Safety assessment of Paeonia lactiflora root extract for a cosmetic ingredient employing the threshold of toxicological concern (TTC) approach.

Botanical extracts, widely used in cosmetics, pose a challenge to safety assessment due to their complex compositions. The threshold of toxicological concern (TTC) approach, offering a safe exposure level for cosmetic ingredients, proves to be a promising solution for ensuring the safety of cosmetic ingredients with low exposure level. We assessed the safety of Paeonia lactiflora root extract (PLR), commonly used in skin conditioning products, with the TTC. We identified 50 constituents of PLR extract from the USDA database and literature exploration. Concentration of each constituent of PLR extract was determined with the information from USDA references, literature, and experimental analysis. The genotoxicity of PLR and its constituents was assessed in vitro and in silico respectively. Cramer class of the constituents of the PLR extract was determined with Toxtree 3.1 extended decision tree using ChemTunes®. Systemic exposure of each constituent from leave-on type cosmetic products containing PLR at a 1% concentration was estimated and compared with respective TTC threshold. Two constituents exceeding TTC threshold were further analyzed for dermal absorption using in silico tools, which confirmed the safety of PLR extract in cosmetics. Collectively, we demonstrated that the TTC is a useful tool for assessing botanical extract safety in cosmetics.

Comparing closure compliance and ease of use for consumer product packs designed to reduce access to children.

Child impeding packs are difficult for children to open so protect them from unintended access to hazardous contents inside the pack. However, if packs are difficult for adults to open, in normal usage scenarios, this may result in a higher occurrence of packs being left open. This research explores differences in ease of usage and closure compliance between two types of child impeding packs of liquid laundry detergent capsules. The two packs, "Pinch & Lift" and "Press & Lift", had different opening and closing mechanisms. "Press & Lift" also included an audible "click" signal to confirm complete closure to the user. The research was performed across two studies. In both studies, the packs were used in participants' homes according to their usual storage and usage practices as replacements to their current liquid laundry detergent capsule pack. All participants had small children living with them in their household. In Study 1, self-reported closure and ease of use data was collected from 99 adult participants in Germany. They used each package in their home for 10 days. Study 2 extended Study 1 by measuring closure rates with an objective assessment using in pack sensors for a 10-day period for each pack. Self-reported closure and ease of use data were also collected. Study 2 was conducted with 87 participants in the United Kingdom. Results across both studies showed "Press & Lift" with the audible "Click" close signal to be rated by participants to be significantly easier to open and close and have a higher self-reported closure rate than "Pinch & Lift". In addition, Study 2 results demonstrated higher closure rates using "Press & Lift" based on the sensor-measured closure compliance. Together, the results suggest transition to a pack with a mechanism that is child impeding and easier for an adult to use with an audible closure signal, like the "Press & Lift" system, has potential to reduce child access to a capsule from a pack by reducing the likelihood of the pack being left open by the adult user. Ultimately, such packs could protect children from potential poisoning injury across a range of consumer products.

A Hazard-Based Framework for Identifying Safer Alternatives to Classes of Chemicals: A Case Study on Phthalates in Consumer Products.

BACKGROUND: Humans are exposed to hazardous chemicals found in consumer products. In 2019, the Pollution Prevention for Healthy People and Puget Sound Act was passed in Washington State. This law is meant to reduce hazardous chemicals in consumer products and protect human health and the environment. The law directs the Washington State Department of Ecology to assess chemicals and chemical classes found in products, determine whether there are safer alternatives, and make regulatory determinations. OBJECTIVES: To implement the law, the Department of Ecology developed a hazard-based framework for identifying safer alternatives to classes of chemicals. METHODS: We developed a hazard-based framework, termed the "Criteria for Safer," to set a transparent bar for determining whether new chemical alternatives are safer than existing classes of chemicals. Our "Criteria for Safer" is a framework that builds on existing hazard assessment methodologies and published approaches for assessing chemicals and chemical classes. DISCUSSION: We describe implementation of our criteria using a case study on the phthalates chemical class in two categories of consumer products: vinyl flooring and fragrances used in personal care and beauty products. Additional context and considerations that guided our decision-making process are also discussed, as well as benefits and limitations of our approach. This paper gives insight into our development and implementation of a hazard-based framework to address classes of chemicals in consumer products and will aid others working to build and employ similar approaches. https://doi.org/10.1289/EHP13549.

