A Safety and Effectiveness Evaluation of a Callus Softener Containing Potassium Hydroxide.

BACKGROUND: Limited safety information has been described in the peer-reviewed literature for callus-softening products containing potassium hydroxide. METHODS: This pilot human use study evaluated the safety and effectiveness of a commercially available callus softener, containing less than 10% potassium hydroxide by weight. Baseline callused skin was scored (grade 1-4) on each study participant's feet (n = 10). Participants' feet were soaked and then a licensed manicurist applied a callus softener product to the right foot, which remained on callused skin for 3 to 5 minutes (no callus softener was applied to the participant's left foot). Both feet were then wiped with a wet towel, and a foot rasp was used to file the callused skin, beginning on the left foot. Callused skin was scored and participants' feet were evaluated by a physician immediately after use, 1 day after use, and 1 week after use for the presence or absence of skin irritation, adverse skin reactions, and chemical burns. RESULTS: No adverse events were reported by study participants or the physician for all evaluation time points. Each participant's highest callus grade score on the treated foot either improved or remained the same following product use (compared to baseline). Mean callus grade scores were 1.75 at baseline, 1.55 immediately after use, 1.25 1 day after use, and 1.50 1 week after use. CONCLUSIONS: Results from this pilot study suggest that callus-softening products containing less than 10% potassium hydroxide are likely to be safe and effective products under intended use scenarios of 3- to 5-minute application times, as dictated by product label instructions.

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.

An Ecological Evaluation of Vinyl Chloride Exposure and Liver Cancer Incidence and Mortality in Texas.

The goal of this analysis was to evaluate the association between county-level ambient vinyl chloride (VC) and county-level liver cancer incidence and mortality rates in Texas. Modeled county-level ambient VC data were obtained from the National Air Toxics Assessment. Age-adjusted county-level liver cancer incidence rates were abstracted from the Texas Cancer Registry and age-standardized county-level liver cancer mortality rates were obtained from the peer-reviewed literature. Multivariable imputation was utilized to impute incidence rates in counties with suppressed liver cancer incidence rates. Negative binomial and Poisson regression models were utilized to evaluate the association between county-level ambient VC and county-level liver cancer incidence and mortality rates, respectively, adjusted for county-level heavy drinking prevalence, hepatitis mortality rates, median income, and race (percent Hispanic). County-level ambient VC was not associated with county-level liver cancer incidence or mortality rates. Specifically, when compared to the lowest tertile of ambient VC, the middle (relative risk [RR]: 1.06, 95% confidence interval [CI]: 0.95-1.19) and highest (RR: 1.03, 95% CI: 0.90-1.17) tertiles of ambient VC were not associated with liver cancer incidence. Similarly, county-level ambient VC in the middle (RR: 0.95, 95% CI: 0.85-1.05) and highest (RR: 0.93, 95% CI: 0.82-1.05) tertiles were not associated with liver cancer mortality. This analysis suggests that county-level ambient VC is not associated with liver cancer incidence or mortality in Texas. Our study provides novel results regarding liver cancer risk from low-level non-occupational exposure to ambient VC.

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.

A human health risk assessment of heavy metal ingestion among consumers of protein powder supplements.

Concerns have recently been raised about the presence of heavy metals in protein powder supplements following a Consumer Reports analysis of 15 protein powder products. The Consumer Reports study found that the average amounts of heavy metals in three servings of protein powder per day exceeded the maximum limits in dietary supplements proposed by U.S. Pharmacopeia. In a follow up to the Consumer Reports analysis, another study reported that 40 % of the 133 protein powder products they tested had elevated levels of heavy metals. The objective of this analysis was to determine whether the heavy metal concentrations reported in protein powder supplements posed any human health risks, based on the reported concentrations of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in the protein powder. The US EPA reference doses (RfD) for As and Cd, and the EPA screening level for Hg were based on the most sensitive health endpoint which were used to calculate hazard quotients (HQs) for each metal. The 'worse-case scenario' assessment for each protein powder product was expressed as a cumulative hazard index (HI), which is the sum of HQs from each heavy metal. Additionally, we utilized the U.S. EPA's Adult Lead Methodology (ALM) model to estimate adult blood lead levels (BLLs), which were compared to the CDC BLL guidance value of 5 µg/dL. All models assumed one or three servings of protein powder per day. Our results indicate that the exposure concentrations of the studied metals do not pose an increased health risk (Hazard Index < 1). We noted that the protein powder HI was mainly driven by the As or Cd content in each product. Interestingly, the highest HI levels (which approached 1) were found in 'mass gain' type protein powder supplements, whereas the lowest calculated HI levels were in whey protein powders. Moreover, background Pb exposure was the primary contributor to estimated BLLs in adults, and all modeled BLLs were below 5 µg/dL. Overall, our results suggest that the typical intake of dietary supplements would not result in adverse health effects due to heavy metals.

