Experimental toxicity of a high molecular weight poly(ethylene oxide)

Smyth, Henry F.; Weil, Carrol S.; Woodside, M.D.; Knaak, James B.; Sullivan, L.J.; Carpenter, Charles P.

doi:10.1016/0041-008x(70)90016-5

Cited by 25 publications

(11 citation statements)

References 2 publications

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“…Toxicity of PEGs has been widely studied in different animals (Ballantyne et al, 1998;David and Saleh, 1978;Smyth et al, 1947Smyth et al, , 1970. PEGs are considered to be inert and possess a low order of toxicity in animals and humans.…”

Section: Introductionmentioning

confidence: 99%

Systemic toxicity and toxicokinetics of a high dose of polyethylene glycol 400 in dogs following intravenous injection

Bao-qiu

Dong²,

Fang³

et al. 2011

Drug and Chemical Toxicology

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Polyethylene glycol 400 (PEG-400) has been used in injections. However, limited data are available concerning the toxicity of a high dose of PEG-400 following intravenous (i.v.) injection. The aim of the present study was to estimate the systemic toxicity and toxicokinetics of a high dose of PEG-400 in dogs following i.v. injection. Twenty-four dogs were divided into four groups: a control group receiving normal saline and three test groups receiving 4.23, 6.34, and 8.45 g/kg of PEG-400, respectively, by i.v. injection once a day for 30 days. The repeated-dose toxicity of PEG-400 was assessed. Toxicokinetic parameters of PEG-400 in dogs were estimated on days 1 and 30. Dry mouth and dry nasal mucus membrane were observed in dogs treated with 6.34 and 8.45 g/kg of PEG-400. Cloudy swelling of kidney cell and increased glomerular volume were observed in dogs treated with 8.45 g/kg of PEG-400 when the animals were sacrificed 24 hours after the last injection. No significant histological changes were found 21 days later. Repeated dosing did not affect the toxicokinetic profile of PEG-400 in dogs. This study has shown that the toxicity of a high dose of PEG-400 following repeated intravenous injections is low, and alterations produced are reversible.

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Section: Introductionmentioning

confidence: 99%

Systemic toxicity and toxicokinetics of a high dose of polyethylene glycol 400 in dogs following intravenous injection

Bao-qiu

Dong²,

Fang³

et al. 2011

Drug and Chemical Toxicology

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“…However, iv administration of high doses (≥ 100 mg/kg) of alginate (~85,000 g/mol M w ) were lethal to mice, rabbits and cats [26]; ip or iv administration of similarly high doses of alginate or alginic acid were also lethal to cats [27]. No adverse events were observed in rats receiving iv injections of 0.01 and 0.025 % PEO (4,000,000 g/mol M w ) solutions in a 4 ml (4 and 10 mg/kg, respectively) dose [28]. Injections of 2.5 ml of 0.05 % PEO or 0.3 ml of 0.10 % PEO (12.5 and 3.0 mg/kg, respectively) caused death however; intense mechanical shearing of the 0.10 % PEO solution to reduce solution viscosity via degradation of the PEO M w abrogated this acute toxicity, even for high doses (40 mg/kg) [28].…”

Section: Discussionmentioning

confidence: 99%

Polymer-coated cannulas for the reduction of backflow during intraparenchymal infusions

Vazquez

Hagel

Willenberg

et al. 2012

J Mater Sci: Mater Med

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Infusate backflow or leak-back along the cannula track can occur during intraparenchymal infusions resulting in non-specific targeting of therapeutic agents. The occurrence of backflow depends on several variables including cannula radius, infusate flow rate, and tip location. In this study, polymer coatings that swell in situ were developed and tested with in vitro hydrogel experiments for backflow reduction. Coatings were applied to the external cannula surface in a dual layer arrangement with a poly(vinyl alcohol) outer layer atop an inner poly(ethylene oxide) and alginate layer. Once these coated cannulas were inserted and allotted an 8–10 min waiting period for hydration, backflow during infusions of 4.0 µl of a macromolecular tracer (Evans Blue labeled albumin) was reduced significantly under flow rates of 0.3–0.6 µl/min, allowing for more effective distribution within targeted regions. Polymer coating thicknesses before and after hydrations were 0.035 and 0.370 mm, respectively. Also, backflow data was fit to a model to estimate the effective local compressive stress caused by the hydrated polymers. After withdrawal of the cannula from the insertion site, the hydrated polymer coatings remained within the cavity left in the hydrogel tissue phantom and formed a seal at the infusion site that prevented further backflow during needle withdrawal. Ex vivo infusions in excised porcine brain tissues also showed significant backflow reduction while also demonstrating the ability to leave a polymer seal in the tissue cavity after cannula removal. Thus, application of these polymers as needle or cannula coatings offers a potentially simple method to improve targeting for local drug delivery.

