Evaluating the Impact of Hair Care Product Exposure on Hair Follicle and Scalp Health.

Human hair follicles traverse the epidermis and dermis, and are comprised of specialised cells including dermal papilla cells (DPCs). DPCs play a critical role in the development and growth of both hair and follicle structure. While exposure of DPCs to undiluted exogenous compounds is unlikely, exposure to diluted compounds is possible should dermal penetration occur. The goal of this study was to evaluate the impact on hair and scalp health following application of a hair care product. Due to the lack of standardised and validated test systems for evaluating hair follicle health, the HairSkin® model, which uses intact human scalp samples, was adapted to evaluate hair follicle and scalp health. Similarly, the Franz diffusion cell assay and matrix-assisted laser desorption ionisation-Fourier transform ion cyclotron resonance (MALDI-FTICR) were adapted to evaluate dermal penetration. The results of this study demonstrate that application of the hair care product does not result in appreciable dermal penetration, suggesting that DPCs are unlikely to be exposed to undiluted product. Additionally, hair follicle health was not impacted following product application. While this study is exploratory, these results suggest that the combination of test systems utilised herein provides valuable insight and warrants further development and validation.

Quantitative Risk Assessment of Dermal Sensitization Potential Following Use of Shampoo Products Containing the Formaldehyde Releasing Preservative DMDM Hydantoin.

Historically, formaldehyde was used as a preservative in personal care products to extend product shelf-life; however, given its skin sensitization potential it has been phased out of use and replaced with formaldehyde-releasing preservatives, such as Dimethyloldimethyl hydantoin (DMDMH). A relationship has been established between positive patch test results following exposure to DMDMH and previous sensitization to formaldehyde. Upon direct contact with the skin, formaldehyde can react with skin proteins and cause an acute inflammatory reaction, which may progress to skin sensitization following repeated exposure. This quantitative risk assessment (QRA) aimed to assess the risk of skin sensitization induction following use of shampoo products containing the maximum allowable concentrations of DMDMH in formulation (1% w/v), translating to a free formaldehyde concentration of 0.02%. To determine a margin of safety (MOS) for exposure to DMDMH from use of shampoo products, consumer exposure levels (CEL) were estimated based on typical use scenarios and then benchmarked against an acceptable exposure level (AEL). The AEL was derived using a weight of evidence approach where a range of no expected sensitization induction levels (NESILs) was utilized. The MOS values for a shampoo product containing 1% DMDMH (.02% formaldehyde) was above 1 for the typical use scenario indicating a low likelihood of skin sensitization induction among healthy individuals. Thus, it can be concluded that shampoo products containing DMDMH at or below current allowable concentrations are not expected to increase the risk of skin sensitization induction.

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).

Estimating inhalation bioavailability for peptides and proteins 1 to 10 kDa in size.

Inhalation is a critical route for occupational exposure. To protect workers from adverse effects, health-based exposure limits (HBELs) are derived using chemical-specific information including inhalation bioavailability. Inhalation bioavailability of large proteins is well studied and generally accepted to be 1% or less. However, the inhalation bioavailability of peptides and proteins 1-10 kDa in size is not well defined. The goal of this study was to expand upon previous analyses and evaluate the inhalation bioavailability of small peptides. Inhalation bioavailability data for 72 peptides and protein samples ranging from 1.1 to 10.9 kDa in size were evaluated. The median inhalation bioavailability was 20%, which is in agreement with previously published analyses. Inhalation bioavailabilities for the vast majority were below 50%. Interestingly, species, peptide size, and peptide identity did not correlate with inhalation bioavailability. Other factors including inhalation dosimetry, peptide degradation, and chemical characteristics also decrease the amount of peptide available for absorption. Together, the median bioavailability of 20% is likely an appropriate estimate of systemic exposure and is sufficiently protective in most cases for the purposes of occupational exposure safety. Thus, in the absence of peptide-specific data or concerns, an inhalation bioavailability default of 20% is recommended for 1-10 kDa peptide and proteins.

Evaluation of chemicals leached from PET and recycled PET containers into beverages.

