Incorporating lines of evidence from New Approach Methodologies (NAMs) to reduce uncertainties in a category based read-across: A case study for repeated dose toxicity.

A group of triazole compounds was selected to investigate the confidence that may be associated with read-across of a complex data gap: repeated dose toxicity. The read-across was evaluated using Assessment Elements (AEs) from the European Chemicals Agency's (ECHA's) Read-Across Assessment Framework (RAAF), alongside appraisal of associated uncertainties. Following an initial read-across based on chemical structure and properties, uncertainties were reduced by the integration of data streams such as those from New Approach Methodologies (NAM) and other existing data. In addition, addressing the findings of the ECHA RAAF framework, complemented with specific questions concerning uncertainties, increased the confidence that can be placed in read-across. Although a data rich group of compounds with a strong mechanistic basis was analysed, it was clearly demonstrated that NAM data available from publicly available resources could be applied to support read-across. It is acknowledged that most read-across studies will not be so data rich or mechanistically robust, therefore some targeted experimentation may be required to fill the data gaps. In this sense, NAMs should constitute new experimental tests performed with the specific goal of reducing the uncertainties and demonstrating the read-across hypothesis.

Quality Control: Personal Protective Equipment for Use When Handling Hazardous Drugs.

United States Pharmacopeia Chapter <800>, concerned with the handling of hazardous drugs in healthcare settings, requires that any entity handling such drugs maintain a hazardous drug list. While this list must include any drug found on the latest NIOSH List of Antineoplastic and Other Hazardous Drugs in Health Settings, entities are expected to include other drugs and substances of concern. The intent of this article is to provide concrete information concerning articles of personal protective equipment, as well as guidance as to where and how they should be donned, used, and removed. This information will cover every aspect of handling hazardous drugs from receipt to disposal, most certainly including both sterile and nonsterile compounding.

Perspectives on trace chemical safety and chemophobia: risk communication and risk management.

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia (i.e., the fear of chemicals). Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.

Perspectives on trace chemical safety and chemophobia: risk communication and risk management.

Safety issues regarding consumer products contaminated with trace amounts of chemicals are of great concern to consumers, with the degree of concern occasionally escalating to the psychological syndrome, chemophobia, i.e., the fear of chemicals. Hazardous substances frequently implicated in safety concerns include heavy metals (arsenic, mercury, cadmium, and lead), volatile organic compounds (VOC) such as benzene and o-toluidine, pesticides, carcinogens, radioactive substances, and endocrine disrupting chemicals (EDC) such as bisphenol A and phthalates. To improve communication of risk to society, members of academia, government, consumer organizations, and industry participated in this workshop to discuss and exchange perspectives on trace chemical safety. From the perspective of academia, integrated risk assessments need to be implemented to encompass various exposure sources and routes. The identification and investigation of new exposure-related biomarkers are also recommended to verify direct causal relationships between specific chemical exposure and effects on human health. As for regulation, governments need to establish and maintain acceptable limits for trace chemicals in products. In addition, harmonized efforts need to be undertaken among government agencies to share regulatory limits and effectively control trace chemicals in consumer products. Manufacturers need to faithfully abide by Good Manufacturing Practice (GMP) guidelines, monitor sources of contamination, and minimize these for consumer safety. To effectively resolve safety issues arising from trace chemicals exposure, collaborative efforts are needed involving academia, government, consumer organizations, and industry. Further, scientific evidence-based risk assessment is a critical approach to effectively manage trace chemical safety issues.

Safe Handling of Hazardous Drugs: ASCO Standards.

PURPOSE: To provide 2019 ASCO standards on the safe handling of hazardous drugs. METHODS: An Expert Panel was formed, and a systematic review of the literature on closed system transfer devices was performed to May 2017 using PubMed. The Cochrane Database of Systematic Reviews, PubMed, and Google Scholar were used to search for studies of medical surveillance and external ventilation/health effects of exposure to vapors to November 2017. Available standards were considered for endorsement. Public comments were solicited and considered in preparation of the final manuscript. RESULTS: The search for primary research found no studies that addressed health outcomes as they relate to the identified interventions of interest. The ASCO Expert Panel endorses the best practices for safe handling of hazardous drugs as issued by the Occupational Safety and Health Administration, US Pharmacopeia Chapter 800, and Oncology Nursing Society with clarifications in four key areas: medical surveillance, closed system transfer devices, external ventilation of containment secondary engineering controls or containment segregated compounding areas, and alternative duties. CONCLUSION: The ASCO standards address the need for clear standards concerning safe handling of hazardous oncology drugs. More research is needed in several key areas to quantify the level of risk associated with handling hazardous drugs in current workplace settings where the hierarchy of controls is consistently applied. Additional information is available at www.asco.org/safe-handling-standards .

