Toxicity report series最新文献

Gum guggul extracts (GGEs) are botanical preparations derived from the oleoresin of the Commiphora mukul tree. The preparations are traditionally used in Ayurvedic medicine to treat hyperlipidemia, obesity, diabetes, atherosclerosis, and inflammatory conditions such as arthritis. In the United States, GGEs are marketed as dietary supplements. GGE toxicity was evaluated due to widespread human exposure through increasing dietary supplement use, demonstrated metabolic and hormone-altering effects, and a lack of available information to adequately assess safe use in humans. Male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice were administered a GGE formulation in corn oil by gavage for 28 days or 3 months. Oral gavage was chosen as the route of exposure for these studies because human exposure primarily occurs by ingestion of encapsulated GGE supplements. (Abstract Abridged).

Multiwalled carbon nanotubes (MWCNTs) are highly ordered hexagonal lattices of carbon atoms arranged into cylinders by hydrogen bonding, dipolar forces, hydrophilic or hydrophobic interactions, gravity, and other forces. MWCNTs are synthesized by applying energy to a carbon source, which produces individual or groups of carbon atoms that reassemble into tubes. One of the primary uses of MWCNTs is in nanotube-reinforced polymer composite materials that take advantage of their low-density and high load-bearing capacity. Nanoscale materials were nominated by the Rice University Center for Biological and Environmental Nanotechnology to the National Toxicology Program for toxicologic testing. Because long-term inhalation toxicity and carcinogenicity studies were being conducted on a relatively short, rigid MWCNT, a representative long and thin MWCNT was selected for these studies. Following an evaluation of 24 different long, thin MWCNTs, the 1020 Long Multiwalled Carbon Nanotube (L-MWNT-1020) (Sun Innovations, Fremont, CA) was selected for study based on availability, high purity (97%), and the low amount of residual nickel catalyst (0.52% by weight). The average L-MWNT-1020 nanotube length was 2,600 nm and the average width was 15.3 nm. Because nickel was shown to be tightly bound to L-MWNT-1020, tissue nickel content was measured to determine lung burden. (Abstract Abridged).

Widespread exposure to several per/polyfluorinated alkyl substances (PFAS) is associated with a variety of toxicities that include liver and endocrine toxicity. The National Toxicology Program (NTP) conducted 28-day toxicity studies in male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats (n = 10/dose; five doses per chemical) to compare the toxicities of seven PFAS (three sulfonic acids or salt: perfluorobutane sulfonic acid [PFBS], perfluorohexane sulfonate potassium salt [PFHxSK], and perfluorooctane sulfonic acid [PFOS], and four carboxylates) via gavage in deionized water with 2% Tween 80. This report describes the studies for the two sulfonic acids (PFBS and PFOS) and salt (PFHxSK); a companion report (NTP Toxicity Study Report 97) describes the studies for the PFAS carboxylates. Doses were 0 to 1,000 mg/kg/day for PFBS, 0 to 10 mg/kg/day for PFHxSK males, 0 to 50 mg/kg/day for PFHxSK females, and 0 to 5 mg/kg/day for PFOS. (Abstract Abridged).

Widespread exposure to several per/polyfluorinated alkyl substances (PFAS) is associated with a wide array of toxicities. The National Toxicology Program (NTP) conducted 28-day toxicity studies in male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats (n = 10/dose; five doses) to compare the toxicities of seven PFAS chemicals (three sulfonic acids or salt: perfluorobutane sulfonic acid, perfluorohexane sulfonate potassium salt, and perfluorooctane sulfonic acid; and four carboxylates: perfluorohexanoic acid [PFHxA], perfluorooctanoic acid [PFOA], perfluorononanoic acid [PFNA], and perfluorodecanoic acid [PFDA]) via gavage in deionized water with 2% Tween 80. This report describes the studies of the four carboxylates (PFHxA, PFOA, PFNA, and PFDA); a companion report (NTP Toxicity Study Report 96) describes the studies of the three PFAS sulfonates. Doses were 0 to 1,000 mg/kg/day for PFHxA, 0 to 10 mg/kg/day for PFOA males, 0 to 100 mg/kg/day for PFOA females, 0 to 10 mg/kg/day for PFNA males, 0 to 25 mg/kg/day for PFNA females, and 0 to 2.5 mg/kg/day for PFDA. (Abstract Abridged).

