Multi- and Trans-Generational Effects on Daphnia Magna of Chlorpyrifos Exposures.

Chlorpyrifos, a broad-spectrum neurotoxic organophosphate insecticide, is subject to atmospheric and hydrolytic transport from application sites to aquatic ecosystems. Across the landscape, concentrations in surface water can vary spatially and temporally according to seasonal use practices. Standardized bioassays can provide a screening-level understanding of aquatic receptor acute and chronic toxicity. However, these bioassays do not address ecologically relevant exposure patterns that may impact fitness and survival within and across generations. The aim of the present study was to evaluate the utility of a second-tier, screening-level methodology employing Daphnia magna multi- and transgenerational bioassays spanning four generations to investigate the effect of variable chronic chlorpyrifos exposure. The multigenerational assay consisted of continuous chlorpyrifos exposure across four consecutive 21-day bioassays using progeny from the previous assay for each successive generation. In the transgenerational assay, only the parent (F0) generation was exposed. For both assays, survival and reproduction were assessed across treatments and generations. Results indicated that (1) following continuous chlorpyrifos exposure at ecologically relevant concentrations to four generations of D. magna, the highest treatment showed an apparent tolerance response for both survival and reproductive success in the F3 generation, and (2) chlorpyrifos exposure to the F0 generation did not result in treatment effects in the unexposed F1, F2, and F3 generations in the apical endpoints of survival and reproduction. Employing a suite of acute and chronic bioassays, including chronic exposures spanning multiple generations, allows for a more robust screening-level evaluation of the potential impact of chlorpyrifos on aquatic receptors for variable periods of exposure. Environ Toxicol Chem 2022;41:1054-1065. © 2021 SETAC.

The chemistry and toxicology of vaping.

Vaping is the process of inhaling and exhaling an aerosol produced by an e-cigarette, vape pen, or personal aerosolizer. When the device contains nicotine, the Food and Drug Administration (FDA) lists the product as an electronic nicotine delivery system or ENDS device. Similar electronic devices can be used to vape cannabis extracts. Over the past decade, the vaping market has increased exponentially, raising health concerns over the number of people exposed and a nationwide outbreak of cases of severe, sometimes fatal, lung dysfunction that arose suddenly in otherwise healthy individuals. In this review, we discuss the various vaping technologies, which are remarkably diverse, and summarize the use prevalence in the U.S. over time by youths and adults. We examine the complex chemistry of vape carrier solvents, flavoring chemicals, and transformation products. We review the health effects from epidemiological and laboratory studies and, finally, discuss the proposed mechanisms underlying some of these health effects. We conclude that since much of the research in this area is recent and vaping technologies are dynamic, our understanding of the health effects is insufficient. With the rapid growth of ENDS use, consumers and regulatory bodies need a better understanding of constituent-dependent toxicity to guide product use and regulatory decisions.

Neurotoxicity of chlorpyrifos and chlorpyrifos-oxon to Daphnia magna.

Chlorpyrifos (CPF) is a widely used broad-spectrum organophosphate insecticide. CPF elicits neurotoxic effects in exposed organisms by inhibiting the activity of acetylcholinesterase enzymes (AChE), which prolongs nerve transmission and results in neurotoxic symptoms and death at high doses. While CPF is capable of eliciting neurotoxic effects, chlorpyrifos-oxon (CPFO) is the primary neurotoxicant agent. Aquatic organisms bioactivate CPF to CPFO through the Cytochrome P450 phase I metabolic pathway following exposure to CPF. Additionally, in the environment, CPF transforms to CPFO, primarily through photo-oxidation. As both compounds can be transported in air and water to aquatic ecosystems, there is the potential for exposure to non-target organisms. The potential for adverse impacts on aquatic receptors depends on patterns of exposure and toxicity of individual compounds and the mixture. To study the neurotoxicity of these compounds, a 48 h acute and 21 d chronic Daphnia magna bioassay was conducted independently with CPF and CPFO. Acute bioassay results show a median lethal concentration (LC50) of 0.76 µg L-1 for CPF and 0.32 µg L-1 for CPFO, suggesting that CPFO is 2.4 times more acutely toxic to D. magna. Acute assay results were also used to derive Benchmark Dose Levels of 0.58 µg L-1 for CPF and 0.25 µg L-1 for CPFO. However, neither compound elicited an effect on reproduction or growth at relevant chronic exposures. As D. magna are a small and relatively sensitive species, and the AChE inhibition adverse outcome pathway is highly conserved, these results may be cautiously extrapolated in assessing adverse impacts on aquatic receptors.1.

Chiral resolution of a caged xanthone and evaluation across a broad spectrum of breast cancer subtypes.

Racemic resolution of (+/-)-MAD28, a representative caged xanthone, was accomplished using (1S, 4R)-(-)-camphanic chloride as the chiral agent. Selective crystallization of the resulting diastereomers in acetonitrile produced, after hydrolysis, the pure enantiomers. Screening of racemic MAD28 and both enantiomers across a broad spectrum of breast cancer cell lines revealed that they: (a) are equipotent in each of the breast cancer subtypes examined; and (b) exhibit a higher degree of cytotoxicity against breast cancer cell lines of basal-like subtype and triple negative receptor status. The results support the notion that MAD28 and related caged xanthones are promising drug leads against chemoresistant and metastatic cancers.