Evaluating the Safety of Sous-Vide Cooking for Beef Products Inoculated with Single Strains of Salmonella enterica and Escherichia coli O157.

Sous-videcooking is a growing trend among retailers and consumers. Foodborne pathogens may survive the cooking if nonvalidated parameters are used or if pathogens have enhanced thermalresistance. Pathogen inactivation from sous-vide cooking was determined when introduced directly to beef products or via contaminated spices, and with or without a finishing step. Beef products (ground beef, tenderized, and nontenderized steaks) were inoculated with pathogens (Salmonella Montevideo and Escherichia coli O157:NM) in three ways: 1) directly onto the meat 2) ground black pepper incorporated into the recipe 3) ground pepper equilibrated at 30% RH (4 d) prior to incorporation. Beef samples were vacuum-packaged and submerged in a 62.5°C water bath for 120 min. Samples were sampled at 5, 10, 20, and 120 min (recommended from a partner quality study), and a duplicate was grilled to a specific internal temperature (74°C for ground beef, 57°C for steaks) and sampled. Sous-vide cooking reduced pathogen populations by >5 log CFU/g after most treatment times, but less than grilled counterparts (ca. 1-2 log CFU/g difference; p < 0.05).There were no statistically significant differences between inoculation methods, but the tenderization of steaks resulted in significantly lower reductions of pathogens from sous-vide cooking (p < 0.05). Thisresearch challenged sous-vide cooking parameters (120 min, 62.5°C). It showed sous-vide alone lowered pathogens by >4 log CFU/g after most 20-min treatments, but 120-min sous-vide treatments or grilling would be needed for >5-log reductions.Contaminated pepper led to less consistent reductions during the cooking process, yet 2-h sous-vide still achieved a 5-log reduction. Sous-vide cooking instructions must be validated as more products and recipes are marketed.

Bootstrapping for Estimating the Conservative Kill Ratio of the Surrogate to the Pathogen for Use in Thermal Process Validation at the Industrial Scale.

A surrogate is commonly used for process validations. The industry often uses the target log cycle reduction for the test (LCRTest) microorganism (surrogate) to be equal to the desired log cycle reduction for the target (LCRTarget) microorganism (pathogen). When the surrogate is too conservative with far greater resistance than the pathogen, the food may be overprocessed with quality and cost consequences. In aseptic processing, the Institute for Thermal Processing Specialists recommends using relative resistance (DTarget)/(DTest) to calculate LCRTest (product of LCRTarget and relative resistance). This method uses the mean values of DTarget and DTest and does not consider the estimating variability. We defined kill ratio (KR) as the inverse of relative resistance.The industry uses an extremely conservative KR of 1 in the validation of food processes for low-moisture foods, which ensures an adequate reduction of LCRTest, but can result in quality degradation. This study suggests an approach based on bootstrap sampling to determine conservative KR, leading to practical recommendations considering experimental and biological variability in food matrices. Previously collected thermal inactivation kinetics data of Salmonella spp. (target organism) and Enterococcus faecium (test organism) in Non-Fat Dried Milk (NFDM) and Whole Milk Powder (WMP) at 85, 90, and 95°C were used to calculate the mean KR. Bootstrapping was performed on mean inactivation rates to get a distribution of 1000 bootstrap KR values for each of the treatments. Based on minimum temperatures used in the industrial process and acceptable level of risk (e.g., 1, 5, or 10% of samples that would not achieve LCRTest), a conservative KR value can be estimated. Consistently, KR increased with temperature and KR for WMP was higher than NFDM. Food industries may use this framework based on the minimum processing temperature and acceptable level of risk for process validations to minimize quality degradation.

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.

Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?"

