A meeting on the health effects of arsenic (As), its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Although arsenite [As(III)] can inhibit more than 200 enzymes, events underlying the induction of the noncarcinogenic effects of As are not understood. With respect to carcinogenicity, As can affect DNA repair, methylation of DNA, and increase radical formation and activation of the protooncogene c-myc, but none of these potential pathways have widespread acceptance as the principal etiologic event. In addition, there are no accepted models for the study of As-induced carcinogenesis. At the final meeting session we considered research needs. Among the most important areas cited were a) As metabolism and its interaction with cellular constituents; b) possible bioaccumulation of As; c) interactions with other metals; d) effects of As on genetic material; e) development of animal models and cell systems to study effects of As; and f) a better characterization of human exposures as related to health risks. Some of the barriers to the advancement of As research included an apparent lack of interest in the United States on As research; lack of relevant animal models; difficulty with adoption of uniform methodologies; lack of accepted biomarkers; and the need for a central storage repository for stored specimens.

Bidrin, 3-(dimethoxyphosphinyloxy)-N,N-dimethyl-c/s-crotonamide, is metabolized to yield trace amounts of 3-(dimethoxyphosphinyloxy)-N-methyl-N-hydroxymethyl-c/s-crotonamide and larger amounts of 3-(dimethoxyphosphinyloxy)-N-methyl-c/s-crotonamide (SD 9129). SD 9129 is further metabolized to yield 3-(dimethoxyphosphinyloxy)-N-hydroxymethyl-c/s-crotonamide and 3-(dimethoxyphosphinyloxy)-c/s-crotonamide. The toxicity to both insects and mammals increased upon successive N-demethylation. Balance studies on the fate of the P32 and C14 from Bidrin-P32, Bidrin-N-methyl-C14, SD 9129-P32, and SD 9129-N-methyl-C14 are considered. Studies on milk residues, urinalysis, and metabolism in houseflies (Musca domestica L.) and bean plants are reported. An unusual pattern of synergism of the toxicity of the Bidrin metabolites in houseflies by sesamex [2-(2-ethoxyethoxy)ethyl-3,4-(methylenedioxy)phenyl acetal of acetaldehyde] was noted.NO. 2 MAR.-APR.

Japanese quail were administered 100 mg/kg chlorophenyl-labeled [UC] fenvalerate, a-cyano-3phenoxybenzyl 2-(4-chlorophenyl)isovalerate, for study of its distribution, elimination, and metabolism. Ninety percent of the administered dose was eliminated in the excreta within the first 24 h. In addition to fenvalerate, the following metabolites were present: benzeneacetic acid, 4-chloro-a-(l-methylethyl)-, cyano(3-phenoxy-4-hydroxyphenyl)methyl ester [4'-OH-fenvalerate]; benzeneacetic acid, 4-chloro-a-(1-methylethyl)-, (aminocarbonyl)(3-phenoxyphenyl)methyl ester [CONH2-fenvalerate]; 4-chloro-a-(lmethylethyl)benzeneacetic acid [Cl-V acid]; 4-chloro-a-(2-hydroxy-1-methylethyl)benzeneacetic acid [4-OH-C1-V acid].In time course studies radiocarbon peaked at 3 h (9 pg/g) in the liver and gradually declined, while in the blood it peaked within 2 h and fell quickly to an equilibrium value of 1.5 pg/mL blood. In liver microsomal and isolated heptatocyte preparations of Japanese quail and rat, the following metabolites were identified: Cl-V acid, 4-OH-C1-V acid, 4'-OH-fenvalerate, CONH2-fenvalerate. Oxidation was found to be the predominant route of degradation either pre-or posthydrolysis of the parent compound. Rapid excretion, lesser absorption, and faster metabolism probably explain the lower toxicity of fenvalerate to birds compared to rats.

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