parking system (4% in total). The findings of sensitivity analysis further disclose that the choice of spending on public transport improvements among respondents who frequently visit the central business district (CBD) is sensitive to the level of the CC charge, while for respondents who frequently enter the CBD by car and have a medium-high income the traffic safety allocation is sensitive to charge.