Review of the standards of proof (of safety) for FDA regulated consumer products and how the generally recognized as safe criteria could be applied to cosmetics.

The Modernization of Cosmetics Regulation Act of 2022 (MoCRA) amends the Food, Drug and Cosmetic Act (FDCA), elevating the standard of proof of safety (better known as a "safety standard") for cosmetics to the standard of a "reasonable certainty … [of] … safe."a standard equal to that of food ingredients. The standards of the proof of safety differ for various classes of FDA-regulated product categories e.g., cosmetics, dietary supplements, food ingredients and food itself. This manuscript describes the various standards of proof, the essential differences between the standards, key elements required to achieve a particular standard and, compares the standards to more familiar legal terms such as "a preponderance of the evidence" or "beyond reasonable doubt." The standards of proof for these product categories are also ranked according to increasing threshold for achievement of "safe" status. Lastly, this manuscript suggests how the requirements for the high standard of a "reasonable certainty of safe" (or "reasonable certainty of no harm") might be met.

Analysis of preservatives and fragrances in topical medical devices: The need for more stringent regulation.

INTRODUCTION: Medical devices (MDs) have a long history of use, and come with regulatory frameworks to ensure user safety. Although topically applied MDs in the form of gels and creams might be used on damaged skin, their composition is often similar to that of cosmetic products applicable to intact skin, especially in terms of preservatives and fragrances. However, unlike cosmetics, these products are not subject to compound-specific restrictions when used in MDs. OBJECTIVE: This study aimed to identify and quantify preservatives and fragrances in topically applied MDs and assess their safety towards the Cosmetic Regulation (EC) 1223/2009. METHOD: Sixty-nine MDs available on the EU market were subjected to previously validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods to identify and quantify occurring preservatives and fragrances. RESULTS: Findings revealed that 32% of the examined MDs did not provide comprehensive ingredient lists, leaving users uninformed about potential risks associated with product use. Furthermore, 30% of these MDs would not meet safety standards for cosmetic products and, most significantly, 13% of the analysed samples contained ingredients that are prohibited in leave-on cosmetics. CONCLUSION: Results highlight the pressing demand for more stringent requirements regarding the labelling and composition of MDs to enhance patient safety. Improved regulation and transparency can mitigate potential risks associated with the use of topically applied MDs.

Cosmetic Contact Lenses in the United Kingdom: Assessment of Online Regulation and Quality of Consumer Health Information.

OBJECTIVES: To determine the compliance of online vendors to the UK Opticians Act 1989 Section 27 requirements and safety regulations for cosmetic contact lens (CCL) sales and the quality of online CCL health information. METHODS: The top 50 websites selling CCLs on each three search engines, namely Google, Yahoo, and Bing, were selected. Duplicates were removed, and the remaining websites were systematically analyzed in February 2023. UK legal authorization for CCL sales was assessed using the Opticians Act Section 27 and safety regulations determined by the presence of Conformité Européene (CE) marking. The quality and reliability of online information was graded using the DISCERN (16-80) and JAMA (0-4) scores by two independent reviewers. RESULTS: Forty-seven eligible websites were analyzed. Only six (12.7%) met the UK legal authorization for CCL sales. Forty-nine different brands of CCLs were sold on these websites, of which 13 (26.5%) had no CE marking. The mean DISCERN and JAMA benchmark scores were 26 ± 12.2 and 1.3 ± 0.6, respectively (intraclass correlation scores: 0.99 for both). CONCLUSIONS: A significant number of websites provide consumers with easy, unsafe, and unregulated access to CCLs. Most online stores do not meet the requirements set out in the Opticians Act for CCL sales in the United Kingdom. A significant number of CCLs lack CE marking, while the average quality of information on websites selling CCLs is poor. Together, these pose a risk to consumers purchasing CCLs from unregulated websites, and therefore, further stringent regulations on the online sales of these products are needed.

Use of a common European approach for nanomaterials' testing to support regulation: a case study on titanium and silicon dioxide representative nanomaterials.

