Mutagenicity of Chlorine-Substituted Furanones and Their Inactivation by Reaction With Nucleophiles

Abstract

The reported high mutagenic potency of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)furanone against Salmonella typhimurium (TA100) was confirmed in the determined value of 6,300 net revertantshmol. Partial inactivation of the furanone by Arochlor 1254-induced rat liver homogenate fraction (S9) was observed. Inactivation by the nucleophiles hydroxide ion, S02, S20$-, pyrrolidine and glutathione, all in aqueous solutions, was determined and the results compared. Mutagenic reduction was observed for all of the nucleophiles but was most pronounced for glutathione. Inactivation by hydroxide ion was most sensitive in the pH range of 9 to 11, was associated with chloride ion formation and paralleled irreversible ultraviolet spectral change resulting in the loss of the 227 nm absorption maximum and the appearance of a new maximum at 255 nm. Neutral aqueous solutions of the furanone and glutathione were marked by two UV maxima, at 250 and 270 nm, and lacked the aldehydic 'H-NMR signal, which was observed in the spectrum of the neutral solution of the furanone alone and was attributed to the presence of its acyclic tautomeric form. Several other furanones were prepared. Their Ames mutagenicities and those of chlorine-substituted intermediates obtained in the synthesis of the furanone were determined and compared, and then related to the reported mutagenicities of some 2-chloropropenals.

Brominated analogs of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone: Preparation of 3‐chloro‐4‐(bromochloromethyl)‐5‐hydroxy‐2(5H)‐furanone and mutagenicity studies

“…Mutagenic potencies observed for MX with TA100 in freshly synthesized products resulted in 3,467 revertants/nmol, which is within the order of magnitude reported by other authors [3,24,25]. Interestingly, the bromo derivatives elicited a significant increase in mutagenic potency with respect to MX, and this potency was proportional to the presence of one, two, or three bromine atoms replacing the chlorine atoms in MX (cf., Fig.…”

A study of inactivation reactions of N-acetylcysteine with mucochloric acid, a mutagenic product of the chlorination of humic substances in water

“…Its mutagenicity in this assay has been reported to range, roughly, from 1 to 10 rev/nmol (9,11,12). Relative to MX, for which several other genotoxic responses have now been recorded (13-17l, MCA was 100-1000-fold less mutagenic in the (TA100) assay (12,18).…”

Glutathione and N-acetylcysteine inactivations of mutagenic 2(5H)-furanones from the chlorination of humics in water

“…One of these is 3,4-dichloro-5-hydroxy-2(5H)-furanoneI or mucochloric acid (MCA)1 (compound 1, Figure 1). Its mutagenicity (M,) has been reported to range from 1000 to 10 000 rev/pmol (9,(11)(12)(13) in the standard plate incorporation assay of Maron and Ames (14) using Salmonella typhimurium (TA100). Another member of this class of genotoxins is 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX, 2).…”