Worldwide internet trends in the public interest related to skin whitening and bleaching creams.

Skin whitening is a practice that is used to obtain lighter skin tone and is most prevalent in Africa and Asia. Substances used for this procedure, such as hydroquinone or mercury have a variety of side effects and are banned in several countries. This study examined the popularity of internet searches for terms related to skin whitening and bleaching creams with the use of GoogleTrends (GT). GT was searched globally for the topic "skin whitening" and two terms "hydroquinone cream" and "mercury cream" throughout a 10-year period (01.09.2013-31.08.2023). The popularity of searches increased during the analyzed period. The topic "skin whitening" was most popular in Sudan, Vietnam, and Sri Lanka. The searches were higher for "hydroquinone cream" than "mercury cream" in almost all countries, besides the Philippines and Indonesia. Our study confirms that skin whitening practices are popular, especially among populations with darker skin tone. Despite potentially toxic side effects, creams with hydroquinone and mercury are increasingly searched worldwide. Education about skin whitening and the usage of bleaching substances should be implemented, especially in the regions of Africa and Asia.

Hyperpigmented Macules and Patches on the Face: Exogenous Ochronosis or Lichen Planus Pigmentosus?

We present a case of a patient with a 10-year history of blue-black macules and patches on the face and an associated history of skin-lightening cream usage. The skin lightening cream contained hydroquinone, which is often associated with exogenous ochronosis (EO). Interestingly, the biopsy did not show characteristic findings of ochronosis, confusing the final diagnosis, however discontinuing the skin-lightening creams halted the progression of the patient's skin lesions supporting a diagnosis of EO. EO presents as asymptomatic hyperpigmentation after using products containing hydroquinone. This condition is most common in Black populations, likely due to the increased use of skin care products and bleaching cream containing hydroquinone in these populations. Topical hydroquinone is FDA-approved to treat melasma, chloasma, freckles, senile lentigines, and hyperpigmentation and is available by prescription only in the US and Canada. However, with the increased use of skin-lightening creams in certain populations, it is important for dermatologists to accurately recognize the clinical features of exogenous ochronosis to differentiate it from similar dermatoses. An earlier diagnosis can prevent the progression to severe presentations with papules and nodules. We summarize the clinical presentations diagnostic features, and treatment pearls, concluding with a discussion of the differential diagnoses.  J Drugs Dermatol. 2024;23(7):567-568.     doi:10.36849/JDD.8248.

Skin lightening: causes and complications.

Skin bleaching, also known as skin lightening, is the deliberate lightening of an individual's skin tone without medical supervision. The causes are complex, multifactorial and often intertwined, although the unifying themes centre around a belief that lighter skin denotes an individual of higher status, socioeconomic background or physical beauty, than their darker-skinned counterpart. Skin lightening is achieved using agents that block the production of melanin and often contain drugs such as hydroquinone, superpotent topical steroids or mercury. These drugs can cause serious local and systemic complication. Skin-lightening compounds are illegal in most countries throughout the world; however the industry is worth billions of dollars annually, and the agents can be easily obtained by individuals seeking to lighten their skin. Dermatologists are in a unique position to identify those at risk of using skin-bleaching agents, manage complications and give advice on the physiological variation in pigmentation and how to avoid using skin-lightening agents to treat dermatological conditions. To manage the belief that lighter skin is better, societal level change is required to ensure that people of all skin tones are represented in the media.

Parallel discourses: leveraging the Black Lives Matter movement to fight colorism and skin bleaching practices.

OBJECTIVES: The 'Black Lives Matter' (BLM) movement in 2020 exemplifies efforts to counter prejudices and the colourist narrative. Harmful use of topical skin lightening agents continues worldwide despite interdiction or restricted use under domestic, European and international regulations. STUDY DESIGN: Commentary. METHODS: Narrative review. RESULTS: In this Short Communication, we consider the significance of societal perspectives of skin colour, glocalized whiteness, efforts to attain self-esteem and social mobility through skin lightening practices, and the role of cosmetic products in fuelling this phenomenon. CONCLUSIONS: Addressing the inadvertent (or indeed conscious) vehicles of systematic racism and sustaining of skin colour prejudices and stereotypes of fair skin beauty by cosmetic companies is warranted. Targeted health messaging is an imperative.