The use of recycled polyethylene terephthalate (rPET) containers, a recent shift in the beverage industry, poses new potential human health concerns including contamination from the original container; use of additives, detergents, and catalysts during recycling; and improper recycling practices. The purpose of this analysis was to evaluate available data regarding: (1) chemicals leached from PET and rPET in bottle form; (2) concentration of these chemicals; and (3) trends between rPET percent and concentration of chemicals leached. This analysis identified 211 scientific articles related to recycled plastic and leachables. Three articles met the inclusion criteria: (1) plastic was in bottle form; (2) plastic was made of PET or rPET; and (3) the study analyzed both PET and rPET using the same methods. This evaluation demonstrated that only nine compounds - benzene, styrene, acetaldehyde, 2-methyl-1,3-dioxolane, furan, bisphenol A (BPA), 2-buta-none, acetone, and limonene - have been studied. Notably, the leachable concentration of benzene, styrene, and BPA increased as the percent of recycled content increased from 0 to 100%. However, 2-methyl-1,3-dioxolane and furan implied a reverse trend, where the leachable concentration decreased as the percent of recycled content increased from 0 to 100%. The concentrations of 2-butanone, acetone, and limonene did not follow any suggested trend. Evidently, recycling PET can lead to changes in the leachables profile. This analysis further identified key areas of research, including testing a variety of liquid types, that need to be addressed to adequately conduct a human health risk assessment.

Setting impurity limits for endogenous substances: Recommendations for a harmonized procedure and an example using fatty acids.

Endogenous substances, such as fatty, amino, and nucleic acids, are often purposefully used in parenterally pharmaceuticals, but may be present as impurities. Currently, no consensus guidance exists on setting impurity limits for these substances. Specific procedures are needed, as the amount and types of toxicity data available for endogenous substances are typically far less than those for other chemical impurities. Additionally, the parenteral route of administration of these substances is inherently non-physiological, resulting in potentially different or increased severity of toxicity. Risk Assessment Process Maps (RAPMAPs) are proposed as a model to facilitate the development of health-based exposure limits (HBELs) for endogenous substances. This yielded a framework that was applied to derive HBELs for several fatty acids commonly used in parenteral pharmaceuticals. This approach was used to derive HBELs with further vetting based on anticipated perturbations in physiological serum levels, impacts of dose-rate, and consideration of intermittent dosing. Parenteral HBELs of 100-500 mg/day were generated for several fatty acids, and a proposed class-based limit of 50 mg/day to be used in the absence of chemical-specific data. This default limit is consistent with the low toxicity of this chemical class and ICH Q3C value for Class 3 solvents.

The utility of hERG channel inhibition data in the derivation of occupational exposure limits.

Inhibition of the human ether-à-go-go (hERG) channel may lead to QT prolongation and fatal arrhythmia. While pharmaceutical drug candidates that exhibit potent hERG channel inhibition often fail early in development, many drugs with both cardiac and non-cardiac indications proceed to market. In this study, the relationship between in vitro hERG channel inhibition and published occupational exposure limit (OEL) was evaluated. A total of 23 cardiac drugs and 44 drugs with non-cardiac indications with published hERG channel IC50 and published OELs were identified. There was an apparent relationship between hERG IC50 potency and the OEL for cardiac and non-cardiac drugs. Twenty cardiac and non-cardiac drugs were identified that had a potent hERG IC50 (≤25 µM) and a contrastingly large OEL value (≥100 µg/m3). OELs or hazard banding corresponding to ≤100 µg/m3 should be sufficiently protective of effects following occupational exposure to the majority of APIs with hERG IC50 values ≤ 100 µM. It is important to consider hERG IC50 values and possible cardiac effects when deriving OEL values for drugs, regardless of indication. These considerations may be particularly important early in the drug development process for establishing exposure control bands for drugs that do not yet have full clinical safety data.

3-Hydroxyisobutyric acid dehydrogenase deficiency: Expanding the clinical spectrum and quantitation of D- and L-3-Hydroxyisobutyric acid by an LC-MS/MS method.

