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Summary.-The present finding that mice metabolize a greater proportion of an oral dose (50 mg/kg) of vinylidene chloride. (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. 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.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),(ii) chloroacetic acid (b) a key metabolite of DOE (a) biotransformation, afforded in vivo several metabolites in common with DCE, and (iii) transformation of DCE (a) into chloroacetic acid (b) involved migration of one C1 atom and the loss of the other one.The experimental evidence implied that the N-acetyl-S-cysteinyl acetyl derivative (e) arises through the reaction of 1,1-dichloroethylene oxide with glutathione, a reaction catalysed by glutathione Sepoxide transferase.The present paper describes the results of an investigation of DCE metabolism in mice vis-a-vis the previous one in rats * Known commercially as VDC.

1. The metabolic fate of [14C]-2-(4-methylsulphonyl-2-nitrobenzoyl)-1,3-cyclohexanedione (mesotrione) has been determined in the male and female rat and mouse following a single oral dose of either 1 or 100 mg kg(-1), in rat given 14 consecutive oral doses of 1 mg kg(-1), and in the surgically prepared, bile duct-cannulated rat following a single oral dose of 50 mg kg(-1). The excretion of a single i.v,. dose of 1 mg kg(-1) in the male and female rat was also investigated. 2. Mesotrione was extensively absorbed and rapidly excreted via urine in both rat and mouse. The absorbed dose was not well metabolized in either species. Unabsorbed material was subject to metabolic action by the gut microflora. 3. The major metabolic pathway was hydroxylation of the aromatic ring. There was evidence for cleavage of the dione and aromatic rings followed by reduction of the nitro group in the gastrointestinal tract. 4. There were no species differences in the metabolism and excretion of mesotrione, which could explain the species differences in toxicity reported for this class of compounds.

The disposition of the pyrethroid insecticide cypermethrin, (RS)‐a‐cyano‐3‐phenoxybenzyl (1RS)‐cis, trans‐3‐(2,2‐dichlorovinly)‐2, 2‐dimethylcyclopropane‐carboxylate, has been studied in male and female rats following a single toxic oral dose (200mg kg−1) of two radiolabelled forms ([14C‐benzyl] and [14C‐cyclopropyl]) of the insecticide. The bioaccumulation and elimination of 14C‐benzyl‐labelled cypermethrin, following repeated administration at a sub‐toxic dose (2mg kg−1), has also been studied in male and female rats. Although, at the toxic dose, radioactivity from the two radiolabelled forms was rapidly eliminated in urine and faeces, the increased excretion in the faeces, over that for low doses, was evidence that absorption was incomplete. The major pathways of metabolism involved cleavage of the ester bond, with subsequent hydroxylation and glucuronidation of the cyclopropyl acid moieties, together with hydroxylation and sulphation of the 3‐phenoxybenzyl moiety. The absence of sex‐ or dose‐dependent changes was reflected by the constant proportions of these metabolites found in the urine. Constant levels of radioactivity in tissues were achieved rapidly, generally within the first week of repeated administration. Elimination was rapid on the cessation of dosing, although less rapid from the fat and skin. The material in the fat was mainly the cis‐isomers of cypermethrin, which were eliminated with a mean half‐life of 18.2 days, compared with 3.4 days for the trans‐isomers.

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