What's new in atopic eczema? An analysis of systematic reviews published in 2018. Part 1: prevention and topical therapies.

This review is part of a series of annual updates that summarize the evidence base for atopic eczema (AE). The aim is to provide a succinct guide for clinicians on the key findings from 14 systematic reviews on the prevention and topical treatment of AE published or indexed in 2018. Various supplements, including long-chain polyunsaturated fatty acids, vitamin D and the probiotic Lactobacillus rhamnosus GG, given prenatally and postnatally, have not been shown to prevent AE in infants, although mixed strains of probiotics may decrease the risk of AE if given to the mother during pregnancy and to the infant for the first 6 months of life. In the postnatal period, there is no evidence that hydrolysed formula, compared with cow's milk formula (CMF), reduces the risk of AE in partially breastfed infants. However, weak evidence suggests that a specific partially hydrolysed whey formula decreases the risk of AE compared with CMF. No specific skin practices can be recommended to reduce the eczema risk in healthy term babies. There is weak evidence of a low risk of reversible hypothalamic-pituitary-adrenal axis suppression following 2-4 weeks of treatment with low-potency topical steroids, and conflicting evidence as to whether bleach bathing affects skin flora or AE severity. A single study demonstrated that the topical Janus kinase inhibitor tofacitinib at 2% significantly reduces the Eczema Area and Severity Index compared with vehicle. Topical naltrexone cream 1% improves pruritus (measured using a visual analogue scale) by 30% more than placebo. There is weak evidence that topical alternative therapies, including antioxidants, micronutrients and some herbal medicines, may improve AE.

Randomized, Double-Blinded, Split-Face Study Comparing the Efficacy and Tolerability of Two Topical Products for Melasma.

BACKGROUND: Melasma is a common disorder of hyperpigmentation that disproportionately affects individuals with skin of color. There is a paucity of studies evaluating non-hydroquinone (HQ) topical therapies for the treatment of melasma in darker skin types. OBJECTIVE: To compare the safety, efficacy, and tolerability of a HQ-free, retinol-free cosmetic topical brightener (CTB) and HQ 4% in the treatment of moderate symmetric facial melasma in patients with Fitzpatrick skin types (FST) III–VI. Methods & Materials: This was a randomized, double-blinded, split-face clinical trial. Eighteen adult patients with facial melasma were treated with CTB and HQ 4%, each to a different side of the face, twice daily for 12 weeks. Clinical assessments included half-face Melasma Area Severity Index (MASI), Overall Hyperpigmentation scale, and Melasma Severity Rating Scale (MSRS). Patients completed a Melasma Quality of Life (MelasQoL) questionnaire and clinical photographs were taken at each visit. RESULTS: CTB and HQ 4% demonstrated statistically significant improvements in half-face MASI, Overall Hyperpigmentation, MSRS and MelasQol compared to baseline. HQ 4% showed statistically significant improvements in MSRS at week 12 compared to CTB, but was non-superior for all other clinical endpoints. CONCLUSION: HQ-free, retinol-free CTB and HQ 4% both are effective and well-tolerated in the treatment of moderate facial melasma in FST III–VI. J Drugs Dermatol. 2020;19(9):822-827. doi:10.36849/JDD.2020.5353.

The Therapeutic Use of Antioxidants for Melasma.

Melasma is a chronic dermatologic condition with an incompletely understood pathogenesis and well-demonstrated impact on patient quality of life. Melasma is a common cause for seeking dermatologic care, and with no universally efficacious therapy or cure, com-bination treatment is the best approach for many cases. Numerous studies have demonstrated the role of oxidative stress in patients with melasma, prompting investigation into several antioxidants for melasma therapy. In this review, we discuss the well-defined role of oxidative stress in melasma and the therapeutic efficacy of various antioxidants for patients suffering from melasma. We focus our discussion on studies investigating the role of vitamin C, azelaic acid, cysteamine, glutathione, carotenoids, and numerous other antioxidants in disorders of hyperpigmentation. There is promising evidence for the use of these antioxidants, as topical, oral, and intra-venous preparations, both in isolation and in conjunction with other melasma therapies. J Drugs Dermatol. 2020;19(8):788-792. doi:10.36849/JDD.2020.5079.

[Topical treatment of pigmentation disorders with cosmetic and pharmaceutical agents]. / Topische Behandlung von Pigmentstörungen mit kosmetischen und pharmazeutischen Wirkstoffen.