Cigarette smoking is positively and robustly associated with cardiovascular disease (CVD), including hypertension, atherosclerosis, cardiac arrhythmias, stroke, thromboembolism, myocardial infarctions, and heart failure. However, after more than a decade of ENDS presence in the U.S. marketplace, uncertainty persists regarding the long-term health consequences of ENDS use for CVD. New approach methods (NAMs) in the field of toxicology are being developed to enhance rapid prediction of human health hazards. Recent technical advances can now consider impact of biological factors such as sex and race/ethnicity, permitting application of NAMs findings to health equity and environmental justice issues. This has been the case for hazard assessments of drugs and environmental chemicals in areas such as cardiovascular, respiratory, and developmental toxicity. Despite these advances, a shortage of widely accepted methodologies to predict the impact of ENDS use on human health slows the application of regulatory oversight and the protection of public health. Minimizing the time between the emergence of risk (e.g., ENDS use) and the administration of well-founded regulatory policy requires thoughtful consideration of the currently available sources of data, their applicability to the prediction of health outcomes, and whether these available data streams are enough to support an actionable decision. This challenge forms the basis of this white paper on how best to reveal potential toxicities of ENDS use in the human cardiovascular system-a primary target of conventional tobacco smoking. We identify current approaches used to evaluate the impacts of tobacco on cardiovascular health, in particular emerging techniques that replace, reduce, and refine slower and more costly animal models with NAMs platforms that can be applied to tobacco regulatory science. The limitations of these emerging platforms are addressed, and systems biology approaches to close the knowledge gap between traditional models and NAMs are proposed. It is hoped that these suggestions and their adoption within the greater scientific community will result in fresh data streams that will support and enhance the scientific evaluation and subsequent decision-making of tobacco regulatory agencies worldwide.

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.

New Approach Methodologies (NAMs) for ad hoc human health risk assessment of food and non-food products - Proceedings of a workshop.

RIVM convened a workshop on the use of New Approach Methodologies (NAMs) for the ad hoc human health risk assessment of food and non-food products. Central to the workshop were two case studies of marketed products with a potential health concern: the botanical Tabernanthe iboga which is used to facilitate mental or spiritual insight or to (illegally) treat drug addiction and is associated with cardiotoxicity, and dermal creams containing female sex hormones, intended for use by perimenopausal women to reduce menopause symptoms without medical supervision. The workshop participants recognized that data from NAM approaches added valuable information for the ad hoc risk assessment of these products, although the available approaches were inadequate to derive health-based guidance values. Recommendations were provided on how to further enhance and implement NAM approaches in regulatory risk assessment, specifying both scientific and technical aspects as well as stakeholder engagement aspects.

Safety Assessment of Alkane Diols as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 alkane diol ingredients as used in cosmetics. The alkane diols are structurally related to each other as small diols, and most are reported to function in cosmetics as solvents. The Panel reviewed the relevant data for these ingredients, and concluded that seven alkane diols are safe in cosmetics in the present practices of use and concentration described in this safety assessment, but that the available data are insufficient to make a determination of safety for three ingredients, namely 1,4-Butanediol, 2,3-Butanediol, and Octanediol.

Detailed aggregate exposure analysis shows that exposure to fragrance ingredients in consumer products is low: Many orders of magnitude below thresholds of concern.

The Research Institute for Fragrance Materials (RIFM) and Creme Global Cremeglobal.com partnered to develop an aggregate exposure model for fragrance ingredients. The model provides a realistic estimate of the total exposure of fragrance ingredients to individuals across a population. The Threshold of Toxicological Concern (TTC) and Dermal Sensitization Threshold (DST) were used to demonstrate the magnitude of low exposure to fragrance materials. The total chronic systemic, inhalation, and dermal 95th percentile exposures on approximately 3000 fragrance ingredients in RIFM's inventory were compared to their respective TTC or DST. Additionally, representative fragrance ingredients were randomly selected and analyzed for exposure distribution by product type (i.e., cosmetic/personal care, household care, oral care, and air care) and route of exposure. It was found that 76 % of fragrance ingredients fall below their respective TTC limits when compared to 95th percentile systemic exposure, while 99 % are below inhalation TTC limits. The lowest 95th percentile aggregate exposure by product type was from household care products, then air care, and oral care products. The highest exposure was from personal care/cosmetic products. The volume of use for most fragrance ingredients (63 %) was <1 metric ton, estimating that environmental exposure to fragrance ingredients is likely low.

Safety Assessment of Zinc Salts as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 27 inorganic and organometallic zinc salts as used in cosmetic formulations; these salts are specifically of the 2+ (II) oxidation state cation of zinc. These ingredients included in this report have various reported functions in cosmetics, including hair conditioning agents, skin conditioning agents, cosmetic astringents, cosmetic biocides, preservatives, oral care agents, buffering agents, bulking agents, chelating agents, and viscosity increasing agents. The Panel reviewed the relevant data for these ingredients, and concluded that these 27 ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.

Opportunities in Assessing and Regulating Organohalogen Flame Retardants (OFRs) as a Class in Consumer Products.

