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All of the 13 possible polychlorinated biphenyl (PCB) isomers and congeners substituted at both para positions, at least two meta positions (but not necessarily on the same ring) and at two ortho positions have been synthesized and tested as rat hepatic microsomal enzyme inducers. The effects of these compounds were evaluated by measuring microsomal benzo[a]pyrene (B[a]P) hydroxylase, 4-chlorobiphenyl (4-CBP) hydroxylase, 4-dimethylaminoantipyrine (DMAP) N-demethylase and NADPH-cytochrome c reductase activities, the cytochrome b5 content and the relative peak intensities and spectral shifts of the carbon monoxide(CO)- and ethylisocyanide(EIC)-difference spectra of ferrocytochrome P-450. The results were compared to the effects of administering phenobarbitone (PB), 3-methylcholanthrene (MC) and PB plus MC (coadministered). At dose levels of 150 [mu]mol [middle dot] kg-1, all of the PCB congeners, except 2,3',4,4',5',6-hexachlorobiphenyl, significantly enhanced hepatic microsomal cytochrome P-450 content, B[a]P hydroxylase and/or DMAP N-demethylase activities compared to the control (corn oil-treated) animals. Only 5 of these compounds, namely 2,3,4,4',5,6-hexa-, 2,2',3,3',4,4'-hexa-, 2,2',3',4,4',5-hexa-, 2,3,3',4,4',6-hexa- and 2,2',3,3',4,4',5-heptachlorobiphenyl, enhanced microsomal B[a]P hydroxylase, 4-CBP hydroxylase, NADPH-cytochrome c reductase and DMAP N-demethylase activities in a manner consistent with a mixed pattern of induction. The results suggest that PCB isomers and congeners substituted at both para positions, at least two meta positions, at two ortho positions and containing a 2,3,4-trichloro substitution pattern on one ring are mixed-type inducers; in addition the effects of 2,3,4,4',5,6-hexachlorobiphenyl were also consistent with a mixed pattern of induction.

A number of highly purified polychlorinated biphenyl (PCB) isomers and congeners were synthesized and administered to male Wistar rats at dosage levels of 30 and 150 [mu]mol [middle dot] kg-1. The effects of this in vivo treatment on the drug-metabolizing enzymes were determined by measuring the microsomal benzo[a]pyrene (B[a]P) hydroxylase, dimethylaminoantipyrine (DMAP) N-demethylase and NADPH-cytochrome c reductase enzyme activities, the cytochrome b5 content and the relative peak intensities and spectral shifts of the reduced microsomal cytochrome P-450: CO and ethylisocyanide (EIC) binding difference spectra. The results were compared to the effects of administering phenobarbitone (PB), 3-methylcholanthrene (MC) and PB plus MC (coadministered) to the test animals. The synthetic PCB congeners used in this study included 3,4,4',5-tetrachlorobiphenyl (TCBP-1), 2,3',4,4'-tetrachlorobiphenyl (TCBP-2), 2,3',4,4',5'-pentachlorobiphenyl (PCBP-1), 2,3,4,4',5-pentachlorobiphenyl (PCBP-2), 2,3,3',4,4',5-hexachlorobiphenyl (HCBP-1), 2,3,3',4',5,6-hexachlorobiphenyl (HCBP-2), 2,3,3',5,5',6-hexachlorobiphenyl (HCBP-3), 2,2',3,5,5',6-hexachlorobiphenyl (HCBP-4) and 2,3,3',4,5,5'-hexachlorobiphenyl (HCBP-5) and were used to reappraise the structure-activity rules for PCBs as hepatic microsomal enzyme inducers. The results suggested that (a) PCBs which induce MC or mixed-type activity must be substituted at both para positions, at least two meta positions but not necessarily on the same phenyl ring and can also contain one ortho chloro substituent; (b) due to the considerable structural diversity of the PB-type inducers the rules for induction of this activity by PCB congeners are not readily defined.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and diben, Addresses: van Leeuwen FXR, WHO, European Ctr Environm & Hlth, Bilthoven Div, POB 10, NL-3730 AA De Bilt, Netherlands. WHO, European Ctr Environm & Hlth, Bilthoven Div, NL-3730 AA De Bilt, Netherlands. Univ Utrecht, Toxicol Res Inst, NL-3508 TD Utrecht, N

