An attempt to explain interindividual variability in 24-h urinary excretion of inorganic arsenic metabolites by C57 BL/6J mice.

Forty C57 BL/6J mice, injected subcutaneously with 0.5 mg/kg arsenic as sodium arsenite, were examined for 24-h urinary excretion of total arsenic metabolites, creatinine and S-adenosylmethionine (SAM) and for 24-h faecal excretion of arsenic and levels of arsenic in the blood, liver, kidneys, lung, skin, spleen and bone at 24-h post-dose. Total urinary arsenic metabolites were calculated by summing up the inorganic (Asi), monomethylated (MMA) and dimethylated (DMA) derivatives directly measured by selective arsine generation-atomic absorption spectrometry (AG-AAS) or were measured by AG-AAS following complete mineralization. Both sets of results showed interindividual differences varying by as much as 7-fold and correlated with the 24-h urinary excretion of both SAM (r = 0.84 and r = 0.86, respectively) and creatinine (r = 0.82 and r = 0.87, respectively). There was interindividual variability of about a 30-fold range in 24-h faecal excretion of arsenic which correlated inversely with 24-h urinary excretion of arsenic metabolites (r = -0.69) and 24-h urinary excretion of both creatinine (r = -0.70) and SAM (r = -0.67). Body tissue levels of arsenic were low and not related to 24-h urinary excretion of arsenic metabolites, SAM and creatinine. Taken together, the results indicate that differences in the profile of urinary arsenic excretion and in the retention of arsenic in a particular organ do not contribute to interindividual variability in 24-h urinary excretion of arsenic metabolites by C57 BL/6J mice, but that variability in faecal excretion does, at least in part. It is speculated that there is most likely a predominant contribution from a diffuse tissue retention of arsenic or from a third route of arsenic elimination, i.e. respiratory, to this phenomenon in view of the small faecal contribution.

Interindividual variability in the urinary excretion of inorganic arsenic metabolites by C57 BL/6J mice: possible involvement of a thiol/disulfide exchange mechanism.

The 24-h urine of 75 C57 BL/6J mice injected s.c. with 0.5 mg/kg arsenic as sodium arsenite were examined for creatinine, S-adenosylmethionine (SAM), urea and inorganic arsenic metabolites including inorganic arsenic (ASi), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). There was interindividual variability of about a 10-fold range in the 24-h urinary excretion of creatinine (80-642 micrograms/24 h, variability (cv) of 33%), SAM (7.5-67.2 micrograms/24 h, cv of 38%), urea (9.5-89.7 mg/24 h, cv of 36%), ASi (0.1-1.6 microgram/24 h, cv of 48%), MMA (0.17-2.1 micrograms/24 h, cv of 50%), DMA (0.73-8.13 micrograms/24 h, cv of 32%) and total arsenic metabolites (1.0-10.4 micrograms/24 h, cv of 31%). Interindividual differences, varying by as much as 5-7-fold, were also found in the urinary proportion of ASi (3-23%, cv of 41%) and MMA (5-22%, cv of 37%), but not in the urinary proportion of DMA (64-90%, cv of 7%). The 24-h urinary excretion of all arsenic metabolites correlated with the 24-h urinary excretion of urea (r = 0.81), creatinine (r = 0.88) and SAM (r = 0.83) as did the 24-h urinary excretion of urea with creatinine (r = 0.94) and SAM (r = 0.86), and the 24-h urinary excretion of creatinine with SAM (r = 0.94). Taken together, these results suggest that the overall intracellular glutathione (GSH)-dependent redox state, as reflected by the 24-h urinary excretion of SAM and creatinine, is involved in the interindividual variability in total arsenic metabolite excretion by C57 BL/6J mice. These preliminary results were also discussed with regard to the involvement of intracellular GSH-dependent redox state in the regulation of the reduction and of the methylation steps of arsenic, and to interindividual variability in the urinary excretion of total arsenic metabolites as a possible complicating factor in the biological monitoring of occupational exposure to arsenic.

Comparison of production of volatile hydrocarbons by phenylhydrazine-induced peroxidation in rats chronically treated with lead.

We have studied the effect of a chronic pretreatment by lead on the peroxidation processes by measuring the production of the four main volatile hydrocarbons: ethane and pentane as index of lipid peroxidation; propane as marker of protein peroxidation and ethylene as index of both lipid and protein peroxidations. Our results have shown that: 1) lead alone did not increase the physiological formation of alkanes indicating that lead is not able per se to initiate the peroxidative processes; 2) after phenylhydrazine injection, lipid peroxidation makers were not modified, except pentane in male lead-treated rats. Conversely, ethylene and propane exhalation were increased 45 min after phenylhydrazine injection in lead-treated rats indicating a potentialisation of the oxidative effect of phenylhydrazine, mainly on proteins, by lead.

[Evaluation of a technique for determining blood ethanol levels by gas chromatography. Committee for "determination of blood ethanol levels"].

