Toxicity report series最新文献

Acetoin and 2,3-pentanedione are highly volatile components of artificial butter flavoring (ABF). Concerns over the inhalation toxicity of these compounds originate from the association between occupational exposures to ABF and adverse fibrotic lung effects, specifically obliterative bronchiolitis (OB) in the distal airways. 2,3-Pentanedione has been used as a replacement for 2,3-butanedione (diacetyl) in some ABF due to concerns about the respiratory toxicity of 2,3-butanedione. However, 2,3-pentanedione is structurally similar to 2,3-butanedione and has been shown to exhibit potency similar to 2,3-butanedione regarding airway toxicity following acute inhalation (whole-body) exposure. This report describes a series of studies to evaluate the 2-week inhalation toxicity of acetoin and the 3-month inhalation toxicity of acetoin and 2,3-pentanedione. (Abstract Abridged).

Oral human exposure to vanadium may occur due to its presence in food and drinking water and its use in dietary supplements. The most prevalent oxidation states of vanadium in food and drinking water have been characterized as tetravalent and pentavalent. Vanadyl sulfate and sodium metavanadate were selected as representative tetravalent (V4+) and pentavalent (V5+) test articles for these studies, respectively. To assess the potential for oral toxicity of vanadium compounds with differing oxidation states under similar test conditions, the 3-month National Toxicology Program (NTP) toxicity studies of sodium metavanadate and vanadyl sulfate were conducted in male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats (including perinatal exposure) and in B6C3F1/N mice. Drinking water concentrations for sodium metavanadate (0, 31.3, 62.5, 125, 250, and 500 mg/L) and vanadyl sulfate (0, 21.0, 41.9, 83.8, 168, and 335 mg/L) were selected on the basis of previously published 14-day drinking water studies conducted as part of the NTP vanadium research program. (Abstract Abridged).

(+)-Usnic acid is a secondary metabolite of lichens belonging to the Usnea genus. Usnea lichens and purified usnic acids have been used historically in traditional herbal medicine as bactericidal and antimicrobial agents. (+)-Usnic acid exhibits membrane proton uncoupling activity, which not only forms the mechanistic basis of its bactericidal action, but also has provided a rationale for its use as a fat-burning, weight-loss agent. Purified (+)-usnic acid has been marketed in the United States for this purpose either alone or in combination with other chemical agents. Use of some of these fat-burning products that contain (+)-usnic acid has resulted in serious liver damage. This study investigated the potential toxicity of (+)-usnic acid in male and female F344/N Nctr rats and B6C3F1/Nctr mice that were exposed via feed for 3 months. F344/N Nctr rats were administered 0, 30, 60, 120, 360, or 720 ppm in feed, while B6C3F1/Nctr mice were administered 0, 15, 30, 60, 180, or 360 ppm in feed. (Abstract Abridged).

Usnea lichens and purified usnic acids have been used historically in traditional herbal medicine as bactericidal and antimicrobial agents. Usnea lichens contain 1%-3% (+/-)-usnic acid and extracts of these lichens are currently marketed in the United States as herbal antimicrobial agents. (+/-)-Usnic acid exhibits membrane proton uncoupling activity, which not only forms the mechanistic basis of its bactericidal action, but also has provided a rationale for its use as a fat burning, weight-loss agent. Purified (+)-usnic acid has been marketed in the United States for this purpose either alone or in combination with other chemical agents. Use of some of these fat burning products that contain (+)-usnic acid has resulted in serious liver damage. This study investigated the potential toxicity of ground Usnea lichens containing (+/-)-usnic acid in male and female Fischer 344/N Nctr rats and B6C3F1/Nctr mice that were exposed via feed for 3 months. F344/N Nctr rats were administered 0, 30, 60, 120, 360, or 720 ppm in feed, while B6C3F1/Nctr mice were administered 0, 15, 30, 60, 180, or 360 ppm in feed. (Abstract Abridged).

Trans-resveratrol (RES) is a polyphenol found in various fruits and plants. Numerous in vitro studies have shown its clear antioxidant and anti-inflammatory effects, which has led to additional in vivo and clinical studies evaluating the use of RES to treat diseases such as cancer, cardiometabolic disease, and neurodegenerative disease. Despite growing interest in and use of RES, limited studies have assessed the safety of RES exposure, especially perinatally. The National Toxicology Program conducted toxicity studies to provide these data. (Abstract Abridged).