BACKGROUND: Esthetically unattractive hyperpigmentation can occur post-inflammatory or as a result of genetic or hormonal influences, UV exposure or medication. Important parameters for the quality of topical treatments are evidence-based in vivo and in vitro efficacy as well as scientifically verified wanted and unwanted effects. OBJECTIVES: This paper will present cosmetic and pharmaceutical topical ingredients against hyperpigmentation that have been proven in scientific studies. MATERIALS AND METHODS: A search of PubMed database was performed in October 2020 using the various ingredient names, "melasma" and "hyperpigmentation." Two reviewers independently screened titles, leading to the selection of 30 papers. RESULTS: Hydroquinone, a tyrosinase inhibitor, has been used for over 40 years to treat hyperpigmentation. It is the most commonly studied agent for lightening pigment. Despite the limited evidence-based research on novel treatment approaches, several ingredients did show efficacy as depigmenting agents, including tyrosinase inhibitors, substances that increase cell turnover, and plant derivatives. CONCLUSIONS: Hydroquinone is still the gold standard for the treatment of hyperpigmentation, along with the triple therapy of hydrochinon, tretinoin, and steroids in different modifications. In summary, hyperpigmentation is best treated using a combination therapy of different approaches that includes consequent UV protection.

Formulation and clinical evaluation of the standardized Litchi chinensis extract for skin hyperpigmentation and aging treatments.

INTRODUCTION: The standardized litchi extract had been revealed on phytochemical actives, in vitro and cellular activities against aging and darkening of skin. However, a formulation containing the extract has never been developed as per clinical evaluated. MATERIALS AND METHODS: The litchi serum was developed, safety and efficacy were clinically evaluated in human volunteers. The stable and none irritated 0.05 and 0.1% litchi serums were randomized-single blind placebo control clinical applied on the inner forearm of 29 volunteers for a consecutive 112 days and monitored by Mexameter® MX18, Cutometer® MPA 580 and Visioscan® VC 98. RESULTS: Skin lightening efficacy of the 0.1% and 0.05% litchi serum was significantly (P<0.001 and P<0.05) higher than the placebo. Skin elasticity and wrinkle reduction was significantly (P<0.05 and P<0.005) achieved by the 0.1% litchi serum. The efficacy of litchi serums was confirmed by a split-face, randomized, single-blind controlled that the 0.1% litchi serum was significantly (P<0.05) better than the 0.05% one of all examined parameters. CONCLUSION: Safety and efficacy of litchi extract are clinically confirmed for hyperpigmentation and aging of skin treatments.

Mercury-associated glomerulonephritis: a retrospective study of 35 cases in a single Chinese center.

BACKGROUND: Long-term exposure of mercury may induce glomerulonephritis. Clinical and pathological features of mercury-associated glomerulonephritis are not fully clear. This study retrospectively analyzed 35 cases of mercury-associated glomerulonephritis in a single Chinese center. METHODS: Thirty-five patients of mercury-associated glomerulonephritis were enrolled. Clinical data on diagnosis and during follow-up were collected. Plasma anti-phospholipase A2 receptor (PLA2R) antibody, glomerular PLA2R and glomerular IgG subclasses deposition were detected in the cases with membranous nephropathy (MN). RESULTS: Mercury exposure was caused by skin lighting cream (20 patients), mercury-containing pills (9 patients), hair-dyeing agents (4 patients), and unidentified reasons (2 patients). All patients presented with proteinuria and normal renal function. The median of urinary protein was 4.6 (range 1.6~19.7) g/24 h. Twenty-two patients (62.9%) had nephrotic syndrome. Renal histopathology showed minimal change disease (MCD) in 21 patients (60.0%), MN in 13 (37.1%) and focal segmental glomerular sclerosis (FSGS) in 1 patient (2.9%). The proportion of MCD increased along with urinary mercury concentration (P = 0.024). In 13 cases of MN, all patients were negative for plasma anti-PLA2R antibody and glomerular PLA2R antigen. IgG1 (61.5%) and IgG4 (46.2%) deposits were noted along the glomerular capillary loops. Among the 16 patients received mercury detoxification monotherapy, 14 patients received 4.5 ± 2.8 (range 1~12) rounds of regimen and achieved complete remission in 4.5 (range 0.3~23.0) months, 2 patients stayed no remission. CONCLUSIONS: MCD was the most common pathological type of mercury-associated glomerulonephritis, followed by MN. The proportion of MCD increased along with the increase of urinary mercury concentration. Most patients could achieve complete remission after mercury detoxification.