Myristicin is derived from the tropical evergreen tree Myristica fragrans. It is a major constituent in essential oil extracted from either the seed, which is the source of the spice nutmeg, or the aril covering the seed, which is the source of the spice mace. Myristicin was nominated for study by the National Cancer Institute due to widespread human exposure from natural sources and extensive consumer exposure. Male and female F344/NTac rats and B6C3F1/N mice received myristicin (greater than 94% pure) in corn oil by gavage at doses of 0, 10, 30, 100, 300, or 600 mg/kg body weight 5 days per week for 13 weeks. Additional groups of 10 male and 10 female clinical pathology study rats were administered the same doses for 21 days. Genetic toxicology studies were conducted in Salmonella typhimurium and in rat and mouse peripheral blood erythrocytes. (Abstract Abridged).

Triethylamine is used primarily as a catalyst to cure the resin systems incorporated into sand cores for foundry molds. It is also used as a curing catalyst in phenol-formaldehyde particle board adhesives, for the precipitation and purification of penicillin and cephalosporin antibiotics, and in the interfacial polymerization process for the production of polycarbonate resins. Triethylamine was nominated by the United Auto Workers Union for long-term toxicity and carcinogenicity studies based on its high production volume, the large number of occupationally exposed workers, and the lack of carcinogenicity data. Male and female F344/N rats and B6C3F1/N mice were exposed to triethylamine (greater than 99% pure) by whole body inhalation for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. (Abstract Abridged).

o-Phthalaldehyde is a high-level chemical disinfectant that is commonly used for disinfection of dental and medical instruments as an alternative to glutaraldehyde, which is a known skin and respiratory sensitizer. o-Phthalaldehyde was nominated by the National Institute for Occupational Safety and Health for toxicologic characterization based on its proposed use as a safer alternative to glutaraldehyde for chemical disinfection, its increasing use, the lack of adequate and publicly available toxicologic data, and because many human case reports document incidences of skin and respiratory sensitization following occupational exposure. Inhalation was chosen as the route of exposure for these studies because inhalation is a major route of human occupational exposure. Male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice were exposed to o-phthalaldehyde (99.7% pure) by whole-body inhalation for 3 months. (Abstract Abridged).

Chitosan is a cationic carbohydrate polymer that is commercially derived from the deacetylation of chitin obtained from seafood shells. The most widespread route of human exposure to chitosan is as a dietary supplement for body weight reduction. Chitosan was nominated by the National Cancer Institute for mechanistic studies designed to measure the potential for vitamin E depletion and osteoporosis following ingestion. Male and female Sprague Dawley rats were exposed to chitosan (86.5% deacetylated, with an average molecular weight of approximately 82 kilodaltons and estimated to be approximately 94% pure) in feed for 6 months. (Abstract Abridged).

Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) is used as a flame retardant in electronics, building and construction materials, and automotive materials. Tetrabromobisphenol A-bis(2,3-dibromopropyl ether) was nominated for toxicology and in vivo genotoxicity study by the National Institute of Environmental Health Sciences because, although human exposure potential may be low, there was concern that this chemical has carcinogenic potential and has not been adequately studied. The compound was also selected for study because dibromo-1-propanol (the core structure of the 2,3-dibromopropyl ether side chain) has been studied by the NTP and found to be carcinogenic. Male and female F344/NTac rats and B6C3F1/N mice were administered tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (approximately 94% pure) in corn oil by gavage for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. (Abstract Abridged).

o-Chloropyridine is used as an intermediate in synthetic organic, pharmaceutical, and agricultural chemical (fungicides, herbicides) manufacture. It is also used as a catalyst for phase transfer and is a key intermediate in the manufacture of pyrithione-based biocides for use in cosmetics and various pharmaceutical products. o-Chloropyridine is available in purified (99%), technical (95%), or crude (80%) grades. o-Chloropyridine was nominated for testing by the NTP based on increasing production and use as a site-limited pharmaceutical and agrochemical intermediate, the potential for occupational and environmental exposures during its manufacture, its persistence in the environment (lasting longer than 6 months), evidence of mutagenicity based on results of several short-term test systems, and suspicion of carcinogenicity based on effects associated with structurally related chemicals. Male and female F344/N rats and B6C3F1/N mice received o-chloropyridine (99% pure) dermally for 2 weeks or in drinking water for 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. (Abstract Abridged).