The European Union (EU) continuously takes ensuring the safe use of manufactured nanomaterials (MNMs) in consumer products into consideration. The application of a common approach for testing MNMs, including the use of optimized protocols and methods' selection, becomes increasingly important to obtain reliable and comparable results supporting the regulatory framework. In the present study, we tested four representative MNMs, two titanium dioxides (NM100 and NM101) and two silicon dioxides (NM200 and NM203), using the EU FP7-NANoREG approach, starting from suspension and dispersion preparations, through to their characterization and final evaluation of biological effects. MNM dispersions were prepared following a refined NANOGENOTOX protocol and characterized by dynamic light scattering (DLS) in water/bovine serum albumin and in media used for in vitro testing. Potential genotoxic effects were evaluated on human bronchial BEAS-2B cells using micronucleus and Comet assays, and pro-inflammatory effects by cytokines release. Murine macrophages RAW 264.7 were used to detect potential innate immune responses using two functional endpoints (pro-inflammatory cytokines and nitric oxide [NO] production). The interaction of MNMs with RAW 264.7 cells was studied by electron microscopy. No chromosomal damage and slight DNA damage and an oxidative effect, depending on MNMs, were observed in bronchial cells. In murine macrophages, the four MNMs directly induced tumor necrosis factor α or interleukin 6 secretion, although at very low levels; lipopolysaccharide-induced NO production was significantly decreased by the titania and one silica MNM. The application of this approach for the evaluation of MNM biological effects could be useful for both regulators and industries.

Expanded FDA regulation of health and wellness apps.

This paper argues that the Food and Drug Administration's (FDA) policy for health and wellness apps is ethically problematic. Currently, the FDA does not regulate health and wellness apps that are not intended for medical use. As a result of this hands-off policy, preventing harm to consumers is left primarily to developers and app marketplaces. We argue that the FDA's duties to prevent harm and maintain accountability to the American public require that they play a much stronger role. We also discuss concerns about efficiency and fostering innovation, and argue that while they should help shape FDA regulation of health and wellness apps, they do not justify complete absence of FDA involvement.

Sensitization to nickel in the Triveneto region: Temporal trend after European Union regulations.

Highlights After the introduction of the EU regulatory interventions, nickel sensitization decreased significantly in the group of females aged ≤25 years. Women born between 1966 and 1975 presented the higheest prevalence of sensitization to nickel, then prevalence of sensitization gradually decreased with a minimum in more recent years. Nickel sensitization is higher in Italian patients compared to people living in other EU coutries. Additional interventions are needed to address nickel sensitization.

Prevalence of contact allergy to metals: nickel, palladium, and cobalt in Southern Sweden from 1995-2016.

BACKGROUND: In 2001, the EU nickel directive was introduced to prevent contact allergy to nickel. Contact allergy to palladium and/or cobalt is often seen together with contact allergy to nickel. OBJECTIVES: To compare the contact allergy prevalence of nickel, palladium, and cobalt allergy before and after the introduction of the EU nickel directive in consecutive patients with dermatitis. METHODS: A retrospective analysis of patch test results from 1995-2016 was performed (n = 18 264). Chi-square tests were used to examine trends for nickel, palladium, and cobalt across test years. Logistic regression was used for associations. RESULTS: The prevalence of nickel allergy decreased significantly in the youngest age group (6-30 years) for both female and male patients from 1995-1999 to 2012-2016: females: 33.4% to 19.1% (P < .001); males: 5.9% to 2.1% (P < .05). The concomitant reactions between nickel and palladium and nickel and cobalt among young females, respectively, also decreased significantly. Isolated palladium and cobalt allergy remained stable (1.4% and 2.3%, respectively) during the same time period for both men and women. CONCLUSIONS: The prevalence of nickel has decreased among young females and males suspected of contact allergy in Southern Sweden after the introduction of the EU nickel directive. There has been no change in isolated palladium or cobalt allergy.

Menthol additives to tobacco products. Reasons for withdrawing mentholated cigarettes in European Union on 20th may 2020 according to tobacco products directive (2014/40/EU).

