Safety Assessment of Poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, Poloxamer 105 Benzoate, and Poloxamer 182 Dibenzoate as Used in Cosmetics

Abstract

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multid...

Poloxamer 188 (P188) as a Membrane Resealing Reagent in Biomedical Applications

“…Toxicology concerns are minimized as some studies and recent clinical trials suggest the use of poloxamers in human may be safe[19]. However, there are other reports that infusion of poloxamers may produce some adverse effects in patients [60-67]. …”

“…The efficacy shown in a number of applications suggests that there are broad uses for P188 in biomedicine. In general, the triblock copolymers are widely available, show minimal toxicity with short term application [60] and are easy to manufacture under current good manufacturing procedure (cGMP) conditions. However, some potential caveats about the use of these in the treatment of disease appear in the scientific literature.…”

“…However, some potential caveats about the use of these in the treatment of disease appear in the scientific literature. Studies have found that elevated doses of P188 that fall into the range required to produce some of the effects presented in the reviewed patents can lead to adverse reactions in humans [60-67], thus potentially complicating the treatment of certain disease types, particularly chronic diseases that would require long term dosing of the patient. In addition, recent studies show that there could be bioavailability concerns associated with the use of P188 in some tissue types [46].…”

Poloxamer 188 Protects Neurons against Ischemia/Reperfusion Injury through Preserving Integrity of Cell Membranes and Blood Brain Barrier

“…P188 can come across blood brain barrier [17]. However, when it comes to the effects on the cerebral ischemia, although Colbassani et al had reported that P188 can increase cerebral blood flow in rabbits following ligation of the middle cerebral artery [18], they didn’t explore whether it had a protective effect on ischemic neuronal injury.…”

Evaluation of a Thermoprotective Gel for Hydrodissection During Percutaneous Microwave Ablation: In Vivo Results

“…As mentioned previously, the close proximity of ablations to vulnerable tissues (mean distance from emission point to non-target tissue = 7 mm) represented an extreme scenario not likely to be attempted in a clinical setting. Ongoing studies are underway to characterize P407’s pharmacologic properties, but previous work indicates it has weak immunogenicity and low toxicity [7, 32]. Human studies to characterize the safety, pharmacodynamics, and pharmacokinetics of intraperitoneal P407 have not yet been performed, but animal studies suggest that intraperitoneal injections of P407 have a half life of approximately 21 h based on urinary excretion [28].…”