In Vitro and In Vivo Efficacy and Tolerability of a Non-Hydroquinone, Multi-Action Skin Tone Correcting Cream

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.

Exogenous ochronosis: the failure of depigmenting creams.

Exogenous ochronosis (EO) is an entity that manifests as black-bluish or grayish-brown cutaneous hyperpigmentation, which is a consequence of the deposition of ochronotic pigment with characteristic banana-like morphology between the collagen fibers of the dermis. Both the clinical presentation and histopathology appearance are superimposable with endogenous ochronosis or alcaptonuria, a hereditary disease in which ochronotic pigment deposition occurs at a multisystemic level. The most frequent cause of EO is the use of facial depigmenting creams containing hydroquinone, a common practice among women with high phototypes. We present a woman who developed EO on the face, upper chest, and back after prolonged use of a depigmenting cream containing hydroquinone.

Skin lighteners and hair relaxers as risk factors for breast cancer: results from the Ghana breast health study.

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1131 invasive breast cancer cases and 2106 population controls. Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first use or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (P for trend < 0.01). This was most pronounced among women with few children and those with smaller tumors, suggesting a possible role for other unmeasured lifestyle factors. This study does not implicate a substantial role for skin lighteners as breast cancer risk factors, but the findings regarding hair relaxers were less reassuring. The effects of skin lighteners and hair relaxers on breast cancer should continue to be monitored, especially given some biologic plausibility for their affecting risk.

Mercury Poisoning in a Toddler from Home Contamination due to Skin-Lightening Cream.

A 17-month-old child presented with hypertension, fussiness, constipation, and arthralgia due to mercury toxicity from a skin-lightening cosmetic used by her mother and grandmother. Blood mercury level was 26 mcg/L and urine level was 243 mcg/g creatinine. She was chelated with succimer. The home was contaminated and needed remediation.

Colourism: a global adolescent health concern.

PURPOSE OF REVIEW: Colourism, a form of prejudice and discrimination based solely upon skin colour, stands to jeopardize the physical health, wellbeing and life chances of adolescents of colour, globally. RECENT FINDINGS: Research shows that adolescents can experience colourism at school and college, in the criminal justice system, at work and in the media they consume. It is therefore unsurprising that adolescents of colour often express a desire for lighter skin tones and/or are dissatisfied with their skin tone. Although research is scarce, some studies include older adolescents in their samples of skin-lightening product users. This is significant as the evidence is clear that the unmonitored use of skin-lightening products can be harmful to physical and psychological health, with evidence linking skin-lightening use to skin damage, kidney failure and depression. SUMMARY: Although it is evident that colourism is central to the lives of adolescents of colour, more research is needed concerning the use of skin-lightening products among adolescents. Media literacy and critical race theory offer avenues in helping attenuate the harmful impact of colourism for adolescents of colour.

YouTube as a source of information on skin bleaching: a content analysis.

BACKGROUND: Skin bleaching is a common, yet potentially harmful body modification practice. AIM: To describe the characteristics of the most widely viewed YouTube™ videos related to skin bleaching. METHODS: The search term 'skin bleaching' was used to identify the 100 most popular English-language YouTube videos relating to the topic. Both descriptive and specific information were noted. RESULTS: Among the 100 manually coded skin-bleaching YouTube videos in English, there were 21 consumer-created videos, 45 internet-based news videos, 30 television news videos and 4 professional videos. Excluding the 4 professional videos, we limited our content categorization and regression analysis to 96 videos. Approximately 93% (89/96) of the most widely viewed videos mentioned changing how you look and 74% (71/96) focused on bleaching the whole body. Of the 96 videos, 63 (66%) of videos showed/mentioned a transformation. Only about 14% (13/96) mentioned that skin bleaching is unsafe. The likelihood of a video selling a skin bleaching product was 17 times higher in internet videos compared with consumer videos (OR = 17.00, 95% CI 4.58-63.09, P < 0.001). Consumer-generated videos were about seven times more likely to mention making bleaching products at home compared with internet-based news videos (OR = 6.86, 95% CI 1.77-26.59, P < 0.01). CONCLUSIONS: The most viewed YouTube video on skin bleaching was uploaded by an internet source. Videos made by television sources mentioned more information about skin bleaching being unsafe, while consumer-generated videos focused more on making skin-bleaching products at home.

