Perfluorooctanoic Acid–Induced Immunomodulation in Adult C57BL/6J or C57BL/6N Female Mice

BackgroundPerfluorooctanoic acid (PFOA), an environmentally persistent compound of regulatory concern, has been reported to reduce antibody responses in mice at a single dose.ObjectiveThe aim of this study was to evaluate PFOA effects on humoral and cellular immunity using standard assays for assessing immune function, and to derive dose–response data.MethodsC57BL/6J mice received 0 or 30 mg PFOA/kg/day for 10 days; half of the exposed groups were switched to vehicle and half continued on PFOA for five days. C57BL/6N mice received 0–30 mg/kg/day of PFOA in drinking water for 15 days. Mice were immunized with sheep red blood cells or sensitized to bovine serum albumin in Freund’s complete adjuvant on day 10 of exposure; immune responses were determined 1 day post-exposure.ResultsWe found that 30 mg PFOA/kg/day given for 10 or 15 days reduced IgM synthesis; serum collected 1 day postexposure contained 8.4 × 104 or 2.7 × 105 ng PFOA/mL, respectively. IgM synthesis was suppressed at exposures ≥ 3.75 mg PFOA/kg/day in a dose-dependent manner, and IgG titers were elevated at 3.75 and 7.5 mg PFOA/kg/day. Serum PFOA at 3.75 mg/kg/day was 7.4 × 104 ng/mL 1 day postexposure, or 150-fold greater than the levels reported in individuals living near a PFOA production site. Using a second-degree polynomial model, we calculated a benchmark dose of 3 mg/kg/day, with a lower bound (95% confidence limit) of 1.75 mg/kg/day. Cell-mediated function was not affected.ConclusionsIgM antibodies were suppressed after PFOA exposure. The margin of exposure for reduced IgM antibody synthesis was approximately 150 for highly exposed human populations

Legacy and Novel Per- and Polyfluoroalkyl Substances in Juvenile Seabirds from the U.S. Atlantic Coast

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic, globally distributed chemicals. Legacy PFAS, including perfluorooctane sulfonate (PFOS), have been regularly detected in marine fauna but little is known about their current levels or the presence of novel PFAS in seabirds. We measured 36 emerging and legacy PFAS in livers from 31 juvenile seabirds from Massachusetts Bay, Narragansett Bay, and the Cape Fear River Estuary (CFRE), United States. PFOS was the major legacy perfluoroalkyl acid present, making up 58% of concentrations observed across all habitats (range: 11–280 ng/g). Novel PFAS were confirmed in chicks hatched downstream of a fluoropolymer production site in the CFRE: a perfluorinated ether sulfonic acid (Nafion byproduct 2; range: 1–110 ng/g) and two perfluorinated ether carboxylic acids (PFO4DA and PFO5DoDA; PFO5DoDA range: 5–30 ng/g). PFOS was inversely associated with phospholipid content in livers from CFRE and Massachusetts Bay individuals, while δ 13C, an indicator of marine versus terrestrial foraging, was positively correlated with some long-chain PFAS in CFRE chick livers. There is also an indication that seabird phospholipid dynamics are negatively impacted by PFAS, which should be further explored given the importance of lipids for seabirds

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

Perfluorooctanoic acid (PFOA) is a known developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg), however, has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Mouse pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in exposed female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. In contrast, an evaluation of serum hormone levels and pubertal timing onset in the same offspring revealed no effects of PFOA compared to controls in either strain. Therefore, our data suggest that the mammary gland is more sensitive to the effects of early low level PFOA exposures compared to other pubertal endpoints, regardless of strain

Microbiota alter metabolism and mediate neurodevelopmental toxicity of 17β-estradiol

Estrogenic chemicals are widespread environmental contaminants associated with diverse health and ecological effects. During early vertebrate development, estrogen receptor signaling is critical for many different physiologic responses, including nervous system function. Recently, host-associated microbiota have been shown to influence neurodevelopment. Here, we hypothesized that microbiota may biotransform exogenous 17-βestradiol (E2) and modify E2 effects on swimming behavior. Colonized zebrafish were continuously exposed to non-teratogenic E2 concentrations from 1 to 10 days post-fertilization (dpf). Changes in microbial composition and predicted metagenomic function were evaluated. Locomotor activity was assessed in colonized and axenic (microbe-free) zebrafish exposed to E2 using a standard light/dark behavioral assay. Zebrafish tissue was collected for chemistry analyses. While E2 exposure did not alter microbial composition or putative function, colonized E2-exposed larvae showed reduced locomotor activity in the light, in contrast to axenic E2-exposed larvae, which exhibited normal behavior. Measured E2 concentrations were significantly higher in axenic relative to colonized zebrafish. Integrated peak area for putative sulfonated and glucuronidated E2 metabolites showed a similar trend. These data demonstrate that E2 locomotor effects in the light phase are dependent on the presence of microbiota and suggest that microbiota influence chemical E2 toxicokinetics. More broadly, this work supports the concept that microbial colonization status may influence chemical toxicity

Analysis of PFOA in dosed CD-1 mice. Part 2: Disposition of PFOA in tissues and fluids from pregnant and lactating mice and their pups