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.

An updated evaluation of potential health hazards associated with exposures to asbestos-containing drywall accessory products.

Following a previously published (2012) evaluation of the potential health hazards related to the use of asbestos-containing drywall accessory products, additional information regarding asbestos exposures during the use of accessory products, as well as studies of chrysotile asbestos risk as a function of exposure, have been published in the peer-reviewed literature. The purpose of this analysis is to update the original evaluation with this new information. It was previously estimated that a professional drywaller performing joint compound-associated tasks could have a lifetime cumulative chrysotile exposure of 12-26 f/cc-year. Using conservative assumptions regarding airborne asbestos levels during different drywalling tasks, task duration, and job tenure, we found that a range of 4.3-36.3 f/cc-year is a plausible estimate of a career drywaller's cumulative asbestos exposure from historical joint compound use. The estimated range for bystander exposures would be below (sometimes significantly below) this range depending on the frequency and duration of work near drywallers. Further, the estimated drywaller and bystander total fiber exposures were well below a recently published "no-observed adverse effect level, best estimate" for predominately chrysotile exposures of 89-168 f/cc-year for lung cancer and 208-415 f/cc-year for mesothelioma. We also determined that, even if the chrysotile or possibly talc ingredients in the drywall products had contained asbestiform tremolite, the cumulative tremolite exposures would have been well below a recently published tremolite no-effect level of 0.5-2.6 f/cc-year. Based on our calculations, typical drywall work using asbestos-containing drywall accessory products is not expected to increase the risk of asbestos-related lung cancer or mesothelioma. These conclusions are consistent with the lack of epidemiological evidence that drywall work resulted in an increased incidence of asbestos-related disease in the drywall trades.

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.

Risk Assessment of the Skin Sensitization Induction Potential of Kathon CG in Rinse-off and Leave-on Personal Care and Cosmetic Products.

BACKGROUND: Kathon CG is a commonly used cosmetic-grade preservative that contains active ingredients methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI). OBJECTIVE: The aim of the study was to perform a skin sensitization induction risk assessment of daily exposure to Kathon CG after use of various personal care and cosmetic products. METHODS: We calculated an estimated daily consumer exposure level for rinse-off and leave-on products using the amount of product applied per application, number of applications per day, a retention factor, the MCI/MI concentration, and body surface area values. We assumed that the products contained the maximum recommended safe concentration of MCI/MI: 15 ppm in rinse-off products and 7.5 ppm in leave-on products. We compared estimated consumer exposure levels with the no expected sensitization induction level for MCI/MI and applied sensitization assessment factors to calculate product-specific margins of safety (MOSs). CONCLUSIONS: The MOSs for rinse-off products ranged from 5 to 63, whereas the MOSs for leave-on products ranged from 0.03 to 1.49. Overall, our results provide evidence that some leave-on products containing the maximum recommended safe concentration of Kathon CG may increase the risk of sensitization induction due to exposure to MCI/MI. In contrast, rinse-off products were not associated with a potential increased risk of skin sensitization induction.

The Cancer Risk Associated with Residential Exposure to Soil Containing Radioactive Coal Combustion Residuals.

Coal combustion residuals (CCRs) are composed of various constituents, including radioactive materials. The objective of this study was to utilize methodology on radionuclide risk assessment from the Environmental Protection Agency (EPA) to estimate the potential cancer risks associated with residential exposure to CCR-containing soil. We evaluated potential radionuclide exposure via soil ingestion, inhalation of soil particulates, and external exposure to ionizing radiation using published CCR radioactivity values for 232 Th, 228 Ra, 238 U, and 226 Ra from the Appalachia, Illinois, and Powder River coal basins. Mean and upper-bound cancer risks were estimated individually for each radionuclide, exposure pathway, and coal basin. For each radionuclide at each coal basin, external exposure to ionizing radiation contributed the greatest to the overall risk estimate, followed by incidental ingestion of soil and inhalation of soil particulates. The mean cancer risks by route of exposure were 2.01 × 10-6 (ingestion), 6.80 × 10-9 (inhalation), and 3.66 × 10-5 (external), while the upper bound cancer risks were 3.70 × 10-6 (ingestion), 1.18 × 10-8 (inhalation), and 6.15 × 10-5 (external), using summed radionuclide-specific data from all locations. The upper bound cancer risk from all routes of exposure was 6.52 × 10-5 . These estimated cancer risks were within the EPA's acceptable cancer risk range of 1 × 10-6 to 1 × 10-4 . If the CCR radioactivity values used in this analysis are generally representative of CCR waste streams, then our findings suggest that CCRs would not be expected to pose a significant radiological risk to residents living in areas where contact with CCR-containing soils might occur.

