Regulation of immune response genes in the skin of allergic and clinically tolerant individuals exposed to p-phenylenediamine.

BACKGROUND: p-Phenylenediamine (PPD) is a potent contact allergen found in many hair colour products. However, not all individuals develop allergic contact dermatitis (ACD) although they are regularly exposed to PPD. It is unclear whether these asymptomatic individuals are true non-responders to PPD or whether they mount a response to PPD without showing any symptoms. METHODS: Skin biopsies were collected from 11 asymptomatic hairdressers regularly exposed to PPD and from 10 individuals with known ACD on day 4 after patch testing with 1% PPD in petrolatum and petrolatum exclusively as control. RNA sequencing and confocal microscopy were performed. RESULTS: T cell activation, inflammation and apoptosis pathways were up-regulated by PPD in both asymptomatic and allergic individuals. Compared to asymptomatic individuals with a negative patch test, individuals with a strong reaction to PPD strongly up-regulated both pro- and anti-inflammatory cytokines genes. Interestingly, PPD treatment induced significant up-regulation of several genes for chemokines, classical type 2 dendritic cell markers and regulatory T cell markers in both asymptomatic and allergic individuals. In addition, apoptosis signalling pathway was activated in both non-responders and allergic individuals. CONCLUSION: This study demonstrates that there are no true non-responders to PPD but that the immune response elicited by PPD differs between individuals and can lead to either tolerance, subclinical inflammation or allergy.

Prioritization of chemicals in personal care products based on persistent, bioaccumulative and toxic (PBT) potential: An Indian perspective.

Numerous organic ingredients present in Personal care products (PCPs) are being detected in sewage which has a high potential to impact the environment. These compounds are called as Emerging contaminants (ECs) or Contaminants of emerging concern. However, the information on the source and occurrence of ECs present in PCPs is very minimal. Specifically, information on the persistence (P), bioaccumulation (B) and toxicity (T) is very scarce. The determination of PBT properties is a complex task given the magnitude of chemicals, thus it is necessary to have a tool to quickly screen and prioritize the most important compounds. Estimation Program Interface (EPI) Suite™ is one such tool authorized by United States Environmental Protection Agency (US EPA) for screening purposes. In the present study, several organic compounds present in the PCPs viz. body lotion, sunscreens, moisturizers, hair dyes, and some hair care products were identified and their PBT property was estimated. The results from the study indicate that the order of increasing occurrence of PBT chemicals is sunscreens > moisturizers > body lotion > hair care products > hair dyes. The prioritized compounds were given rank 1 (maximum concern) to rank 4 (minimum concern). From the results, the compounds octocrylene in sunscreens and butylphenyl methylpropional in body lotions were prioritized as Rank 1.

Suitability of different reconstructed human skin models in the skin and liver Chip2 microphysiological model to investigate the kinetics and first-pass skin metabolism of the hair dye, 4-amino-2-hydroxytoluene.

The HUMIMIC skin-liver Chip2 microphysiological systems model using the epidermal model, EpiDerm™, was reported previously to mimic application route-dependent metabolism of the hair dye, 4-amino-2-hydroxytoluene (AHT). Therefore, we evaluated the use of alternative skin models-SkinEthic™, EpiDermFT™ and PhenionFT™-for the same purpose. In static incubations, AHT permeation was similar using SkinEthic™ and EpiDerm™ models. Older Day 21 (D21) SkinEthic™ models with a thicker stratum corneum did not exhibit a greater barrier to AHT (overall permeation was the same in D17 and D21 models). All epidermal models metabolised AHT, with the EpiDerm™ exhibiting higher N-acetylation than SkinEthic™ models. AHT metabolism by D21 SkinEthic™ models was lower than that by D17 SkinEthic™ and EpiDerm™ models, thus a thicker stratum corneum was associated with fewer viable cells and a lower metabolic activity. AHT permeation was much slower using PhenionFT™ compared to epidermal models and better reflected permeation of AHT through native human skin. This model also extensively metabolised AHT to N-acetyl-AHT. After a single topical or systemic application of AHT to Chip2 model with PhenionFT™, medium was analysed for parent and metabolites over 5 days. The first-pass metabolism of AHT was demonstrated, and the introduction of a wash step after 30 min decreased the exposure to AHT and its metabolites by 33% and 40%-43%, respectively. In conclusion, epidermal and FT skin models used in the Chip2 can mimic the first-pass skin metabolism of AHT. This highlights the flexibility of the Chip2 to incorporate different skin models according to the purpose.

Early presentation of allergic contact dermatitis due to paraphenylenediamine.

