John R. Caldwell

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This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavouring substances under conditions of intended use. In this review, scientific data relevant to(More)
Cytochrome P450 mediated metabolism of methyleugenol to the proximate carcinogen 1'-hydroxymethyleugenol has been investigated in vitro. Kinetic studies undertaken in liver microsomes from control male Fischer 344 rats revealed that this reaction is catalyzed by high affinity (Km of 74.9 +/- 9.0 microM, Vmax of 1.42 +/- 0.17 nmol/min/nmol P450) and low(More)
1. The metabolic fates of the naturally occurring food flavours trans-anethole and estragole, and their synthetic congener p-propylanisole, have been investigated in human volunteers using the [methoxy-14C]-labelled compounds. The doses used were close to those encountered in the diet, 1 mg, 100 micrograms and 100 micrograms respectively. 2. In each case,(More)
1. The metabolites of (+/-)-2-methylamino-1-phenyl[1-(14)C]propane ([(14)C]methamphetamine) in urine were examined in man, rat and guinea pig. 2. In two male human subjects receiving the drug orally (20mg per person) about 90% of the (14)C was excreted in the urine in 4 days. The urine of the first day was examined for metabolites, and the main metabolites(More)
The urine was the major route of excretion of radioactivity (50-80% of dose) following the oral administration (2.5 and 25 mg/kg body weight) of allyl[14C]isothiocyanate (AITC) to male and female Fischer 344 rats and B6C3F1 mice. Smaller amounts were found in the faeces (6-12%) and expired air (3-7%). The major difference between the two species was the(More)
The major metabolic pathways of estragole have been established in rats and mice, and in both species the relative importance of the different pathways has been shown to be dose related. At low doses, estragole mainly undergoes detoxication reactions, notably O-demethylation and side-chain cleavage, but as the dose is increased, the extent of(More)
The metabolism of a 900 mg oral dose of aspirin has been investigated in 129 healthy volunteers. For this purpose, the 0-12 h urine was collected and analysed for the following excretion products: salicylic acid, its acyl and phenolic glucuronides, salicyluric acid, its phenolic glucuronide and gentisic acid. The total excretion of salicylate and(More)
The comparative absorption of the fragrance and industrial compound, benzyl acetate, has been studied in rat and human skin, using shaved, full-thickness dorsal skin of male Fischer 344 rats and full-thickness human skin obtained from patients undergoing surgical resection. Penetration of the compound through rat and human skin was evaluated in vitro in(More)
While the alkenylbenzenes alpha- and beta-asarone are hepatocarcinogenic in rodents, myristicin and elimicin, two other alkenylbenzenes, are not. The present study investigated the mechanism of genotoxicity of the asarones to elucidate the role of cytochrome P-450 and obtain further information about the relationships between the structure, metabolism and(More)
A knowledge of the fate of a drug, its disposition (absorption, distribution, metabolism, and excretion, known by the acronym ADME) and pharmacokinetics (the mathematical description of the rates of these processes and of concentration-time relationships), plays a central role throughout pharmaceutical research and development. These studies aid in the(More)