Skin sensitization testing needs and data uses by US regulatory and research agencies.

United States regulatory and research agencies may rely upon skin sensitization test data to assess the sensitization hazards associated with dermal exposure to chemicals and products. These data are evaluated to ensure that such substances will not cause unreasonable adverse effects to human health when used appropriately. The US Consumer Product Safety Commission, the US Environmental Protection Agency, the US Food and Drug Administration, the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, and the US Department of Defense are member agencies of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). ICCVAM seeks to identify opportunities for the use of non-animal replacements to satisfy these testing needs and requirements. This review identifies the standards, test guidelines, or guidance documents that are applicable to satisfy each of these agency's needs; the current use of animal testing and flexibility for using alternative methodologies; information needed from alternative tests to fulfill the needs for skin sensitization data; and whether data from non-animal alternative approaches are accepted by these US federal agencies.

Characteristics and magnitude of acute pesticide-related illnesses and injuries associated with pyrethrin and pyrethroid exposures--11 states, 2000-2008.

BACKGROUND: Excluding disinfectants, pyrethrins and pyrethroids are the pesticides used most commonly in and around homes. Respiratory effects and paresthesia are among the concerns about pyrethrin/pyrethroid exposures. METHODS: Acute pesticide-related illness/injury cases were identified from the Sentinel Event Notification System for Occupational Risks-Pesticides Program and the California Department of Pesticide Regulation from 2000-2008. Characteristics and incidence rates were determined for acute pyrethrin/pyrethroid-related illness/injury cases. Logistic regression analyses were performed to determine odds of respiratory and dermal symptoms in persons with illness/injury following pyrethrin/pyrethroid exposure compared to persons with illness/injury following exposure to other pesticides. RESULTS: A total of 4,974 cases of acute pyrethrin/pyrethroid-related illness were identified. Incidence rates increased over time, reaching 8 cases/million population in 2008. The majority of cases were low severity (85%) and 34% were work-related. Respiratory effects were the most common symptoms reported (48%). Risk of acute respiratory effects were significantly elevated among persons exposed only to pyrethrins (adjusted odds ratio [aOR] 1.79; 95% confidence interval [95% CI]: 1.49-2.16), only to pyrethroids (aOR 1.99 95% CI: 1.77-2.24), to a mixture of pyrethroids (aOR 2.36; 95% CI: 1.99-2.81) or to a mixture containing both pyrethrins and pyrethroids (aOR 2.99; 95% CI: 2.33-3.84) compared to those with illness arising from exposure to other pesticides. The most common factors contributing to pyrethrin/pyrethroid-related illness included exposure from spills/splashes, improper storage, and failure to evacuate during pesticide application. CONCLUSIONS: The magnitude of acute pyrethrin/pyrethroid-related illness/injury is relatively low but is increasing. As such, additional measures to prevent them are needed.

Investigation of respiratory and dermal symptoms associated with metal working fluids at an aircraft engine manufacturing facility.

BACKGROUND: Each year, 1.2 million metalworkers are exposed to metalworking fluids (MWFs), which can cause dermal and respiratory disease. The National Institute for Occupational Safety and Health (NIOSH) conducted a health hazard evaluation of MWF exposures at an aircraft engine manufacturing facility. The objectives were to determine employee exposures to endotoxin and MWFs in the air, characterize symptoms experienced by employees working with MWFs, compare them to symptoms of employees unexposed to MWFs, and make recommendations for reducing exposures based on results. METHODS: Four hundred seven workers were categorized as MWF exposed or MWF unexposed and completed questionnaires. Estimated prevalence ratios (PR) of dermatitis, asthma, and work-related asthma (WRA) symptoms were calculated. Airborne concentrations of MWF and endotoxin were measured, and work practices observed. RESULTS: MWF exposed workers had a significantly higher prevalence of dermatitis on wrists/forearms (PR 2.59; 95% CI 1.22, 5.46), asthma symptoms (PR 1.49; 95% CI 1.05, 2.13), and WRA symptoms (PR 2.10; 95% CI 1.22, 3.30) than unexposed workers. Airborne concentrations of MWF were below the NIOSH recommended exposure limit (REL) for MWF aerosols (thoracic particulate mass). CONCLUSIONS: Despite MWF exposures below the NIOSH REL, exposed workers had a higher prevalence of asthma, WRA, and dermatitis symptoms than unexposed workers. Recommendations to reduce exposure included configuring mist collectors to automatically turn on when the machine is in use, and enforcing enclosure use.

Cumulative Risks from Stressor Exposures and Personal Risk Factors in the Workplace: Examples from a Scoping Review.

