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 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  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  To determine the potential environmental persistence and toxic effects of agent simulants Diethyl Malonate (DEM) and Methyl Salicylate (MS), plants, soils, earthworms, and oil microbial populations were exposed to projected aerosolized simulant concentrations of (approximately)100 (low) and (approximately)1000 (high) mg/m(sup 3). Both simulants exhibited biphasic residence times on foliar and soil surfaces following aerosol exposure. Half-times of DEM on soil and foliar surfaces were 1 to 3 h and 5 to 22 H, respectively, and 2 to 2 h and 5 to 31 h for the MS, respectively. Persistence was longer on the foliar surfaces than that of the soils. Both simulants proved phytotoxic to vegetation with a lower threshold of 1 to 2 (mu)m/cm(sup 2) for the MS versus that of 10 (mu)g/cm(sup 2) for the DEM. However, neither significantly affected chloroplast electron transport in vitro at concentrations of up to 100 (mu)g/mL. Results from in vitro testing of DEM indicated concentrations below 500 (mu)g/g dry soil generally did not adversely impact soil microbial activity, while the theshold was 100 (mu)g/g dry soil for MS. Earthworm bioassays indicated survival rates of 66% at soil doses of 204 (mu)g DEM/cm(sup 2) soil and 86% at soil doses of 331 (mu)g MS/cm(sup 2).

Abstract  During research on nematocidal toxins produced by microorganisms, a metabolite has been found active and identified as a volatile fatty acid (monocarboxylic), namely acetic acid. That volatile fatty acid showed selective nematotoxic activity against some plant-parasitic nematodes, but linked to pH and with recovery effect. To improve its efficacy, a structure/activity study on some derivatives has been performed with biological tests on different nematode species. Adding a second carboxylic function and a double bond in the volatile fatty acid hydrocarbonic chain provided unsaturated dicarboxylic acids; these compounds exhibited a significant selective nematocidal activity in considerably shorter periods of time than the monocarboxylic acids, at lower concentrations, in a broad range of pH and without reversible effect of juvenile paralysis. The methyl esters of those dicarboxylic acids and cyclic derivatives exhibited toxicological activity without pH dependency. The importance of the spatial configuration of those molecules which triggered the appearance of significant nematocidal properties is discussed.

Abstract  JETOC has been carrying out classification of the chemical substances, for which SIDS Initial Assessment Report (SIAR) were published, under the Globally Harmonized System (GHS) since autumn of 2004 and published the results in the Information Sheet (Issue No.53-56). Meanwhile, MHLW, METI and MOE launched a project to classify ca.1500 chemical substances based on the GHS in 2005 and published the results on the website: http://www.safe.nite.go.jp/english/ghs_index.html. As the Project released the GHS Classification Manual (Manual) on October 2005, we have reviewed our former results so that they are consistent with the Manual. We will continue the work for substances not classified by the Project based on the information in SIAR. Followings are proposed allocation of the hazard categories. Proposed toxicological classification for 40 chemicals: methacrylamide, linalool, DL-pantolactone, 2-hydroxyethyl m?thacrylate, 2,4-dichlorotoluene, diphenyl carbonate, isobutanal,1,3-dimethyl-urea, 2-methylpropyl-2-methyl-2 propanoate, tetrahydro-2-furanmethanol, 4-methyl-benzenesulfonyl chloride, nicotinamide, m-toluic acid, 1,2-dichloro-4-nitrobenzene, 2-propoxy-ethanol, 2-butoxyethyl acetate, 2-(hexyloxy) ethanol, 2,2'-thiodiethanol, dimethyl malonate, 1,2,3,4-tetrahydronaphthalene, ethyleneglycolmonophenylether, sodium methoxide, potassium methoxide, tetramethylenesulfone, diallyl phthalate, 4-(1,1,3,3-tetramethylbutyl)phenol, 6,10-dimethyl 3,5,9-undecatrien-2 one, butanedioic acid disodium salt, 1H-imidazole, triethylene glycol monobutylether, pentafluoroethane, cyanoguanidine, 2-(1,3-dihydro-3oxo-2H-indol-2-ylidene)-1,2-dihydro-3H-indol-3-one, triacetin, p-chlorotoluene, @eg-caprolactone, isophytol, trimethyl phosphate, 2-methyl-2-butene.