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“…Some low molecular weight polymers have weights in the range of 200-600 (31), but can be up to 10,000 (33,182). High molecular weight resins are described as having molecular weights !100,000, !ut can be as high as 4,000,000 (33, 182).…”

Section: Molecular Weightmentioning

confidence: 99%

“…In an older report (182), solutions of 0.1% commercial material killed rats when first administered intravenously at a dosage of 3 mg/kg (0.3 mL). This may have been due to clumping of cells and death from embolism.…”

Section: Experimental Studiesmentioning

confidence: 99%

Synthetic Polymers: Polyesters, Polyethers, Polysulfones, and Other Polymers

Benson¹

2012

Patty's Toxicology

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Commercial use of polyester resins dates from the early twentieth century, when alkyd resins were first used in surface coatings. The polyesters are found today as fibers, films, laminating resins, molding resins, and engineering plastics. Many of the high molecular weight polyethers are used as engineering plastics, as are the polysulfides and the polysulfones. Important properties of these compounds and production data for the general categories are provided. Processing techniques vary widely and are discussed in the sections in this chapter. Although toxicity data for some of these polymers are limited, information is discussed in the sections in this chapter. In many cases, the finished polymers are associated with low toxicity. However, some chemicals within the finished products have been known to migrate from the polymers (although usually in small amounts). Further, some of the polymers described in this chapter are used in biomedical equipment, including grafts and other implants, dialysis membranes, or as vehicles for intravenous injections, and there may be toxicity associated with these uses. For specific medical applications, any risks should be weighed against benefits derived from the products. Consultation with medical professionals is necessary before deciding on whether to use particular devices. Certainly some of the highest potentials for concern associated with these polymers are for workers at manufacturing or processing sites. Workers may be exposed to volatile chemicals (e.g., monomers, flame retardants, additives) generated during processing of flammable solvents, elevated temperatures, or fires. Workers may also be exposed to dust or particulates generated in the manufacturing and processing of polyester fibers. Finally, explosion hazards might be possible where static charges are generated (e.g., during physical processing of polyester films over rollers) where flammable materials are used. Industrial hygiene concerns with these polymers depend on the type of resin. Examples of such concerns include the following: significant quantities of styrene may be released during the fabrication of unsaturated polyester resins; particulates that have biologically significant consequences when inhaled in large amounts may be generated in the manufacturing and processing of polyester fibers; processing of polyoxymethylene in a poorly ventilated space may release biologically significant amounts of formaldehyde into the adjacent atmosphere; or sulfur‐containing engineering resins may yield hydrogen sulfide or sulfur dioxide if heated to decomposition temperatures. The chemical inputs typically used to synthesize each of the polymers as well as relevant additives are discussed in the sections in this chapter. Toxicity data for most of these inputs can be found in other chapters of this edition of Patty's Industrial Hygiene and Toxicology . No specific standards are known that pertain to ordinary industrial use of the finished polymeric products. However, there may be occupational exposure limits for the chemicals used to synthesize or process these polymers. In addition, there are occupational exposure limits for dust and particles that may be applicable. There are also several examples of general protection measures that might be required such as using a continuous supply of fresh air to the workplace together with removal of processing fumes through exhaust systems is recommended. Also, processing fume condensates that are toxic or are fire hazards should be removed periodically from exhaust hoods, ductwork, and other surfaces by individuals using appropriate personal protection. Ventilation requirements must be locally determined to limit exposure to materials at their point of use. Use of proper personal protection while cleaning or handling condensates and plastic processing fumes should be observed. The polymers described in this chapter have generally little or no data on toxicity from burning. The toxicological aspects of plastic combustion products can be very complex in part because it is very difficult to simulate real‐world environments under controlled conditions. Also, depending on a variety of factors, the qualitative and quantitative nature of chemicals present in the combustion product mixtures will vary. Some factors that may contribute to toxicity of combustion products of these polymers include increase of carbon monoxide and carbon dioxide, decrease of oxygen, and the presence of irritant gases. The primary effects from fires are often asphyxia due to oxygen deficiency, poisoning from carbon monoxide, heat damage to tissues, and irritation of the respiratory tract by combustion gases. Some polymers are used in packaging (or directly in food), and clearances for direct or indirect food contact applications are listed under Title 21 of the Code of Federal Regulations, and are listed in the sections in this chapter. Other polymers have been approved for use in specific medical devices that may be implanted in the body or used in dialysis machines.

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Experimental toxicity of a high molecular weight poly(ethylene oxide)

Cited by 25 publications

References 2 publications

Systemic toxicity and toxicokinetics of a high dose of polyethylene glycol 400 in dogs following intravenous injection

Systemic toxicity and toxicokinetics of a high dose of polyethylene glycol 400 in dogs following intravenous injection

Polymer-coated cannulas for the reduction of backflow during intraparenchymal infusions

Synthetic Polymers: Polyesters, Polyethers, Polysulfones, and Other Polymers

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