Abstract  The production and use pattern of Diethylmalonate (DEM) and Dimethylmalonate (DMM) are comparable. The two chemicals have very similar physico-chemical properties and both esters are hydrolyzed via a two step reaction to malonic acid and the corresponding alcohol, methanol or ethanol. It is likely that unspecific esterases in the body catalyze the hydrolysis. The alcohols and malonic acid are physiological substances that are metabolized via physiological pathways. Ethanol (CAS No. 64-17-5) and methanol (CAS No. 67-56-1) were assessed at SIAM 19. For ethanol it was concluded that the chemical is currently of low priority for further work, because the hazardous properties of ethanol are manifest only at doses associated with consumption of alcoholic beverages. As it is impossible to reach these exposure levels as a consequence of the manufacture and use of malonates, it can be expected that malonic acid will be the metabolite that determines the toxicity of DEM. For methanol, SIAM 19 decided that this chemical is a candidate for further work. Methanol exhibits potential hazardous properties for human health (neurological effects, CNS depression, ocular effects, reproductive and developmental effects, and other organ toxicity). The effects of methanol on the CNS and retina in humans only occur at doses at which formate accumulates due to a rate-limiting conversion to carbon dioxide. In primates, formate accumulation was observed at methanol doses greater than 500 mg/kg bw (which would require a DMM dose of more than 1000 mg/kg bw). As there were no indications of a methanol associated toxicity from a well performed repeated dose toxicity study with DMM in rodents (which are, however, known to be less sensitive to methanol toxicity than humans), and because methanol toxicity would not be expected up to doses as high as 1000 mg DMM/kg bw/day, it was concluded that methanol does not make a relevant contribution to the toxicity profile of DMM. A possible mode of action for systemic toxicity of DMM and DEM can only be deduced from the repeated dose study with DMM, indicating a reversible liver hypertrophy at the cellular level at high doses of 1000 mg/kg bw/day. This effect can be an indication of an induction of metabolism in the liver rather than a clear systemic toxicity.

Abstract  A combination of in situ one-dimensional H-1 magnetic resonance profiling and two-dimensional imaging has been applied to study the shape and subsequent dynamic evaporation behaviour of a single liquid droplet after impact onto a porous surface. Diethyl-malonate (DEM) droplets are initially embedded in the porous substrate by impingement, and are then evaporated over a period of several hours; the surface of the substrate being ventilated by a controlled airflow. The configuration is intended to mimic the behaviour of droplets evaporating into atmospheric flows. In order to evaluate the influence of the airflow at the surface of the porous medium, different experimental configurations were tested by varying the speed of the airflow stream above the porous surface. The method produces several types of data, including images of impinged droplets inside the porous substrate and their development with time during the evaporation episode, one-dimensional concentration profiles through the substrates, and corresponding estimates of the mass fraction of liquid remaining, evaporation rate and mass flux per unit area. The results obtained show that although liquid droplets tend to evaporate faster and present larger evaporation rates when exposed to a more efficient removal of vapour from the surface, the limiting effects of the porous medium are even more evident. (c) 2005 Elsevier Ltd. All rights reserved.

Abstract  The evaporation model of Roberts and Griffiths (1995 Atmospheric Environment 29, 1307-1317) has been subjected to an extensive validation exercise based on a major campaign of field experiments on evaporation from surfaces composed of sand and of concrete. This complements the previous validation which was limited to wind tunnel experiments on sand surfaces. Additionally, the validation using wind tunnel data has been extended to include concrete surfaces. The model describes the constant-rate and falling-rate periods that characterise evaporation from porous media. During the constant-rate period, the evaporation is solely determined by the vapour transport rate into the air. During the falling-rate period, the process in the porous medium is modelled as a receding evaporation front, the overall evaporation rate being determined by the combined effects of vapour transport through the pore network and subsequently into the air. The field trials programme was conducted at sites in the USA and the UK, and examined the evaporation of diethyl malonate droplets from sand and concrete surfaces. Vapour concentrations at several heights in the plume were measured at the centre of a 1 m radius annular source (of width 10 cm) contaminated by uniformly sized droplets (2.4 or 4.1 mm in diameter), key meteorological data being measured at the same time. The evaporation was quantified by coupling concentration and wind speed data. In all, 22 trials were performed on sand and concrete; a further 8 were performed an non-pore us surfaces (aluminium foil and slate) as references. The model performance was evaluated against the experimental data in terms of two quantities, the initial evaporation rate of the embedded droplets, and the mass-fraction remaining in the substrate at intervals over the evaporation episode. Overall, the model performance was best in the case of the field experiments for concrete, and the wind tunnel experiments for sand; the performance for wind tunnel experiments for concrete was reasonably good; in the case of the field experiments for sand there was significant underprediction of evaporation rates, though the trends with the determining variables were well predicted. (C) 1999 Elsevier Science Ltd. All rights reserved.