Menthol, which is a natural cyclic monoterpene alcohol with a minty smell, is one of the main constituents of essential oils that naturally occur in some aromatic plants, such as Mentha × piperita L. This natural compound shows many biological properties, such as anesthetic, analgesic, antibacterial and antifungal, immunomodulating, and skin penetration-enhancing. It is added to a variety of goods, such as food, oral-care products, OTC products, cosmetics, and tobacco products. Menthol is not just a simple flavoring agent, especially when it comes to tobacco products. Its ability to 'mask' the negative effects of nicotine and its additional positive sensory effects makes it the most common additive in such products. For the customers, mentholated tobacco products may be mistakenly perceived as less harmful for health, which may increase their consumption. However, as the evidence shows, menthol cigarettes are no safer than conventional cigarettes and may lead to more frequent disease exacerbation during prolonged exposure to smoke from such products. In addition, because of its complex interactions with nicotine, menthol may affect smoking behavior and may increase addiction to nicotine. For those reasons, the European Union banned flavored cigarettes (whose sale size reached more than 3% of the total tobacco product market) by implementing the Tobacco Products Directive (2014/40/EU) on 20th May 2020. While the menthol ban was based on health concerns, the ultimate effect on consumers, regarding potential quitting, is yet to be determined.

Are current EU policies on GMOs justified?

The European Court of Justice's recent ruling that the new techniques for crop development are to be considered as genetically modified organisms under the European Union's regulations exacerbates the need for a critical evaluation of those regulations. The paper analyzes the regulation from the perspective of moral and political philosophy. It considers whether influential arguments for restrictions of genetically modified organisms provide cogent justifications for the policies that are in place, in particular a pre-release authorization requirement, mandatory labelling, and de facto bans (in the form of withholding or opting out of authorizations). It is argued that arguments pertaining to risk can justify some form of pre-release authorization scheme, although not necessarily the current one, but that neither de facto bans nor mandatory labelling can be justified by reference to common arguments concerning naturalness, agricultural policy (in particular the promotion of organic farming), socio-economic effects, or consumers' right to choose.

Exploring the science, safety, and benefits of air care products: perspectives from the inaugural air care summit.

Seventy-one percent of US households purchase air care products. Air care products span a diverse range of forms, including scented aerosol sprays, pump sprays, diffusers, gels, candles, and plug-ins. These products are used to eliminate indoor malodors and to provide pleasant scent experiences. The use of air care products can lead to significant benefits as studies have shown that indoor malodor can cause adverse effects, negatively impacting quality of life, hygiene, and the monetary value of homes and cars, while disproportionately affecting lower income populations. Additionally, studies have also shown that scent can have positive benefits related to mood, stress reduction, and memory enhancement among others. Despite the positive benefits associated with air care products, negative consumer perceptions regarding the safety of air care products can be a barrier to their use. During the inaugural Air Care Summit, held on 18 May 2018 in the Washington, DC, metropolitan area, multidisciplinary experts including industry stakeholders, academics, and scientific and medical experts were invited to share and assess the existing data related to air care products, focusing on ingredient and product safety and the benefits of malodor removal and scent. At the Summit's completion, a panel of independent experts representing the fields of pulmonary medicine, medical and clinical toxicology, pediatric toxicology, basic science toxicology, occupational dermatology and experimental psychology convened to review the data presented, identify potential knowledge gaps, and suggest future research directions to further assess the safety and benefits of air care products.

Consumer protection provided by the European medical device and cosmetic legislation for condoms and lubricants.

Personal lubricants and lubricants used in condoms contain a number of ingredients which are also present in cosmetic products. These have to comply to the medical device regulation (745/2017) which should provide the same level of consumer protection, if not more, as foreseen in the legal framework of cosmetics (1223/2009). In the current study we developed an analytical method capable of identifying and quantifying 15 ingredients, commonly found in lubricants and cosmetics. Based upon their most important toxicological endpoint, the substances involved were grouped in three toxicological classes provoking either irritation, contact allergic dermatitis or systemic toxicity. The method was applied on 30 condoms and 54 personal lubricants present on the EU market. Their safety was assessed using the same reasoning as commonly applied for cosmetic ingredients. Higher mucosae susceptibility, the main exposed area for lubricants, was taken into account in this assessment. The results show that the majority of the products studied are safe. Nevertheless, for some products the safety could not be confirmed. The results also highlight the fact that there is no consensus for a number of ingredients, used as well in cosmetics as in medical devices. Alignment between both legislations would improve the safety of these products and further raise the general level of consumer protection.

Sunscreen bans: Coral reefs and skin cancer.