Nine catfish fillets, three catfish nuggets, two feed samples, and one pond sediment were analyzed for PCDD, PCDF, and-PCB. Farm-raised catfish from Mississippi, Alabama, and Arkansas contained significant levels of 2,3,7,8-substituted PCDD and PCDF. In addition, a large number of non-2,3,7,8-substituted congeners were present in all samples. The catfish fillets and catfish nuggets also contained high concentrations of dioxin-like PCB, as well as a number of non-dioxin-like PCB. The TEQ based on PCDD and PCDF ranged from 9.5 to 43.0 pg/g lipid and the TEQ based on PCB ranged from 0.45 to 4.9 pg/g lipid for all catfish samples. The dioxin-like PCB contributed 4-16% to the total TEQ (PCDD/PCDF/PCB) for the catfish samples. The major source for the PCDD, PCDF, and PCB appears to be from feed and not from pond sediment. Immunoreactive CYP1A protein was elevated 2.5 fold in the pond-raised catfish compared to the aquarium-raised one. The results of this study suggest that the PCDD/PCDF are more important than the PCB in the CYP1A induction.

The human diet contains industrial-derived, endocrine-active chemicals and higher levels of naturally occurring compounds that modulate multiple endocrine pathways. Hazard and risk assessment of these mixtures is complicated by noadditive interactions between different endocrine-mediated responses. This study focused on estrogenic chemicals in the diet and compared the relative potencies or estrogen equivalents (EQs) of the daily consumption of xenoestrogenic organochlorine pesticides in food (2.44 micrograms/day) with the EQs in a single 200-ml glass of red cabernet wine. The reconstituted organochlorine mixture contained 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, endosulfan-1, endosulfan-2, p,p'-methoxychlor, and toxaphene; the relative proportion of each chemical in the mixture resembled the composition reported in a recent U.S. Food and Drug Administration market basket survey. The following battery of in vitro 17 beta-estradiol (E2)-responsive bioassays were utilized in this study: competitive binding to mouse uterine estrogen receptor (ER); proliferation in T47D human breast cancer cells; luciferase (Luc) induction in human HepG2 cells transiently cotransfected with C3-Luc and the human ER, rat ER-alpha, or rat ER-beta; induction of chloramphenicol acetyltransferase (CAT) activity in MCF-7 human breast cancer cells transfected with E2-responsive cathepsin D-CAT or creatine kinase B-CAT plasmids. For these seven in vitro assays, the calculated EQs in extracts from 200 ml of red cabernet wine varied from 0.15 to 3.68 micrograms/day. In contrast, EQs for consumption of organochlorine pesticides (2.44 micrograms/day) varied from nondetectable to 1.24 ng/day. Based on results of the in vitro bioassays, organochlorine pesticides in food contribute minimally to dietary EQ intake.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in viva evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties. VA:IBN

Mass spectra and ion kinetic energy spectra of mono-, di-, and trichloroanilines are reported and discussed.

The effect of aerobic and oxygen limiting (anaerobic) growth conditions upon the fatty acid and lipid composition of Mucor rouxii has been examined. The aerobic cells contained a range of fatty acids typical of phycomycetes, i.e. gamma-linolenic acid, with an unsaturation index of 1.20, whereas the anerobic cells contained relatively high levels of shorter chained fatty acids and very low concentrations of unsaturated acids (unsaturation index = 0.025). The unsaturated compounds were monoolefinic tetra-, hexa-, and octadecenoic acids. These results were consistent with a microaerobic biosynthetic pathway. In addition, there were major quantitative differences in the lipid composition of the two types of cells; and it was evident that the differences in growth environment markedly affected the cellular lipid and fatty acid compositions. (Modified author abstract)

