Developmental and reproductive toxicity hazard characterization of 2-amino-2-methyl-1-propanol (AMP).

2-Amino-2-methyl-1-propanol (AMP™) is a widely used pH stabilizer in personal care products (PCPs); thus, the safety implications of dermal AMP exposure remain of interest. We have previously reported that exposure to AMP in PCPs when used as intended is not anticipated to result in an increased risk of hepatotoxicity (primarily steatosis and altered phospholipid homeostasis). The current study focuses on AMP in PCP's potential for developmental and reproductive toxicity (DART) in humans, based on data from animal studies.

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.

Can oral toxicity data for PFAS inform on toxicity via inhalation?

Per- and poly-fluoroalkyl substances (PFAS) are ubiquitous in the environment and are detected in wildlife and humans. With respect to human exposure, studies have shown that ingestion is the primary route of exposure; however, in certain settings, exposure via inhalation could also be a significant source of exposure. While many studies examined toxicity of PFAS via ingestion, limited information is available for PFAS toxicity via the inhalation route, translating into a lack of exposure guidelines.

Dose and exposure route analyses inform relationships between liver steatosis and 2-amino-2-methyl-1-propanol: Implications for hazard characterization.

2-Amino-2-methyl-1-propanol (AMP™) is widely used as a neutralizer/pH stabilizer in personal care products (PCPs); however, the potential health implications of dermal AMP exposure remain to be fully elucidated. Consequently, an in-depth analysis was performed to determine if PCPs containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity.

A comparative evaluation of dietary exposure to glyphosate resulting from recommended U.S. diets.

Since its commercial introduction in 1974, national and international regulatory agencies have consistently reported no human health concerns associated with the herbicide glyphosate when used according to label directions. However, in 2015, the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen. Despite IARC being the sole outlier in its conclusion, dietary exposure to glyphosate remains a health concern to some members of the public.

A hazard evaluation of the reproductive/developmental toxicity of cobalt in medical devices.

Cobalt (Co) is an essential element with human exposure occurring from the diet, supplement ingestion, occupational sources, and medical devices. The European Chemical Agency (ECHA) recently voted to classify Co metal as a Reproductive Hazard Category 1B; presumed human reproductive toxicant due to adverse testicular effects in male rodents. A weight of evidence evaluation of the preclinical reproductive and developmental toxicity studies and available clinical data was performed to critically evaluate the relevance of this proposed classification for Co in medical devices.

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.

A comprehensive weight of evidence assessment of published acetaminophen genotoxicity data: Implications for its carcinogenic hazard potential.

In 2019, the California Office of Environmental Health Hazard Assessment initiated a review of the carcinogenic hazard potential of acetaminophen, including an assessment of its genotoxicity. The objective of this analysis was to inform this review process with a weight-of-evidence assessment of more than 65 acetaminophen genetic toxicology studies that are of widely varying quality and conformance to accepted standards and relevance to humans. In these studies, acetaminophen showed no evidence of induction of point or gene mutations in bacterial and mammalian cell systems or in in vivo studies.

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).

Assessment of the biochemical pathways for acetaminophen toxicity: Implications for its carcinogenic hazard potential.

In 2019 California's Office of Environmental Health Hazard Assessment (OEHHA) initiated a review of the carcinogenic hazard potential of acetaminophen. In parallel with this review, herein we evaluated the mechanistic data related to the steps and timing of cellular events following therapeutic recommended (≤4 g/day) and higher doses of acetaminophen that may cause hepatotoxicity to evaluate whether these changes indicate that acetaminophen is a carcinogenic hazard. At therapeutic recommended doses, acetaminophen forms limited amounts of N-acetyl-p-benzoquinone-imine (NAPQI) without adverse cellular effects.

An 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 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 human skin explant test.

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.

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.

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.

Cobalt-containing dust exposures: Prediction of whole blood and tissue concentrations using a biokinetic model.

Biokinetic models estimating cobalt (Co) tissue burden can help assess the potential for systemic effects. Such models, however, have not been used to estimate remote tissue concentrations associated with inhalation exposure to Co-containing dust in general environments, work spaces, or animal toxicity tests. We have therefore updated a Co biokinetic model previously developed for oral dosing to include the inhalation pathway by incorporating the International Commission on Radiological Protection (ICRP) Human Respiratory Tract Model.

Derivation of cancer no significant risk levels and screening safety assessment for 2-nitropropane in spray products.

Two proposition 65 no-significant-risk level (NSRL)-type values were derived for 2-nitropropane (2-NP), in the absence of a Californian published NSRL. In addition, a safety assessment was performed based on estimated typical consumer inhalation and dermal exposure to 2-NP during indoor application of paint from a spray can containing the solvent 1-nitropropane. For the NSRL derivation, benchmark dose (BMD) modeling was performed using hepatocellular carcinoma incidence data from 2-NP single exposure inhalation studies in Sprague-Dawley rats.

Understanding outcomes and toxicological aspects of second generation metal-on-metal hip implants: a state-of-the-art review.

Hip implants have improved the mobility and quality of life in millions of individuals. This review presents the evolution of scientific knowledge regarding the history and understanding of systemic and local metal toxicological concerns of hip implants designs utilizing metal-on-metal (MoM) bearing surfaces used in hip resurfacing arthroplasty (HRA) and total hip arthroplasty (THA). This analysis addresses: (1) the history of the development of MoM hip implants; (2) the clinical and toxicological rationale for introducing second-generation MoM implants in the early 2000s as an alternative to metal-on-polyethylene bearings; (3) the subsequent history regarding success and failure of second-generation MoM devices; (4) a detailed review of the history of MoM toxicology, including carcinogenic potential, metal blood levels, hypersensitivity, and release of wear particles; and (5) a review of local tissue effects and MoM patient management.

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.

Derivation of an occupational exposure limit for diacetyl using dose-response data from a chronic animal inhalation exposure study.

Occupational exposure limits (OELs) have been previously proposed for diacetyl; however, most of these values are based on worker cohort studies that are known to have several limitations and confounders. In this analysis, an 8 hour time-weighted average (TWA) OEL for diacetyl was derived based on data from a chronic, 2 year animal inhalation study recently released by the US National Toxicology Program. In that study, complete histopathology was conducted on male and female mice and rats exposed to 0, 12.

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

Unlabelled: 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.

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.

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 Th, Ra, U, and Ra from the Appalachia, Illinois, and Powder River coal basins.