Skin-lightening practices among female high school students in Ghana.

OBJECTIVE: The practice of skin lightening (SL) persist despite warnings about its harmful health effects. Adolescents are particularly vulnerable and at risk of prolonged use of SL products. We explored SL practices among high school students in Ghana, West Africa. STUDY DESIGN: Cross-sectional survey. METHODS: We used a self-administered questionnaire in a survey on SL practices among randomly selected female students in five Senior High Schools in the Brong Ahafo Region of Ghana. We determined prevalence and used bivariate and multivariate analysis to identify factors associated with the practice. RESULTS: A total of 410 students with a mean age of 17.6 years (±1.6) participated in the study. While 71.5% of students indicated that they had been approached by relatives and friends to use SL creams, 65.6% admitted to actually using it. Most (85.5%) students identified at least five friends who were using SL products at the time of the survey. Between 22.0% and 44.0% of students knew female teachers who practiced SL. Students in first year were twice as likely to practice SL compared with students in third year (odds ratio [OR] = 1.90, 95% confidence interval [CI] 1.15-3.13). Compared with those who had never been approached, students who had been approached by relatives and friends to use SL products were likely to be using it (OR = 2.24, 95% CI 1.43-3.53). Students who had sisters who used SL products were twice as likely to be users themselves (OR = 1.82, 95% CI 1.12-2.95). CONCLUSION: The practice of SL among female students in this study is high, and about the same as reported among adults in Ghana and other parts of sub-Saharan Africa. This suggests that the practice is well entrenched. A ban on the sale of SL products to adolescents in Ghana should be considered.

Melanogenesis Inhibitors from the Rhizoma of Ligusticum Sinense in B16-F10 Melanoma Cells In Vitro and Zebrafish In Vivo.

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC50 values of 78.9 and 31.1 µM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 µM) compared to arbutin (20 µM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.

Health Knowledge, Cosmetic Interests, Attitude, and the Need for Health Education Regarding the Use of Topical Bleaching Agents Among Women in West Saudi Arabia: A Cross-Sectional Study.

We aimed at investigating the cosmetic interests, public confidence in cosmetic industry, health knowledge, practice, and need for health education regarding using topical bleaching agents (TPAs) among a relatively big sample size in Al-Madinah (west Saudi Arabia, a conservative eastern society that acquires its social customs from Islam). Islamic values increased women respect and esteem in this society. This is reflected on cosmetic practices and attitude, e.g. women use face cover outdoors. This issue is vital for both women health and beauty, and is rarely discussed. TPAs use is affected by culture, social customs, and health awareness regarding TPAs chemical constituents, e.g. hydroquinone, mercury, steroids that may harm skin and general health. Ethical committee approval was done for our study that included 531 women (attending the outpatient clinics in March-April 2016) of targeted 571 (response rate was 89.8%). 43.3% (230 women) are current TPAs users. Three hundred and eight-nine women (73.3%) regularly used TPAs to heal pigmented areas like freckles (75.8%) and just to lighten skin color (58.7%). Side effects of discontinuation were restoration of normal skin color (44.3%) or even darker skin (27%), skin dryness (20%) and rash (9.6%). Mercury is recognized as harmful to human health by 30.2%, whereas cortisone was chosen by others (53.2%). Unexpectedly, minority of investigated women (10%) considered using TPAs safe and recognized harms of some ingredients as mercury whereas the majority (70.2%) does not encourage others for TPAs use although they themselves kept using TPAs for different reasons. Cosmetic interest is high among women using TPAs, highest among the middle age (26-40 years), and lowest among women more than 40 years (50% versus 17.9%) (p < 0.001). Using skin TPAs in west Saudi Arabia is comparable with international standards, higher among educated women, house wives and employed women. This denotes care of married employed women to use TPAs to express beauty to husbands. This is not reduced by work duties and is controlled by conservative Islamic modesty. Health education is mandatory regarding TPAs components and use during pregnancy and lactation. Cosmetic science and industry needs more research to improve TPAs use through providing better safe alternatives for many TPAs components, e.g. mercury and hydroquinone.