Allergic contact dermatitis (ACD) is a more frequent pathology in adults than in children, because, in most cases, allergic sensitization requires a prolonged exposure time to the allergen, mostly months or years. In fact, the actual incidence and prevalence of ACD in children and adolescents is unknown. However, there is a hypothesis that ACD is increasing in the pediatric population. Among the allergens involved in ACD, the frequency of paraphenylenediamine (PPDA) is increasing. PPDA is one of the five most common contact allergens in the general population and one of the 10 most common contact allergens in children. The most relevant sources today are henna tattoos and hair dyes. Currently, European Union legislation limits the use of PPDA in hair dyes and prohibits its use in henna tattoos. Despite this legislation, the use of henna tattoos with PPDA is becoming more frequent in younger ages. We report an early presentation of ACD by PPDA, with a permanent hypopigmented skin area as an aftermath, in a 7-year-old male child. We believe that health authorities should advise against making these tattoos in children.

Safety Assessment of Basic Red 76 as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of Basic Red 76, which is reported to function in cosmetics as a hair colorant and hair-conditioning agent. The Panel reviewed the available data to determine the safety of this ingredient. The Panel concluded that Basic Red 76 is safe for use as a hair dye ingredient in the present practices of use and concentration described in the safety assessment.

Toxic potential assessment of hair dye developer 2,4,5,6-tetraaminopyrimidine sulfate exposed under ambient UVB radiation.

Synthetic cosmetics, particularly hair dyes, are becoming increasingly popular among people of all ages and genders. 2,4,5,6-tetraaminopyrimidine sulfate (TAPS) is a key component of oxidative hair dyes and is used as a developer in several hair dyes. TAPS has previously been shown to absorb UVB strongly and degrade in a time-dependent manner, causing phototoxicity in human skin cells. However, the toxic effects of UVB-degraded TAPS are not explored in comparison to parent TAPS. Therefore, this research work aims to assess the toxicity of UVB-degraded TAPS than TAPS on two different test systems, that is, HaCaT (mammalian cell) and Staphylococcus aureus (a bacterial cell). Our result on HaCaT has illustrated that UVB-degraded TAPS is less toxic than parent TAPS. Additionally, UVB-exposed TAPS and parent TAPS were given to S. aureus, and the bacterial growth and their metabolic activity were assessed via CFU and phenotype microarray. The findings demonstrated that parent TAPS reduced bacterial growth via decreased metabolic activity; however, bacteria easily utilized the degraded TAPS. Thus, this study suggests that the products generated after UVB irradiation of TAPS is considered to be safer than their parent TAPS.

Diagnostics and Prevention of Occupational Allergy in Hairdressers.

PURPOSE OF REVIEW: This study aims to provide an overview on current knowledge on occupational allergic diseases in hairdressers and up-to-date perspectives of prevention. RECENT FINDINGS: Hand eczema (dermatitis) is common in hairdressers, often caused by contact allergy to one or multiple small molecules (haptens) used, e.g., for dyeing, bleaching, and waving/relaxing or by ancillary substances such as preservatives. Hairdressers, compared to other patch-tested patients, have an up to fivefold increased risk to be found sensitized, e.g., against p-phenylenediamine, ammonium persulfate, and glyceryl thioglycolate. Some of these small molecules may induce respiratory sensitization causing allergic rhinitis and/or asthma, notably persulfate salts. Occupational hazards in hairdressing are well described. This knowledge needs to be put into use for risk reduction, mainly by substitution of allergenic ingredients by less allergenic ones, education, and use of ventilation and suitable single-use gloves.

Do hairdressers comprise a high risk group for genotoxicity? A systematic review.

BACKGROUND AND OBJECTIVES: Nowadays, hair dye products are widely used for aesthetic purposes, in which it generates chemical exposure to customers and, mainly, hairdressers. The aim of this systematic review was designed to elucidate the following question: are hair dye products able to induce DNA damage in hairdressers? METHODS: Studies were included in our analyses if they met the following criteria: (1) studies measuring genetic damage in vivo; (2) studies published in English; (3) studies that provided data clearly presented in scientific standards. RESULTS: Full manuscripts from 13 studies were carefully selected in this setting. Our results demonstrate that hair dye products may contain chemical agents able to induce DNA strand breaks or chromosome damage since the majority of studies demonstrated positive findings for genotoxicity. A total of 7 studies (out of 13) had strong or moderate rates in the quality assessment. The type of genotoxicity assay and sample selection criteria time influenced the outcome. CONCLUSION: In summary, our results reveal that hairdressers are occupationally exposed to genotoxic agents. Such findings are very important for protecting these professionals who are continuously exposed to chemicals for long periods.