Examination of the sterols produced by Mucor rouxii showed significant variations in the relative amounts of free (i.e. lipid extractable) and bound sterols contained in the aerobic and anaerobic cells. The filamentous aerobic cells contained primarily free sterols with only small amounts of the bound material. The reverse situation was true for the yeast-like anaerobic cells in which over 75% of the total sterols were bound and were released only after treatment with methanolic KOH solution. Extensive examination of the sterol fractions revealed a number of different sterols present; in the aerobic cells ergosterol was the main sterol (approx. 85%) but in the anaerobic cells (i.e. oxygen limiting) the concentration of this component was considerable diminished (36.5%) with increased amounts of ergosta-5,7,24(28)-trien-3 beta-ol (37.0%), ergosta-5,7-dien-3 beta-ol and ergosta-7,22,24(28)-trien-3 beta-ol present. (Modified author abstract)

The mass spectra of several substituted diphenylacetylenes are reported and the (metastable ion)/(daughter ion) ratios for the isomeric chloro- and bromodiphenylacetylenes suggested substituent scrambling in their respective molecular ions. The fragmentation patterns for the amino- and nitrodiphenylacetylenes differed somewhat from most other aromatic amino and nitro compounds. The mass spectra of several deuterated substituted diphenylacetylenes clearly showed extensive (but not complete) H/D equilibration in the molecular ion or some subsequent decomposition ion. (Modified author abstract), Revision of report dated 18 Jan 73.

A number of reagents for the exhaustive chlorination of aromatic compounds were investigated. Antimony pentachloride-iodine and the BMC reagent (sulfuryl chloride-aluminum chloride-disulfur dichloride) were found to be the most effective and convenient reagents. They are liquids which can be used without special precautions to prepare the perchloro-derivatives of biphenyl, terphenyl, naphthalene, dibenzofuran, dibenzodioxin and DDE. The structures, mass spectra and GLC properties of these compounds are discussed. (Author)

The mass spectra of several di- and tetra-chlorobiphenyls suggested randomization of chlorine over both phenyl rings in the molecular ion prior to fragmentation. The exceptions, 2,2'- and 2,6-dichloro-, 2,2',4,4'-,2,2',5,5'-, 2,3,5,6-, and 2,2',6,6'-tetrachloro-biphenyls, all contain two or more chlorine atoms ortho to the Ph--Ph bond and their metastable ion intensities which result from the M to M - Cl2 reaction are markedly different from those of the other isomers. The primary ion spectra of most isomeric compounds are similar, with successive losses of Cl radical from the molecular ion. This process is often accompanied by expulsion of HCl from the lower chlorine homologues. The ion kinetic energy spectra of the di- and tetra-chloroisomers confirm the suggested fragmentation pathways. (Author)

Chetomin, one of the antibiotic metabolites of Chaetomium cochliodes and C. globosium has been isolated as an amorphous, glass-like solid. Elemental analysis of chetomin, its diacetate, and its bistrimethylsilyl ether, mass spectroscopy of its tetrathiomethyl derivative, and n.m.r. spectroscopy indicate the molecular formula to be C31H30N6O6S4. The formation of a tetra-S-methyl derivative and a bismonosulphide indicated the presence of two epidithiodioxopiperazine ring systems like those present in chaetocin, a metabolite of C. minutum, a conclusion supported by the close similarity of the c.d. of the two metabolites. The u.v. spectrum of chetomin was the same as that of echinulin. These facts, and an interpretation of the n.m.r. spectra of chetomin and its derivatives, lead one to believe that the molecule contains an indole, an indoline, and two epidithiodioxopiperazine systems. (Author), See also AD-742 577.

When the tail fractions from chromatograms of sporidesmin E (I; n=3) were rechromatographed, a new crystalline metabolite of Pithomyces chartarum was isolated with molecular formula C18H20ClN3O6S4. The new compound, named, sporidesmin G (I; n=4), gave sporidesmin (I; n=2) on irradiation of treatment with triphenylphosphine, and sporidesmin D (V) after reduction and methylation. It was shown that the model compound, 1,4-dimethyl-3,6-epidithiopiperzine-2,5-dione, gave the cyclic tetraulphide on treatment with dihydrogen disulphide. Similarly, sporidesmin and sporidesmin E when treated with dihydrogen disulphide gave the new metabolite. (Author), See also AD-742 579.

