PubMed HealthSearch

Biomedical subjects

E D Barber

Publications and source records attributed to E D Barber.

14 recordsLinked to original sources

A comparative study of the rates of in vitro percutaneous absorption of eight chemicals using rat and human skin.

In vitro percutaneous absorption studies were carried out for eight chemicals using full thickness rat skin and human stratum corneum. The purpose of the studies was to compare the rates of absorption for the two species. For each of the chemicals, the observed rate using full thickness rat skin was greater than that observed for human stratum corneum. The ratios of the rates (rat/human) varied from 1.7 to 5.8 with a mean value of 3.1. The chemicals tested were tritiated water, 2-ethoxyethyl acetate, diethylene glycol monobutyl ether, urea, di(2-ethylhexyl) phthalate, 2-ethylhexanol, ethyl 3-ethoxypropionate, and 2-propoxyethanol. The chemicals were chosen to represent a wide range of physical properties and permeability constant values. It was concluded that rat skin was more permeable than human skin for each of these eight chemicals. This conclusion is supported by similar findings from studies in other laboratories and suggests that results from studies in the rat overestimate skin absorption in man.

Animals

Peroxisome induction studies on seven phthalate esters.

Seven phthalate esters, representing a variety of chain lengths and degrees of branching in the alcohol moiety, were tested for their ability to produce peroxisome proliferation in the Fischer 344 rat. Di(2-ethylhexyl)adipate (DEHA) was tested using the same protocol and di(2-ethylhexyl)phthalate (DEHP) was run with each study as an internal control. Each ester was administered in the feed for a period of 21 days at levels of 2.5%, 1.2% and either 0.6% or 0.3%. DEHP and DEHA were also fed at levels of 0.1% and 0.01%. The animals were sacrificed and samples of liver were prepared for both light and electron microscopy. Serum samples were assayed for both triglyceride and cholesterol. The remaining portion of the liver was homogenized and assayed for cyanide-insensitive palmitoyl-CoA oxidation, lauric acid 11-hydroxylase and lauric acid 12-hydroxylase. The results show that there is approximately a ten-fold difference between the weakest and strongest esters in terms of their potency to induce changes in relative liver weight and in several of the biochemical parameters. In general, the longer chain esters were more potent than the shorter chain ones, and branched chain esters seemed more potent than straight. Several statistical analyses of the dataset have been performed and all render similar conclusions. The results of one of these evaluations are presented elsewhere in this volume (Lin, 1987).

Animals

Methods for measuring mutagenicity in urine of rats dosed with [14C]di(2-ethylhexyl)phthalate.

Di(2-ethylhexyl)phthalate (DEHP) is extensively used as a plasticizer for vinyl plastic articles. It has been found to be positive in an NCI rodent bioassay but has generally given negative results in in vitro genotoxicity tests. We therefore decided to test the urine of rats fed [14C]DEHP for mutagenic activity in the Ames Salmonella test. The recovery of radioactivity from the urine of rats dosed with [14C]DEHP was examined by solvent extraction and XAD-2 resin absorption procedures. Both of these procedures were inadequate for quantitative recovery of urinary metabolites required for subsequent mutagenicity testing using the Ames Salmonella/microsome procedure. Recoveries of less than 5% were observed using standard solvent extraction techniques whereas the XAD-2 adsorption technique gave about 67% at high resin/urine ratios. Treatment of the urine with beta-glucuronidase/aryl sulfatase did not affect these recoveries. The direct urine plating procedure represents a viable alternative to the above concentration procedures for this phthalate ester. The effects of L-histidine and the beta-glucuronidase/aryl sulfatase preparation on the background reversion frequencies of the Ames tester strains is discussed.

Animals

Bacterial mutagenicity testing of urine from rats dosed with 2-ethylhexanol derived plasticizers.

Di-(2-ethylhexyl)phthalate (DEHP) produced hepatocellular carcinomas in rodents at high doses in a NTP/NCI bioassay. DEHP has not shown evidence of genotoxic activity in in vitro mutagenicity tests. We extended these studies by examining the mutagenicity of urine from rats dosed with DEHP, 2-ethylhexanol (2-EH), and several other 2-EH derived plasticizers, i.e. di-(2-ethylhexyl)adipate (DEHA), di-(2-ethylhexyl)terephthalate (DEHT) and tri-(2-ethylhexyl)trimellitate (TEHT). A modified Ames Salmonella/microsome assay was used to determine mutagenicity. Urine was pooled from male Sprague--Dawley rats dosed daily for 15 days with 2000 mg/kg of each test substance with the exception of 2-EH which was given at 1000 mg/kg. Direct plating procedures were used to determine the presence of mutagens in urine. Urine from rats dosed with 8-hydroxyquinoline was used as a positive control. There was no evidence that mutagenic substances were excreted in the urine by rats dosed with either DEHP, DEHA, DEHT, TEHT or 2-EH as determined in the presence or absence of rat liver microsomes, and with or without treatment with beta-glucuronidase/aryl sulfatase. Our findings indicate that the above test compounds were not converted to urinary metabolites that were mutagenic. These observations provide no evidence for a genotoxic mechanism for DEHP carcinogenicity in rodents.