Art. R.24-1 of the Code governing distribution of beverages and preventive measures against alcoholism: "If the verifications are performed following a traffic accident having occurred under the conditions provided at article L.88 of the present code or in application of articles L.1 and L.3 of the traffic code, the requesting authority keeps a copy of form A and sends: 1. The first blood specimen samples, along with four copies of forms A, B and C, to a laboratory of an establishment part of the public hospital system as defined at article 3 of law n. 70-1318 of December 31 1970 or to an expert biologist registered on the list held by the court of appeals as provided by article R.32 of the code governing distribution of beverages and preventive measures against alcoholism; 2. The second sample, along with one copy of forms A, B and C, to another expert biologist registered on the same list and in charge of eventually performing a control analysis. The laboratory or the expert biologist having performed the analysis reports the results on forms C and forwards one copy of forms A, B and C directly, under separate cover and stamped confidential to the competent Procureur de la Republique, to the region in which the misdemeanor or the accident occurred. The results reported on the form are immediately transmitted to the requesting authority.

Effect of pretreatment with cimetidine or phenobarbital on lipoperoxidation in carbon tetrachloride- and trichloroethylene-dosed rats.

Lipid peroxidation (LP) in vivo as reflected by the exhalation of ethane and n-pentane and by thiobarbituric acid reactive substances (TBARS) in liver microsomes was studied in rats injected with carbon tetrachloride (CCl4) and trichloroethylene (TCE), each at 2 dose levels. Interactions between these chlorinated solvents and cimetidine (CM), an inhibitor of cytochrome P-450-dependent monooxygenases, or phenobarbital (PB) the well known inducer of microsomal enzyme activities were also assessed. A non-hepatotoxic dose of CCl4 did not cause a significant increase in ethane production except in PB-induced rats but did enhance n-pentane elimination, whereas an hepatotoxic dose increased the emission of both hydrocarbons. No interaction between CM and CCl4 could be shown but, as expected, PB potentiated the effect of CCl4. TCE administration led to a moderate dose-independent elevation of n-pentane production but did not affect that of ethane and the effect of TCE was smaller in PB-induced than in CM- or non-pretreated rats. There was no difference in microsomal TBARS content in rats injected with the chlorinated hydrocarbons. The use of butylated hydroxytoluene (BHT) and ethylene diaminetetraacetic acid (EDTA) revealed that direct measurement of TBARS gave inadequate results due to substantial chemical LP in vitro during the whole procedure. With the "ethane-pentane test" it was established that: CM cannot prevent CCl4-induced LP; and TCE hepatotoxicity does not involve increased LP of membrane lipids.

[Effects of organohalogenated compounds on the emission of ethane and pentane in expired air]. / Effets de dérivés organiques halogénés sur l'émission d'éthane et de pentane dans l'air expiré.

Effects of two halogenated acetamides (chloroacetamide-iodoacetamide) and of three chlorinated volatile solvents on the ethane-pentane test, as an index of in vivo lipid peroxidation have been studied. Chloroacetamide stimulates alcanes production. Iodoacetamide acts only on pentane exhalation. The three chlorinated solvents seem to induce moderate lipoperoxidation, and the apparent increase of hydrocarbons might also result from decreased metabolism.

[Modifications of disulfiram and its metabolites in blood in alcoholic hepatopathy (author's transl)]. / Modifications des taux sanguins du disulfiram et de ses métabolites dans l'insuffisance hépato-cellularie d'origine alcoolique.

In cirrhotic, steatosic and healthy subjects, the authors studied the metabolism of disulfiram (TETD) administrated orally (500 mg) 3 consecutive days. Carbon disulfide (CS2) and the whole TETD, diethyl dithiocarbamate (DDC) disulfides, were determined by a gas chromatographic method. The evolution of metabolites is similar in steatosic and healthy subjects. In cirrhotics the CS2, DDC and disulfides level increase within the 3 days. This phenomenon may be related with hepatic toxicity of TETD and with the persistence of disulfiram-alcohol reaction. The authors suggest to use low doses of disulfiram in cirrhotic.

[Dismutation as a metabolic pathway : transformation of the trimethyl 3,5,5, cyclohexanone (author's transl)]. / La dismutation comme voie de transformation métabolique - cas de la triméthyl 3,5,5, cyclohexanone.

Besides novel routes of biotransformation of xenobiotic substances recently reported, such as N-glucuronidation of teritary amines and quaternary ammonium componds, N-glucosylation, N-carbamylglucuronide formation from a primary amine, C-glucuronidation, conjugation with long-chain fatty acids, with polypeptides, carbon-chain elongation, stereospecific inversion of configuration at a satured carbon atom, formation of methylthio metabolites, the authors have described a new metabolic pathway: dismutation, in the case of 3,5,5, - trimethylcyclohexanone (dihydroisophorone). As a matter of fact, this compound leads, in vivo, to the formation of isophorone alpha and of cis and trans 3,5,5, - trimethyl cyclohexanols. These compounds, extracted from the urine of treated rats and rabbits, have been identified by gas-liquid chromatography and thin-layer chromatography.