The mass spectra of the seven isomeric methylindoles were recorded and the (metastable ion)/(daughter ion) ratios for the reactions m/e 130 to m/e 103 and m/e 103 to m/e 77 have been obtained. The ratios indicate that the decomposing (M - 1) ions (m/e 130) from the 4, 5, 6 and 7 isomers are energetically similar as are the (M - 1) ions from the 2 and 3 isomers. The results observed for the m/e 103 to m/e 77 reaction showed that the decomposing m/e 103 ions from the 2, 3, 4, 5, 6 and 7 isomers all have the same energy distribution. N-Methylindole gave ratios which were similar to the 4 to 7 isomers at 70 eV but different at 20 eV. The ion kinetic energy (IKE) spectra of all the isomeric methlindoles were also obtained and the results compared with the data obtained from the (metastable ion)/(daughter ion) approach. (Author), Revision of report dated 28 Dec 70.

The role of beta gamma unsaturated fatty acids has become significant in the biochemistry of plants and microorganisms. Bloch and co-workers have also shown the importance of trans-3-decenoic acid as a key intermediate in the synthesis of unsaturated fatty acids via the anaerobic pathway. It was therefore of interest to prepare a series of labelled beta gamma unsaturated fatty acids for various biosynthetic studies. The synthesis of these acids is shown. (Author)

In recent years the number of 2,5-epipolythia-3,6-dioxopiperazine antibiotics has increased significantly due to isolation of new members of the series and by chemical transformations of the naturally-occurring compounds. By extensive chemical and/or X-ray crystallographic investigations the structure of gliotoxin (I), sporidesmin (II, X = 2, R = OH) and dehydrogliotoxin (III, X = 2) was determined and other closely related compounds have since been isolated or synthesized. The report deals with the thin-layer chromatographic behavior of fifteen of these sulfur-containing compounds. The separation of polysulfides (II, X = 1, 2, 3, 4, R = OH) and (III, X = 1, 2, 3, 4) differing only in the number of sulfur atoms in the 2,5 bridge is particularly noted. (Author)

The structure of sporidesmin E suggests that it is biosynthesised from sporidesmin by a sulphurising enzyme analogous to a peroxidase. Accordingly, the reaction of dihydrogen disulphide with sporidesmin, dehydroglio-toxin, and other disulphides, has been studied. Polysulphides were obtained in all cases, but the reaction of dibenzyl disulphide with dihydrogen disulphide was slow. By contrast phenylmethanethiol reacted smoothly with the reagent to give di-, tri-tetra-, and penta-sulphides, and this oxidation appears to be general. The epitrithiadioxopiperazines were light-sensitive and were converted photolytically into equimolecular mixtures of di-, and tetra-sulphides. By use of 35S-labelled polysulphides it was shown that the photolysed sulphur was that inserted by the dihydrogen disulphide. (Author), See also AD-643 568.

The mass spectra of halogenosubstituted diphenylacetylenes show hydrogen scrambing between the two phenyl rings. As with the halogenobenzenes the randomization process occurs in the molecular ion rather than in the (M - 1) ion as is the case for methyldiphenylacetylene. (Author), Revision of report dated 22 Sep 69.

A few natural products having asymmetric polysulphide moieties have been isolated, and improved methods of synthesis have enabled other asymmetric polysulphides to be secured. The availability of these compounds has enabled n.m.r. studies to be made, and these investigations have shown that the chemical shift of atomic nuclei adjacent to a sulphur group depends on its asymmetry. In addition, these compounds exhibit different circular dichroism. These advances have led to an increase in our knowledge of the stereochemistry of sulphur compounds and it therefore seems appropriate to present a review of the subject at this time. The review is divided into four sections dealing with sulphur, acyclic polysulphides, organic cyclic polysulphides, and inorganic cyclic polysulphides. (Author)

Iodobenzene-d5 was prepared from readily available benzene-d6. Benzene-d6 was monoiodinated by treatment with either iodic acid, iodine, acetic acid-d4 deuterium oxide and sulfuric acid-d2 to give iodobenzene-d5 in 60-80% yield. (Author)