J. Ronald Hass

Effects of pentachlorophenol on hepatic drug-metabolizing enzymes and porphyria related to contamination with chlorinated dibenzo-p-dioxins and dibenzofurans☆

Abstract The hepatic effects of technical and pure grade pentachlorophenol were investigated in female rats fed 20, 100 and 500 ppm of each for 8 months. Technical pentachlorophenol was contaminated with 8 ppm hexa-, 520 ppm hepta-, and 1380 ppm octachlorodibenzodioxtns and with 4 ppm tetra-, 42 ppm penta-, 90 ppm hexa-, 1500 ppm hepta- and 200 ppm octachlorodibenzofurans; pure pentachlorophenol contained less than 0.1 ppm of each of these contaminants. Technical pentachlorophenol produced hepatic porphyria and increased hepatic aryl hydrocarbon hydroxylase activity, glucuronyl transferase activity, liver weight, cytochrome P-450 and microsomal heme, but not N-demethylase activity. The peak of the CO-difference spectrum of cytochrome P-450 was shifted to 448 nm, and there was a dramatic increase in the 455-430 ratios of the ethyl isocyanide difference spectrum. The enzyme changes were observed at 20 ppm of technical pentachlorophenol. Porphyria occurred at 100 and 500 ppm. Pure pentachlorophenol had no significant effect on aryl hydrocarbon hydroxylase activity, liver weight, cytochrome P-450, microsomal heme, the ethyl isocyanide difference spectrum or N-demethylase activity at any dose level, but did increase glucuronyl transferase at 500 ppm. In contrast, both pure and technical pentachlorophenol decreased body weight gain comparably at 500 ppm. It is concluded that technical pentachlorophenol produces a number of liver changes which cannot be attributed to pentachlorophenol itself, but are consistent with the effects of biologically active chlorinated dibenzo-p-dioxins and dibenzofurans.

Comparison of Five Ionization Methods for Producing Mass Spectra of Typical Organophosphorus Pesticides

Positive ion mass spectra obtained by conventional electron impact and by methane chemical ionization were compared with the negative ion mass spectra of 16 typical organophosphorus pesticides using methane, a methane-oxygen mixture, and oxygen as enhancement/reagent gases. In the negative ion spectra, phosphate and phenate anions typically carry a large fraction of the ion current. Displacement of chlorine by oxygen is noted in some cases, and migration of aryl groups from oxygen to sulfur is occasionally noted. Ion-molecule reactions between two species derived from sample molecules have been observed. The sensitivity of the negative ion techniques for the pesticides examined is greater than conventional electron impact or methane positive chemical ionization techniques, and can be up to 800 times more sensitive for some compounds.

Conversion of kinetic energy to internal energy in the 2-pentanone molecular ion at threshold in low-energy collisions with helium target atoms

Abstract Values of the threshold kinetic energy for formation of m/z 58 and m/z 43 from 2-pentanone molecular ion after collisional activation (CA) with He were studied in a hybrid tandem quadrupole system. These values indicate that the fraction of kinetic energy converted to internal energy and available for fragmentation is 0.14–0.25. Onset of conversion to internal energy through an electronically excited state was observed at 2.0 eV. Uses of He and heavier gases as collision gases in low-energy CA are projected to differ, He being used to screen classes of compounds and heavier gases to provide more complete structural information for ions.

Optimization of a hybrid-mass spectrometer method for the analysis of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans

Abstract Experiments were conducted to evaluate the effect of collision energies and argon pressure on the formation of daughter ions (M-COCI) selective to the analysis of PCDDs and PCDFs. The results show that sensitivity is enhanced at higher pressures and lower collision energies. The detection sensitivity of the method for the analysis of 2, 3, 7, 8 - TCDD and 2, 3, 7, 8 - TCDF is S N =43 : 1 on 8.7 pg and S N =34 : 1 on 11.6 pg, respectively. The selectivity of the method is demonstrated through the analysis of municipal incinerator ash and pulp effluent extracts. In these cases, interferences were eliminated by HRGC/MS/MS and not by HRGC/MS at resolving powers of 10,000 and 18,000.