Personal use of hair dyes and risk of leukemia: a systematic literature review and meta-analysis.

The objective of this study was to examine the association between personal use of hair dyes and the risk of leukemia. We conducted a systematic literature review of epidemiology studies reporting leukemia-specific cancer risks among hair dye users, and estimated the meta-relative risk (meta-RR) and corresponding 95% confidence interval (95% CI) of leukemia, comparing hair dye users to nonusers. When data from all 20 studies that met the inclusion criteria were combined, ever use of hair dye was associated with a nonstatistically significant increased risk of leukemia, meta-RR = 1.09 (95% CI: 0.97-1.22). When restricted to studies that adjusted for smoking, ever use of hair dye was not associated with leukemia, meta-RR = 0.99 (95% CI: 0.76-1.29). A statistically significant increased risk of leukemia was associated with permanent hair dye use (meta-RR = 1.19 [95% CI: 1.07-1.33]), dark hair dye use (meta-RR = 1.29 [95% CI: 1.11-1.50]), hair dye use among males (meta-RR = 1.42 [95% CI: 1.01-2.00]), hair dye use pre-1980 (meta-RR = 1.49 [95% CI: 1.21-1.83]), and hair dye use for ≥15 years (meta-RR = 1.35 [95% CI: 1.13-1.62]). Overall, findings suggest that ever use of hair dye is not a significant risk factor for leukemia. Certain hair dye use characteristics were associated with a statistically significant increased risk, but further research is required to determine whether these associations truly reflect a risk of leukemia due to methodological limitations in the underlying studies.

An Assessment of Gender-Specific Risk of Implant Revision After Primary Total Hip Arthroplasty: A Systematic Review and Meta-analysis.

BACKGROUND: Total hip arthroplasty (THA) has been a successful reconstructive procedure to mitigate pain associated with diseases of the hip joint. However, some THA procedures require revision due to mechanical or biological failure. The purpose of this study was to synthesize and examine the evidence on the relative risk of revision in men and women after primary THA procedures. METHODS: We conducted a systematic literature review of cohort studies reporting THA revision risk estimate by gender. Study quality scoring and a random effects meta-analysis were performed to estimate the meta-relative risk (meta-RR) and corresponding 95% confidence interval (95% CI) of revision, comparing men to women. RESULTS: Males had a statistically significant increased risk of revision after primary THA (meta-RR = 1.33 [95% CI: 1.13-1.57]), when compared to females. When stratified by cause of revision, males had a statistically significant increased risk of revision due to any cause (meta-RR = 1.16 [95% CI: 1.01-1.33]), aseptic loosening (meta-RR = 1.54 [95% CI: 1.05-2.25]), and infection (meta-RR = 1.55 [95% CI: 1.11-2.15]). For primary THA operations performed during the 2000s, males in Europe had a statistically significant increased risk of revision (meta-RR 1.42 [95% CI: 1.25-1.61]) while males in the United States had a statistically significant decreased risk of revision (meta-RR 0.80 [95% CI: 0.72-0.89]). CONCLUSION: These results provide evidence for an increased risk of revision after THA among males, which may be impacted by geographic location and time period of operation. Findings suggest that a better understanding of the underlying drivers of gender-specific risks would help reduce postsurgery complications.

A trematode parasite alters growth, feeding behavior, and demographic success of invasive rusty crayfish (Orconectes rusticus).

Nonindigenous species can cause major changes to community interactions and ecosystem processes. The strong impacts of these species are often attributed to their high demographic success. While the importance of enemy release in facilitating invasions has often been emphasized, few studies have addressed the role of parasites in the invasive range in controlling demographic success of potential invaders. Here we examine whether a trematode parasite (Microphallus spp.) can contribute to previously documented alternate states in the abundance of invasive rusty crayfish (Orconectes rusticus) in north temperate lakes in Wisconsin, USA. Microphallus infect O. rusticus after emerging from their first intermediate host, a hydrobiid snail. As previously documented, O. rusticus reduce densities of hydrobiid snails through direct predation and destruction of macrophyte habitat. Therefore, if Microphallus substantially reduce O. rusticus fitness, these parasites may reinforce a state of low crayfish abundance, and, at the other extreme, abundant crayfish may repress these parasites, reinforcing a state of high crayfish abundance. From samples collected from 109 sites in 16 lakes, we discovered (1) a positive relationship between crayfish infection intensity and hydrobiid snail abundance, (2) a negative relationship between parasite prevalence and crayfish abundance, and (3) a negative relationship between parasite prevalence and crayfish population growth. With experiments, we found that infection with Microphallus reduced foraging behavior and growth in O. rusticus, which may be the mechanisms responsible for the population reductions we observed. Overall results are consistent with the hypothesis that Microphallus contributes to alternate states in the abundance and impacts of O. rusticus.