A deficiency of 3-hydroxyisobutyric acid dehydrogenase (HIBADH) has been recently identified as a cause of primary 3-hydroxyisobutyric aciduria in two siblings; the only previously recognized primary cause had been a deficiency of methylmalonic semialdehyde dehydrogenase, the enzyme that is immediately downstream of HIBADH in the valine catabolic pathway and is encoded by the ALDH6A1 gene. Here we report on three additional patients from two unrelated families who present with marked and persistent elevations of urine L-3-hydroxyisobutyric acid (L-3HIBA) and a range of clinical findings. Molecular genetic analyses revealed novel, homozygous variants in the HIBADH gene that are private within each family. Evidence for pathogenicity of the identified variants is presented, including enzymatic deficiency of HIBADH in patient fibroblasts. This report describes new variants in HIBADH as an underlying cause of primary 3-hydroxyisobutyric aciduria and expands the clinical spectrum of this recently identified inborn error of valine metabolism. Additionally, we describe a quantitative method for the measurement of D- and L-3HIBA in plasma and urine and present the results of a valine restriction therapy in one of the patients.

Active pharmaceutical contaminants in dietary supplements: A tier-based risk assessment approach.

The presence of active pharmaceutical ingredients (APIs) in adulterated or contaminated dietary supplements is a current product safety concern. Since there are limited guidelines, and no published consensus methods, we developed a tier-based framework incorporating typical lines of evidence for determining the human health risk associated with APIs in dietary supplements. Specifically, the tiered approach outlines hazard identification and decision to test for APIs in products based on criteria for likelihood of contamination or adulteration, and evaluation of manufacturer production standards. For products with detectable levels of APIs, a variety of default approaches, including the use of fraction of the therapeutic dose and the threshold of toxicological concern (TTC), as well as health-based exposure limits (HBELs) are applied. In order to demonstrate its practical use, as well as any limitations and/or special considerations, this framework was applied to five dietary supplements (currently available to the public). We found that the detected levels of APIs in some dietary supplements were above the recommended dose of the drugs, and thus, pose a significant health risk to consumers and potentially workers involved in manufacturing of these supplements. The results support the value of increased product quality surveillance and perhaps regulatory activity.

Derivation of an occupational exposure limit for ß-glucans.

ß-Glucans are abundant bacterial, yeast, and fungal cell wall polysaccharides that have been shown to activate the immune system. Establishment of an occupational exposure limit (OEL) for ß-glucan exposure is critical to the protection of worker health, as these exposures have been linked to immunosuppressive and inflammatory reactions and possibly the development of respiratory diseases. Detectable concentrations of ß-glucans have been identified in common occupational inhalation exposure scenarios, such as in the agricultural and waste management sectors. However, no published exposure benchmarks for inhalation of ß-glucans are available for workers or the general population. Thus, a health-based OEL for inhalation exposure of workers to ß-glucans was derived based on consideration of human and non-human effect data for this class of compounds and contemporary risk assessment methods. The weight of the evidence indicated that the available data in humans showed significant methodological limitations, such as lack of a representative study size, appropriate control population, and clear dose-response relationship. Thus, an OEL of 150 ng/m3 was derived for ß-glucans based on the most relevant nonclinical study. This OEL provides an input to the occupational risk assessment process, allows for comparisons to worker exposure, and can guide risk management and exposure control decisions.

An evaluation of the FDA adverse event reporting system and the potential for reporting bias.

BACKGROUND: The FDA maintains the Adverse Event Reporting System (CAERS) database, which contains product complaint reports for foods, dietary supplements, and cosmetics. Product line perception and subsequent adverse event reporting may be impacted by negative media attention. METHODS: The purpose of this analysis was to use the CAERS database to analyze temporal trends in adverse event reporting before and after media coverage of alleged health effects, using WEN by Chaz Dean (WCD) cleansing conditioners as a case study. WCD cleansing conditioner adverse event reports from January 2005 to December 2018 were abstracted from the CAERS database. Zero-inflated negative binomial regression models were used to analyze the rate of adverse events (WCD events/10,000 WCD cleansing conditioner units sold/month), adjusted for temporal trends in CAERS. RESULTS: There was a statistically significant higher rate of adverse event reporting after negative media coverage in December 2015 (IRR 16.71 [95% CI: 7.89-35.39]) when compared to the rate of adverse event reporting before December 2015. CONCLUSIONS: This analysis highlights the importance of assessing potential external factors, such as negative news media coverage, that may alter reporting behaviors due to societal shifts in product-specific risk perception. Consideration of these factors in post-market surveillance programs would result in more comprehensive safety evaluations.

Evaluation of potential gastrointestinal carcinogenicity associated with the ingestion of asbestos.