Cocoa Farmers' Compliance with Safety Precautions in Spraying Agrochemicals and Use of Personal Protective Equipment (PPE) in Cameroon.

The inability of farmers to comply with essential precautions in the course of spraying agrochemicals remains a policy dilemma, especially in developing countries. The objectives of this paper were to assess compliance of cocoa farmers with agrochemical safety measures, analyse the factors explaining involvement of cocoa farmers in the practice of reusing agrochemical containers and wearing of personal protective equipment (PPE). Data were collected with structured questionnaires from 667 cocoa farmers from the Centre and South West regions in Cameroon. Data analyses were carried out with Probit regression and Negative Binomial regression models. The results showed that average cocoa farm sizes were 3.55 ha and 2.82 ha in South West and Centre regions, respectively, and 89.80% and 42.64% complied with manufacturers' instructions in the use of insecticides. Eating or drinking while spraying insecticides and fungicides was reported by 4.20% and 5.10% of all farmers in the two regions, respectively. However, 37.78% and 57.57% of all farmers wore hand gloves and safety boots while spraying insecticides in the South West and Centre regions of Cameroon, respectively. In addition, 7.80% of all the farmers would wash agrochemical containers and use them at home, while 42.43% would wash and use them on their farms. Probit regression results showed that probability of reusing agrochemical containers was significantly influenced (p < 0.05) by region of residence of cocoa farmers, gender, possession of formal education and farming as primary occupation. The Negative Binomial regression results showed that the log of number PPE worn was significantly influenced (p < 0.10) by region, marital status, attainment of formal education, good health, awareness of manufacturers' instructions, land area and contact index. It was among others concluded that efforts to train farmers on the need to be familiar with manufacturers' instructions and use PPE would enhance their safety in the course of spraying agrochemicals.

The Molecular Design Research Network.

Herein, we provide an overview of a research network that is aimed at fostering interdisciplinary collaboration between chemists and toxicologists with the goal of rationally designing safer commercial chemicals. The collaborative is the Molecular Design Research Network (MoDRN) that was created in 2013 with funding from the EPA-National Science Foundation Networks for Sustainable Molecular Design and Synthesis (NSMDS) program. MoDRN is led by 4 universities, Baylor University, University of Washington, The George Washington University, and Yale University. The overarching goal of the network is to enable and empower the design of safer chemicals based on the fourth Principle of Green Chemistry that states, "chemical products should be designed to preserve efficacy of function while minimizing toxicity."

Green Toxicology-Know Early About and Avoid Toxic Product Liabilities.

Toxicology uniquely among the life sciences relies largely on methods which are more than 40-years old. Over the last 3 decades with more or less success some additions to and few replacements in this toolbox took place, mainly as alternatives to animal testing. The acceptance of such new approaches faces the needs of formal validation and the conservative attitude toward change in safety assessments. Only recently, there is growing awareness that the same alternative methods, especially in silico and in vitro tools can also much earlier and before validation inform decision-taking in the product life cycle. As similar thoughts developed in the context of Green Chemistry, the term of Green Toxicology was coined to describe this change in approach. Here, the current developments in the alternative field, especially computational and more organo-typic cell cultures are reviewed, as they lend themselves to front-loaded chemical safety assessments. The initiatives of the Center for Alternatives to Animal Testing Green Toxicology Collaboration are presented. They aim first of all for forming a community to promote this concept and then for a cultural change in companies with the necessary training of chemists, product stewards and later regulators.

The Need for, and the Role of the Toxicological Chemist in the Design of Safer Chemicals.

During the past several decades, there has been an ever increasing emphasis for designers of new commercial (nonpharmaceutical) chemicals to include considerations of the potential impacts a planned chemical may have on human health and the environment as part of the design of the chemical, and to design chemicals such that they possess the desired use efficacy while minimizing threats to human health and the environment. Achievement of this goal would be facilitated by the availability of individuals specifically and formally trained to design such chemicals. Medicinal chemists are specifically trained to design and develop safe and clinically efficacious pharmaceutical substances. No such formally trained science hybrid exists for the design of safer commercial (nonpharmaceutical) chemicals. This article describes the need for and role of the "toxicological chemist," an individual who is formally trained in synthetic organic chemistry, biochemistry, physiology, toxicology, environmental science, and in the relationships between structure and commercial use efficacy, structure and toxicity, structure and environmental fate and effects, and global hazard, and trained to integrate this knowledge to design safer commercially efficacious chemicals. Using examples, this article illustrates the role of the toxicological chemist in designing commercially efficacious, safer chemical candidates.

