Variability of Microcystin-LR Standards Available from Seven Commercial Vendors.

Microcystins (MCs) are a large group of heptapeptide cyanobacterial toxins commonly produced in harmful algal blooms (HABs) and associated with adverse health effects in wildlife, livestock, pets, and humans. MC chemical standards are extracted from cyanobacteria biomass rather than produced synthetically and are used in water assessment methods and toxicological studies. MC standards are generally supplied in less than 1 mg quantities, and verification of the mass can only be accomplished by analytical chemistry methods using a certified reference of the specific MC for comparison.

A rapid assessment bioaccumulation screening (RABS) study design for emerging per-and polyfluoroalkyl substances in mice exposed to industrially impacted surface water.

The shift away from PFOS and PFOA production in the past 20 years towards shorter chain and replacement PFAS has led to the environmental release of complex mixtures of emerging PFAS for which bioaccumulation potential and toxicology are largely unknown. The rate at which emerging PFAS can be prioritized for research in these complex mixtures is often limited by the lack of available chemical standards. We developed a study design that rapidly assesses which emerging PFAS in an environmentally derived mixture have the potential for mammalian bioaccumulation and thus prioritize these emerging chemicals for standard synthesis and toxicity testing.

Dose-Response Study of Microcystin Congeners MCLA, MCLR, MCLY, MCRR, and MCYR Administered Orally to Mice.

Microcystins are common freshwater cyanobacterial toxins that affect liver function. The toxicities of five microcystin congeners (microcystin-LA (MCLA), MCLR, MCLY, MCRR, and MCYR) commonly observed in harmful algal blooms (HABs) were evaluated in BALB/c mice after a single oral administration of doses ranging from those that were no observed adverse effect levels (NOAELs) to lowest observed adverse effect levels (LOAELs). Animals were monitored for changes in behavior and appearance, and euthanized 24 h after dosing.

Toxicity of Balb-c mice exposed to recently identified 1,1,2,2-tetrafluoro-2-[1,1,1,2,3,3-hexafluoro-3-(1,1,2,2-tetrafluoroethoxy)propan-2-yl]oxyethane-1-sulfonic acid (PFESA-BP2).

1,1,2,2-tetrafluoro-2-[1,1,1,2,3,3-hexafluoro-3-(1,1,2,2-tetrafluoroethoxy)propan-2-yl]oxyethane-1-sulfonic acid (PFESA-BP2) was first detected in 2012 in the Cape Fear River downstream of an industrial manufacturing facility. It was later detected in the finished drinking water of municipalities using the Cape Fear River for their water supply. No toxicology data exist for this contaminant despite known human exposure.

The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity.

Microcystins (MCs) are common cyanobacterial toxins that occur in freshwaters worldwide. Only two of the >200 MC variants have been tested for potential toxicity after oral exposure. This paper reports on the toxicity of 10 different MC congeners identified in algal blooms, microcystin-LR (MCLR), MCLA, MCLF, MCLW, MCLY, MCRR, [Asp3]MCRR, [Asp3,Dhb7]MCRR, MCWR, and MCYR after single administrations to BALB/c mice.

Pathology in Ecological Research With Implications for One Health: Session Summary.

This session explored the effects of pollutants on One Health at the ecosystem level that included microbes, insects, fish, and humans. The concept of One Health seeks to synergize medical, veterinary, and other health science disciplines to more effectively advance human and animal health. Presentations explored the interactions of pesticides, pathogens, phytochemicals, and xenobiotic biotransformation in bee colony losses critical for food security (bees have been recently listed under the 2017 US Food and Drug Administration (FDA) veterinary feed directive); the role of pathology in identifying the effects of pollutants on fish as sentinels for human health; the effects in rats of per- and polyfluoroalkyl substances (PFAS) that can persist in the environment and contaminate drinking water; harmful algal blooms and toxin production leading to animal and human disease; and the processing of environmental carcinogens by intestinal microbiota.

The analysis of underivatized β-Methylamino-L-alanine (BMAA), BAMA, AEG & 2,4-DAB in Pteropus mariannus mariannus specimens using HILIC-LC-MS/MS.

β-Methylamino-L-alanine (BMAA) has been identified as the potential cause of the amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) observed in the Chamorro people of Guam. The principal hypothesis for BMAA exposure and intoxication relies on the biomagnification of BMAA in flying fox specimens ingested by the Chamorro people. Although high levels of BMAA were quantitated in flying fox specimens utilizing liquid chromatography-fluorescence (LC-FL), there have not been any confirmatory analyses conducted to date.

pH dependent octanol-water partitioning coefficients of microcystin congeners.

Hazardous algal blooms can generate toxic compounds with significant health impacts for exposed communities. The ubiquitous class of algal toxins known as microcystins exhibits significant heterogeneity in its peptide structure, which has been minimally studied, given the significant impact this has on hydrophobicity, acid/base character and related environmental fate and health effects. Octanol-water partition coefficients for the microcystin congeners MCLR, MCRR, MCLY, MCLF, and MCLA were calculated over an environmentally and physiologically relevant pH range.