Abstract  There is substantial evidence implicating mitochondrial dysfunction and free radical generation as major mechanisms of neuronal death in neurodegenerative diseases. The major free radical scavenging enzyme in mitochondria is manganese superoxide dismutase (SOD2). In the present study we investigated the susceptibility of mice with a partial deficiency of SOD2 to the neurotoxins 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), 3-nitropropionic acid (3-NP), and malonate, which are commonly used animal models of Parkinson's and Huntington's disease. Heterozygous SOD2 knockout (SOD2(+/-)) mice showed no evidence of neuropathological or behavioral abnormalities at 2-4 months of age. Compared to littermate wild-type mice, mice with partial SOD2 deficiency showed increased vulnerability to dopamine depletion after systemic MPTP treatment and significantly larger striatal lesions produced by both 3-NP and malonate. SOD2(+/-) mice also showed an increased production of "hydroxyl" radicals after malonate injection measured with the salicylate hydroxyl radical trapping method. These results provide further evidence that reactive oxygen species play an important role in the neurotoxicity of MPTP, malonate, and 3-NP. These findings show that a subclinical deficiency in a free radical scavenging enzyme may act in concert with environmental toxins to produce selective neurodegeneration.

Abstract  A piscicide screening program was conducted with 1,888 different chemicals mostly at concentrations of 10 ppm. The times at which fish lost their equilibrium and died are given for 2,552 separate 24-hour assays. The species tested were the northern squawfish (Ptychocheilus oregonensis), chinook salmon (Oncorhynchus tshawytscha), coho salmon (Oncorhynchus kisutch), and steelhead (Salmo gairdneri).

Abstract  Methylmalonate and propionate, the major metabolites of the propionate pathway of fatty and amino acid metabolism used at 1-4 mM cause selective inhibition of succinate and palmitoyl carnitine oxidation in liver mitochondria. Methylmalonate is more specific towards succinate, whereas propionate--towards palmitoyl carnitine oxidation. Methylmalonate is transported to mitochondria at a high rate with no effect on succinate transport. Being injected intramusculary methylmalonate has no inhibiting effect on the oxidative activity of mitochondria but is able to activate succinate and palmitoyl carnitine oxidation. The inhibiting effect of propionate on palmitoyl carnitine oxidation is a long-term one. Injections of these metabolites precursors, isoleucine, methionine and valine, produce an activating effect on succinate oxidation. Thus, propionate pathway metabolites may participate in the regulation of lipid-carbohydrate metabolism.

Abstract  The effects of branched-chain amino acid metabolites on granulocyte-macrophage progenitor cell proliferation in marrow culture are reported. Isovalerate and propionate profoundly suppress granulopoiesis at both 3.2 and 6.4 mM concentrations, whereas methylmalonate and other metabolites suppress to a lesser degree. The parent branched-chain amino acids leucine, isoleucine, and valine do not suppress in vitro granulopoiesis at similar concentrations. Because the concentrations of the organic acids tested fall within the pathophysiologic ranges observed in patients with isovaleric, propionic, and methylmalonic acidemias, we suggest that elevated in vivo levels of isovalerate, propionate, and to a lesser degree methylmalonate are responsible for the neutropenia observed in these disorders.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. Regression analysis has been applied to examine the structure-activity relationships regarding the acute fish toxicity (96 h LC50 fathead minnow) of organic chemicals. The log P dependent baseline toxicity model has been confirmed for a data set composed of 618 compounds from 24 chemical classes associated with a putative common mode of action. Covariance analysis of the discrete by class regression functions resulted in the combination of chemicals to subsets associated with their mode of action. Separate models were derived for nonpolar (Class I) and polar (Class II and III) compounds. Chemicals which are more toxic than estimated from the baseline model are identified.

Abstract  Retention factors on a minimum of eight stationary phases at various temperatures by gas-liquid chromatography and in acetonitrile-water and methanol-water mobile phases by reversed-phase liquid chromatography on a Synergi Polar-RP column were combined with further values taken from the literature and liquid-liquid partition coefficients for up to eight totally organic biphasic systems to estimate descriptors for 24 esters (phthalate, oleate, stearate, arbietate, adipate, succinate, sebacate, and diethylmalonate) widely used as plasticizers and solvents in industry. The descriptors facilitated the estimation of several properties of environmental interest (octanol-water, air-octanol, and air-water partition coefficients, and soil-water distribution coefficients, vapor pressure, and water solubility). The descriptors are suitable for use in the solvation parameter model and facilitate the estimation of a wide range of physicochemical, chromatographic, biological, and environmental properties using existing models.

Abstract  Decontamination of chemical agents from the skin uses both dry and wet decontamination processes. Recent studies have shown that wet decontamination frequently results in stratum corneum hydration. To evaluate the hydration effect of wet decontamination on the skin barrier function and hence on the decontamination efficiency, a series of comparative studies were carried out on human skin contaminated with the nerve agent simulant diethylmalonate, using decontamination media having different salinity and surfactants. The results showed that, compared to non-decontaminated skin, remnant diethylmalonate on decontaminated skin penetrated at an accelerated rate in the immediate 2 h following decontamination. This transient enhancement effect, ranging from 20 to 98%, was depended on the nature of the decontamination media used and was more obvious in skin samples that were decontaminated 1 h postexposure. All decontamination media exhibited this effect, with the greatest enhancement observed in the following order: anionic surfactant > cationic surfactant > non-ionic surfactant > deionized water > 0.9% saline > 9% saline.