The inhalation of asbestos, depending on the fiber type and dose, may be associated with the development of mesothelioma and other asbestos-related diseases. However, little is known about the potential adverse effects associated with the ingestion of asbestos. Evidence of asbestos fibers released from asbestos-cement pipes used in water distribution systems has led to concerns of potentially contaminated drinking water. The purpose of this study is to determine whether ingestion of asbestos fibers may lead to cancerous effects on the gastrointestinal (GI) tract. Data from animal and human studies were analyzed using a weight-of-evidence approach to evaluate the potential risk of GI cancers associated with asbestos ingestion. Seventeen human and 23 animal studies were identified and evaluated in this study. Animal studies were conducted in multiple species with inconsistent dosing protocols. Overall, animal studies reported that the asbestos fibers, irrespective of fiber type and dose, failed to produce any definitive GI carcinogenic effect. The 17 identified human epidemiological studies reported the ingestion of asbestos-contaminated water with concentrations from 1 to 71,350 million fibers per liter (MFL). A majority of the epidemiology studies reported statistically significant increases in multiple GI-specific cancers. However, these findings are confounded due to several critical study limitations including flawed study design, small sample size, selection bias, lack of individual exposure history, lack of adequate latency, and the inability to account for confounders including occupational history, diet, and smoking history. Based on our weight-of-evidence assessment, there is insufficient evidence of causality between the ingestion of asbestos and an increased incidence of GI cancers.

An in vitro human assay for evaluating immunogenic and sensitization potential of a personal care and cosmetic product.

With the reduction or elimination of animal testing, manufacturers are left with limited options, as few robust in vitro tests are available and human studies are costly. Recently, concerns have been raised regarding potential adverse health effects associated with use of WEN by Chaz Dean (WCD) cleansing conditioners. The purpose of this study was to evaluate the immunogenic potential of a WCD hair cleansing conditioner by utilizing a novel in vitro human skin explant test. Peripheral blood mononuclear cells (PBMCs) and human skin biopsies were obtained from healthy volunteers. Monocyte derived dendritic cells (MoDCs) were generated, primed by 0.01% WCD cleansing conditioner exposure for 24 h, co-cultured with autologous lymphocytes for 4 days, and then cultured with skin biopsies for 3 days. The skin biopsies then underwent histopathological evaluation, and T cell proliferation and IFNγ levels were determined. Overall, this study showed that treatment with 0.01% WCD cleansing conditioner resulted in a negative prediction for in vivo immune response. Further, this analysis shows that the skin explant test is a viable alternative to animal testing for complex mixtures or commercially available products.

Hair dye and risk of skin sensitization induction: a product survey and quantitative risk assessment for para-phenylenediamine (PPD).

BACKGROUND: Para-Phenylenediamine (PPD) is a commonly used dye intermediate in permanent hair dye formulations, and exposure to PPD has been associated with allergic contact dermatitis at certain doses. PURPOSE: Determine the concentration of PPD in a survey of self-application permanent hair dye products, and perform a quantitative risk assessment to determine the risk of skin sensitization induction following application of these products. METHODS: Consumer exposure levels (CELs) to PPD following application of hair dye products were estimated using the maximum amount of hair dye that can adhere to the surface area of the scalp, the measured concentration of PPD in the hair dye product, a retention factor, the dermal absorption of PPD, and the surface area of the scalp. CELs were calculated for various exposure scenarios, and were stratified by hair dye shade. RESULTS: All estimated CELs did not exceed the acceptable exposure level. Specifically, margins of safety ranged from 2.3 to 1534 for black dyes, 2.9 to 5031 for brown dyes, and 26 to 5031 for blonde dyes. CONCLUSIONS: Findings suggest that use of the evaluated permanent hair dyes, under the evaluated exposure scenarios, would not be expected to induce skin sensitization due to PPD exposure at concentrations ≤0.67%.

Devising a Tier-based Skin Sensitisation Screening Strategy for Personal Care and Cosmetic Products.

