Use of Short-Term Inhalation Study to Obtain Initial Hazard Data and Prepare for Subacute and Subchronic Inhalation Studies, and Toxicokinetic Studies

2019 ◽  
pp. 67-77
Author(s):  
Ki Soo Jeon ◽  
Jae Seong Yi ◽  
Il Je Yu
Keyword(s):  
Short Term ◽  
Inhalation Study

scholarly journals Final Report on the Safety Assessment of Stearoxy Dimethicone, Dimethicone, Methicone, Amino Bispropyl Dimethicone, Aminopropyl Dimethicone, Amodimethicone, Amodimethicone Hydroxystearate, Behenoxy Dimethicone, C24–28 Alkyl Methicone, C30–45 Alkyl Methicone, C30–45 Alkyl Dimethicone, Cetearyl Methicone, Cetyl Dimethicone, Dimethoxysilyl Ethylenediaminopropyl Dimethicone, Hexyl Methicone, Hydroxypropyldimethicone, Stearamidopropyl Dimethicone, Stearyl Dimethicone, Stearyl Methicone, and Vinyldimethicone

2003 ◽  
Vol 22 (2_suppl) ◽  
pp. 10-35
Keyword(s):  
Adverse Effects ◽  
Expert Panel ◽  
Developmental Toxicity ◽  
Oral Exposure ◽  
Final Report ◽  
Short Term ◽  
Fluid Mixture ◽  
Inhalation Study ◽  
Cosmetic Formulations ◽  
Siloxane Polymers

Dimethicone is a fluid mixture of fully methylated linear siloxane polymers end-blocked with trimethylsiloxy units. Methicone is a linear monomethyl polysiloxane. The other dimethicones and methicones covered in this review are siloxane polymers of Dimethicone and Methicone. Most of these ingredients function as conditioning agents in cosmetic formulations at current concentrations of use of ≤ 15%. Clinical and animal absorption studies reported that Dimethicone was not absorbed following oral or dermal exposure. Dimethicone, Methicone, and Vinyldimethicone were not acutely toxic following oral exposure. No adverse reactions were found in rabbits following short-term dermal dosing with 6% to 79% Dimethicone, yet adverse effects were noted with a hand cream formulation containing 1% Dimethicone, suggesting something else in the preparation was toxic. Mice and rats were dosed for 90 days with up to 10% Dimethicone without adverse effect. Dimethicone did not produce adverse effects in acute and short-term inhalation-route studies, Methicone and Vinyldimethicone were negative in acute exposure studies using rats, but Hexyl Methicone was toxic to rats at 5 mg/L delivered in small particle (mean diameter of 0.29 μ) aerosols. Most dermal irritation studies using rabbits classified Dimethicone as a minimal irritant. Dimethicone (tested undiluted and at 79%) was not a sensitizer in four assays using mice and guinea pigs. It was not a sensitizer at 5.0% in a clinical repeated insult patch test using 83 panelists. Most ocular irritation studies using rabbits classified Dimethicone as a mild to minimal irritant. Dimethicone was tested in numerous oral-dose (using rats) and dermal-dose (using rats, rabbits, and monkeys) reproductive and developmental toxicity studies. In a few studies, treated males had significantly decreased body weight and/or decreased testes or seminal vesicles weights. No treatment-related adverse findings were noted in dosed pregnant females or fetuses. Dimethicone was negative in all genotoxicity assays. It was negative in both an oral (tested at 91%) and dermal (tested at an unknown concentration) dose carcinogenicity assay using mice. The Cosmetic Ingredient Review (CIR) Expert Panel considered it unlikely that any of these polymers would be significantly absorbed into the skin due to their large molecular weight. Although adverse effects were noted in one inhalation study with small aerosol particles, the expected particle sizes for cosmetic products would primarily be in the range of 60 to 80 μ, and less than 1% would be under 10 μ, which is an upper limit for respirable particles. Overall, the safety test data support the safety of these ingredients at the concentrations they are known to be used in cosmetic formulations. Accordingly, the CIR Expert Panel was of the opinion that Stearoxy Dimethicone, Dimethicone, Methicone, Amino Bis-propyl Dimethicone, Aminopropyl Dimethicone, Amodimethicone, Amodimethicone Hydroxystearate, Behenoxy Dimethicone, C24–28 Alkyl Methicone, C30–45 Alkyl Methicone, C30–45 Alkyl Dimethicone, Cetearyl Methicone, Cetyl Dimethicone, Dimethoxysilyl Ethylenediaminopropyl Dimethicone, Hexyl Methicone, Hydroxypropyldimethicone, Stearamidopropyl Dimethicone, Stearyl Dimethicone, Stearyl Methicone, and Vinyldimethicone are safe as used in cosmetic formulations.

scholarly journals A short-term inhalation study to assess the reversibility of sensory irritation in human volunteers

2020 ◽  
Vol 94 (5) ◽  
pp. 1687-1701 ◽  
Author(s):  
Stefan Kleinbeck ◽  
Michael Schäper ◽  
Marlene Pacharra ◽  
Marie Louise Lehmann ◽  
Klaus Golka ◽  
...  
Keyword(s):  
Sensory Irritation ◽  
Short Term ◽  
Inhalation Study ◽  
Human Volunteers

1,1,1,3,3,3-Hexamethyldisilazane (2018)

2019 ◽  
Vol 35 (3) ◽  
pp. 189-195
Keyword(s):  
Inhalation Exposure ◽  
Male Rats ◽  
Feed Consumption ◽  
High Dose ◽  
Exposure Level ◽  
Short Term ◽  
Adhesion Promoter ◽  
Inhalation Study ◽  
Short Term Exposure ◽  
Dose Inhalation

