The differential environmental fates and toxicities of the various hexachlorocyclohexane (HCH) isomers including lindane and isomers in the technical mixture will be the focus of this review. HCHs are one of the most widely used and most readily detected organochlorine pesticides in environmental samples. The relatively high volatility of HCH has led to global transport, even into formerly pristine locations such as the Arctic. Certain HCHs cause central nervous system, reproductive, and endocrine damage. Because γ-HCH is rapidly metabolized, the β-HCH isomer is consistently found in higher concentrations in human fat, blood, and breast milk. In contrast, Rand γ-HCH are the most prevalent isomers in soil, water, and air samples. The ratio of the Rto γ-isomers can be used to track global transport of HCHs. A new area of HCH research focuses on the selective degradation of the two R-HCH enantiomers in various environmental matrices. These HCH issues and recommendations for future HCH research are presented in this review.

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The H4IIE rat hepatoma cell bioassay has been extensively used to assess the toxic equivalents (TEQs) of complex mixtures of halogenated aromatic hydrocarbons in environmental samples. However, there is often a discrepancy between bioassay induction results and toxic equivalents calculated from chemical analysis of samples; the former generally yield higher bioassay-TEQs. Polynuclear aromatic hydrocarbons (PAHs) are a class of chemicals which can significantly contribute to induction-TEQs. Benzo(a)pyrene (BAP), dibenz(a, h)anthracene (DBA), benz(a)anthracene (BA), benzo(k)fluoranthene (BkF), benzo(b)fluoranthene (BbF), chrysene (Chr), and indeno(1,2,3-c,d) pyrene (IdP) are carcinogenic PAHs found in environmental samples, including oysters collected from Galveston Bay. The induction potency of these PAHs relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was determined individually in rat hepatoma H4IIE cells seeded in 6-well plates, and the induction-derived equivalency factors (EFs) relative to TCDD were 0. 000354, 0.00203, 0.000025, 0.00478, 0.00253, 0.00020, 0.0011 for BAP, DBA, BA, BkF, BbF, Chr, and IdP, respectively. Dilutions of a reconstituted PAH mixture containing 23 PAHs (744 to 4466 ng/g total PAHs) with constant percentages of BAP (4.5%), DBA (3.5%), BA (2.4%), BkF (3.7%), BbF (3.5%), Chr (4.7%), and IdP (4.2%) yielded bioassay-derived induction-EQs that ranged from 0.52 to 1.44 ng/g. Oysters exposed in the laboratory to the same PAH mixture for 30 days differentially accumulated the PAHs with time. Bioassay-EQs for these oyster extracts ranged from 0.94 to 5.79 ng/g. These results were similar to the chemically calculated EQs which varied from 0.81 to 3.13 ng/g.

Four new manzamine-type alkaloids, 12,28-oxamanzamine E (2), 12,34-oxa-6-hydroxymanzamine E (3), 8-hydroxymanzamine B (5), and 12,28-oxaircinal A (11), were isolated from three collections of an Indonesian sponge of the genus Acanthostrongylophora together with 13 known manzamine alkaloids, ircinal A, ircinol A, xestomanzamine A, manzamines A, E, F, J, and Y, manadomanzamines A and B, neo-kauluamine, 8-hydroxymanzamine A, and manzamine A Noxide. The structures of the new compounds were elucidated by means of 1D and 2D NMR spectroscopic methods. Three of these compounds (2, 3, and 11) possess a unique manzaminetype aminal ring system generated through an ether linkage between carbons 12-28 or between carbons 12-34. In the case of manzamine B and related metabolites, carbons 11 and 12 of the typical manzamine structure have an epoxide group and add to our growing understanding of manzamine structure-activity relationships (SAR) and metabolism. The bioactivity and SAR for a number of previously reported manzamine-related metabolites against malaria, leishmania, tuberculosis, and HIV-1 are also presented. Manzamine Y (9) showed significant inhibitory activity of GSK3, an enzyme implicated in Alzheimer's disease pathology. The toxicity of manzamine A and neo-kauluamine was evaluated against both medaka fry and eggs.A common Indo-Pacific sponge, Acanthostrongylophora sp., has been shown to be a highly rich source of bioactive manzamine-related alkaloids. [1][2][3] This class of alkaloids has been reported previously to show a number of significant biological activities including cytotoxic, 4 insecticidal, 5 antibacterial, 6 anti-inflammatory, 7 anti-infective, 8 and antiparasitic 9 * To whom correspondence should be addressed. . mthamann@olemiss.edu. HHS Public AccessAuthor manuscript J Nat Prod. Author manuscript; available in PMC 2016 June 22. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript activities, with the greatest potential for possible clinical applications existing for the control of Plasmodium falciparum and Mycobacterium tuberculosis. 10 As part of our ongoing investigations to identify new manzamines and to define the SAR as well as utilize the natural products as synthetic starting materials, [1][2][3][11][12][13] extracts of the Indonesian sponge Acanthostrongylophora sp. were investigated. In an earlier investigation, this sample yielded two new manzamine alkaloids, named 12,28-oxamanzamine A and 12,28-oxa-8-hydroxymanzamine A, and a unique ircinol A analogue together with manzamines A and F and neo-kauluamine. 2 Manzamine A (1) exhibits potent in vitro bioactivity against chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indo-China) strains of P. falciparum. Reisolation of manzamine A for pharmacokinetic and toxicology studies as well as for preparation of analogues necessitated a major collection of Acanthostrongylophora sp., yielding four new manzamine alkaloids (2, 3, 5, and 11)together with the 13 known manzamine alkaloids, which are the subject of this re...

In the aquatic environment, adverse outcomes from dietary polycyclic aromatic hydrocarbon (PAH) exposure are poorly understood, and multigenerational developmental effects following exposure to PAHs are in need of exploration. Benzo[a]pyrene (BaP), a model PAH, is a recognized carcinogen and endocrine disruptor. Here adult zebrafish (F0) were fed 0, 10, 114, or 1012 μg BaP/g diet at a feed rate of 1% body weight twice/day for 21 days. Eggs were collected and embryos (F1) were raised to assess mortality and time to hatch at 24, 32, 48, 56, 72, 80, and 96 hours post fertilization (hpf) before scoring developmental deformities at 96 hpf. F1 generation fish were raised to produce the F2 generation followed by the F3 and F4 generations. Mortality significantly increased in the higher dose groups of BaP (2.3 and 20 μg BaP/g fish) in the F1 generation while there were no differences in the F2, F3, or F4 generations. In addition, premature hatching was observed among the surviving fish in the higher dose of the F1 generation, but no differences were found in the F2 and F3 generations. While only the adult F0 generation was BaP-treated, this exposure resulted in multigenerational phenotypic impacts on at least two generations (F1 and F2). Body morphology deformities (shape of body, tail, and pectoral fins) were the most severe abnormality observed, and these were most extreme in the F1 generation but still present in the F2 but not F3 generations. Craniofacial structures (length of brain regions, size of optic and otic vesicles, and jaw deformities), although not significantly affected in the F1 generation, emerged as significant deformities in the F2 generation. Future work will attempt to molecularly anchor the persistent multigenerational phenotypic deformities noted in this study caused by BaP exposure.