Concerns regarding the use of potential skin sensitisers in personal care and cosmetic products continue to grow. The goal of this study was to develop a proof-of-concept tier-based screening strategy for the assessment of skin sensitisation potential by using non-animal methodologies. As a case example, this screening framework was applied to three WEN® by Chaz Dean cleansing conditioners. The first tier of testing utilised the Organisation for Economic Co-operation and Development (OECD) Quantitative Structure Activity Relationship Toolbox profiler to evaluate the skin sensitisation potential of individual ingredients within the formulation; a literature review was performed on the substances that generated in silico alerts. Tier 2 testing utilised the OECD in chemico Test Guideline (TG) 442C to evaluate these substances. Tier 3 testing adapted OECD TG442C to evaluate the formulated product. The literature review on the four substances that generated in silico alerts revealed that they were not sensitising at the concentrations reported in the formulated products. Tier 2 testing demonstrated that these substances were not sensitising at the concentrations tested. Finally, Tier 3 testing revealed that the evaluated cleansing conditioners had low mean percentage peptide depletion at the concentrations tested. Together, the results obtained suggest that the products tested are unlikely to induce skin sensitisation under the given experimental conditions. These findings are in agreement with other in vitro and clinical studies. The proposed tier-based testing approach may be used as a conceptual framework for the prospective safety screening of other personal care and cosmetic products. However, to establish the validity of the proposed testing strategy, further studies must be performed, including comparisons with established models.

PBPK modeling characterization of potential acute impairment effects from inhalation of ethanol during e-cigarette use.

Objective: Ethanol is used as a solvent for flavoring chemicals in some electronic cigarette (e-cigarette) liquids (e-liquids). However, there are limited data available regarding the effects of inhalation of ethanol on blood alcohol concentration (BAC) during e-cigarette use. In this study, a modified physiologically based pharmacokinetic (PBPK) model for inhalation of ethanol was used to estimate the BAC time-profile of e-cigarette users who puffed an e-liquid containing 23.5% ethanol. Materials and Methods: A modified PBPK model for inhalation of ethanol was developed. Use characteristics were estimated based on first-generation and second-generation e-cigarette topography parameters. Three representative use-case puffing profiles were modeled: a user that took many, short puffs; a typical user with intermediate puff counts and puff durations; and a user that took fewer, long puffs. Results and Discussion: The estimated peak BACs for these three user profiles were 0.22, 0.22, and 0.30 mg/L for first-generation devices, respectively, and 0.85, 0.58, and 0.34 mg/L for second-generation devices, respectively. Additionally, peak BACs for individual first-generation users with directly measured puffing parameters were estimated to range from 0.06 to 0.67 mg/L. None of the scenarios modeled predicted a peak BAC result that approached toxicological or regulatory thresholds that would be associated with physiological impairment (roughly 0.01% or 100 mg/L). Conclusions: The approach used in this study, combining a validated PBPK model for a toxicant with peer-reviewed topographical parameters, can serve as a screening-level exposure assessment useful for evaluation of the safety of e-liquid formulations. Abbreviations: BAC: blood alcohol concentration; e-cigarette: electronic cigarette; e-liquid: e-cigarette liquid or propylene glycol and/or vegetable glycerin-based liquid; HS-GC-FID: headspace gas chromatography with flame-ionization detection; HS-GC-MS: headspace gas chromatography-mass spectrometry; PBPK: physiologically based pharmacokinetic; Cair: puff concentration expressed as ppm; Cair,mass: ethanol air concentration expressed on a mass basis; Cv: ethanol concentration in the venous blood; ρ: density; EC: ethanol concentration in the liquid; PLC: liquid consumption per puff; PAV: air volume of the puff; Cair,mass: puff concentration expressed as ppm; MW: molecular weight; P: pressure; T: temperature; PK: pharmacokinetic.

Carnitine Profile Changes in Pediatric Hematopoietic Stem Cell Transplant: New Role for Carnitine?

Carnitine is an essential cofactor for mitochondrial import and oxidation of fatty acids. High-dose chemotherapy and radiation, often required for hematopoietic stem cell transplant (HSCT), leads to tissue damage, mitochondrial dysfunction, and alterations in carnitine metabolism. The aim of this pilot cohort study was to describe plasma and urinary carnitine profiles during pediatric HSCT and their relationships with clinical outcomes. Plasma and urinary carnitine samples were collected from 22 pediatric patients before and through day 180 post-HSCT. Associations were observed between graft-versus-host disease and an elevated plasma total carnitine (P=0.019), and also increased plasma acyl:free carnitine ratio with veno-occlusive disease (P=0.016). Mortality was observed in those with their highest urinary total carnitine losses on day 0 (P=0.005), and in those with an abnormal day 28 plasma ratio either above or below the reference range (P=0.007). Changes in carnitine profiles were more reflective of metabolic stress and negative outcomes than of inadequate dietary intake. Associations observed direct larger studies to assess the validity of carnitine profiles as a prognostic indicator and also to assess whether prophylactic carnitine supplementation pre-HSCT could reduce mitochondrial injury and urinary losses and help mitigate inflammatory and metabolic comorbidities of HSCT.