Survey of reaction types in low-energy colliosional activation of protonated methyl alkyl ketones

Abstract In contrast to high-energy collisions, where simple cleavages are commoner, rearrangements typically account for 96–100% of products in low-energy collisions of the [M + 1] + ions of aliphatic methyl ketones. Rules for predicting low-energy helium collsional-activated decomposition (CAD) spectra of the ketones are based on proton affinities of fragments formed by simple rearrangements. The commonest reaction is equivalent to the energetically improbable four-center 1,3-H or 1,3-R shift; other rearrangements equivalent to processes with five-, six-, or seven-center activated complexes are less important. In larger ions, loss of water followed by loss of alkene dominates. O -Protonated enol forms either lose water to give a carbonium ion that rearranges to forms capable of losing olefin fragments, or rearranges to an intermediate in the formation of acetyl ion and an alkane. O -Protonated keto forms rearrange to alkanes and protonated smaller carbonyl compounds. The ion kinetic energies necessary to produce several intense daughter ions at threshold establish the order of sequential fragmentations. When helium is the collisional gas and the ion energy is 30 eV in the laboratory frame (the maximum value studies), the ion energy is only 0.8–1.9 eV in the center-of-mass frame depending on its size. Only a fraction of this kinetic energy is converted to internal energy, so that onsets of reaction channels differing by several tenths of an electron-volt are easily studied. Some isomers of methyl ketones can be easily distinguished by He-CAD spectra of their [M + 1] + ions.

Adduct formation between the carcinogen N-acetoxy-2-acetylaminofluorene and synthetic polydeoxyribonucleotides

The chemical carcinogen N-acetoxy-2-acetylaminofluorene (NA-AAF) was reacted with poly(dG-dC) - poly(dG-dC); poly dG - poly dC; poly(dA-dT) - poly (dA-dT); and poly dA - poly dT under a variety of conditions. Poly (dG-homo GC polymer and 10--20 more reactive the A + T polymers. Lowering the ionic strength increased the extent of reaction, while pH change (8.9 vs. 5.5) had only a small effect. If ionic strength was adjusted so that the two guanine-containing polymers showed equal thermal stability (as judged by Tm) then the alternating copolymer was 7 times as reactive as the homopolymer. In aggreement with previous investigators, the major product was found to be 8-(N-2-fluorenylacetamido) deoxyguanosine.

Data evaluation in combined gas chromatography—infrared spectroscopy—mass spectrometry

Abstract The technique of gas chromatography—infrared spectroscopy—mass spectrometry (g.c./i.r./m.s.) has great potential m qualitative and quantitative analysis. The utility of g.c./i.r./m.s. is presently limited by the lack of methods for reduction of the large amounts of data produced from complex mixtures. Approaches to qualitative and quantitative data evaluation which take into account differences in instrumental configuration are presented.

Applications of isotope differentiation for metabolic studies with di‐(2‐ethylhexyl) phthalate

The pervasiveness of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) in the environment and especially in the laboratory results in a background that may cause severe interference with analytical studies. Animal-to-animal variability in the distribution of DEHP metabolites in excreta normally makes it necessary to use large groups of animals when different treatments are compared. Finally, radioactive tracers are usually considered undesirable for metabolic studies involving human subjects. All of these problems can be overcome through the use of multiple isotopic labels, especially 12C/13C/14C. Examples are given involving rats and monkeys, and applicability to humans is discussed. The principles involved are not limited to any particular class of test compounds. In rats, the competing pathways for metabolism of phthalate esters produce a different distribution of metabolites from a small intravenous dose of DEHP than from a large oral dose.

Survey of reactions of protonated acetate esters induced on low-energy collisions with helium and nitrogen

Abstract The major fragmentations induced by collisions of 30-eV (laboratory coordinate) protonated acetate esters with helium and nitrogen are the rearrangements observed in earlier high-energy collisional activation studies, except for the diagnostic loss of alkane observed in the high-energy process, which is missing. The kinetic energy dependence of fragmentation is reflected in peak intensities at 30 eV. As proposed earlier, helium collisions are useful for categorization of the compounds, and nitrogen for their identification.

A mixture of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non-ortho polychlorinated biphenyls (PCBs) changed the lipid content of pregnant Long Evans rats

Pregnant Long Evans rats received 1.0 microg/kg of dioxin toxic equivalents (TEQ) by oral gavage on the 15th gestational day (GD 15), using a dosing mixture that contained two polychlorinated dioxins, four polychlorinated furans and three non-ortho polychlorinated biphenyls (PCBs). Rats were sacrificed on GD 16, GD 21 and postnatal day 4 (PND 4). The lipid content of fetus, pup, placenta and maternal liver, serum and adipose tissue were determined. Treated GD 16 and GD 21 fetuses had identical lipid content to the control group, yet the lipid content of treated pups on PND 4 was 32% higher than that of the control group. On the other hand, the lipid content of placenta, liver, and serum from the treated dams was 44-50%, 24%, and 38% lower than that of the control group, respectively. Thus, a low-dose mixture of dioxin-like compounds can cause changes in lipid content. The lipid content of offspring was not affected until they were exposed via lactation.