1,1,1,3,3,3-Hexamethyldisilazane (HMDZ) is used industrially to treat the surface of silica, as an intermediate adhesion promoter or silylating agent in the semiconductor industry, as a chemical modifier of inorganic fillers, and as a water scavenger silicone sealant. In animal studies, HMDZ is considered to be slightly to at most moderately toxic following acute administration via oral, dermal, and inhalation routes of exposure. HMDZ is neither an eye irritant nor was it dermally irritating under semiocclusive conditions; however, it caused dermal necrosis in two studies under occlusive conditions. HDMZ is not genotoxic or mutagenic in in vitro assays and was not reproductively or developmentally toxic in an inhalation screening study in rats. Short-term and subacute, high-dose inhalation exposure to HMDZ produced respiratory tract irritation, reduced feed consumption, changes in clinical chemistry parameters, and reversible central nervous system depression in rats. In a 90-day inhalation exposure study in rats, HMDZ exposure-related effects were observed in the kidneys of male rats but were determined to be alpha-2µ-nephropathy, thus, not relevant to humans. Based on the results of the 90-day (subchronic) inhalation study, 75 ppm was determined to be the no-observed adverse effect level (NOAEL) and was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, interindividual variability, and intraindividual variability. The resulting 8-h TWA WEEL value of 10 ppm is fully expected to provide a significant margin of safety against any potential adverse health effects in workers following long-term inhalation exposure to HMDZ vapor. A 15-min short-term exposure limit of 50 ppm was also established to protect workers from reversible effects produced by acute, high-dose inhalation of HMDZ vapor. A skin notation (Skin) is warranted because of the potential for the dermal route to significantly contribute to the overall exposure to HMDZ.

Short-Term Rat Inhalation Study With Aerosols of Acrylic Ester-Based Polymer Dispersions Containing a Fraction of Nanoparticles

2012 ◽  
Vol 31 (1) ◽  
pp. 46-57 ◽  
Author(s):  
Lan Ma-Hock ◽  
Robert Landsiedel ◽  
Karin Wiench ◽  
Dominik Geiger ◽  
Volker Strauss ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Raw Materials ◽  
Inhalation Exposure ◽  
Male Rats ◽  
Short Term ◽  
Limit Values ◽  
Inhalation Study ◽  
Acrylic Ester ◽  
Materials Used ◽  
Polymer Dispersions

Aqueous polymer dispersions are important raw materials used in a variety of industrial processes. They may contain particles with diameters ranging from 10 to 1500 nm. Polymer exposure alone may cause pulmonary lesions after inhalation exposure. Polymer dispersions with increased proportions of nano-sized particles are being developed for improved material characteristics, and this may pose even increased pulmonary hazards upon potential inhalation exposure. In a 5-day screening study, male rats were nose-only exposed to aerosols generated from 2 dispersions of acrylic ester polymers with identical chemical composition but different nano-sized particle proportions at particle concentrations of 3 and 10 mg/m3. Immediately and 19 days after the end of inhalation, necropsies were conducted with major emphasis on respiratory tract histopathology. Three and 23 days after the end of inhalation, bronchoalveolar lavage was performed to screen for early pulmonary injury and inflammation. In contrast to the adverse effects known for other materials in short-term inhalation studies, none of the tested preparations of acrylic ester polymers elicited any adverse effect at the end of the inhalation or postinhalation periods. No shift in toxicity could be observed by the increased proportion of nano-sized polymer particles. Under the conditions of this study, the no observable adverse effect levels for both preparations were >10 mg/m3, that is 2- to 3-fold beyond current nuisance dust threshold limit values.

A Short-Term Inhalation Study Protocol: Designed for Testing of Toxicity and Fate of Nanomaterials

2014 ◽  
pp. 207-212 ◽  
Author(s):  
Lan Ma-Hock ◽  
Thomas Hofmann ◽  
Robert Landsiedel ◽  
Bennard van Ravenzwaay
Keyword(s):  
Study Protocol ◽  
Short Term ◽  
Inhalation Study

scholarly journals Short-term inhalation study of graphene oxide nanoplates

2018 ◽  
Vol 12 (3) ◽  
pp. 224-238 ◽  
Author(s):  
Young Hun Kim ◽  
Mi Seong Jo ◽  
Jin Kwon Kim ◽  
Jae Hoon Shin ◽  
Jin Ee Baek ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Short Term ◽  
Inhalation Study

Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter
Keyword(s):  
Working Memory ◽  
Rapid Serial Visual Presentation ◽  
Language Comprehension ◽  
Short Term Memory ◽  
Visual Presentation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

Ultrastructural Changes of Canine Kidneys During 24-Hour Perfusion on a LI-400 Preservation System

1971 ◽  
Vol 29 ◽  
pp. 316-317
Author(s):  
M. O. Magnusson ◽  
D. G. Osborne ◽  
T. Shimoji ◽  
W. S. Kiser ◽  
W. A. Hawk
Keyword(s):  
Electron Microscopy ◽  
Electrolyte Solution ◽  
Ultrastructural Changes ◽  
Midline Incision ◽  
Short Term ◽  
Pentobarbital Anesthesia ◽  
Pulsatile Perfusion

Short term experimental and clinical preservation of kidneys is presently best accomplished by hypothermic continuous pulsatile perfusion with cryoprecipitated and millipore filtered plasma. This study was undertaken to observe ultrastructural changes occurring during 24-hour preservation using the above mentioned method.A kidney was removed through a midline incision from healthy mongrel dogs under pentobarbital anesthesia. The kidneys were flushed immediately after removal with chilled electrolyte solution and placed on a LI-400 preservation system and perfused at 8-10°C. Serial kidney biopsies were obtained at 0-½-1-2-4-8-16 and 24 hours of preservation. All biopsies were prepared for electron microscopy. At the end of the preservation period the kidneys were autografted.

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