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International audience; This review aims to provide an update on our current knowledge of the various effects of pesticide cocktails. We have collected data from studies conducted in mammalian models in vitro and in vivo that was published between 2000 and 2014. All ecotoxicological studies were voluntarily excluded. Cocktail effects were classified according to how they had been classified by each author. The frequency of the various cocktail effects and the classes and chemical families of pesticides involved in the observed effects were assessed. When focusing on the function of pesticides (i.e. herbicide, insecticide or fungicide), 46% of the mixtures contained insecticides alone, 15% fungicides alone, and 4.5% herbicides alone. Mixtures with effects associated with neurotoxicity were mainly composed of insecticides, and most studies on the effects of fungicide mixtures (90%) were associated with effects on endocrine regulation and/or reproduction. Dose addition was observed with each kind of mixture except herbicide combinations. In contrast, synergic interactions or greater-than-additive effects were mainly reported for insecticide mixtures. There were few examples of potentiating and antagonistic interactions. We have identified chemical families of compounds specifically involved in synergy, addition, potentiation and antagonism, and those that do not interact when combined. The chemical families identified as being involved in synergy are in agreement with data from another recently published compilation of ecotoxicological studies. For most mixtures investigated, further validation data is still needed from experiments using other compounds and other experimental models but this update provides useful information to help in human health risk assessments. more...

60 patients with HIV-1 infection in Walter Reed stages 2-4 were randomised to treatment with intravenous or oral dithiocarb (diethyldithiocarbamate, DTC) or placebo for 24 weeks in a paired double-blind design. 55 patients were evaluable at the end of the study: no patient who had received DTC but 6 placebo patients had AIDS, a significant difference. Significantly delayed disease progression was observed in the intravenous DTC group compared with its matching placebo. The benefit in the oral DTC group was not statistically significant. During an 18-month follow-up 3 deaths occurred in the original placebo groups, whereas no patient who had initially received DTC died. A significant delay in progression to AIDS was observed in the DTC groups. more...

The influence of intravenously administered mixtures of paraquat and the chelating agents CaNa 2 -EDTA or dithiocarb on the toxicity of oxygen at normal pressure was studied in rats. No increase in toxic effects of the combination paraquat-oxygen was seen by additionally administered chelate-forming agents. This paper completes the investigations on oxygen toxicity after administration of various chelate-forming agents in mice 1 . more...

Dithiocarb and (+)-cyanidanol-3-prevented paracetamol-induced liver injury in rats in vivo. Both, as well as two other antihepatotoxic agents, deanol and DMSO, inhibited covalent binding of [3H]-paracetamol to rat liver microsomal proteins in vitro. Dithiocarb and (+)-cyanidanol-3 were the most effective inhibitors. The concentrations of the antidotes yielding 50% inhibition (I50) valued 1 . 8 x 10(-5) M for dithiocarb and 2 . 1 x 10(-5) M for (+)-cyanidanol-3. more...

1. After i.p. injection of [2,3-14C]acrylonitrile to rats, a significant portion of radioactivity becomes irreversibly attached to proteins of liver, lung, spleen and other tissues. 2. When rat liver microsomes were incubated with [2,3-14C]acrylonitrile, a time-dependent irreversible binding of radioactivity occurred to microsomal proteins. This binding was not dependent on NADPH. A high extent of binding to heat-inactivated microsomes indicated that no enzymic metabolic step was involved. 3. The irreversible binding of [2,3-14C]acrylonitrile to rat liver microsomal protein in vitro was inhibited by thiols (cysteine, glutathione, mercaptoethanol). The greatest inhibitory potency was displayed by dithiocarb (diethyl dithiocarbamate). more...

A dose-dependent increase of paracetamol serum half-life (t1/2) was found after oral and intravenous application in rats and oral application in mice. The hepatotoxic effects of paracetamol were not correlated with this prolongation of t1/2. Dithiocarb protected rats against paracetamol liver damage but did not change paracetamol t1/2. Paracetamol t1/2 was not influenced either by a hepatotoxic dose of carbon tetrachloride. In conclusion, the dose-dependent prolongation of paracetamol serum half-life is not due to paracetamol-induced liver damage but merely the consequence of saturated elimination processes. more...

Metabolic balance studies carried out on a thirty-four year old woman with Wilson's disease who was treated with sodium diethyldithiocarbamate ("dithiocarb") during a period of five months are described. Intravenous administration of dithiocarb in daily dosages of 10 and 20 mg. per kg. of body weight resulted in clinical improvement and increased excretion of copper in the urine but did not reverse the pre-existing positive copper balance. Oral administration of dithiocarb in daily dosage of 30 mg. per kg. of body weight produced a threefold increase in the fecal excretion of copper and thereby resulted in negative copper balance. Measurements of nickel revealed that the patient maintained a positive nickel balance. Administration of dithiocarb intravenously in dosage of 20 mg. per kg. of body weight, or orally, in dosage of 30 mg. per kg., resulted in a negative metabolic balance for nickel. Treatment with dithiocarb was accompanied by a striking clinical response. The patient's neurologic involvement had been so severe that she had been unable to walk, to feed herself or to speak intelligibly. Following dithiocarb therapy she became able to speak clearly and to return to light housework. The Kayser-Fleischer corneal rings became less intense, and measurements of hepatic function returned to the normal ranges. more...