The biological fate of vinylidene chloride in rats

Differences in Metabolism of Vinylidene Chloride Between Mice and Rats

“…Furthermore, the previously assumed ,B-thionase hydrolysis of thiodiglycollic acid (Jones and Hathway, 1977) is now established in vivo, and the possible biogenesis of the N-acetyl-S-cysteinyl acetyl derivative is verified by another tracer study. The conclusion is drawn that the DCE metabolites, 1,1 -dichloroethylene oxide and chloroacetyl chloride, may be important to murine DCE carcinogenicity.WIDESPREAD use of the polymer of vinylidene chloride* (1,1 -dichloroethylene, DCE) for packaging film and for coating other packaging materials, and the recent discovery of DCE tumorigenicity in the kidneys of mice (Maltoni et al, 1977) but not in rats, warrants a systematic search for possible species differences in DCE metabolism which might account for the species susceptibility observed.Previous work (Jones and Hathway, 1977;Walker and Hathway, 1977) on the metabolism of DCE (Fig. 1(a)) in rats showed that: (i) thiodiglycollic acid (g) and an N-acetyl-S-cysteinyl acetyl derivative (e) (where R is considered to be OH and R' is unknown) where the major urinary metabolites associated with substantial amounts of chloroacetic acid (b) dithioglycollic acid (j) and thioglycollic acid (h),…”

“…Quantitatively, (i) the relative proportions of the N-acetyl-S-cysteinyl acetyl derivative that are formed in mice and rats parallel the activity of liver glutathione-S-epoxide transferase in these rodents, and (ii) there are marked differences in the proportions of DCE metabolites belonging to the chloroacetic acid branch of the metabolic pathway. Furthermore, the previously assumed ,B-thionase hydrolysis of thiodiglycollic acid (Jones and Hathway, 1977) is now established in vivo, and the possible biogenesis of the N-acetyl-S-cysteinyl acetyl derivative is verified by another tracer study. The conclusion is drawn that the DCE metabolites, 1,1 -dichloroethylene oxide and chloroacetyl chloride, may be important to murine DCE carcinogenicity.…”

“…(1,1 -dichloroethylene, DCE) than rats implies (a) that the efficiency of DCE metabolism follows the known activity of cytochrome P -450 in the organs of these animals, and (b) that, in accordance with the LD50 values, the real exposure (expressed as the amount of DCE metabolized) is relatively higher for orally dosed mice than rats, and (c) that DCE carcinogenicity would appear to be more likely in mice than rats.Mice metabolize DCE similarly to rats (Jones and Hathway, 1977) but there are some differences. Thus, qualitatively, treated mice (but not rats) excrete a small amount of N-acetyl-S-(2-carboxymethyl)cysteine.…”

“…Mice metabolize DCE similarly to rats (Jones and Hathway, 1977) but there are some differences. Thus, qualitatively, treated mice (but not rats) excrete a small amount of N-acetyl-S-(2-carboxymethyl)cysteine.…”

“…Previous work (Jones and Hathway, 1977;Walker and Hathway, 1977) on the metabolism of DCE ( Fig. 1(a)) in rats showed that: (i) thiodiglycollic acid (g) and an N-acetyl-S-cysteinyl acetyl derivative (e) (where R is considered to be OH and R' is unknown) where the major urinary metabolites associated with substantial amounts of chloroacetic acid (b) dithioglycollic acid (j) and thioglycollic acid (h),…”