Dermal exposure and hair dye: Assessing potential bladder cancer risk from permanent hair dye.

Hair dye products include a range of chemicals, depending on the type and color. A common primary intermediate compound used to achieve the permanent effect of hair dye is para-phenylenediamine (PPD). 4-aminobiphenyl (4-ABP) has reportedly been found as a trace contaminant (presumably from the para-phenylenediamine [PPD] ingredient) in consumer permanent hair dye. While several regulatory agencies have designated 4-ABP as a human bladder carcinogen based on evidence in humans and experimental animals, only the Office of Environmental Health Hazard Assessment (OEHHA) have established a cancer risk value for 4-ABP of 0.03 µg/day based on liver tumors developed in mice. A hypothetical dermal risk assessment was performed to estimate the bladder cancer risk associated with exposure to 4-ABP from personal use of permanent hair dye potentially containing incidental 4-ABP. Previously published laboratory analyses characterizing 4-ABP concentrations in consumer hair dyes indicate the concentrations can range from below the limit of detection to 8120 ppb. Precautionary estimates of human scalp surface area, maximum skin adherence, hair dye retention factor, and percent dermal absorption were used to estimate the daily systemic exposure doses (SEDs) from dermal application of hair dye. The estimated SEDs ranged from 0.05 to 3000 pg/day. A margin of safety (MOS) was calculated as the ratio of the NSRL to the SED and ranged from 10 to 570,000. The results of this study suggest that there is no indication of increased risk of bladder cancer in humans from exposure to 4-ABP in consumer hair dye, especially as it is extremely unlikely that a consumer would use permanent hair dye on a daily basis (as this assessment models).

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Contact sensitizers in commercial hair dye products in the Indian market: A consumer exposure study.

BACKGROUND: Hair dye is a concoction of various ingredients that can result in allergic contact dermatitis (ACD) which is a common problem encountered by dermatologists. OBJECTIVES: To find out the presence of potent contact sensitizers in commercially available hair dyes in Puducherry, a union territory in South India, and to compare the findings with similar studies conducted in different countries. METHODS: Ingredients labels of 159 hair dye products from 30 brands that were manufactured and marketed in India screened for the presence of contact sensitizers. RESULTS: A total of 25 potent contact sensitizers were found in 159 hair dye products. p-Phenylenediamine and resorcinol were the most frequent contact sensitizer found in the study. The mean contact sensitizer concentration in a single hair dye product is 3.72 ± 1.81. The number of potent contact sensitizers in individual hair dye products ranged from 1 to 10. CONCLUSION: We observed that most of the consumer-available hair dyes contain multiple contact sensitizers. Also, an inadequacy in mentioning the p-Phenylenediamine content, and appropriate warning contents regarding hair dye use were not mentioned in the cartons.

Contact allergy to ingredients of hair cosmetics in female hairdressers and female consumers-An update based on IVDK data 2013-2020.

BACKGROUND: Hair cosmetic products contain several, partly potent contact allergens, including excipients like preservatives. Hand dermatitis in hairdressers is common, scalp and face dermatitis in clients or self-users (summarised here as 'consumers') may be severe. OBJECTIVE: To compare frequencies of sensitization to hair cosmetic ingredients and other selected allergens between female patch tested patients working as hairdressers and consumers without professional background, respectively, who were tested for suspected allergic contact dermatitis to such products. METHODS: Patch test and clinical data collected by the IVDK (https://www.ivdk.org) between 01/2013 and 12/2020 were descriptively analysed, focusing on age-adjusted sensitization prevalences in the two subgroups. RESULTS: Amongst the 920 hairdressers (median age: 28 years, 84% hand dermatitis) and 2321 consumers (median age: 49 years, 71.8% head/face dermatitis), sensitization to p-phenylenediamine (age-standardised prevalence: 19.7% and 31.6%, respectively) and toluene-2,5-diamine (20 and 30.8%) were most common. Contact allergy to other oxidative hair dye ingredients was also more commonly diagnosed in consumers, whereas ammonium persulphate (14.4% vs. 2.3%) and glyceryl thioglycolate (3.9 vs. 1.2%) as well as most notably methylisothiazolinone (10.5% vs. 3.1%) were more frequent allergens in hairdressers. CONCLUSIONS: Hair dyes were the most frequent sensitizers both in hairdressers and in consumers; however, as indication for patch testing may differ, prevalences cannot directly be compared. The importance of hair dye allergy is evident, often with marked coupled reactivity. Workplace and product safety need to be further improved.