WHAT IS KNOWN AND OBJECTIVE: Hawaii will ban two major ingredients of sunscreens. This article reviews the reasons and future directions. Hawaii recently enacted legislation that will ban the use of two major ingredients of the majority of commonly used sunscreens. The reason for the ban is the ingredients' putative deleterious impact on marine ecosystems, particularly coral reefs. But sunscreens also save lives by decreasing the risk of UV-induced skin cancers. We review both sides of the issue and potential implications for the healthcare system. COMMENT: Coral reefs consist of organisms in delicate equilibria that are susceptible to small changes in their surroundings. Recent natural and man-made disruptions, direct or indirect, such as changes in ocean temperature and chemistry, ingress of invasive species, pathogens, pollution and deleterious fishing practices, have been blamed for the poor health, or even the outright destruction, of some coral reefs. The most popular sunscreen products contain two ingredients-oxybenzone and octinoxate-that have also been implicated in coral toxicity and will be banned. This creates a healthcare dilemma: Will the protection of coral reefs result in an increase in human skin cancers? WHAT IS NEW AND CONCLUSION: Concentration estimates and mechanism studies support an association-direct or indirect (via promotion of viral infection)-of sunscreens with bleaching of coral reefs. A ban on the two most common sunscreen ingredients goes into effect in Hawaii on January 1, 2021. Proponents suggest that this is a trend, just the first of many such bans worldwide; opponents warn of a dire increase in human skin cancers. As a result, alternative sunscreen compounds are being sought.

Ocular Cosmetics: Public Safety Problem or Harmless Products?

PURPOSE: This perspective explores the safety profile of ocular cosmetics and explores the role ophthalmologists can play in mitigating potential ocular harm from unsafe products. METHODS: N/A. RESULTS: Cosmetics and personal care products represent a large industry that is currently unregulated in any meaningful way. Products intended for use around the eyes carry a risk of serious side effects including contact dermatitis and bacterial infection. Currently, legislation has been proposed to change regulation to provide more meaningful oversight of cosmetics. CONCLUSIONS: Ophthalmologists are often the first to recognize patterns in harmful products intended for use around the eye and can help mitigate potential future ocular harm by reporting adverse events to the Food and Drug Administration and by advocating for cosmetic regulation change.

Review of emerging concepts in nanotoxicology: opportunities and challenges for safer nanomaterial design.

Nanotoxicology and nanosafety has been a topic of intensive research for about more than 20 years. Nearly 10 000 research papers have been published on the topic, yet there exists a gap in terms of understanding and ways to harmonize nanorisk assessment. In this review, we revisit critically ignored parameters of nanoscale materials (e.g. band gap factor, phase instability and silver leaching problem, defect and instability plasmonic versus inorganic particles) versus their biological counterparts (cell batch-to-batch heterogeneity, biological barrier model design, cellular functional characteristics) which yield variability and nonuniformity in results. We also emphasize system biology approaches to integrate the high throughput screening methods coupled with in vivo and in silico modeling to ensure quality in nanosafety research. We emphasize and highlight the recommendation regarding bridging the mechanistic gaps in fundamental research and predictive biological response in nanotoxicology. The research community has to develop visions to predict the unforeseen problems that do not exist yet in context with nanotoxicity and public health hazards due to the burgeoning use of nanomaterial in consumer's product.

Eating out with a food allergy in the UK: Change in the eating out practices of consumers with food allergy following introduction of allergen information legislation.

BACKGROUND: Strict allergen avoidance is important in day-to-day management of food allergy and avoidance when eating outside the home can present particular difficulties. EU legislation (EU FIC) introduced in December 2014 aimed to improve food allergen information provision for customers by requiring retailers of non-prepacked foods to provide information related to the content of one or more of 14 specified food allergens within their foods. OBJECTIVES: To investigate the impact of EU FIC on the behaviours, experiences and attitudes of consumers with food allergy when eating out. METHODS: As part of longitudinal research, participants with food allergy from across the UK took part in either (A) pre and post legislation in-depth interviews, or (B) pre and post legislation surveys. In-depth interviews were carried out with 28 participants pre and post legislation and analysed using the framework approach. Self-report surveys were completed by 129 participants pre and post legislation, and responses were subject to quantitative analyses. RESULTS: Improvements in allergen information provision and raised awareness of food allergy in eating out venues were reported following introduction of EU FIC. Whilst participants favoured written allergen information, they expressed greater confidence in communicating with eating out staff and in trusting the allergen information that they provided. Improvements were judged to be gradual, sporadic or inconsistent in implementation. CONCLUSION & CLINICAL RELEVANCE: For many participants, the "ideal" eating out experience was one in which a range of information resources were available and where written allergen information was complemented by proactive and accommodating staff within an allergy-aware environment. Whilst the onus is on legislators and food providers to ensure that adequate allergen information is provided, clinicians play an important role in encouraging patients with food allergy to pursue their legal right to make allergen enquiries to avoid accidental allergen ingestion when eating out.

