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D Howes

Publications and source records attributed to D Howes.

39 records · Page 3Linked to original sources

Percutaneous penetration of 2-phenoxyethanol through rat and human skin.

2-Phenoxyethanol applied in methanol was absorbed (64 +/- 4.4% at 24 hr) through unoccluded rat skin in vitro in the static diffusion cell with ethanol/water as receptor fluid. By comparison (43 +/- 3.7% in 24 hr) was absorbed in the flow-through diffusion system with tissue culture medium as receptor fluid. 2-Phenoxyethanol applied in methanol was absorbed (59.3 +/- 7.0% at 6 hr) through unoccluded human skin in vitro in the flow-through diffusion cell with tissue culture medium. With both unoccluded cells, 2-phenoxyethanol was lost by evaporation but occlusion of the static cell reduced evaporation and increased total absorption to 98.8 +/- 7.0%. Skin, post mitochondrial fraction, metabolized phenoxyethanol to phenoxyacetic acid at 5% of the rate for liver. Metabolism was inhibited by 1 mM pyrazole, suggesting involvement of alcohol dehydrogenase. However, first-pass metabolism of phenoxyethanol to phenoxyacetic acid was not detected during percutaneous penetration through viable rat skin in the flow-through system. First-pass metabolism in the skin does not therefore have an influence on systemic availability of dermally absorbed phenoxyethanol. These measures of phenoxyethanol absorption through rat and human skin in vitro agree well with those obtained previously in vivo.

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The fate of ingested glyceran esters of condensed castor oil fatty acids [polyglycerol polyricinoleate (PGPR)] in the rat.

Samples of the emulsifier polyglycerol polyricinoleate (PGPR) were synthesized using the radiolabelled precursors [1-14C]glycerol ([14C]polyglycerol PGPR), [9,10-3H] or [12-3H]ricinoleic acid ([3H] PGPR) or [1-14C]stearic acid ([14C]stearyl PGPR). The absorption, tissue distribution, metabolism and excretion of these 14C- or tritium-labelled PGPR samples administered to rats was studied. The effects of intestinal and porcine pancreatic lipases on PGPR preparations were examined. Rats were dosed with [1-14C]glycerol, [14C]polyglycerol and ([14C]polyglycerol)PGPR by gavage and their urine. faeces and expired CO2 monitored for 14C. The results from the [1-14C]glycerol treated animals showed extensive metabolism of glycerol. For [14C]polyglycerols, the lower polyglycerols were preferentially absorbed from the intestine and were excreted unchanged in the urine while the higher polyglycerols were found in the faeces. After 4 days, 93% of the dose of polyglycerols was recovered, of which some 30% was found in the urine and 60% in the faeces. Traces of 14C activity were found in depot fat and liver. The excretory pattern and urinary metabolites from ([14C]polyglycerol) PGPR was very similar to that of [14C]polyglycerol. Analysis of urinary and faecal 14C material indicated that the PGPR polymer was digested to give free polyglycerol and polyricinoleic acid. PGPR was synthesised incorporating [1-14C]stearic into polyricinoleic acid which was then esterified with polyglycerol. The resulting [14C]PGPR or [1-14C] stearic acid in a dietary slurry was administered to groups of fed or starved rats by gavage. The results indicated complete digestion of PGPR and absorption of the fatty acids. The 14C-material absorbed was extensively laid down in depot fat and some metabolism to 14CO2 was demonstrated. The fate of the stearic acid was similar whether dosed alone or incorporated into the PGPR polymer. Samples of PGPR were synthesized containing 3H-labelled ricinoleic acid. The resulting [3H]PGPR was intubated into rats as a component of a dietary slurry. The results indicated that the polymer is extensively digested and 90% of the administered tritium is absorbed. The absorbed material was extensively metabolized within 24 hr so that large amounts of tritium were present in the aqueous phase of the tissues examined. After 24 hr, less than 5% of the administered material was present as lipid material, of which a large proportion was as non-hydroxy fatty acids. No traces of polymer material were found in the tissues examined. In vitro digestion of PGPR by porcine pancreatic lipase and rat intestinal fractions was demonstrated. The results indicate very extensive digestion of the PGPR polymer to polyglycerols and fatty acids. The fatty acids are metabolized extensively. The mono-, di- and triglycerols are extensively absorbed from the intestinal tract and rapidly excreted in the urine unchanged but the hexa-, penta- and higher polyglycerols are essentially not absorbed and excreted in the faeces unchanged.

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Overview of the preparation, use and biological studies on polyglycerol polyricinoleate (PGPR).

The esterification of condensed castor oil fatty acids with polyglycerol gives a powerful water-in-oil emulsifier which is used by the food industry in tin-greasing emulsions and as an emulsifier with lecithin in chocolate couverture and block chocolate. A safety evaluation programme was undertaken in the late 1950s and early 1960s to determine whether this food emulsifier polyglycerol polyricinoleate (PGPR). (Quest International trade name ADMUL WOL) presented any health implications for consumers. This programme included acute toxicity tests, subacute rat and chicken toxicity studies, a rat chronic toxicity/multigeneration reproduction study, rodent metabolism, carcinogenicity testing in rat and mouse and a human clinical evaluation. PGPR was found to be 98% digested by rats and utilized as a source of energy superior to starch and nearly equivalent to groundnut oil. There was no interference with normal fat metabolism in rats or in the utilization of fat-soluble vitamins. Despite the intimate relationship with fat metabolism, no evidence was found of any adverse effects on such vital processes as growth, reproduction and maintenance of tissue homeostasis. PGPR was not carcinogenic in either 2-year rat or 80-week mouse feeding studies. The human studies showed no adverse effects on tolerance, liver and kidney function, and fat balance at levels up to 10 g/day PGPR. The acceptable daily intake for PGPR which was set by JECFA in 1974 and the EC/SCF in 1979 is 7.5 mg/kg body weight/day. The UK FAC in 1992 estimated that the maximum per capita mean daily intake of PGPR is 2.64 mg/kg body weight/day. It can be concluded that the use of ADMUL WOL brand of PGPR in tin-greasing emulsions or in chocolate couverture does not constitute a human health hazard.

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