Aspergillus fumigatus is a thermotolerant, soil-borne fungal species that is ubiquitous in the environment. Mold was nominated to the National Toxicology Program (NTP) by a private individual due to suspected adverse health effects associated with personal exposure in indoor and occupational settings. A. fumigatus is of particular concern in the biowaste industry as the species can contaminate self-heating compost piles. Because of this potential for personal and occupational exposure and the lack of available toxicity data, toxicity studies were conducted in which male and female B6C3F1/N mice were exposed to A. fumigatus conidia (spores) two times a week for 3 months. All in-life procedures, including inhalation exposure, test article preparation, and hematology analysis, were completed by the National Institute for Occupational Safety and Health (NIOSH, Morgantown, WV). Battelle (Columbus, OH) conducted terminal necropsies, measured terminal body and organ weights, and evaluated gross lesions on-site at NIOSH. Tissue processing and histopathology were completed at Battelle. Grocott's methenamine silver (GMS) staining was performed at NIOSH. Genetic toxicology studies on mouse peripheral blood erythrocytes were conducted by Integrated Laboratory Systems, LLC (Research Triangle Park, NC). (Abstract Abridged).

Despite the cessation of its production and use in many parts of the world, hexachlorobenzene (HCB) remains highly persistent in the environment, and chronic, low-dose exposure to HCB in humans continues. Its structural resemblance to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), ability to activate the aryl hydrocarbon (Ah) receptor, TCDD-like toxicities, and bioaccumulative nature suggest HCB be included in the toxic equivalency factor (TEF) methodology. Consequently, the National Toxicology Program conducted this subchronic study of HCB, including measurement of a variety of toxicological and biochemical endpoints, to allow comparison to TCDD data obtained in a previous 2-year bioassay. (Abstract Abridged).

Trimethylsilyldiazomethane (TMSD) is a methylating reagent widely used in organic chemistry. TMSD is structurally related to the compound diazomethane, which is a known lethal respiratory toxicant in humans and in animal models. TMSD is less reactive (with lower explosive potential) than diazomethane and is considered a safer, less toxic alternative. Few toxicity data are available to support this claim, however, and TMSD is readily available commercially from chemical suppliers. Concern over the inhalation toxicity of TMSD originates from reports of the death of two chemists resulting from lung injury and acute respiratory distress syndrome following exposure to TMSD in the workplace. Other concerns include the known inhalation toxicity of diazomethane and the absence of inhalation toxicity data for TMSD. The National Toxicology Program (NTP) conducted this study to evaluate the acute inhalation toxicity of TMSD in vivo.(Abstract Abridged).

Fullerene C60 (C60), a primary allotrope of carbon, is used in a variety of consumer applications including microelectronics, photovoltaics, batteries and fuel cells, and water treatment methods. Human exposure to engineered C60 due to industrial applications may occur via inhalation, oral, dermal, or parenteral routes. In these toxicity and tissue burden studies, male and female Wistar Han rats and B6C3F1/N mice were exposed to fullerene C60 (at least 95% pure) via nose-only inhalation for 3 months. Two different C60 fullerene aggregate sizes, 1 µm diameter (micro-C60) and 50 nm diameter (nano-C60) were studied to assess the potential for differential effects based on particle size. (Abstract Abridged).

Abrasive blasting, commonly known as sandblasting, involves forcibly projecting a stream of abrasive particles through compressed air or steam against a surface to change its quality or to remove contaminants. Silica blasting sand contains high levels of crystalline silica--which can cause pulmonary fibrosis (silicosis) after exposure through inhalation and is considered a lung carcinogen--and constitutes approximately 63% of all abrasives used in abrasive blasting. Other abrasives, including specular hematite, are recommended as alternative blasting agents. Due to the health risks associated with using blasting sand in the abrasive blasting process and the lack of toxicity data on alternatives to blasting sand, the National Institute for Occupational Safety and Health (NIOSH) proposed testing blasting sand and alternative abrasives to characterize their associated toxicity. (Abstract Abridged).