Skin Sensitization Induction Risk Assessment of Common Ingredients in Commercially Available Cleansing Conditioners.

BACKGROUND: An essential step in ensuring the toxicological safety of cosmetic or personal care products is the evaluation of the skin sensitizing potential of product ingredients. OBJECTIVE: We used a standardized protocol from cosmetic trade industry and consumer safety groups to evaluate the sensitization potential of ingredients in 3 commercially available cleansing conditioners. METHODS: A total of 33 ingredients were evaluated. Each ingredient underwent (1) dermatological evaluation, (2) in silico analysis for irritation and sensitization potential, and (3) a literature evaluation to determine risk of sensitization. Consumer exposure level was compared with the weight-of-evidence no-expected sensitization induction level for the constituent. If a no-expected sensitization induction level for a specific ingredient was not available, the dermal sensitization threshold approach was used. A margin of safety was calculated for each constituent. RESULTS: The margins of safety for all evaluated ingredients in the cleansing conditioners were greater than 1. CONCLUSIONS: This analysis indicates that exposure to the individual ingredients present in these cleansing conditioners would not be expected to induce dermal sensitization in a consumer under the examined exposure scenario.

Tier-based skin irritation testing of hair cleansing conditioners and their constituents.

Purpose/Aim: The U.S. Food and Drug Administration (FDA) does not require specific testing to demonstrate the safety of personal care and cosmetic products or their ingredients. Recently, there have been reports of skin irritation associated with the use of commercially available cleansing conditioners. The goal of this study was to implement a tier-based safety assessment to evaluate the skin irritation potential of six commercially available cleansing conditioners and their ingredients. MATERIALS AND METHODS: The first tier of testing utilized the Organization for Economic Co-operation and Development (OECD) QSAR Toolbox to perform an in silico evaluation of the skin irritation potential of the product ingredients, and the second tier of testing utilized an OECD in vitro guideline test to evaluate the skin irritation potential of each product. RESULTS: Thirty-two ingredients were evaluated using the OECD QSAR Toolbox profiler for the tier one analysis; nine ingredients received a structural alert for skin irritation/corrosion. In the tier two in vitro analysis, the evaluated cleansing conditioner products were all classified as non-irritants. CONCLUSIONS: These results provide evidence that use of the evaluated commercially available cleansing conditioners would not be expected to cause skin irritation among consumers. Additionally, this study demonstrates that the presence of structural alerts does not always accurately predict the safety of a product, as focused tier-based testing is necessary to comprehensively evaluate a product. This study illustrates a tier-based safety assessment approach, applicable to a wide variety of health endpoints, which efficiently and adequately evaluates the safety of personal care and cosmetic products and their ingredients.

Skin Sensitization Induction Potential From Daily Exposure to Fragrances in Personal Care Products.

BACKGROUND: Many chemicals used for fragrance purposes in a diversity of products have allergenic potential. Based on such concerns, industry groups developed concentration limits for use of fragrance chemicals in personal care and cosmetic products. OBJECTIVE: The aim of this study was to use a quantitative risk assessment to evaluate the potential for skin sensitization induction resulting from daily exposure to fragrance chemicals present in personal care and cosmetic products. METHODS: Product-specific dermal consumer exposure levels were calculated based on product use data in US adult females and benchmarked against acceptable exposure levels based on reported no expected sensitization induction levels to determine a margin of safety for each fragrance under evaluation. CONCLUSIONS: The results demonstrate an increased risk of skin sensitization induction for several leave-on products (lipstick, solid antiperspirant, eye shadow, face cream) for most of the evaluated fragrance chemicals, particularly under high-use exposure scenarios. In contrast, rinse-off products (shampoo, conditioner, facial cleanser) were not associated with risk of skin sensitization induction. Because the approach was based on maximum use limits for fragrance chemicals with skin sensitization concerns, the results suggest these limits may not be protective, particularly in the United States.