Diethylene glycol, toxicity

The primary function of the kidneys is to rid the body of waste materials that are either ingested or produced by metabolism, and to control the volume and composition of the body fluids. The toxins absorbed by the different routes are biotransformed and enter the blood. They are then eliminated through the urine, feces, and air. Since the kidneys receive approximately a quarter of the cardiac output, it is an important organ for the exposure of toxicants and their metabolites. Recent incidents of pet food toxicity and diethylene glycol toxicity indicate that contamination of animal and human food and drugs, respectively, can lead to severe mortahty and morbidity as a result of renal toxicity. 

Ethylene glycol DIethylene glycol (toxic) Propylene glycol... 

Effects of repeated ethylene glycol peroral overexposure in treated rats and mice can result in kidney, Hver, and nervous system damage. The most sensitive indicators of ethylene glycol toxicity are disturbances in acid—base balance and nephrotoxic (kidney) effects. Effects of repeated chronic peroral overexposure of diethylene glycol in treated rats result in kidney and Hver damage (48). 

Unlike chloroformates, diethyl and dimethyl carbonates are only mildly irritating to the eyes, skin, and mucous membranes. Diethylene glycol bis(aHyl carbonate) may be irritating to the skin, but it is not classified as a toxic substance however, it is extremely irritating to the eyes. 

Fatty Acid Esters. Defoamers that are more environmentally acceptable than convential products are based on fatty acid esters of hydroxy alcohols, such as sorbitan monooleate [1908] or sorbitan monolaurate in combination with diethylene glycol monobutyl ether as a cosolvent [451]. These defoamer compositions are as effective as conventional materials, for example, those based on acetylenic alcohols are less toxic, especially to marine organisms, and are readily biodegradable. The defoamer compositions are used in water-based hydrocarbon well fluids during oil/gas well drilling, completion, and workover, especially in marine conditions. 

Calvary, H.O. and Klump, T.G. (1939). The toxicity for human beings for diethylene glycol with sulfanilimide. Southern Med. J. 32 1105. 

The major FDA concern came to be better comprehension of diethylene glycol s toxicology. The imminent trial in court required this. In a more basic sense, the crisis made FDA scientists aware of inadequacies in the state of the discipline. In constant contact with their peers at the AMA and at the University of Chicago and Johns Hopkins, a team of FDA scientists launched a project that "developed the first valid process for determining the comparative toxicity of compounds, a statistically based and legally defensible process that opened the door to modern toxicological testing methods" (77). 

A Division of Pharmacology had been formally set up in the Food and Drug Administration in 1935, composed mostly—as one of its members, Edwin P. Laug, remembered—of "biochemists who then changed sails and became pharmacologists" (7] ). To study the toxicity of lead and arsenic pesticide residues formed the division s initial purpose, but the Elixir Sulfanilamide crisis brought an almost total shift of effort to diethylene glycol. 

Limited information is available regarding the influence of other chemicals on the toxicity of 1,3-DNB or 1,3,5-TNB. One study reported that a chemical mixture containing 1,3-DNB was not toxic and did not induce methemoglobin formation. The mixture contained 1,3-DNB (0.5%), ethylene glycol (77.5% or less), and diethylene glycol (15% or more) (Ishihara and Ikeda 1979). As the mixture was made more polar either by adding water or short-chain dicarboxylic acids, methemoglobin formation was favored. The specific mechanism of this interaction is not known. 

It seems incredible now that no one bothered to check the toxicity of the solvent Watkins used. Had they bothered to peruse the scientific literature, they would have discovered that diethylene glycol is metabolized in the body to oxalic acid, a potent kidney toxin that can kill. Simple animal experiments would have confirmed the risk. 

Fatty acid esters would be predicted to have little irritation or toxic effects. Ex vivo permeability studies conducted in porcine buccal mucosa showed significant permeation enhancement of an enkephalin from liquid crystalline phases of glycerine monooleate [32]. These were reported to enhance peptide absorption by a cotransport mechanism. Diethylene glycol monoethyl ether was reported to enhance the permeation of essential oil components of Salvia desoleana through porcine buccal mucosa from a topical microemulsion gel formulation [33]. Some sucrose fatty acid esters, namely, sucrose laurate, sucrose oleate, sucrose palmitate, and sucrose stearate, were investigated on the permeation of lidocaine hydrochloride [34], with 1.5% w/v sucrose laurate showing a 22-fold increase in the enhancement ratio. 

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