Animals

The relationship between growth and reversion in the Ames Salmonella plate incorporation assay.

Growth curves of the 5 commonly used Ames Salmonella tester strains have been measured turbidimetrically in semi-solid agar. Lag times, doubling times and maximum cell densities have been calculated for each of the 5 strains. The time dependence of reversion has been studied in the standard plate incorporation assay using 1-h pulsed doses of (a) bromoethane, a volatile chemical mutagen, and (b) 1-h exposures to visible light. Essentially no reversion takes place during the first 4 h after plating. Reversion is detectable between hours 4 and 16. The cumulative or integrated revertants versus time curve has the characteristics of a growth curve. Conversely the derivatives of the growth curves resemble the curves obtained in the pulsed mutagenicity studies. Thus, the reversion rate in any given 1 h interval is proportional to the growth rate during that same interval. These results suggest that mutagenic chemicals must be present during the bacterial growth cycle (about 4-16 h after plating) in order to revert the tester strains. Short-lived chemical mutagens, then, should produce enhanced results if plated 6-8 h after the bacteria. We have confirmed this for N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 9-aminoacridine and 2-aminoanthracene (with S9).

Cell Division

Quantitative effects of unsaturated fatty acids in microbial mutants. VI. Selective growth responses of yeast and bacteria to cis-octadecenoate isomers.

The full series of positional isomers of cis-octadecenoate were tested for their suitability in meeting the nutritional requirement for unsaturated fatty acids by mutants of Escherichia coli and Saccharomyces cerevisiae that were unable to synthesize unsaturated fatty acids. Quantitative comparisons of the efficiencies of the various isomers showed a range from 0-48 cells per femtomole for the prokaryotic cells and 0-5 for eukaryotic cells. The delta 5 isomer was much more effective than the delta 6 isomer with the bacterial cells whereas the reverse was true with the yeast cells. In general, isomers containing a cis ethylenic bond between carbons 7 and 12 were able to support extensive growth of either type of mutant. Since all of the various isomers were incorporated into cellular lipids by both types of microorganism, the different efficiencies observed in supporting growth were not a simple reflection of the inability of an acid to be esterified. The differences may reflect the suitability of the resultant esterified product to function as a normal membrane lipid. The contents of various fatty acids in the cellular phospholipids when growth ceases may have a linearly cumulative relationship to the degree of expansion of the acyl chains.

Cell Division

Quantitative measurement of the effectiveness of unsaturated fatty acids required for the growth of Saccharomyces cerevisiae.

The growth response of a mutant of Saccharomyces cerevisiae which is unable to synthesize unsaturated fatty acids has been measured in the presence of variable concentrations of exogenous unsaturated fatty acids. Final cell yields, doubling times, and lag times were all found to vary as a function of the initial concentration of the added unsaturated acid. The cell yield was found to be a convenient quantitative measurement to use in comparing the effectiveness of various unsaturated acids. Values for the acids ranged from 1.7 to 11 cells per femtomole with values for oleate and palmitoleate at 2.7 and 4.3 cells per femtomole, respectively. In general, the effectiveness of unsaturated acids was found to increase with an increasing number of double bonds. Saturated fatty acids of a chain length of 5 to 18 carbon atoms were completely ineffective. The varied efficiencies of different unsaturated fatty acids indicate that unsaturation per se was not the basis of the nutritional requirement and indicate certain acids that would be useful in further studies of the role of unsaturated acids in cell function.

Arachidonic Acids

Unit orientation for experienced nurses. Process and evaluation.

In order to recruit and retain registered nurses during an era of nursing shortages, staff development educators must provide orientation programs that are highly satisfactory. This article describes a program that effectively links the perspectives of nurse managers, nursing staff, and nurse educators. Orientation evaluation questionnaires completed by orientees and staff nurses who served as their buddies show that new employees believe this program meets their learning needs. Such satisfied nurses can recruit their colleagues to employment.

Attitude of Health Personnel