A review on cylindrospermopsin: the global occurrence, detection, toxicity and degradation of a potent cyanotoxin.

Cylindrospermopsin is an important cyanobacterial toxin found in water bodies worldwide. The ever-increasing and global occurrence of massive and prolonged blooms of cylindrospermopsin-producing cyanobacteria poses a potential threat to both human and ecosystem health. Its toxicity is associated with metabolic activation and may involve mechanisms that adversely affect a wide variety of targets in an organism.

ILSI/HESI maternal toxicity workshop summary: maternal toxicity and its impact on study design and data interpretation.

Workshops on maternal toxicity were held at the annual Society of Toxicology, Teratology Society, and European Teratology Society meetings in 2009. Speakers presented background information prior to a general discussion on this topic. The following recommendations/options are based on the outcome of the discussions at the workshops: 1.

Hypoxia and the Edema Syndrome: elucidation of a mechanism of teratogenesis.

The elucidation of mechanisms and pathogenesis of birth defects is exceedingly complex. Consequently, there are few examples where the etiology of birth defects caused by a specific agent has been well described. One such example is the "Edema Syndrome" first described by Casimer Grabowski in the 1960s as a mechanism of hypoxia-induced malformations in the chick embryo.

Altered axial skeletal development.

The axial skeleton is routinely examined in standard developmental toxicity bioassays and has proven to be sensitive to a wide variety of chemical agents. Dysmorphogenesis in the skull, vertebral column and ribs has been described in both human populations and in laboratory animals used to assess potential adverse developmental effects. This article emphasizes vertebrae and rib anomalies both spontaneous and agent induced.

Short-term exposures to dihaloacetic acids produce dysmorphogenesis in mouse conceptuses in vitro.

The haloacetic acids (HAAs) are a family of xenobiotics found in tap water as a result of drinking water disinfection. Administration of HAAs to rats produces a variety of adverse effects, including developmental toxicity. The dysmorphogenic potencies of all nine bromo/chloro-acetic acids have been determined in rodent whole embryo culture using standard 26-h exposure.

Bromochloro-haloacetic acids: effects on mouse embryos in vitro and QSAR considerations.

The haloacetic acids (HAA) are a family of chemicals that are drinking water disinfection by-products. We previously reported that haloacetic acids, including several bromo- and chloro-HAAs, alter embryonic development when mouse conceptuses are directly exposed to these xenobiotics in whole embryo culture. Craniofacial dysmorphogenesis was observed in exposed embryos and a quantitative structure activity relationship (QSAR) for induction of cranial neural tube dysmorphogenesis was established for a series of 10 HAAs, which also included fluoro- and iodo-HAA representatives.

Evaluation and interpretation of maternal toxicity in Segment II studies: issues, some answers, and data needs.

Biologically rational regulatory policies with regards to developmental toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process.

Supernumerary ribs in developmental toxicity bioassays and in human populations: incidence and biological significance.

Supernumerary or accessory ribs (SNR), either lumbar (LR) or cervical (CR), are a common finding in standard developmental toxicology bioassays. The biological significance of these anomalies within the regulatory arena has been problematic and the subject of some debate. In rodents, the spontaneous incidence of SNR is species and strain related and ranges from <1% to >30%.

Chemically induced supernumerary lumbar ribs in CD-1 mice: size distribution and dose response.

Supernumerary ribs (SNR) of differing sizes are commonly observed in rodent developmental toxicity studies, and the significance of treatment-related increases in SNR in standard studies has been contentious. We induced dose-related increases in SNR in fetal CD-1 mice by treating on gestation days 7-8 with benomyl (BEN; 0, 75, 150 mg/kg/d), dinoseb (DIN; 0, 30, 50 mg/kg/d); 2-methoxyethanol (2-ME; 0, 75, 150 mg/kg/d), or valproic acid (VPA; 0, 125, 250 mg/kg/d). Incidences of SNR were 9.

Periods of vertebral column sensitivity to boric acid treatment in CD-1 mice in utero.

Boric acid (BA) has many uses as an industrial compound and is widely distributed in the environment. BA has been shown to produce rib agenesis, a rare effect in laboratory animals. This study was conducted to determine if there is a period of sensitivity to this unusual effect.

5-Aza-2'-deoxycytidine-induced cytotoxicity and limb reduction defects in the mouse.

Background: 5-Aza-2'-deoxycytidine (dAZA), causes hindlimb phocomelia in CD-1 mice. Studies in our laboratory have examined the hypothesis that compound- induced changes in gene expression may uniquely affect hindlimb pattern formation. The present study tests the hypothesis that dAZA causes limb dysplasia by inducing cytotoxicity among rapidly proliferating cells in the limb bud mesenchyme.