Previous studies in mice with multiple gestational exposures to perfluorooctanoic acid (PFOA) demonstrate numerous dose dependent growth and developmental effects which appeared to worsen if offspring exposed in utero nursed from PFOA-exposed dams. To evaluate the disposition of PFOA in the pregnant and lactating dam and her offspring, time-pregnant CD-1 mice received a single 0, 0.1, 1, or 5 mg PFOA/kg BW dose (n = 25/dose group) by gavage on gestation day 17. Maternal and pup fluids and tissues were collected over time. Pups exhibited significantly higher serum PFOA concentrations than their respective dams, and their body burden increased after birth until at least postnatal day 8, regardless of dose. The distribution of milk:serum PFOA varied by dose and time, but was typically in excess of 0.20. These data suggest that milk is a substantial PFOA exposure route in mice and should be considered in risk assessment modeling designs for this compound

Nitrogen and phosphorus requirements for the bioremediation of oil in saltwater

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references: 71-82.Issued also on microfiche from Lange Micrographics.Nitrogen and phosphorus are two of the limiting factors in the bioremediation of oil in sea water, Laboratory experiments were conducted to determine the maximal flux of NH4' and P and concentrations of NH4' and P required by microorganisms utilizing oil in water. Treatments were concentrations of NH4+, and P, and inoculum size. Treatments were inoculated with a microbial consortium from Galveston Bay, Texas sea water grown by enrichment on oil. All treatments were incubated at 30'C with shaking to promote aeration. For determination of nutrient flux, disappearance of NH4' and P from the media was analyzed during microbial growth on oil. Microscopic counts of microbial populations using acridine-orange staining were done to determine growth rates of oil degrading microorganisms in sea water at different concentrations Of NH4' and P. Maximal NH4' uptake was 475.5 mg. NH4' L-1 hr-' for oil degrading populations in excess of 5.0 x 107 cells ml-'and maximal P uptake was 85.5 mg. P L" hr-'. Ammonium concentrations of 0.289 mg. NH4+ mL-' and P concentrations of 0.082 [mg P mL" did not limit cell growth so long as the concentrations could be maintained. Rapid generation times for microorganisms grown on oil in sea water generally ranged from 1. 19 to 2.97 hours when NH4+ and P was not limiting and cell populations were below 1.0 x 107 cells mL-1. At high cell populations maintenance of low concentrations of nutrients was difficult due to high microbial consumption. In estuaries concentrations and fluxes of nutrients have the potential to limit microbial utilization of oil in sea water. Concentrations of NH4+ and P that occur in estuaries may not limit microbial growth on oil, provided an adequate flux can be maintained

Perfluorinated compounds in whole fish homogenates from the Ohio, Missouri, and Upper Mississippi Rivers, USA

A method for the analysis of 10 perfluorinated compounds (PFCs) in whole fish homogenate is presented and applied to 60 fish samples collected from the Ohio, Missouri, and upper Mississippi Rivers in 2005. Method accuracy ranged between 86 and 125% with limits of quantitation between 0.2 and 10 ng/g wet weight. Intra- and inter-batch precision was generally ±20%. Perfluorooctane sulfonate (PFOS) was the predominant compound identified in these samples, contributing over 80% of total PFC composition in the fish from these rivers, with median PFOS concentrations of 24.4, 31.8, and 53.9 ng/g wet wt in the Missouri, Ohio, and Mississippi Rivers, respectively. Median PFOS levels were significantly (p = 0.01) elevated in piscivorous fish (88.0 ng/g) when compared with non-piscivorous fish (15.9 ng/g). The 10 samples with PFOS concentrations above 200 ng/g were broadly scattered across all three rivers, providing evidence of the widespread presence of this compound in these US waterways

Tissue-Specific Distribution of Legacy and Novel Per- and Polyfluoroalkyl Substances in Juvenile Seabirds

Of the thousands of per- and polyfluoroalkyl substances (PFAS) in the environment, few have been investigated in detail. In this study, we analyzed 36 legacy and emerging PFAS in multiple seabird tissues collected from individuals from Massachusetts Bay, Narragansett Bay and the Cape Fear River Estuary. PFOS was the dominant compound across multiple tissues, while long-chain perfluorinated carboxylic acids (PFCAs) dominated in brain (mean = 44% of total concentrations). Emerging perfluoroalkyl ether acids (PFEAs)—Nafion byproduct-2 and PFO5DoDA – were detected in greater than 90% of tissues in birds obtained from a nesting region downstream from a major fluorochemical production site. Compound ratios, relative body burden calculations, and electrostatic surface potential calculations were used to describe partitioning behavior of PFEAs in different tissues. Novel PFEAs preferentially partition into blood compared to liver, and were documented in brain for the first time. PFO5DoDA showed a reduced preference for brain compared to PFCAs and Nafion BP2. These results suggest future monitoring efforts and toxicological studies should focus on novel PFAS and long-chain PFCAs in multiple tissues beyond liver and blood, while exploring the unique binding mechanisms driving uptake of multi-ether PFEAs