Protecting worker and public health involves an understanding of multiple determinants, including exposures to biological, chemical, or physical agents or stressors in combination with other determinants including type of employment, health status, and individual behaviors. This has been illustrated during the COVID-19 pandemic by increased exposure and health risks for essential workers and those with pre-existing conditions, and mask-wearing behavior. Health risk assessment practices for environmental and occupational health typically do not incorporate multiple stressors in combination with personal risk factors. While conceptual developments in cumulative risk assessment to inform a more holistic approach to these real-life conditions have progressed, gaps remain, and practical methods and applications are rare. This scoping review characterizes existing evidence of combined stressor exposures and personal factors and risk to foster methods for occupational cumulative risk assessment. The review found examples from many workplaces, such as manufacturing, offices, and health care; exposures to chemical, physical, and psychosocial stressors combined with modifiable and unmodifiable determinants of health; and outcomes including respiratory function and disease, cancers, cardio-metabolic diseases, and hearing loss, as well as increased fertility, menstrual dysfunction and worsened mental health. To protect workers, workplace exposures and modifiable and unmodifiable characteristics should be considered in risk assessment and management. Data on combination exposures can improve assessments and risk estimates and inform protective exposure limits and management strategies.

Tobacco use: a chronic illness?

Tobacco use is a modifiable risk factor that has many characteristics of a chronic illness. We analyzed longitudinal data from participants in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS) and compared tobacco use to other chronic illnesses to evaluate effects on mortality. We limited our analysis to 20,293 participants aged 45 and older at baseline. We determined smoking status, diabetes status, hypertension, cardiovascular disease (ASCVD), and lung disease status at baseline. We developed Cox proportional hazard models, adjusting for age, sex and race and all comorbid diseases, to determine the effect of disease on mortality at up to 13 years of follow-up, 3,022 study participants died during the follow-up period. Adjusted proportional hazard models found that the risk of smoking for death had a hazard ratio (HR) of 2.0 (95% confidence interval [CI] 1.8, 2.2). This was similar to the mortality risk for ASCVD (HR 1.8, 95% CI 1.7, 2.0), diabetes (HR 1.9, 95% CI 1.7, 2.0), and chronic obstructive pulmonary disease (COPD) (HR 2.1, 95% CI 1.9, 2.4). The risk in former smokers were significantly less than that of current smokers (HR 1.1, 95% CI 1.01, 1.2). In the adjusted models, current cigarette smoking has a mortality risk that is in the same range of that seen in other "chronic diseases", whereas the risk in former smokers is greatly reduced. These data suggest that current smoking should be approached as aggressively as other chronic diseases that are amenable to interventions.

Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity.

OBJECTIVE: To analyze a cluster of 30 industrial coworkers with Parkinson's disease and parkinsonism subjected to long-term (8-33 years) chronic exposure to trichloroethylene. METHODS: Neurological evaluations were conducted on the 30 coworkers, including a general physical and neurological examination and the Unified Parkinson's Disease Rating Scale. In addition, fine motor speed was quantified and an occupational history survey was administered. Next, animal studies were conducted to determine whether trichloroethylene exposure is neurotoxic to the nigrostriatal dopamine system that degenerates in Parkinson's disease. The experiments specifically analyzed complex 1 mitochondrial neurotoxicity because this is a mechanism of action of other known environmental dopaminergic neurotoxins. RESULTS: The three workers with workstations adjacent to the trichloroethylene source and subjected to chronic inhalation and dermal exposure from handling trichloroethylene-soaked metal parts had Parkinson's disease. Coworkers more distant from the trichloroethylene source, receiving chronic respiratory exposure, displayed many features of parkinsonism, including significant motor slowing. Neurotoxic actions of trichloroethylene were demonstrated in accompanying animal studies showing that oral administration of trichloroethylene for 6 weeks instigated selective complex 1 mitochondrial impairment in the midbrain with concomitant striatonigral fiber degeneration and loss of dopamine neurons. INTERPRETATION: Trichloroethylene, used extensively in industry and the military and a common environmental contaminant, joins other mitochondrial neurotoxins, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and some pesticides, as a risk factor for parkinsonism.

Can fluorescence spectrometry be used as a surrogate for the Biochemical Oxygen Demand (BOD) test in water quality assessment? An example from South West England.

