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Bone, Muscle, and Tooth
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
John L. Vahle, Joel R. Leininger, Philip H. Long, D. Greg Hall, Heinrich Ernst
Mechanistically, bone necrosis is most often attributed to ischemia and has been most widely studied in the context of animal models of aseptic necrosis of the femoral head (Boss and Misselevich 2003). The femoral head is not routinely examined in the majority of toxicity studies, and bone necrosis, regardless of location, is not a common spontaneous event in strains of animals typically used in toxicology. Femoral head necrosis is reported in the Wistar Kyoto (WKR) and spontaneously hypertensive (SHR) rat strains (Hirano et al. 1988; Naito et al. 2009). Small foci of bone necrosis have been observed in the femoral head in untreated, young (6–8 weeks of age) Sprague–Dawley rats in routine toxicity studies (Figure 17.1d, personal observations). Corticosteroids and bisphosphonates can cause osteonecrosis in humans and a number of animal species (Jones and Allen 2011). Osteonecrosis and physeal alterations subsequent to thrombosis have been described following administration of 2-butoxyethanol (Nyska et al. 1999).
Outdoor Emissions
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
The main components of crude oil are aliphatic and aromatic hydrocarbons. Lower-molecular-weight aromatics, such as benzene, toluene, and xylene, are VOCs and evaporate within hours after the oil reaches the surface. VOCs can cause respiratory irritation and CNS depression. Benzene is known to cause leukemia in humans, and toluene is a recognized teratogen at high doses. Higher-molecular-weight chemicals such as naphthalene evaporate more slowly. Naphthalene is “reasonably anticipated to cause cancer in humans” based on olfactory neuroblastomas, nasal tumors, and lung cancers in animals. Oil can also release hydrogen sulfide gas and contains traces of heavy metals, as well as nonvolatile PAHs that can contaminate the food chain. Hydrogen sulfide gas is neurotoxic and has been linked to both acute and chronic CNS effects; PAHs include mutagens and probably carcinogens. Burning oil generates PM, which is associated with cardiac and respiratory symptoms and premature mortality. The Gulf oil spill is unique because of the large-scale use of dispersants to break up the oil slick. By late July, more than 1.8 million gallons of dispersant had been applied in the Gulf. Dispersants contain detergents, surfactants, and petroleum distillates, including respiratory irritants such as 2,1-butoxyethanol, propylene glycol, and sulfonic acid salts. In addition to oil and its products (Chapter 6), these dispersants cause havoc with the chemically sensitive, causing an exacerbation of their symptoms (Figures 1.10 and 1.11).
Overview of Approach to Noncancer Risk Assessment
Published in John C. Lipscomb, Edward V. Ohanian, Toxicokinetics and Risk Assessment, 2016
Another example of a risk value developed using a CSAF is the Health Canada tolerable daily concentration (TDC)i for 2-butoxyethanol (also called ethylene glycol butyl ether, EGBE) (39,40) developed for effects on the blood (hemolytic anemia). Health Canada determined that a simple comparison of the AUCs in blood for humans and rats for the active metabolite is as informative for interspecies scaling as the available PBPK model, and therefore calculated a CSAF for interspecies kinetics based on this dose metric. Health Canada also developed a CSAF for interspecies TD, based on in vitro data on the sensitivity of erythrocytes to hemolysis caused by the active metabolite. The usual approach for calculating the CSAF for interspecies TD is based on a specified response level, such as the EC10 (16). However, in this case, the quantitative data were sufficient to show that humans are at least 10 times less sensitive than rats, but the human EC10 was not reached. Therefore, the CSAF was not quantitatively derived from the ratio of EC10 values. Further details on calculating CSAFs are provided in Chapter 2.
Comparison of ConsExpo estimated exposure levels to glycol ethers during professional cleaning work to existing regulatory occupational exposure limit values
Published in International Journal of Occupational Safety and Ergonomics, 2023
Bello et al. [25], using direct measuring equipment, reported values of 2-butoxyethanol for cleaning bathroom sinks with an undiluted product in a large bathroom at around 6 ppm (∼21 mg/m3) and in a small bathroom without ventilation at 21 ppm (∼69 mg/m3), with activity duration of 10 min and concentration at 5–7%. Zhu et al. [30] reported an emission factor for 2-butoxyethanol for 1 h in the range of ∼2–62 mg/m3. Singer et al. [28], investigating emission profiles of the same ether from several cleaning products, reported concentrations of 0.33–2.3 mg/m3 for 1-h exposure. These studies provide evidence of exposure of cleaning workers to glycol ethers and form a basis for further investigation of exposure levels under different scenarios and from different products.
Decontamination efficacy of soapy water and water washing following exposure of toxic chemicals on human skin
Published in Cutaneous and Ocular Toxicology, 2020
Emma Forsberg, Linda Öberg, Elisabet Artursson, Elisabeth Wigenstam, Anders Bucht, Lina Thors
To examine the generalisability of decontamination procedures, five chemicals with skin absorption properties were included in the present study of which three have been assessed as risk chemicals for harmful skin penetration. The choice of toxic industrial chemicals was based on risk assessment for percutaneous toxicity in occupational settings16–18. Acrylonitrile is used as an intermediate in the production of acrylic fibres, styrene plastics and adhesives. The chemical is rapidly absorbed via all routes of exposure and its toxic effects are ranging from headache and nausea to cardiovascular collapse19. Several chemical accidents with acrylonitrile have been reported, e.g. Belgium in 2013 and Germany in 200820,21. 2-Butoxyethanol is a high-production-volume glycol ether widely used within the industry, commonly included as a solvent in surface coatings in addition to metal and household cleaners and paints. The chemical is readily absorbed following inhalation, oral and dermal exposure and causes headache, vomiting, breathing difficulties and effects on the blood circulation22. Human exposure has mainly been accidental in occupational settings or through contact with household products23. Tributylamine is utilized as an intermediate in a variety of chemical processes24. The chemical has also been used a stabilizer for the nerve agent sarin25. The main exposure routes are via the respiratory tract and through skin and following exposure both local effects, such as membrane irritation and breathing difficulties, in addition to systemic effects, e.g. convulsions, are observed24. Two simulants for highly toxic chemical warfare agents were also included in the study; ethyl lactate and methyl salicylate which previously been used as simulants for chemical warfare agents in in vivo decontamination studies on human volunteers18. Ethyl lactate is a simulant for the nerve agent sarin which is highly toxic whether inhaled or via skin uptake26. Sarin was used in two terrorist attacks in Matsumoto and Tokyo, Japan, in 1994 and 1995, which led to the death of 19 people and causing thousands to seek medical care27,28. There was also confirmed use of sarin in the Ghouta attack in 201329. Methyl salicylate is utilized as a simulant for sulphur mustard, which is a vesicant chemical warfare agent that upon skin contact causes blistering in the skin and mucous membranes30,31. It was used extensively in the Iran–Iraq war during 1980–1988 and most recently in the Syria conflict32.