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1. The metabolism of fomocaine following its oral administration to male and female Wistar rats and male beagle dogs has been qualitatively investigated. 2. The drug is metabolized in both species by aromatic hydroxylation, N-oxidation, splitting of the ether link and, in the dog, by removal of the morpholine group. 3. The rat and dog excrete some unchanged fomocaine in the urine together with p-hydroxyfomocaine (free and conjugated), fomocaine-N-oxide, p-hydroxyfomocaine-N-oxide and p-(gamma-morpholinopropyl)benzoic acid. In addition, the dog excretes morpholine in the urine.

Decabromodiphenyl oxide (DBDPO) and octabromobiphenyl (OBBP) perform well as fire-retardant additives for thermoplastics. Both compounds have low acute oral toxicity and low skin absorption toxicity. They are neither primary skin irritants or skin sensitizers and are only mildly irritating to the eyes. A 30-day dietary feeding study in rats established 8 mg DBDPO/kg-day as an unequivocal no-effect level and 80 mg/kg-day as a marginal effect level. A no-effect level was not established for OBBP in a comparative study. A 2-yr rat study providing 0.1 mg DBDPO/kg-day in the diet revealed the bromine concentration reached a plateau in the liver within 30 days, while the concentration in adipose tissue slowly increased. A comparable OBBP study revealed bromine concentration in the liver and adipose tissue increased steadily and rapidly with no attainment of a plateau during 180 days of the study. Neither compound produced an accumulation of bromine in other tissues. After administration of 14C DBDPO, all 14C activity was eliminated via the feces within 2 days. After administration of 14C OBBP, 62% was eliminated with a half-life of less than 24 hr; the half-life for the remainder was greater than 16 days. In a teratology study, 10, 100, or 1000 mg DBDPO/kg-day had no effect in rats. Reproductive capacity of rats was not effected at 3, 30, or 100 mg DBDPO/kg-day. No effects were observed on cytogenetic examination of bone marrow cells of parents and weanlings from the reproduction study.

A series of new heterocyclic derivatives of triiodophenyl and triiodophenoxy alkanoic acids was prepared; some of these compounds showed high billiary excretion and low acute toxicity in rats. One compound, 2-ethyl-3-[3-N-butyrolactamyl-2,4,6-triiodophenyl]-propionic acid, showed such characteristics that encouraged us to carry out further preclinical and clinical investigations.

Many general aspects of the subjects were covered by the two previous reviews. Important recent changes in handling harvested cereal grains include more bulk transportation--particularly containerisation,processing closer to the site of production, resistance topesticides in many granivorous insects and the alarmingly unpredictable cross-resistance spectra in some sppecies, and a hardening in the attitude of governments and the food industry to the use of pesticides. Pesticide manufacturers arecurrently restricting their involvement in the stored grain area. The market is small and unpredictable due to crossresistance. However, a number of interesting and potentially useful compounds have appeared, notable )(bio) resmethrin, pirimiphos-methyl, andDursban-methyl, which reflect attempts to provide somewhat morepersistent compounds under adverse storage conditionnnnns than ismalathion--currently the most widely-used control agent.Inevitably, there is interest also in alternative methods, of control, from the obvious physical methods (drying, cooling, air-tight storage)to use of pheromones, insect hormone anaogues, and larvicides, all of which may have some future potential...

The phenoxyalkanoix acids are bound to bovine serum albumin at a single site of high affinity, where the interaction is most importantly influenced by strong hydrophobic bonding, with ionic bonding being of lesser importance, and also at several sites of lower affinity. The hydrophobic binding site has almost equal affinity for the phenoxy groups of 2,4-dichlorophenoxyacetic acid, 4-(2,4-dichlorophenoxy)butyric acid and 2-(2,4,5-trichlorophenoxy)propionic acid and greater affinity for the phenoxy group of 2,4,5-trichlorophenoxyacetic acid. The properties of the high affinity binding site bear some resemblance to the properties of the amino acid sequence adjoining the tryptophan residue of human serum albumin, and evidence is presented for the presence of tryptophan at the high affinity binding site of bovine serum albumin.

1. Urinary and faecal excretion of radioactivity in 120 h after oral administration of [U-14-C]phenyl o-(2-N-morpholinoethoxy)phenyl ether hydrochloride (200 mg/kg) were 92 and 3% dose in the rabbit, and 60 and 35% in the rat. 2. Urinary metabolites were produced by aromatic hydroxylation and aryl alkyl ether bond cleavage. Some evidence for formation of dioxomorpholino, oxohydroxymorpholino, and ethanolamino derivatives of the drug was obtained. 3. The aromatic hydroxylation product, p-hydroxyphenyl o-(2-N-morpholinoethoxy)phenyl ether hydrochloride had vasopressor activity comparable with the parent compound, but with shorter duration of action.