Systematic review on skin adverse effects of important hazardous hair cosmetic ingredients with a focus on hairdressers.

BACKGROUND: The burden of occupational hand eczema in hairdressers is high, and (partly strong) allergens abound in the hair cosmetic products they use. OBJECTIVES: To systematically review published evidence concerning contact allergy to an indicative list of active ingredients of hair cosmetics, namely, p-phenylenediamine (PPD), toluene-2,5-diamine (PTD), persulfates, mostly ammonium persulfate (APS), glyceryl thioglycolate (GMTG), and ammonium thioglycolate (ATG), concerning the prevalence of sensitization, particularly in terms of a comparison (relative risk; RR) between hairdressers and non-hairdressers. METHODS: Following a PROSPERO-registered and published protocol, eligible literature published from 2000 to February 2021 was identified, yielding 322 publications, and extracted in standardized publication record forms, also considering risk of bias. RESULTS: Based on 141 publications, the contact allergy prevalence to PPD was 4.3% (95% CI: 3.8-4.9%) in consecutively patch tested patients. Other ingredients were mostly tested in an aimed fashion, yielding variable, and partly high contact allergy prevalences. Where possible, the RR was calculated, yielding an average increased sensitization risk in hairdressers of between 5.4 (PPD) and 3.4 (ATG). Additional evidence related to immediate-type hypersensitivity, experimental results, exposures, and information from case reports was qualitatively synthesized. CONCLUSIONS: An excess risk of contact allergy is clearly evident from the pooled published evidence from the last 20 years. This should prompt an improvement in working conditions and product safety.

Exposure estimates of parabens from personal care products compared with biomonitoring data in human hair from Northeast China.

Parabens (PBs), a class of endocrine-disrupting chemicals (EDCs), are extensively used as additives in personal care products (PCPs); however, distinguishing between endogenous and exogenous contamination from PCPs in hair remains a challenge. We conducted a comprehensive analysis of the levels, distribution patterns, impact factors, and sources of PBs in 119 human hair samples collected from Changchun, northeast China. The detection rates of methylparaben (MeP), propylparaben (PrP), and ethylparaben (EtP) in hair samples were found to be 100%. The concentration of PBs in hair followed the order of MeP (57.48 ng/g) > PrP (46.40 ng/g) > EtP (6.80 ng/g). The concentration of PrP in female hair was significantly higher (65.38 ng/g) than that observed in male hair (7.82 ng/g) (p < 0.05). The levels of excretion rates of MeP (ERMeP) and excretion rates of PrP (ERPrP) in the hair-dying samples (ERMeP: 17.89 ng/day; ERPrP: 14.15 ng/day) were found to be 2.52 and 2.40 times higher, respectively, compared to the non-hair-dying samples (ERMeP: 7.09 ng/day; ERPrP: 6.05 ng/day). However, the system exposure dosage (SED) results revealed that although hair dyes exhibited higher PBs, human exposure was found to be lower than certain PCPs. The results of the correlation analysis revealed that toner, face cream, body lotion, and hair conditioner were identified as the primary sources of PBs in male hair. Furthermore, the human exposure resulting from the utilization of female hair dye and serum exhibited a positive correlation with hair ERMeP and ERPrP levels, indicating in the screening of samples, excluding hair samples using hair dye and haircare essential oil can effectively avoid the interference caused by exogenous contamination from PCPs.

Acid Orange 3.

The Expert Panel for Cosmetic Ingredient Safety reviewed updated information that has become available since their original assessment from year 2000, along with updated information regarding product types, and frequency and concentrations of use, and reaffirmed their original conclusion that Acid Orange 3 is safe for use in hair dye formulations at concentrations <.2%.

HC Yellow 5.

The Expert Panel for Cosmetic Ingredient Safety reviewed updated information that has become available since their original assessment from 2007, along with updated information regarding product types, and frequency and concentrations of use, and reaffirmed their original conclusion that HC Yellow 5 is safe as a hair dye ingredient in the practices of use and concentration as described in this report.

Pre- and postnatal maternal hair dye use and risk of wheeze and asthma in 5-year-old Japanese children: the Kyushu Okinawa Maternal and Child Health Study.