Are fire safe cigarettes actually fire safe? Evidence from changes in US state laws.

OBJECTIVE: To estimate the effects of fire safe cigarette laws on fire mortality and cigarette-related fires in the USA. METHODS: We examined the gradual implementation of the laws to identify their average effects, using difference-in-differences analysis to account for common year effects, time-invariant state effects, state-specific trends and observable time-varying state-level covariates. RESULTS: We found no statistically significant effects on all-cause fire mortality, residential fire mortality or cigarette-caused fire rates. The estimates for cigarette-caused fire deaths were significant under some specifications, but were not robust to the inclusion of state-specific trends or comparisons to effects on other cause-determined fires. CONCLUSIONS: Given the mixed state of our results, we conclude that previous claims regarding the effects of fire safe cigarette laws may be premature.

The effects of the lower ignition propensity cigarettes standard in Estonia: time-series analysis.

BACKGROUND: In 2011, the lower ignition propensity (LIP) standard for cigarettes was implemented in the European Union. Evidence about the impact of that safety measure is scarce. OBJECTIVE: The aim of this paper is to examine the effects of the LIP standard on fire safety in Estonia. METHODS: The absolute level of smoking-related fire incidents and related deaths was modelled using dynamic time-series regression analysis. The data about house fire incidents for the 2007-2013 period were obtained from the Estonian Rescue Board. RESULTS: Implementation of the LIP standard has reduced the monthly level of smoking-related fires by 6.2 (p<0.01, SE=1.95) incidents and by 26% (p<0.01, SE=9%) when estimated on the log scale. Slightly weaker evidence was found about the fatality reduction effects of the LIP regulation. All results were confirmed through counterfactual models for non-smoking-related fire incidents and deaths. CONCLUSIONS: This paper indicates that implementation of the LIP cigarettes standard has improved fire safety in Estonia.

Surveillance of paediatric exposures to liquid laundry detergent pods in Italy.

OBJECTIVE: To analyse paediatric exposures to pod and traditional laundry detergents in Italy and changes in exposure trends. METHODS: Analyses of a series of patients aged <5 years and exposed to laundry detergents between September 2010 and June 2015, identified by the National Poison Control in Milan. RESULTS: In comparison with patients exposed to traditional laundry detergents (n=1150), a higher proportion of those exposed to pods (n=1649) were managed in hospital (68% vs 42%), had clinical effects (75% vs 22%) and moderate/high severity outcomes (13% vs <1%). Exposure rates were stable over time for traditional detergents (average 0.65 cases/day), but an abrupt decline in major company pods was seen in December 2012, 4 months after the introduction of opaque outer packaging (from 1.03 to 0.36 cases/day and from 1.88 to 0.86 cases/million units sold). The odds of clinical effects was higher for exposure to pods than for traditional detergents (OR=10.8; 95% CI 9.0 to 12.9). Among patients exposed to pods, the odds of moderate/high severity outcomes was four times higher for children aged <1 years than for the other age groups (OR=3.9; 95% CI 2.2 to 7.0). Ten children exposed to laundry detergent pods had high severity outcomes while no children exposed to traditional laundry detergents developed high severity effects. CONCLUSIONS: The study confirms that exposure to laundry detergent pods is more dangerous than exposure to traditional detergents. In Italy, 4 months after the introduction of opaque outer packaging by a major company, product-specific exposure rates decreased sharply, suggesting that reducing visibility of laundry detergent pods may be an effective preventive measure. Further efforts are needed to improve safety.