Propylene glycol toxicity

Cawley MJ. Short-term lorazepam infusion and concern for propylene glycol toxicity case report and review. Pharmacotherapy 2001 21(9) 1140-4. 

Van de Wiele, B. Rubinstein, E. Peacock, W. Martin, N. Propylene glycol toxicity caused by prolonged infusion of etomidate. J. Neurosurg. Anesthesiol 1995, 7 (4), 259-262. 

Savolainen H (2005). Propylene glycol toxicity. Chest eLetters, http // www.chestjournal.org/cgi/eletters/128/3/1674 (accessed 19 October 2006). 

Wilson K, Reardon C, Theodore A C, etal. (2005) Propylene glycol toxicity a severe iatrogenic illness in ICU patients receiving IV benzodiazepines a case series and prospective, observational pilot study. Chest 128 1674-1681. 

Yahwak JA, Riker RR, Fraser GL, Subak-Sharpe S. Determination of a lorazepam dose threshold for using the osmol gap to monitor for propylene glycol toxicity. Pharmacotherapy 2008 28(8) 984—91. 

Metabolism Probable propylene glycol toxicity has been reported in a patient receiving a continuous infusion of pentobarbital for refractory status epilepticus [63 ]. 

All of the propylene glycols display a low acute oral toxicity in laboratory rats as shown in Table 7 (30). Information for sucrose is shown for comparison. 

Table 7. Acute Oral Toxicity of Propylene Glycols ...

Propylene Glycol. Propylene glycol, the second largest use of propylene oxide, is produced by hydrolysis of the oxide with water. Propylene glycol has very low toxicity and is, therefore, used direcdy in foods, pharmaceuticals (qv), and cosmetics, and indirectly in packaging materials (qv). Propylene glycol also finds use as an intermediate for numerous chemicals, in hydrauhc fluids (qv), in heat-transfer fluids (antifreeze), and in many other apphcations (273). 

Propylene glycol is veiy similar to ethylene glycol, but it is not toxic... 

Elsewhere, in a series of Japanese patents, mixtures of resorcinol + sodium nitrate, glycerine + sodium nitrate, lithium hydroxide + tungstate, etc., have been claimed to be effective. An example of the use of inhibited cooling mixtures of low toxicity is provided by a patent which describes a mixture of silicate-I- polyphosphate -I- a saccharide, e.g. sucrose or fructose, as the inhibitor formulation in a propylene glycol -I- potassium-hydrogen-carbonate mixture used in aluminium cooler boxes for ice-cream. 

NOTE Glycol selection should also take into account the risk of leaks to the environment and the ultimate safe disposal of the material. Propylene glycol is a safer alternative to ethylene glycol because of its very low mammalian toxicity. 

Where low-toxicity, propylene glycol is employed (rather than the more common ethylene glycol), the inhibitor is more usually simply 30% dipotassium phosphate (K2HP04), so as to maintain the low-toxicity feature, and is then used at 3,000 ppm product. This same inhibitor is employed in the food industry in sweet water systems. 

Ethylene glycol is common in automotive antifreeze mixtures. Because of its toxicity, it is sometimes replaced by propylene glycol, which is FDA approved for use in food, and is considered generally accepted as safe. Ethylene glycol has a sweet taste, and accidental poisoning in children is a danger. 

Two options are being developed at the moment. The first is to produce 1,2-propanediol (propylene glycol) from glycerol. 1,2-Propanediol has a number of industrial uses, including as a less toxic alternative to ethylene glycol in anti-freeze. Conventionally, 1,2-propanediol is made from a petrochemical feedstock, propylene oxide. The new process uses a combination of a copper-chromite catalyst and reactive distillation. The catalyst operates at a lower temperature and pressure than alternative systems 220°C compared to 260°C and 10 bar compared to 150 bar. The process also produces fewer by-products, and should be cheaper than petrochemical routes at current prices for natural glycerol. The first commercial plant is under construction and the process is being actively licensed to other companies. 

The aquatic toxicity of antifreeze agents is not strictly a function of the main component. Aquatic toxicity may come also from minor components in the formulation. Both ethylene glycol and propylene glycol are believed to be essentially nontoxic for aquatic life. 

A toxic propylene glycol plasma level breakpoint remains to be determined. 

In 1974 the US Army approved the use of CR. CR has much greater irritating properties than CS and is about 5x more effective. In addition, CR is much less toxic than CS. CR is not used in its pure form (a yellow powder), but is dissolved in a solution of 80 parts of propylene glycol and 20 parts of water to form a 0.1% CR solution. It is used in solution as a riot control agent. 

Acute Toxicity. The LD50 following oral administration of parathion, either in propylene glycol solutions or in aqueous suspensions of the 15% wettable powder, has been determined for rats, mice, and guinea pigs. The lethal dose was approximated for rabbits and dogs. The results of these experiments are summarized in Table I. Statistical evaluation was by the method of Wilcoxon and Litchfield (11). 

As the concentration of parathion in the propylene glycol solutions is increased, it follows that the area covered by the solution is decreased. That this is a factor in toxicity is indicated by the greater toxicity of the 10 mg. per ml. solution than the 50 mg. per ml. solution. This relationship appears to be true also of the various dry preparations, in that the 1% powder is somewhat more toxic than the 15%. The addition of water to convert the powder to paste does not appreciably influence the toxicity. In comparable concentrations the wettable powder formulation is less toxic than the propylene glycol solution. 

ATSDR. 1993a. Technical report on ethylene glycol and propylene glycol. Agency for Toxic Substances and Disease Registry, Division of Toxicology, Atlanta, GA. 

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