The present study investigated the association between pre- and postnatal maternal hair dye use and the risk of wheeze and asthma in Japanese children aged 5 years. Study participants were 1199 mother-child pairs. Information on the variables under study was obtained using repeated questionnaires completed by parents. Prenatal maternal hair dye use was associated with an increased risk of current wheeze and ever doctor-diagnosed asthma; the adjusted odds ratios (ORs) (95% confidence intervals [CIs]) were 1.44 (1.02-2.02) and 1.51 (1.00-2.25), respectively. Postnatal maternal hair dye use was related to the risk of doctor-diagnosed asthma; the adjusted OR (95% CI) was 1.58 (1.03-2.40). Children who were exposed to maternal hair dye use both prenatally and postnatally had an increased risk of childhood current wheeze and ever doctor-diagnosed asthma; the adjusted ORs (95% CIs) were 1.59 (1.03-2.42) and 1.76 (1.06-2.88), respectively. Our findings suggest that perinatal maternal hair dye use is associated with the risk of wheeze and asthma in children.

Hair dye use and prostate cancer risk: A prospective analysis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort.

BACKGROUND: According to the International Agency for Research on Cancer, some hair dye chemicals are considered mutagenic and carcinogenic in humans. One hospital-based study reported a positive association between hair dye use and prostate cancer risk, but no prospective analyses have been conducted. METHODS: This study investigated the association between hair dye use and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort, a large, well-characterized cohort of 29,133 male Finnish smokers. Participants completed questionnaires regarding lifestyle, medical, and risk factor information, including the use of hair dye, which was available for 98.8% of the cohort (28,795 men). Prostate cancer cases were identified through linkage with the Finnish Cancer Registry and the Finnish Mortality Register. Hazard ratios (HRs) and confidence intervals (CIs) were estimated via multivariable Cox proportional hazards regression. RESULTS: During a 28-year period of observation, 2703 incident prostate cancer cases were diagnosed. As reported at the baseline, 75 men used hair dye, and 13 of these men were subsequently diagnosed with prostate cancer. After adjustments for potential confounders, men who used hair dyes experienced substantially higher prostate cancer risk than men who did not (HR, 1.77; 95% CI, 1.03-3.05). CONCLUSIONS: This first prospective investigation of hair dye use and prostate cancer suggests that personal hair dye use may be related to increased risk. The findings warrant re-examination in other prospective cohorts along with studies evaluating specific hair dyes and possible underlying biological mechanisms.

Highly sensitive and rapid detection of resorcinol by forming fluorescent azamonardine with dopamine.

We propose a sensitive, selective, and rapid fluorescent assay for detecting resorcinol (RC) based on its specific chemical reaction with dopamine. Under alkaline condition, RC would react with dopamine to yield fluorescent azamonardine, which emits strong blue fluorescence and has a superior excitation wavelength at 416 nm and an emission wavelength at 461 nm. The azamonardine with a molecular weight of 258.1 confirmed by ICP-MS has a quantum yield of 71.3%. The reaction is completed within 1 min showing great potential for point-of-care testing. This assay showed high sensitivity and had a good relationship between fluorescent intensity at 461 nm and RC concentration (I461 = 106.4 + 93.6*CRC; R2 = 0.9904) over the range of 0-40 µM. More importantly, the assay showed a prominent anti-interference from various substances and even can distinguish RC from its isomers, o-dihydroxybenzene and p-dihydroxybenzene. Finally, our assay successfully quantified RC contents in wheat powder and hair dyes with high accuracy.

Hair Dye Ingredients and Potential Health Risks from Exposure to Hair Dyeing.

Given the worldwide popularity of hair dyeing, there is an urgent need to understand the toxicities and risks associated with exposure to chemicals found in hair dye formulations. Hair dyes are categorized as oxidative and nonoxidative in terms of their chemical composition and ingredients. For several decades, the expert panel's Cosmetic Ingredient Review (CIR) has assessed the safety of many of the chemicals used in hair dyes; however, a comprehensive review of hair dye ingredients and the risk of exposure to hair dyeing has not been documented. Herein, we review the safety of the various chemicals in oxidative and nonoxidative hair dyes, toxicities associated with hair dyeing, and the carcinogenic risks related to hair dyeing. While many compounds are considered safe for users at the concentrations in hair dyes, there are conflicting data about a large number of hair dye formulations. The CIR expert panel has ratified a number of coloring ingredients for hair dyes and banned a series of chemicals as carcinogenic to animals and unsafe for this application. The use of these chemicals as raw materials for producing hair dyes may result in the synthesis of other contaminants with potential toxicities and increased risk of carcinogenesis. It is an open question whether personal or occupational hair dyeing increases the risk of cancer; however, in specific subpopulations, a positive association between hair dye use and cancer occurrence has been reported. To address this question, a better understanding of the chemical and mechanistic basis of the reported toxicities of hair dye mixtures and individual hair dye ingredients is needed. It is anticipated that in-depth chemical and systems toxicology studies harnessing modern and emerging techniques can shed light on this public health concern in the future.