The fluorescence intensities of tryptophan-like, tyrosine-like and humic-like materials were determined using excitation-emission-matrices (EEMs) for a wide range of samples including natural surface waters, sewage and industrial effluents and waters that have experienced known pollution events from the South West of England (n=469). Fluorescence intensities reported in arbitrary fluorescence units (AFU) were correlated with standard five day Biochemical Oxygen Demand (BOD(5)) values which were used as an indicator of the amount of biodegradable organic material present. Tryptophan-like fluorescence, which has been found to relate to the activity of the biological community, showed the strongest correlation with BOD(5). Fluorescence analysis of the tryptophan-like peak (excitation/emission wavelength region 275/340 nm) is found to provide an accurate indication of the presence, and relative proportions of bioavailable organic material present (natural or anthropogenic). It therefore provides an insight relating to its oxygen depleting potential. Thus fluorescence spectroscopy is recommended as a portable or laboratory tool for the determination of the presence of biodegradable organic matter with intrinsic oxidising potential in natural waters. The novel application of Geographically Weighted Regression (GWR) to the data illustrates that strong local relationships exist between the two parameters and that site specific character may be a strong factor in the strength of the tryptophan-like fluorescence/BOD(5) relationship.

The Dermal Exposure Risk Management and Logic eTookit: Characterizing and managing dermal exposure during emergency management operations.

OBJECTIVE: Emergency management and operations (EMO) personnel require up-to-date information to make informed decisions during natural and man-made disasters. However, information gaps present challenges for accessing human health risk assessment and risk management strategies for dermal exposure. This article describes the development of a decision support system, the Dermal Exposure Risk Management and Logic (DERMaL) eToolkit. DESIGN: The DERMaL eToolkit provides information on key resources used in emergency incidents. Resources were classified according to response phase, resource categories, and information category and evaluated on reliability, accessibility, and preference by subject matter experts in emergency management fields. These rankings were used to generate a value of information score, unique for each resource, which aids in developing reference lists for users during each incident phase. RESULTS: This tool will identify and prioritize information resources on dermal risks, and can readily find the most relevant information to suit EMO needs. CONCLUSION: The DERMaL eToolkit can be used as an aid in finding information resources targeted to scenario-driven needs by providing well-vetted and prioritized resources related to dermal hazards, exposure, and risk assessments for EMO.

A decision support framework for characterizing and managing dermal exposures to chemicals during Emergency Management and Operations.

Emergency Management and Operations (EMO) personnel are in need of resources and tools to assist in understanding the health risks associated with dermal exposures during chemical incidents. This article reviews available resources and presents a conceptual framework for a decision support system (DSS) that assists in characterizing and managing risk during chemical emergencies involving dermal exposures. The framework merges principles of three decision-making techniques: 1) scenario planning, 2) risk analysis, and 3) multicriteria decision analysis (MCDA). This DSS facilitates dynamic decision making during each of the distinct life cycle phases of an emergency incident (ie, preparedness, response, or recovery) and identifies EMO needs. A checklist tool provides key questions intended to guide users through the complexities of conducting a dermal risk assessment. The questions define the scope of the framework for resource identification and application to support decision-making needs. The framework consists of three primary modules: 1) resource compilation, 2) prioritization, and 3) decision. The modules systematically identify, organize, and rank relevant information resources relating to the hazards of dermal exposures to chemicals and risk management strategies. Each module is subdivided into critical elements designed to further delineate the resources based on relevant incident phase and type of information. The DSS framework provides a much needed structure based on contemporary decision analysis principles for 1) documenting key questions for EMO problem formulation and 2) a method for systematically organizing, screening, and prioritizing information resources on dermal hazards, exposures, risk characterization, and management.

A decision support framework for characterizing and managing dermal exposures to chemicals during Emergency Management and Operations.

Emergency Management and Operations (EMO) personnel are in need of resources and tools to assist in understanding the health risks associated with dermal exposures during chemical incidents. This article reviews available resources and presents a conceptual framework for a decision support system (DSS) that assists in characterizing and managing risk during chemical emergencies involving dermal exposures. The framework merges principles of three decision-making techniques: 1) scenario planning, 2) risk analysis, and 3) multicriteria decision analysis (MCDA). This DSS facilitates dynamic decision making during each of the distinct life cycle phases of an emergency incident (ie, preparedness, response, or recovery) and identifies EMO needs. A checklist tool provides key questions intended to guide users through the complexities of conducting a dermal risk assessment. The questions define the scope of the framework for resource identification and application to support decision-making needs. The framework consists of three primary modules: 1) resource compilation, 2) prioritization, and 3) decision. The modules systematically identify, organize, and rank relevant information resources relating to the hazards of dermal exposures to chemicals and risk management strategies. Each module is subdivided into critical elements designed to further delineate the resources based on relevant incident phase and type of information. The DSS framework provides a much needed structure based on contemporary decision analysis principles for 1) documenting key questions for EMO problem formulation and 2) a method for systematically organizing, screening, and prioritizing information resources on dermal hazards, exposures, risk characterization, and management.