Carcinogen Sultone

Toxieology. Propane sultone is a carcinogen in experimental animals and a suspected human carcinogen. No human data are available. ... 

The lARC has determined that there is sufficient evidence for carcinogenicity of propane sultone in experimental animals and that it is possibly carcinogenic to humans. ... 

Ulland B, et al Carcinogenicity of the industrial chemicals propylene imine and propane sultone. Nature 230 460-461, 1971... 

Van Durren BL, et al Carcinogenicity of isoesters of epoxides and lactones Aziridine ethanol, propane sultone and related compounds. J Natl Cancer Inst 46 143-149, 1971... 

Druckery H, Kruse H, Preussman R Propane sultone, a potent carcinogen. Nautrwiessen-schaften 55 449, 1968... 

Table 14.9 Critical structural features which can affect the carcinogenicity oflactones and sultone...

The American Conference of Governmental Industrial Hygienists (ACGIH) (1997) has not proposed any occupational exposure limit for 1,3-propane sultone in workplace air but does list it as an animal carcinogen. Australia, Belgium, Finland, France, Germany, Sweden and Switzerland list 1,3-propane sultone as a probable human carcinogen (International Labour Office, 1991). 

Propane sultone was tested for carcinogenicity by oral, intravenous and prenatal exposure in rats, producing tumours at various sites a local carcinogenic effect was induced in mice and rats when it was given subcutaneously. It was carcinogenic in rats after single-dose exposures (lARC, 1974). 

Propanc sultone is carcinogenic in rats by all routes of administration (oral, dermal, intravenous, subcutaneous or prenatal), producing tumours at various sites... 

No epidemiological data relevant to the carcinogenicity of 1,3-propane sultone were available. 

Propanc sultone is possibly carcinogenic to humans (Group 2B). 

Doak, S.M., Simpson, B.J., Hunt, P.F. Stevenson, D.E. (1976) The carcinogenic response in mice to the topical application of propane sultone to the skin. Toxicology, 6, 139-154... 

Sultaines are made by condensing propane sultone with a tertiary amine. These products are relatively rare in industry. Propane sultone is a known human carcinogen, so it must be handled with great care and thus the cost of these products is fairly high. The properties are similar to those of hydroxysultaines which are made by condensing epichlorohydrin with sodium bisulfite to make a propanechlorohydrin sulfonate which is then reacted with a tertiary amine to make a hydroxysultaine with sodium chloride as a by-product (see Figure 6.16). 

With one important exception, dioxoles and oxathioles do not appear to be a particularly toxic class of compounds. The exception is 1,2-oxathiolane 2,2-dioxide (propane sultone) which produces brain tumors, leukaemias and adenocarcinomas of the small intestine in rats treated with 28 mg kg-1 orally twice a week for 60 weeks. If the toxicity is associated with its ability to act as an alkylating agent, then higher homologs should have similar, but reduced, carcinogenic potential. 

Sultones were the earliest anionic stabilisers used in cyanoacrylates but fell from favour because of their potential carcinogenicity. Chelates of boric acid derivatives with polyhydroxy compounds also were considered as anionic inhibitors. Anionic inhibitors are normally added at concentrations between 0.001 and 0.01% depending on the application. 

The electrophiles or electrophilic intermediates that are or are postulated to be responsible for the carcinogenic action of chemicals include (i) positively charged carbonium, nitrenium, oxonium and episulfonium ions, (ii) free radicals, (iii) polarized double bonds, (iv) aldehydes, (v) strained rings such as epoxide, aziridine, lactones and sultones, and (vi) quinone/ quinoid/quinoneimine structures. Based on their reactivity (Table I), electrophiles may be graded from "soft" to "hard" similar to the concept of "soft" and "hard" acids and bases (18). In general, soft electrophiles react preferentially with soft nucleophiles whereas hard electrophiles react preferentially with hard nucleophiles. Thus, since the nucleophilic sites in the purine and pyrimidine bases in DNA are moderately hard nucleophiles, moderately hard electrophiles tend to have the greatest likelihood of covalent binding to DNA. Soft electrophiles often deplete the cellular pool of noncritical soft nucleophiles (such as GSH) before they can react with DNA. 

The presence of a sterically strained ring (e.g., epoxide, aziridine, lactones and sultones) in any type of structure. The likelihood of carcinogenicity may increase if the compound contains two or more of these reactive ring structures. 

An alternative route to sulfobetaines is the reaction of a tertiary amine with 1,3-propanesultone (Figure 15.9). This route leads to salt-free products. Since propane-sultone is a highly carcinogenic chemical, the products must be checked carefully for residual sultone content. The production of these propylsulfobetaines is limited to a few specialized producers. 

The classic preparation method of sulfo betaines utilizes the conversion of tertiary amines with propane sultone. Following the discovery that propane sultone is carcinogenic, this reaction is of limited... 

Sultones are cyclic sulfonic esters. The term sultone arises from sulfonate lactone. Sultones, in particular 1,3-propane sultone, undergo alkylating reactions easily and are potential carcinogens (83-86). 

Propane sultone. 1,3-Propane sultone is a versatile intermediate compound that can react with a wide variety of compounds to introduce a propane sulfonic functionality (87). 1,3-Propane sultone is shown in Figure 2.22. 1,3-Propane sultone is toxic, carcinogenic. 

Sulfobetaines [187,205-208] were usually prepared by a reaction of a tertiary amine with propane sultone [205,206,209]. However, propane sultone has been found to be a carcinogen and is no longer used for this purpose. Instead of propane sultone, chlorosulfonic acid or its salt [210] and sodium 3-chloro-propanesulfonate [207,208] are used as quatemizing agents to obtain fluorinated sulfobetaines. 

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