Allergic contact dermatitis from acrylic nails in a flamenco guitarist.

Acrylates are molecules that are well known for their strong sensitizing properties. Historically, many beauticians and individuals using store-bought artificial nail products have developed allergic contact dermatitis from acrylates. More recently, the use of acrylic nails among flamenco guitarists to strengthen their nails has become very popular. A 40-year-old non-atopic male patient working as a flamenco guitarist developed dystrophy, onycholysis and paronychia involving the first four nails of his right hand. The lesions were confined to the fingers where acrylic materials were used in order to strengthen his nails to play the guitar. He noticed improvement whenever he stopped using these materials and intense itching and worsening when he began reusing them. Patch tests were performed and positive results obtained with 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxyethyl acrylate (2-HEA), ethyleneglycol-dimethacrylate (EGDMA) and 2-hydroxypropyl methacrylate (2-HPMA). The patient was diagnosed with occupational allergic contact dermatitis likely caused by acrylic nails. Artificial nails can contain many kinds of acrylic monomers but most cases of contact dermatitis are induced by 2-HEMA, 2-HPMA and EGDMA. This is the first reported case of occupational allergic contact dermatitis from acrylates in artificial nails in a professional flamenco guitar player. Since the practice of self-applying acrylic nail products is becoming very popular within flamenco musicians, we believe that dermatology and occupational medicine specialists should be made aware of the potentially increasing risk of sensitization from acrylates in this setting.

A Call to Action for Hazardous Drug Safety: Where We Have Been and Where We Are Now.

BACKGROUND: The dangers associated with handling hazardous drugs (HDs) have been well documented. Contamination of the healthcare environment, which can occur during compounding and administration, may lead to drug absorption by healthcare workers. Studies have proven that HD exposure causes numerous side effects and chromosomal aberrations. OBJECTIVES: This article examines the complex issues surrounding HD safety, including workplace culture, current guidelines, and misconceptions regarding the risks associated with exposure. Discussions include suggestions for creating a workplace culture where HD safety is an expectation, along with an update on laws and significant impending changes. METHODS: Historical data and current research are presented. FINDINGS: Although improvements have been made in the use of personal protective equipment, studies indicate that nurses continue to be unnecessarily at risk. Inability to fully understand the dangers, a lack of organizational safety culture, and the general inability to enforce guidelines continue to be challenging. Fortunately, a number of upcoming changes will help to build momentum for increasing nursing safety.

Quality of Chemical Safety Information in Printing Industry.

OBJECTIVES: Employees in printing industries can be exposed to multiple solvents in their work environment. The objectives of this study were to investigate the critical components of chemical solvents by analyzing the components of the solvents and collecting the Safety data sheets (SDSs), and to evaluate the hazard communication implementation status in printing industries. METHOD: About 152 printing-related industries were recruited by area-stratified random sampling and included 23 plate-making, 102 printing and 27 printing-assistance companies in Taiwan. We analyzed company questionnaires (n = 152), SDSs (n = 180), and solvents (n = 20) collected from this sample of printing-related companies. RESULTS: Analytical results indicated that benzene and ethylbenzene, which were carcinogen and possibly carcinogen, were detectable in the cleaning solvents, and the detection rate were 54.5% (concentrations: <0.011-0.035 wt%) and 63.6% (concentrations: <0.011-6.22 wt%), respectively; however, neither compound was disclosed in the SDS for the solvents. Several other undisclosed components, including methanol, isopropanol and n-butanol, were also identified in the printing inks, fountain solutions and dilution solvents. We noted that, of the companies we surveyed, only 57.2% had a hazard communication program, 61.8% had SDSs on file and 59.9% provided employee safety and health training. We note that hazard communication programs were missing or ineffective in almost half of the 152 printing industries surveyed. CONCLUSIONS: Current safety information of solvents components in printing industries was inadequate, and many hazardous compounds were undisclosed in the SDSs of the solvents or the labels of the containers. The implementation of hazard communications in printing industries was still not enough for protecting the employees' safety and health.