BACKGROUND: In 2015, the U.S. Consumer Product Safety Commission (CPSC) received and then, in 2017, granted a petition under the Federal Hazardous Substances Act to declare certain groups of consumer products as banned hazardous substances if they contain nonpolymeric, additive organohalogen flame retardants (OFRs). The petitioners asked the CPSC to regulate OFRs as a single chemical class with similar health effects. The CPSC later sponsored a National Academy of Sciences, Engineering, and Medicine (NASEM) report in 2019, which ultimately identified 161 OFRs and grouped them into 14 subclasses based on chemical structural similarity. In 2021, a follow-up discussion was held among a group of scientists from both inside and outside of the CPSC for current research on OFRs and to promote collaboration that could increase public awareness of CPSC work and support the class-based approach for the CPSC's required risk assessment of OFRs. OBJECTIVES: Given the extensive data collected to date, there is a need to synthesize what is known about OFR and how class-based regulations have previously managed this information. This commentary discusses both OFR exposure and OFR toxicity and fills some gaps for OFR exposure that were not within the scope of the NASEM report. The objective of this commentary is therefore to provide an overview of the OFR research presented at SOT 2021, explore opportunities and challenges associated with OFR risk assessment, and inform CPSC's work on an OFR class-based approach. DISCUSSION: A class-based approach for regulating OFRs can be successful. Expanding the use of read-across and the use of New Approach Methodologies (NAMs) in assessing and regulating existing chemicals was considered as a necessary part of the class-based process. Recommendations for OFR class-based risk assessment include the need to balance fire and chemical safety and to protect vulnerable populations, including children and pregnant women. The authors also suggest the CPSC should consider global, federal, and state OFR regulations. The lack of data or lack of concordance in toxicity data could present significant hurdles for some OFR subclasses. The potential for cumulative risks within or between subclasses, OFR mixtures, and metabolites common to more than one OFR all add extra complexity for class-based risk assessment. This commentary discusses scientific and regulatory challenges for a class-based approach suggested by NASEM. This commentary is offered as a resource for anyone performing class-based assessments and to provide potential collaboration opportunities for OFR stakeholders. https://doi.org/10.1289/EHP12725.

Temperature status of domestic refrigerators and its effect on the risk of listeriosis from ready-to-eat (RTE) cooked meat products.

Inadequate domestic refrigeration is frequently cited as a factor that contributes to foodborne poisoning and infection, and consumer behaviour in this regard can vary largely. This study provides insight into the temperature profiles of domestic refrigerators in the Netherlands and the impact on the number of listeriosis cases related to ready-to-eat (RTE) cooked meat products. A survey was conducted among Dutch consumers (n = 1020) to assess their knowledge and behaviour related to refrigerators. Out of these participants, 534 measured their refrigerator's temperature, revealing an average temperature of 5.7 °C (standard deviation (SD) of 2.2 °C) with a maximum of 17 °C. Elderly people (65 years and older) had refrigerators with temperatures that were on average 0.6 °C higher than those of younger people (35 years or younger). The 24-hour temperature profiles of an additional set of actively surveyed refrigerators (n = 50) showed that the temperature measured on the upper shelf was significantly higher (mean 7.7 °C, SD 2.7 °C) than the temperature measured on the bottom shelf (5.7 °C, SD 2.1 °C). Quantitative Microbiological Risk Assessment (QMRA) predicted that the primary factors contributing to the risk of listeriosis were the initial concentration and the time and temperature during household storage. Scenario analysis revealed that storing opened RTE cooked meat products at home for either <7 days or at temperatures <7 °C resulted in a significant reduction of over 80 % in predicted illness cases. Among all illness cases, the elderly represented nearly 90 %. When assessing the impact of the disease in terms of Years of Life Lost (YLL), the contribution of the elderly was 59 %. Targeted communication, particularly directed towards the elderly, on the importance of storing RTE cooked meat products at the recommended temperature on the bottom or middle shelf as well as consuming within two to three days after opening, holds the potential to significantly reduce the number of cases.

Safety Assessment of Butyrospermum parkii (Shea)-Derived Ingredients as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 13 Butyrospermum parkii (shea)-derived ingredients, which are most frequently reported to function in cosmetics as skin and hair conditioning agents. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. Industry should use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel concluded that these ingredients are safe in the present practices of use and concentration when formulated to be non-sensitizing.