Crown toxicity

Often poly(ethylene glycol)s or derivatives thereof can be used instead of crowns or onium salts advantageously, although their catalytic activity frequently tends to be somewhat lower. The possible toxicity of crowns and cryptands and the price difference between these compounds and onium salts (100 1 to 10 1) are other important factors to be considered. Thus (1) [17455-13-9] (2) [14187-32-7] and (3) [16069-36-6] and cryptands are used more often in laboratory work, whereas onium salts are more important for industrial processes. 

Caution Crown ethers may be toxic. Due care should be exercised in the preparation and handling of l8-croum-6. An explosion has been reported... 

Kulstad and Malmsten tested a number of derivatives of l,10-diaza-18-crown-6 (9) for toxicity in mice (intravenous). Compound 9 and the bis-N-2-hydroxyethyl,bis-N-2-carboxamidomethyl, and bis-N-2-carboxymethyl derivatives of 9 were tested and all were found to be toxic in the range of 5—50 mg/kg. At a dose level of 5 mg/kg of 9, the two mice tested were still alive after a week, but at a dose level of 25 mg/kg, the mice died in less than 24 h If these data could be translated directly to human beings, a 100 kg human would require something between 0.5—2.5 g of compound (i.v.) to produce a lethal effect. 

Although crown ethers were often found to be as effective as the best onium salts in PTC, they have only found limited commercial application because of their high cost (10 to 100 times that of quats) and perceived toxicity. Cryptands are even more expensive than crown ethers. 

Not all crown ethers have been tested for ecological or toxicological properties. Some are irritants and some are known to be toxic, although those tested do not show high toxicity. Nevertheless, amongst those that have not been tested, some may be hazardous to health. 

It was a result of demand from industry in the mid-1960s for an alternative to be found for the expensive traditional synthetic procedures that led to the evolution of phase-transfer catalysis in which hydrophilic anions could be transferred into an organic medium. Several phase-transfer catalysts are available quaternary ammonium, phosphonium and arsonium salts, crown ethers, cryptands and polyethylene glycols. Of these, the quaternary ammonium salts are the most versatile and, compared with the crown ethers, which have many applications, they have the advantage of being relatively cheap, stable and non-toxic [1, 2]. Additionally, comparisons of the efficiencies of the various catalysts have shown that the ammonium salts are superior to the crown ethers and polyethylene glycols and comparable with the cryptands [e.g. 3, 4], which have fewer proven applications and require higher... 

Despite the highly efficient performance of crown ethers in reducing the irreversible capacity at the anode side, especially when PC-based electrolytes were used, the toxic nature of these compounds still prevented their application in commercial lithium ion cells. 

Elemental sulfur is a yellow solid, in which eight snlfnr atoms form a crown-shaped ring Ss. Unlike elemental white phosphorus, elemental snlfnr has very low toxicity. Years ago, people in the United States took a preparation of snlfnr and molasses as a spring tonic. Taken orally, sulfur has a mild laxative effect. Beyond that, it is not clear to me what favorable effects this tonic may have had, if any. There is a lot of snlfnr aronnd. When taken in all its forms, it accounts for nearly 2% of the weight of the crnst of the Earth. 

Dicyclohexyl-18-crown-6 polyether possesses unusual physiological properties which require care in its handling. It is likely that other cyclic polyethers with similar (iomplcxing power are also toxic, and should be handled with ccpml care. 

Oral toxicity. The approximate lethal dose of the dicyclo-hexyl-18-crown-6 polyether for ingestion by rats was 300 mg./ kg. In a 10-day subacute oral test, the compound did not exhibit any cumulative oral toxicity when administered to male rats at a dose level of 60 mg./kg./day. It should be noted that dosage at the approximate lethal dose level caused death in 11 minutes, but that a dose of 200 mg./kg. was not lethal in 14 days. 

No teratogenic effects have been reported in limited developmental toxicity studies in rodents. Decreased fetal body weight and crown-rump length were noted in rats and mice after parenteral administration. ... 

Embryonic effects were only observed at treatment levels associated with severe maternal toxicity. Administered to rats on days 9-13 of gestation 360mg/kg/day caused retarded embryonic development in the form of reduced head length, crown-rump length, somite number, and protein content maternal deaths (2/9 rats) and significantly decreased body weight gain were also seen. 

Table 1 lists some allelopathlc plants of interest to foresters, together with the classes of toxic compounds produced and examples of species they are reported to suppress. The list is not exhaustive many species that may be allelopathlc have not been studied in depth. One easily observed effect—though sometimes difficult to distinguish from effects of competition—is the exclusion of shrubs, herbs, and other trees from beneath the crowns of particular tree species. 

A major problem in the development of crown ethers and cryptands as drugs is their alleged toxicity. Pedersen has reported that dicyclohexyl[18]crown-6 exhibits significant... 

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